tbuckley/cabot-search huggingface dataset:
Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)
Authors: Junzo Hamanishi, Nobuhiro Takeshima, Noriyuki Katsumata, Kimio Ushijima, Tadashi Kimura, Satoshi Takeuchi, Koji Matsumoto, Kimihiko Ito, Masaki Mandai, Hidekatsu Nakai, Noriaki Sakuragi, Hidemichi Watari, Nobutaka Takahashi, Hidenori Kato, Kosei Hasegawa, Kan Yonemori, Mika Mizuno, Kazuhiro Takehara, Hitoshi Niikura, Takashi Sawasaki, Sari Nakao, Toshiaki Saito, Takayuki Enomoto, Satoru Nagase, Nao Suzuki, Takashi Matsumoto, Eiji Kondo, Kenzo Sonoda, Satomi Aihara, Yoichi Aoki, Aikou Okamoto, Hirokuni Takano, Hiroshi Kobayashi, Hisamori Kato, Yoshito Terai, Akira Takazawa, Yusuke Takahashi, Yoshinobu Namba, Daisuke Aoki, Keiichi Fujiwara, Toru Sugiyama, Ikuo Konishi
Journal: Journal of Clinical Oncology (2021)

This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer.
Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan
Authors: Szu-Min Hsieh, Ming-Che Liu, Yen-Hsu Chen, Wen-Sen Lee, Shinn-Jang Hwang, Shu-Hsing Cheng, Wen-Chien Ko, Kao-Pin Hwang, Ning-Chi Wang, Yu-Lin Lee, Yi-Ling Lin, Shin-Ru Shih, Chung-Guei Huang, Chun-Che Liao, Jian-Jong Liang, Chih-Shin Chang, Charles Chen, Chia En Lien, I-Chen Tai, Tzou-Yien Lin
Journal: The Lancet Respiratory Medicine (2021)
Tumor Immunogenomic Features Determine Outcomes in Patients with Metastatic Colorectal Cancer Treated with Standard-of-Care Combinations of Bevacizumab and Cetuximab
Authors: Federico Innocenti, Akram Yazdani, Naim Rashid, Xueping Qu, Fang-Shu Ou, Scott Van Buren, Monica M. Bertagnolli, Omar Kabbarah, Charles David Blanke, Alan P. Venook, Heinz-Josef Lenz, Benjamin G. Vincent
Journal: Clinical Cancer Research (2022)

CALGB/SWOG 80405 was a randomized phase III trial in first-line patients with metastatic colorectal cancer treated with bevacizumab, cetuximab, or both, plus chemotherapy. We tested the effect of tumor immune features on overall survival (OS).Primary tumors (N = 554) were profiled by RNA sequencing. Immune signatures of macrophages, lymphocytes, TGFβ, IFNγ, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured.Increased M2 macrophage score [HR, 6.30; 95% confidence interval (CI), 3.0-12.15] and TGFβ signature expression (HR, 1.35; 95% CI, 1.05-1.77) were associated with shorter OS. Increased scores of plasma cells (HR, 0.55; 95% CI, 0.38-0.87) and activated memory CD4+ T cells (HR, 0.34; 95% CI, 0.16-0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0-1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8-47.8) to 31.0 (28.8-34.4), 25.2 (20.6-27.9), and 17.7 (13.5-20.4) months respectively (P = 3.48e-11).New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.
Abstract MP12: Association Of Peripheral Neuropathy With Injurious Falls And Fractures In The Atherosclerosis Risk In Communities Study
Authors: Caitlin W Hicks, Dan Wang, Natalie R Daya, B Gwen Windham, Stephen P Juraschek, Kuni Matsushita, Elizabeth Selvin
Journal: Circulation (2022)

