tbuckley/cabot-search huggingface dataset:
Defining Multimorbidity and Its Impact in Older United States Veterans Newly Treated for Multiple Myeloma
Authors: Nathanael R Fillmore, Clark DuMontier, Cenk Yildirim, Jennifer La, Mara M Epstein, David Cheng, Diana Cirstea, Sarvari Yellapragada, Gregory A Abel, J Michael Gaziano, Nhan Do, Mary Brophy, Dae H Kim, Nikhil C Munshi, Jane A Driver
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM). Methods We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations. Results Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P &amp;lt; .001). Older veterans with cardiovascular and metabolic disease (30.9%, hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.21 to 1.45), psychiatric and substance use disorders (9.7%, HR = 1.58, 95% CI = 1.39 to 1.79), chronic lung disease (15.9%, HR = 1.69, 95% CI = 1.53 to 1.87), and multisystem impairment (13.8%, HR = 2.25, 95% CI = 2.03 to 2.50) had higher mortality compared with veterans with minimal comorbidity (29.7%, reference). Associations with mortality were maintained after adjustment for sociodemographic variables, measures of disease risk, and the count-based Charlson Comorbidity Index. Multimorbidity patterns were also associated with emergency department visits and hospitalizations. Conclusions Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions.
Empagliflozin Effects on Pulmonary Artery Pressure in Patients With Heart Failure
Authors: Michael E. Nassif, Mohammed Qintar, Sheryl L. Windsor, Rita Jermyn, David M. Shavelle, Fengming Tang, Sumant Lamba, Kunjan Bhatt, John Brush, Andrew Civitello, Robert Gordon, Orvar Jonsson, Brent Lampert, Jamie Pelzel, Mikhail N. Kosiborod
Journal: Circulation (2021)

Sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors) prevent heart failure (HF) hospitalizations in patients with type 2 diabetes and improve outcomes in those with HF and reduced ejection fraction, regardless of type 2 diabetes. Mechanisms of HF benefits remain unclear, and the effects of SGLT2 inhibitor on hemodynamics (filling pressures) are not known. The EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) was designed to address this knowledge gap.EMBRACE-HF is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of ejection fraction, with or without type 2 diabetes) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary end point was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Secondary end points included health status (Kansas City Cardiomyopathy Questionnaire score), natriuretic peptides, and 6-min walking distance.Overall, 93 patients were screened, and 65 were randomized (33 to empagliflozin, 32 to placebo). The mean age was 66 years; 63% were male; 52% had type 2 diabetes; 54% were in New York Heart Association class III/IV; mean ejection fraction was 44%; median NT-proBNP (N-terminal pro B-type natriuretic peptide) was 637 pg/mL; and mean PADP was 22 mm Hg. Empagliflozin significantly reduced PADP, with effects that began at week 1 and amplified over time; average PADP (weeks 8-12) was 1.5 mm Hg lower (95% CI, 0.2-2.8; P=0.02); and at week 12, PADP was 1.7 mm Hg lower (95% CI, 0.3-3.2; P=0.02) with empagliflozin versus placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in Kansas City Cardiomyopathy Questionnaire scores, natriuretic peptide levels, and 6-min walking distance.In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030222.
Astrocyte-derived extracellular vesicles enhance the survival and electrophysiological function of human cortical neurons in vitro
Authors: Changho Chun, Alec S.T. Smith, Hyejin Kim, Dana S. Kamenz, Jung Hyun Lee, Jong Bum Lee, David L. Mack, Mark Bothwell, Claire D. Clelland, Deok-Ho Kim
Journal: Biomaterials (2021)
Functional and Taxonomic Dysbiosis of the Gut, Urine, and Semen Microbiomes in Male Infertility
Authors: Scott D. Lundy, Naseer Sangwan, Neel V. Parekh, Manesh Kumar Panner Selvam, Sajal Gupta, Peter McCaffrey, Kovi Bessoff, Ayin Vala, Ashok Agarwal, Edmund S. Sabanegh, Sarah C. Vij, Charis Eng
Journal: European Urology (2021)

Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility. To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men. We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls. We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling. We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct β-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis. This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease. We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future.
Sex- and Age-Related Differences in the Distribution of Metastases in Patients With Upper Urinary Tract Urothelial Carcinoma
Authors: Marina Deuker, Giuseppe Rosiello, Lara Franziska Stolzenbach, Thomas Martin, Claudia Collà Ruvolo, Luigi Nocera, Zhe Tian, Frederik C. Roos, Andreas Becker, Luis A. Kluth, Derya Tilki, Shahrokh F. Shariat, Fred Saad, Felix K.H. Chun, Pierre I. Karakiewicz
Journal: Journal of the National Comprehensive Cancer Network (2021)

