tbuckley/cabot-search huggingface dataset:
TAp63-Regulated miRNAs Suppress Cutaneous Squamous Cell Carcinoma through Inhibition of a Network of Cell-Cycle Genes
Authors: Andrew John Davis, Maksym Tsinkevich, Jason Rodencal, Hussein A. Abbas, Xiao-hua Su, Young-Jin Gi, Bin Fang, Kimal Rajapakshe, Cristian Coarfa, Preethi H. Gunaratne, John M. Koomen, Kenneth Y. Tsai, Elsa R. Flores
Journal: Cancer Research (2020)

Abstract TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63−/− mice exhibit an increased susceptibility to ultraviolet radiation–induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these miRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either miRNA showed downregulation of cell-cycle progression and mitosis-associated proteins. A mouse to human and cross-platform comparison of RNA-sequencing and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Knockdown of these factors in cuSCC cell lines suppressed tumor cell proliferation and induced apoptosis. In addition, selective inhibition of AURKA suppressed cuSCC cell proliferation, induced apoptosis, and showed antitumor effects in vivo. Finally, treatment with miR-30c-2* or miR-497 miRNA mimics was highly effective in suppressing cuSCC growth in vivo. Our data establish TAp63 as an essential regulator of novel miRNAs that can be therapeutically targeted for potent suppression of cuSCC. Significance: This study provides preclinical evidence for the use of miR-30c-2*/miR-497 delivery and AURKA inhibition in the treatment of cuSCC, which currently has no FDA-approved targeted therapies. See related commentary by Parrales and Iwakuma, p. 2439
HYBRID CORONARY REVASCULARIZATION VERSUS CORONARY ARTERY BYPASS GRAFT IN PATIENTS WITH MULTIVESSEL CORONARY ARTERY DISEASE: A META-ANALYSIS
Authors: Ziad SayedAhmad, Fahed Darmoch, Homam Moussa Pacha, Mohamad Soud, Yasser Al-Khadra, Anwar Zaitoun, Marvin Kajy, Zaher Hakim, Amir Kaki, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2020)
EFFECTS OF LOW-DOSE EMPAGLIFLOZIN TREATMENT ON DIASTOLIC HEART FUNCTION IN INFARCTED DIABETIC RATS
Authors: Bruno Durante Da Silva, Leandro Eziquiel de Souza, Maikon Barbosa da Silva, Paula Lázara Cruz, Paulo Dourado, Consolim-Colombo Fernanda, Maria Cláudia Irigoyen
Journal: Journal of the American College of Cardiology (2020)
Predicting length of survival for adult, outpatient oncology patients using clinic visit data.
Authors: Laura E. Brown, Brian Decker, David A. Decker
Journal: Journal of Clinical Oncology (2012)

9095 Background: The ability to predict a patient’s length of survival (LOS) has the potential to become an extremely valuable tool to aid in patient care, treatment, and end-of-life decisions made by the patient, their clinician, and extended support network. Methods: This preliminary study constructed models to predict LOS. Data from 10,667 patients was collected in an Electronic Medical Record over two years with LOS determined by matching records with the Social Security Death Index. The patient information available to construct the models consisted of basic patient demographics (single-entry information: e.g., age, cancer diagnosis, cancer stage, gender), transcriptions of physicians’ notes (to mine for other factors), and laboratory values (time-series or time-stamped information: e.g., weight, blood pressure, hemoglobin, creatinine, medication and treatments administered, etc.). A 5-fold nested cross-validation experimental design was used to train (using several possible representations of the data), test, and compare least-squares and support vector regression (SVR) models. Evaluations based on standard error are reported. Results: Linear, polynomial (up to 4 th degree), and radial basis kernels were considered for SVR with the best model selected as the 2 nd order polynomial. Preliminary results show that the best linear least-squares model is able to predict LOS with a standard error of +/- 34 days. The best support vector regression model has a slightly better prediction performance with standard error of +/- 32 days. Conclusions: This preliminary research shows the feasibility of predicting LOS from outpatient, clinical data. Further work is planned to improve the model performance, test other models, and determine which clinical indicators in oncology are most important for accurate predictions.
Economic burden of rheumatoid arthritis: a systematic review of literature in biologic era
Authors: Ping-Hsuan Hsieh, Olivia Wu, Claudia Geue, Emma McIntosh, Iain B McInnes, Stefan Siebert
Journal: Annals of the Rheumatic Diseases (2020)