Background: Peripheral neuropathy (decreased sensation in the foot) as assessed by monofilament testing is associated with all-cause and cardiovascular mortality. We aimed to assess the association of peripheral neuropathy with incident injurious falls and fractures in older adults. Methods: All black and white participants in the Atherosclerosis Risk in Communities Study (ARIC) who underwent monofilament testing at visit 6 (2016-2017) were included. Incident injurious falls and fractures were identified based on ICD-9 and -10 codes from active surveillance of all hospitalizations and linkage to Medicare claims. We used Kaplan Meier curves and Cox regression to assess the association of peripheral neuropathy with injurious falls and fractures (combined and as separate outcomes) after adjusting for demographics, diabetes status, and risk factors for falls. Results: There were 3,597 ARIC participants (mean age 79.4, SD 4.7 years), of which 1,236 (34.4%) had peripheral neuropathy based on monofilament testing. During a median follow-up of 2.5 years, 371 participants had a documented fall and 475 participants had a documented fracture. The incidence rate (per 1,000 person-years) for incident injurious falls/fracture, falls, and fractures was higher for participants with peripheral neuropathy compared to those without ( Table ). After adjustment, peripheral neuropathy was consistently and independently associated with all outcomes. Further adjustment for cognitive status, medication use, prior fall or fractures, and analyses accounting for the competing risk of death did not substantially change our results. Conclusions: Peripheral neuropathy as measured by monofilament testing is associated with incident injurious falls and fracture in older adults. Screening with monofilament testing is inexpensive and simple and may be warranted to identify older adults at high risk for falls.
Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self
Authors: Roshni Roy Chowdhury, Jessica D’Addabbo, Xianxi Huang, Stefan Veizades, Koki Sasagawa, David M. Louis, Paul Cheng, Jan Sokol, Annie Jensen, Alexandria Tso, Vishnu Shankar, Ben Shogo Wendel, Isaac Bakerman, Grace Liang, Tiffany Koyano, Robyn Fong, Allison N. Nau, Herra Ahmad, Jayakrishnan Gopakumar, Robert Wirka, Andrew S. Lee, Jack Boyd, Y. Joseph Woo, Thomas Quertermous, Gunsagar Singh Gulati, Siddhartha Jaiswal, Yueh-Hsiu Chien, Charles Kwok Fai Chan, Mark M. Davis, Patricia K. Nguyen
Journal: Circulation Research (2022)

Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies.
Thrombin Generation As a Predictive Biomarker for Venous Thromboembolism in Patients with Pancreatic and Lung Cancer Undergoing Systemic Therapy
Authors: Lukas P Emery, Michael Y. Cho, Aderonke Ajala, Lauren T. Salvatore, Deborah L. Ornstein, Monic R. Drescher
Journal: Blood (2021)
Abstract P175: Combined Metabolic Health And Obesity Status Is Associated With Markers Of High-Density Lipoprotein Metabolism: Dallas Heart Study
Authors: William A Clarkson, Jacob L Barber, Bridget Armstrong, Yuan Wang, Fiona C McGillicuddy, Suzanne Saldanha, Oludamilola Akinmolayemi, Ian J Neeland, Anand Rohatgi, Mark A Sarzynski
Journal: Circulation (2022)

Introduction: While high-density lipoprotein (HDL) cholesterol is a component of metabolic syndrome, an ASCVD risk factor, other markers of HDL metabolism better associate with ASCVD. However, it is unclear whether these markers better discriminate between metabolic health and obese groups. Hypothesis: We hypothesized that higher cholesterol efflux capacity (CEC) and a favorable HDL profile would be associated with metabolically healthy profiles within each weight category. Methods: Data from the second phase of the Dallas Heart Study were used to classify participants (n=2156) into four groups based on a harmonized definition of metabolic health and obesity status: Metabolically Healthy, Normal Weight (MHNW); Metabolically Unhealthy, Normal Weight (MUNW); Metabolically Healthy, Obese (MHO); Metabolically Unhealthy, Obese (MUO). MU was classified as having one or more of the following: elevated blood pressure (SBP/DBP ≥130/85 mmHg), fasting glucose (≥100 mg/dL), or fasting triglycerides (≥150 mg/dL); a history of CVD or diabetes; or any medications for these conditions. Obesity was defined as BMI ≥ 30kg/m 2 . CEC was measured using J774 macrophages, BODIPY- and radio-labeled cholesterol, and apoB-precipitated plasma. HDL particle (HDL-P) subfractions were quantified by NMR spectroscopy. Generalized linear models were used to compare paired means of CEC and HDL traits between groups controlling for age, sex, race, and smoking. Results: Small HDL-P concentration was higher in MU groups regardless of weight status. Total and medium HDL-P concentrations and radio-labeled CEC were higher in NW groups, regardless of metabolic health status. Mean HDL-P size and large HDL-P concentrations were different across all groups, with the rank order being MHNW, MUNW, MHO, MUO (Table 1). Conclusions: In conclusion, associations between HDL subfractions, CEC and metabolic/weight status are heterogeneous, highlighting the complexity of HDL physiology as it pertains to body weight and metabolic disease.
Focal PSMA-Positive Pleural Lesion in a Patient With Stage II Prostate Carcinoma
Authors: Rutger J. Lensing, Wouter A.M. Broos, Friso M. van der Zant, Remco J.J. Knol
Journal: Clinical Nuclear Medicine (2022)