The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC.Within the Nationwide Inpatient Sample database (2000-2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64-72, 73-79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests.Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women).Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.
Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft
Authors: Qingjin Cai, Wanshan Liao, Fangchao Xue, Xiaochen Wang, Weiming Zhou, Yanzhao Li, Wen Zeng
Journal: Bioactive Materials (2021)

Tissue-engineered vascular grafts (TEVGs) have enormous potential for vascular replacement therapy. However, thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs (<6 mm) after transplantation. Endothelialization of TEVGs is a key point to prevent thrombosis. Here, we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts. Meanwhile, endothelial heterogeneity is also discussed. Based on it, we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.
Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)
Authors: José S.A. Belderbos, Dirk K.M. De Ruysscher, Katrien De Jaeger, Friederike Koppe, Maarten L.F. Lambrecht, Yolande N. Lievens, Edith M.T. Dieleman, Jaap P.M. Jaspers, Jan P. Van Meerbeeck, Fred Ubbels, Margriet H. Kwint, Marianne A. Kuenen, Sabine Deprez, Michiel B. De Ruiter, Willem Boogerd, Karolina Sikorska, Harm Van Tinteren, Sanne B. Schagen
Journal: Journal of Thoracic Oncology (2021)
Reduced CXCL4/PF4 expression as a driver of increased human hematopoietic stem and progenitor cell proliferation in polycythemia vera
Authors: Fabienne Meier-Abt, Witold E. Wolski, Ge Tan, Sandra Kummer, Sabine Amon, Markus G. Manz, Ruedi Aebersold, Alexandre P. A. Theocharides
Journal: Blood Cancer Journal (2021)
Evaluating Depressive Symptoms Among Low-Socioeconomic-Status African American Women Aged 40 to 75 Years With Uncontrolled Hypertension
Authors: Angel Gabriel, Hossein Zare, Wehmah Jones, Manshu Yang, Chidinma A. Ibe, Yidan Cao, Michele Balamani, Marilyn Gaston, Gayle Porter, Denise L. Woods, Darrell J. Gaskin
Journal: JAMA Psychiatry (2021)

Depression is one of the leading causes of disability in the United States. African American women of low socioeconomic status with uncontrolled hypertension are at risk of having severe depressive symptoms, yet there is limited research about the mental health of this vulnerable population. Data from the Prime Time Sister Circles randomized clinical trial (PTSC-RCT) study can shed light on the prevalence of depressive symptoms among low-socioeconomic-status older African American women with hypertension.To determine the prevalence of depressive symptoms among low-socioeconomic-status African American women aged 40 to 75 years with uncontrolled hypertension who receive their care from a federally qualified health center (FQHC) and to identify risk factors associated with depressive symptoms.Cross-sectional analysis of data from the PTSC-RCT of depressive symptomology, measured using an adapted version of the 10-item Center for Epidemiological Studies Depression Scale Revised (CES-D-10). Descriptive statistics were used to characterize the study population. We used logistic regression models to investigate the factors associated with participants with or without symptoms of depression. We used baseline data from the PTSC-RCT study, including 316 African American English-speaking women between ages 40 and 75 years with hypertension (systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg), who received their primary care at a FQHC in Washington, DC, in 2017 and 2018 and were flagged by the FQHC as uncontrolled.We used the CES-D-10 from the Center for Epidemiologic Studies Depression Scale to measure presence of depressive symptoms.A total of 57.0% of the women in the study (180 of 316) scored greater than or equal to 10 on the CES-D-10. Depressive symptoms had a negative association with a postsecondary education (adjusted odds ratio [aOR], 0.492; 95% CI, 0.249-0.968) and a positive association with the number of chronic conditions (aOR, 1.235; 95% CI, 1.046-1.460) and smoking (aOR, 1.731; 95% CI, 1.039-2.881).In this study of low-income African American women with uncontrolled hypertension, more than half had symptoms of depression that was associated with less than high-school education, chronic conditions, and smoking. Low-income African American women with uncontrolled hypertension should be screened and adequately treated for depressive symptoms.ClinicalTrials.gov Identifier: NCT04371614.
Immunotherapy for targeting cancer stem cells in hepatocellular carcinoma
Authors: Xiaomeng Dai, Yixuan Guo, Yan Hu, Xuanwen Bao, Xudong Zhu, Qihan Fu, Hangyu Zhang, Zhou Tong, Lulu Liu, Yi Zheng, Peng Zhao, Weijia Fang
Journal: Theranostics (2021)