The past decades have seen rapid advances in the treatment of rheumatoid arthritis (RA). In particular, the introduction of biologic and targeted synthetic disease-modifying antirheumatic drugs have improved clinical outcomes and reconfigured traditional RA cost compositions.To map the existing evidence concerning cost of illness of RA, as the treatment pathway evolves in the biologic era, and examine how costs have been measured and estimated, in order to assemble and appropriately interpret available data.Systematic review of studies that estimated the costs of patients with RA. Multiple electronic databases were searched to identify studies published between 2000 and 2019. The reported total costs and cost components were evaluated according to the study and population characteristics. The Cochran-Armitage test was used to determine statistically significant trends in increasing or decreasing proportions over time.Overall, 72 studies were included. Drug costs compromised the main component (up to 87%) of direct costs with an increasing trajectory over time, although not statistically significant. The proportion of costs for hospitalisation showed a statistically significant decrease chronologically (p=0.044). Indirect costs, primarily associated with absenteeism and work disability accounted for 39% to 86% of total costs. The reported indirect costs are highly sensitive to the approach to estimation.A decreasing trend in inpatient costs chronologically suggested a cost shift in other components of direct costs. Indirect costs still contributed a considerable proportion of total costs, with work disability being the main cost component. Economic analyses that do not incorporate or appropriately measure indirect costs will underestimate the full economic impact of RA.
Changes in Internet utilization by cancer patients in the Veteran’s Administration (VA) hospital setting
Authors: C. Vachani, M. K. Hampshire, R. W. Whittington, A. Vachani, J. M. Metz
Journal: Journal of Clinical Oncology (2006)

16042 Background: A previous study (2002) showed only 5% of VA cancer patients access the Internet to investigate information related to their cancer or cancer treatment. Since this study was published, access to the Internet and computers has changed over the interval. This study was designed to evaluate Internet usage patterns and factors that may promote Internet usage among cancer patients at a Veteran’s Administration (VA) hospital. Methods: From 09/2005 to 12/2005 a 15-item questionnaire was administered to 44 radiation oncology patients presenting for consultation and/or daily radiation treatments. The questionnaire evaluated basic demographics, Internet access and utilization, and interest in educational programs to promote utilization. Results were compared to a questionnaire study of 201 patients performed at the same institution in 2002. Results: The population is predominantly male (98%), with a racial distribution of 39% African American and 61% Caucasians. Two-thirds of the population are between the ages of 50 and 70. The most common primary tumor sites were prostate (65%), lung (11%), and head and neck (7%). Overall, 28% reported using the Internet to find information about their cancer, compared to only 5% in 2002 (p &lt; .0001). An additional 42% reported a friend or family member searched the Internet on behalf of the patient. Seventy-four percent of subjects knew where to gain access to the Internet, which included public library (36%), personal computer (34%), friend/family’s home (13%). Of the 44 patients 18 (42%) were interested in free classes to learn how to access information on the Internet. African-American patients were somewhat more interested in taking educational classes on Internet utilization (OR 2.6, 95% CI 0.6–11.1). Conclusions: Internet use among VA cancer patients has increased over the last 3 years. A majority of VA patients know where to access Internet resources. Many patients are interested in educational programs to teach them how to utilize cancer based Internet resources. Future studies will assess the impact of this educational intervention in the VA population. No significant financial relationships to disclose.
IMPACT OF UNRECOGNIZED MYOCARDIAL SCAR DETECTED BY CARDIAC MAGNETIC RESONANCE IMAGING IN PATIENTS PRESENTING WITH SYMPTOMS OF CORONARY ARTERY DISEASE
Authors: Panagiotis Antiochos, Yin Ge, Kevin Steel, Scott Bingham, Shuaib Abdullah, J. Ronald Mikolich, W. Patricia Bandettini, Andrew E. Arai, Amit Patel, Afshin Farzaneh-Far, John Heitner, Chetan Shenoy, Steve Leung, Jorge A. Gonzalez, Dipan J. Shah, Subha V. Raman, Victor A. Ferrari, Jeanette Schulz-Menger, Mathias Stuber, Orlando Simonetti, Raymond Y. Kwong
Journal: Journal of the American College of Cardiology (2020)
Cancer cachexia syndrome (CS): A symptom complex associated with yet distinct from fatigue in ambulatory cancer patients.
Authors: Wilson C. Mertens, Gregory Scott Emmons, Deborah Katz, Ruth Barham, Lucinda Jane Cassells, Saurabh Dahiya, Leslie M. Howard
Journal: Journal of Clinical Oncology (2012)

e19543 Background: Fatigue and CS (Lancet Oncol 2011;12:489) are common, multifactorial symptoms in ambulatory cancer patients. Clinical and laboratory correlates require further evaluation, although erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), nausea and weight loss have been associated with both CS and fatigue. A practical classification of cancer-associated fatigue is lacking. Methods: Patients with cancer—newly diagnosed, receiving treatment, as well as those undergoing post-treatment surveillance and recurrent/persistent disease—were consented and screened with a visual aid. Those reporting moderate fatigue were asked to participate in a study assessing the degree and impact of fatigue using the FACT-G and study-specific questionnaires, followed by focused laboratory testing. Results: 102 patients were accrued. Mean age 60.2 years (95%CI: 58.0, 62.5); 80% female; no evidence of disease 55.9%; disease present/initial presentation 18.6%, persistent/recurrent disease 25.5%; &gt;5% weight loss 35%; CS 39%; anorexia-CS 18%; increased ESR 49% and CRP 32%; currently receiving chemotherapy 16%. Patients currently receiving chemotherapy had more fatigue (p=.011); none of CS, &gt;5% weight loss, disease presence/recurrence, histologic diagnosis, gender, age, pain, appetite, nausea, depression, exercise, blood pressure (BP), hemoglobin level, ESR or CRP were statistically associated with fatigue. CS was associated with increased ESR and reduced BP and appetite (all p&lt;.001), and increased nausea and CRP (both p&lt;.05) as well as disease presence/recurrence (p=.003). FACT-G total and physical scale scores did not differ between CS and other fatigued patients. Conclusions: CS affects a substantial proportion of ambulatory cancer patients screened for moderate fatigue; however, CS patients did not exhibit increased fatigue or poorer FACT-G scores despite differences in weight, disease extent, weight loss, or laboratory markers of inflammation when compared to other sampled patients. CS patients may represent a distinct subset of cancer fatigue, or this symptom complex may be distinct from fatigue even though present in the same patient.
The incremental economic burden of clostridium-difficile associated diarrhea among hospitalized immunocompromised patients undergoing chemotherapy.
Authors: Ralph A. Quimbo, Swetha Palli, Marcie Strauss, Sheila Thomas
Journal: Journal of Clinical Oncology (2012)