A 70-year-old man with histopathologically proven prostate carcinoma (Gleason, 5 + 5; prostate-specific antigen level, 6.2 μg/mL) was referred for an 18F-PSMA-1007 PET/CT scan. The scan revealed bilateral PSMA uptake in the prostate, representing the primary tumor, but no evidence of PSMA-positive lymph nodes. However, a left-sided ventral pleural thickening showed focal PSMA uptake. Lesion biopsy showed no signs of malignancy, and prostatectomy was performed. The 1-year follow-up CT thorax showed growth of approximately 20% of the pleural lesion. Subsequently, video-assisted thoracic surgery of the lesion was performed. Histopathology showed a solitary fibrous tumor, a rare mesenchymal tumor.
Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation
Authors: Joseph J Wanford, Ryan G Hames, David Carreno, Zydrune Jasiunaite, Wen Y Chung, Fabio Arena, Vincenzo Di Pilato, Kornelis Straatman, Kevin West, Robeena Farzand, Mariagrazia Pizza, Luisa Martinez-Pomares, Peter W Andrew, E Richard Moxon, Ashley R Dennison, Gian Maria Rossolini, Marco R Oggioni
Journal: The Lancet Microbe (2021)
Representing knowledge, belief, and everything in between: Representational complexity in humans and other apes
Authors: Kresimir Durdevic, Christopher Krupenye
Journal: Behavioral and Brain Sciences (2021)

Abstract Building on Phillips and colleagues' case for the primacy of knowledge, we advocate for attention to diversity in mentalizing constructs within, as well as between, knowledge and belief. Ultimately, as great apes and other animals show, the development and evolution of theory of mind may reflect a much greater range of incremental elaborations of representational or computational complexity.
The Role of mRNA Translational Control in Tumor Immune Escape and Immunotherapy Resistance
Authors: Michaël Cerezo, Caroline Robert, Lunxu Liu, Shensi Shen
Journal: Cancer Research (2021)

Abstract Tremendous advances have been made in cancer immunotherapy over the last decade. Among the different steps of gene expression, translation of mRNA is emerging as an essential player in both cancer and immunity. Changes in mRNA translation are both rapid and adaptive, and translational reprogramming is known to be necessary for sustaining cancer cell proliferation. However, the role of mRNA translation in shaping an immune microenvironment permissive to tumors has not been extensively studied. Recent studies on immunotherapy approaches have indicated critical roles of mRNA translation in regulating the expression of immune checkpoint proteins, tuning the secretion of inflammation-associated factors, modulating the differentiation of immune cells in the tumor microenvironment, and promoting cancer resistance to immunotherapies. Careful consideration of the role of mRNA translation in the tumor-immune ecosystem could suggest more effective therapeutic strategies and may eventually change the current paradigm of cancer immunotherapy. In this review, we discuss recent advances in understanding the relationship between mRNA translation and tumor-associated immunity, the potential mechanisms of immunotherapy resistance in cancers linked to translational reprogramming, and therapeutic perspectives and potential challenges of modulating translational regulation in cancer immunotherapy.
Abstract P229: The Association Of Cumulative Socioeconomic Status And Incident Type 2 Diabetes Among African Americans: The Jackson Heart Study
Authors: LaShaunta M Glover, Chantel Martin, Reuben Adatorwovor, Laura R Loehr, Brooke Staley, Kari E North, Mario Sims
Journal: Circulation (2022)