The rapid development and remarkable success of checkpoint inhibitors have provided significant breakthroughs in cancer treatment, including hepatocellular carcinoma (HCC). However, only 15-20% of HCC patients can benefit from checkpoint inhibitors. Cancer stem cells (CSCs) are responsible for recurrence, metastasis, and local and systemic therapy resistance in HCC. Accumulating evidence has suggested that HCC CSCs can create an immunosuppressive microenvironment through certain intrinsic and extrinsic mechanisms, resulting in immune evasion. Intrinsic evasion mechanisms mainly include activation of immune-related CSC signaling pathways, low-level expression of antigen presenting molecules, and high-level expression of immunosuppressive molecules. External evasion mechanisms are mainly related to HBV/HCV infection, alcoholic/nonalcoholic steatohepatitis, hypoxia stimulation, abnormal angiogenesis, and crosstalk between CSCs and immune cells. A better understanding of the complex mechanisms of CSCs involved in immune evasion will contribute to therapies for HCC. Here we will outline the detailed mechanisms of immune evasion for CSCs, and provide an overview of the current immunotherapies targeting CSCs in HCC.
Abstract PO002: Inducing homologous recombination deficiency in uterine serous cancer (USC) using AVB-500, a receptor tyrosine kinase AXL inhibitor
Authors: Michael D. Toboni, Barbara Blachut, Elena Lomonosova, Dineo Khabele, Lindsay Kuroki, Andrea Hagemann, Carolyn McCourt, Premal Thaker, David Mutch, Matthew Powell, Katherine Fuh
Journal: Clinical Cancer Research (2021)

Abstract Background: Evidence suggests that inducing homologous recombination deficiency (HRD) can be a therapeutic target in endometrial cancer (EC). Given this, we determined whether AVB-500, an AXL inhibitor, could induce HRD measured by a reduction of RAD51 foci in response to DNA damage in a uterine serous cancer (USC). Methods: Baseline homologous recombination (HR) status was determined after inducing DNA damage by radiating USC cell lines (ARK1 and ARK4) with 10Gy radiation treatment (RT) and identifying RAD51 foci by immunofluorescence (IF). Both radiated and non-radiated cells were quantified in both cell lines. Cell lines were considered to be HR proficient if over 30% of the cells expressed RAD51 (&amp;gt;5 foci per cell). AVB-500 (Aravive Biologics, Houston, TX) was given prior to radiation after baseline HR status was established. IF was conducted using a Leica confocal microscope and foci were quantified using FociCounter. Results: Both ARK1 and ARK4, showed HR proficiency at baseline. After radiation, there was an increase in gamma-H2Ax indicative of DNA damage and an appropriate increase in RAD51 foci in response. However, when cells were treated with AVB-500 prior to radiation, there was a decrease in RAD51 foci when compared to radiation alone in both ARK1 (2.7 foci for AVB + RT vs 7.3 foci for RT only, p=0.0003) and ARK4 (6.3 foci for AVB + RT vs 13.0 foci for RT only, p=0.0054). Furthermore, after treatment with AVB-500 followed by RT, the proportion of ARK1 cells expressing RAD51 decreased to 21%, indicating HR deficiency. Conclusions: ARK1 and ARK4 are HR proficient at baseline. Pretreatment with AVB500 followed by RT led to a decrease in RAD51 foci suggestive of inducing HRD. Additional therapeutic and mechanistic experiments are ongoing. Citation Format: Michael D. Toboni, Barbara Blachut, Elena Lomonosova, Dineo Khabele, Lindsay Kuroki, Andrea Hagemann, Carolyn McCourt, Premal Thaker, David Mutch, Matthew Powell, Katherine Fuh. Inducing homologous recombination deficiency in uterine serous cancer (USC) using AVB-500, a receptor tyrosine kinase AXL inhibitor [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO002.
Epilepsy Detection From EEG Using Complex Network Techniques: A Review
Authors: Supriya Supriya, Siuly Siuly, Hua Wang, Yanchun Zhang
Journal: IEEE Reviews in Biomedical Engineering (2021)