Background: The burden of type 2 diabetes (T2D) is disproportionately higher among racial and ethnic minorities, particularly African American individuals who have low socioeconomic status (SES). According to the cumulative SES life-course model, stressful experiences in early life and later life can accumulate to influence disease risk. Yet, little is known about the association between cumulative SES, or the combined effects of different SES phenotypes (i.e., education, wealth, income, etc.), over the life course and development of T2D. Objective: To estimate the association of cumulative SES and incident T2D among men and women without T2D and cardiovascular disease at baseline (2000-2004) from the Jackson Heart Study (JHS) (n=3078). Methods: Using cohort data from JHS (mean age 52.8 years; 1969 women, 1109 men), we derived standardized cumulative SES scores at baseline, conceptualized using 6 SES indicators (e.g. educational attainment, wealth, income, occupation, employment status and mother’s education) and dichotomized the score as high SES (median and above - referent) and low SES (below the median). Incident T2D was defined at exam 2 (2005-2008) or exam 3 (2009-2013) based on a fasting glucose ≥126 mg/dL, or HbA1c ≥ 6.5, or those who had been on diabetic medication 2 weeks prior to these visits, or those who reported a physician diagnosis. Interval censoring proportional hazards regression was used to estimate the association between cumulative SES and incident T2D using hazard ratios (HR, 95% confidence interval-CI), where time-to-event was approximated as the interval between the first visit and the visit in which T2D was ascertained. Sex differences were evaluated using interaction terms and descriptive statistics. The fully-adjusted model included baseline covariates: age, waist circumference, health behaviors, and family history of diabetes. Results: There were 544 total incident T2D cases and 65% (351) of cases were characterized as having low SES. The dichotomized cumulative score was associated with incident T2D ( p &lt;0.05) in unadjusted chi square analyses. In the fully-adjusted models, low (vs. high) cumulative SES and the standardized score were marginally associated with incident T2D (HR 1.14; 95% CI (0.95, 1.38) and HR 0.99; 95% CI (0.90, 1.08), respectively). There were no significant sex differences in the association between cumulative SES and incident T2D. Conclusion: Low cumulative SES was not significantly associated with development of T2D when adjusting for potential confounders. Future work should consider examination of adverse experiences related to low SES and other environmental factors such as built environment and neighborhood SES.
HOW TO INCORPORATE MRD IN CLINICAL TRIALS
Authors: Jesus San-Miguel
Journal: HemaSphere (2022)

Depth of response is the key element to evaluate treatment efficacy and predict survival. Eradicating all tumor cells is necessary to cure most malignancies and this requires achieving and maintaining the deepest response possible. Both next generation flow (NGF) cytometry, and next generation sequencing (NGS) affords a sensitivity of 10-6. Patients that achieve a negative MRD status at the level of 10-5 or 10-6, display significantly longer progression-free (PFS) and overall survival (OS) when compared to those with positive MRD. The prognostic impact of MRD apply to newly-diagnosed transplant eligible and ineligible MM as well as relapsed/refractory patients and there is growing consensus that MRD is the most relevant prognostic factor in MM. Nevertheless, an MRD negative result should be confirmed and sustained for 12 or more months to minimize the risk of false-negative results. Mass spectrometry is also emerging as a potent technique to detect low levels of paraprotein as a surrogate for residual disease. In addition imaging techiques, particularly PET-CT, has an important role for MRD assessment outside of the BM. Currently MRD has been incorporated in numerous clinical trials with different aims: 1. to evaluate treatment efficacy; 2. to compare two treatment approaches; 3. adapted therapy intensity according to MRD follow-up; 4. to adapt maintenance duration; 5. to introduce Early Rescue Intervetion (ERI) strategies. The implantation of MRD should help in avoiding over and under treatment and may become a surrogate biomarker for accelerated drug development and operational cure.
Abstract P221: ASSOCIATION OF PSYCHOLOGICAL RESILIENCE WITH ALL-CAUSE AND CARDIOVASCULAR MORTALITY IN A GENERAL POPULATION IN ITALY: PROSPECTIVE FINDINGS FROM THE MOLI-SANI STUDY
Authors: anwal ghulam, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, francesca santonaso, Augusto F Di Castelnuovo, chiara cerletti, Maria Donati, Giovanni De Gaetano, Francesco Gianfagna, Licia Iacoviello
Journal: Circulation (2022)

Introduction: Psychological resilience (PR) is understood as the capacity to adapt positively in face of adverse events. Its role as an independent protective factor for health has been increasingly acknowledged in recent years. Hypothesis: We tested the hypothesis that psychological resilience could act as a protective factor towards disease, in particular, could decrease risk of premature death from cardiovascular (CVD) or all causes. We further investigated the association of single domains of PR with all cause and CVD mortality. Methods: We analysed prospective data on 10,406 individuals (mean age 52±10 y, 50.4% women) from the Moli-sani Study cohort, recruited between 2005 and 2010 and followed up for all-cause and CVD mortality for a median of 11.2 y. PR was assessed at baseline by the 25-item Connor and Davidson resilience scale (CD-RISC). A polychoric factor analysis was used to identify main domains reflecting different aspects of PR. Association of PR (or its domains) with all-cause and CVD mortality was tested using multivariable Cox proportional hazard models. Results: Higher levels of PR were associated with reduced all-cause mortality as compared to lower PR in a model adjusted for sex and age (HR=0.78; 95%CI 0.62-1.00 for Q4 vs Q1; p for trend=0.029). The association decreased after inclusion of socioeconomic, clinical, and behavioural factors into the model (HR=0.80; 95%CI 0.62-1.03; p for trend=0.059). No relation was observed with CVD mortality in the fully adjusted model (HR=0.89; 95%CI 0.56-1.39 for Q4 vs Q1). The polychoric factor analysis resulted in 5 main factors: Factor 1 reflected positive acceptance of change; Factor 2 reflected faith and hope; Factor 3 reflected secure attachment and secure relationships; Factor 4 reflected external locus of control and confidence in one’s abilities; and Factor 5 reflected strengthening effects of stress and self-efficacy. When individual PR factors were considered, an inverse association of Factor 1 with all-cause mortality (HR=0.89; 95%CI 0.82-0.98; p value=0.01) was apparent. Conclusions: Though at a borderline not significant way, PR total score predicts all-cause mortality in a general population of CVD-free adult Italians. This is supported by the finding that PR’s domain reflecting a positive acceptance of change is significantly associated with all-cause mortality. However, no association between PR and CVD mortality was found.
196P An international consensus on actions to improve lung cancer survival: A clinical review by the international cancer benchmarking partnership (ICBP)
Authors: C. Lynch, S. Harrison, J. Butler, D.R. Baldwin, P. Dawkins, J. van der Horst, E. Jakobsen, J. McAleese, A. McWilliams, K. Redmond, A. Swaminath, C. Finley
Journal: Annals of Oncology (2022)
The Genetic Evolution of Metastasis
Authors: Aljosja Rogiers, Irene Lobon, Lavinia Spain, Samra Turajlic
Journal: Cancer Research (2022)

Abstract Cancer is an evolutionary process that is characterized by the emergence of multiple genetically distinct populations or clones within the primary tumor. Intratumor heterogeneity provides a substrate for the selection of adaptive clones, such as those that lead to metastasis. Comparative molecular studies of primary tumors and metastases have identified distinct genomic features associated with the development of metastases. In this review, we discuss how these insights could inform clinical decision-making and uncover rational antimetastasis treatment strategies.
Abstract MP48: Daily Spiritual Experiences And Allostatic Load Trajectories In Midlife African American Women
Authors: Elizabeth A Williams, Yamnia I Cortes, Shuo Zhang, Latesha K Harris
Journal: Circulation (2022)

Introduction: African American women have a significantly higher risk for cardiovascular disease (CVD) with an earlier age of onset than non-Hispanic whites. Recent evidence suggests that psychological stress may contribute to the disproportionate burden of CVD in midlife African American women. Religion and spirituality have been associated with lower risk of CVD and improved psychological distress. Hypothesis: We assessed the hypothesis that daily spirituality may have cardioprotective effects among midlife African American women. Methods: We performed a secondary analysis of public-use data from 727 African American women enrolled in the Study of Women’s Health Across the Nation (SWAN), a multi-site longitudinal cohort study. Biological, psychosocial, and physical measures were collected approximately annually. Allostatic load (AL) was calculated at each visit using 10 biomarkers representing neuroendocrine, immune, metabolic, and cardiovascular system functioning. Group-based trajectory modeling identified women with similar patterns of AL over a 7-year period. The Daily Spiritual Experiences Scale was used to categorize daily spiritual experiences (some days or less, most days, daily, many times a day). We used logistic regression to estimate associations between daily spiritual experiences and AL trajectory group. Models adjusted for baseline age, education, and depressive symptoms. Results: Three distinct trajectories of AL were identified: low (35.1% = 255 of 727), moderate (44.7% = 325 of 727), and high (20.2% = 147 of 727). We found that women who reported daily comfort in religion and spirituality were less likely to be represented in the high AL trajectory group when controlling for age. Conclusions: Our findings suggest that spirituality may have cardioprotective effects among midlife African American women. Further investigation on sociocultural factors that may buffer the negative effects of psychological distress on CVD risk in midlife African American women is needed. This work can inform culturally relevant interventions to improve cardiovascular health outcomes in this population.