Epilepsy is one of the most chronic brain disorder recorded from since 2000 BC. Almost one-third of epileptic patients experience seizures attack even with medicated treatment. The menace of SUDEP (Sudden unexpected death in epilepsy) in an adult epileptic patient is approximately 8-17% more and 34% in a children epileptic patient. The expert neurologist manually analyses the Electroencephalogram (EEG) signals for epilepsy diagnosis. The non-stationary and complex nature of EEG signals this task more error-prone, time-consuming and even expensive. Hence, it is essential to develop automatic epilepsy detection techniques to ensure an appropriate identification and treatment of this disease. Nowadays, graph-theory has been considered as a prominent approach in the neuroscience field. The network-based approach characterizes a hidden sight of brain activity and brain-behavior mapping. The graph-theory not even helps to understand the underlying dynamics of EEG signals at microscopic, mesoscopic, and macroscopic level but also provide the correlation among them. This paper provides a review report about graph-theory based automated epilepsy detection methods. Furthermore, it will assist the expert's neurologist and researchers with the information of complex network-based epilepsy detection and aid the technician for developing an intelligent system that improving the diagnosis of epilepsy disorder.
Medications for Idiopathic Pulmonary Fibrosis: IPF Part 2
Authors: Sabina A. Guler, Kathleen O. Lindell, Jeff Swigris, Christopher J. Ryerson
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Medications for Idiopathic Pulmonary Fibrosis: IPF Part 2." American Journal of Respiratory and Critical Care Medicine, 203(3), pp. P7–P8
Abstract 12668: A Novel Anti-inflammation and Anti-fibrosis Agent, Vcp979, Treatment Attenuates Ventricular Remodeling and Improves Cardiac Function in Murine Model of Myocardial Ischemia/Reperfusion Injury
Authors: Bing H Wang, Jing Liu, Qingshu Meng, Hao Cao, Xiaoting Liang, Rulin Zhuang, Xinyu Ge, Fang Lin, Kevin W Huang, Huimin Fan, Peter Scammells, Xiaohui Zhou, Zhongmin Liu
Journal: Circulation (2019)

Introduction: Myocardial ischemia/reperfusion (MI/R) injury results in persistent ventricular remodeling with no effective treatment leading to cardiac functional decline and eventually progression...
A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695)
Authors: Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Alva, Seth P. Lerner, M. Scott Lucia, David J. McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) and gemcitabine-cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cancer. The aim of this study was to validate the score from a coexpression extrapolation (COXEN) algorithm–generated gene expression model (GEM) as a biomarker in patients undergoing radical cystectomy. Patients and Methods: Eligibility included cT2-T4a N0 M0, urothelial bladder cancer, ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy; 237 patients were randomized between ddMVAC, given every 14 days for four cycles, and GC, given every 21 days for four cycles. The primary objective assessed prespecified dichotomous treatment-specific COXEN score as predictive of pT0 rate or ≤ pT1 (downstaging) at surgery. Results: Among 167 evaluable patients, the OR for pT0 with the GC GEM score in GC-treated patients was 2.63 [P = 0.10; 95% confidence interval (CI), 0.82–8.36]; for the ddMVAC COXEN GEM score with ddMVAC treatment, the OR was 1.12 (P = 0.82, 95% CI, 0.42–2.95). The GC GEM score was applied to pooled arms (GC and ddMVAC) for downstaging with an OR of 2.33 (P = 0.02; 95% CI, 1.11–4.89). In an intention-to-treat analysis of eligible patients (n = 227), pT0 rates for ddMVAC and GC were 28% and 30% (P = 0.75); downstaging was 47% and 40% (P = 0.27), respectively. Conclusions: Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment. The COXEN GEM GC score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.
Long-Term Follow-up of a Prospective Phase II Trial of Extended Treatment with Rituximab in Patients with B-Cell Post-Transplant Lymphoproliferative Disease and Comparison with a Cohort of Patients Treated in Real Life. Analysis on Behalf of the Spanish Lymphoma Group (GELTAMO)
Authors: Eva Gonzalez-Barca, Francisco Javier Capote Huelva, Jose Gomez Codina, Carlos Panizo, Antonio Salar, Eva Domingo Domenech, Alicia Bailen, Josep-Maria Ribera, Andres Lopez, Javier Briones, Andres Muñoz, Maite Encuentra, Alberto Fernandez de Sevilla
Journal: Blood (2017)