e16542 Background: Hospital-acquired Clostridium-difficile associated diarrhea (CDAD) results in an estimated $1.3 billion in excess costs in the US. Patients undergoing chemotherapy are at elevated risk of CDAD due to diminished immune response and increased exposure to health care facilities. This study describes the incremental economic burden of CDAD in hospitalized immunocompromised (IC) patients. Methods: IC cases (undergoing chemotherapy or other qualifying conditions) hospitalized with a diagnosis of CDAD having ≥12 months of prior health plan eligibility and age ≥18 years between 1/1/2005 and 10/31/2010 were identified from the HealthCore Integrated Research Database (HIRD SM ). Cases were matched to hospitalized IC controls without CDAD diagnosis based on: age±10 years, gender, selected preceding/in-hospital comorbidities and use of antibiotics. Incremental hospital length of stay (LOS) and costs were calculated between matched cases and controls via multivariate methods using a Gamma distribution. Covariates were determined from post-match univariate analysis of baseline characteristics. Results: 3,586 cases were matched to 10,758 controls. Chemotherapy occurred among 91.3% of cases and controls. While age (65±15), gender (53% female), and selected comorbidities were balanced between cases and controls, post-match disparities persisted (p&lt;.001): geographic region (37% vs. 32% Midwest), type of health plan (24 vs. 18% HMO), overall comorbidity burden (6.0±3.6 vs. 6.5±3.7 Deyo-Charlson Comorbidity Index). Cases had a lower incidence of mortality during their index hospitalization (6.7% vs. 7.8%; p&lt;0.0001). Adjusted hospital LOS was significantly greater for cases vs. controls (22.1 days (20.61 to 23.69) vs. 13.67 days (12.74 to 14.67); p&lt;.0001). Incremental hospitalization costs indicated a significantly greater economic burden among cases vs.controls (Δ = $32K ($29K to $35K); p&lt;0.0001). Conclusions: This study indicates that the acquisition of CDAD among immunocompromised patients, of which chemotherapy recipients represented the majority, presents significant incremental economic burden within the hospital setting.
Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases
Authors: Renato G. S. Chirivi, Jos W. G. van Rosmalen, Maarten van der Linden, Maximilien Euler, Gonny Schmets, Galina Bogatkevich, Konstantinos Kambas, Jonas Hahn, Quinte Braster, Oliver Soehnlein, Markus H. Hoffmann, Helmuth H. G. van Es, Jos M. H. Raats
Journal: Cellular and Molecular Immunology (2020)

Excessive release of neutrophil extracellular traps (NETs) is associated with disease severity and contributes to tissue injury, followed by severe organ damage. Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models, indicating that NETs are potential therapeutic targets. Here, we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody (tACPA) has broad therapeutic potential. Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology, including inflammatory arthritis (IA), pulmonary fibrosis, inflammatory bowel disease and sepsis. We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention, whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects. Because citrullinated histones are generated during NET release, we investigated the ability of tACPA to inhibit NET formation. tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli. Moreover, tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo, which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA. To our knowledge, we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases, as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.
Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China
Authors: Joseph T. Wu, Kathy Leung, Mary Bushman, Nishant Kishore, Rene Niehus, Pablo M. de Salazar, Benjamin J. Cowling, Marc Lipsitch, Gabriel M. Leung
Journal: Nature Medicine (2020)

As of 29 February 2020 there were 79,394 confirmed cases and 2,838 deaths from COVID-19 in mainland China. Of these, 48,557 cases and 2,169 deaths occurred in the epicenter, Wuhan. A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9-2.1%), which is substantially lower than both the corresponding crude or naïve confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator
LIPOPROTEIN(A) CONFERS INCIDENT CORONARY ARTERY DISEASE RISK AMONG 243,474 INDIVIDUALS WITHOUT A FAMILY HISTORY OF HEART DISEASE
Authors: Phoebe Finneran, Akhil Pampana, Sumeet Khetarpal, Krishna Aragam, Pradeep Natarajan
Journal: Journal of the American College of Cardiology (2020)
Re: Aurélie Kamoun, Aurélien de Reyniès, Yves Allory, et al. A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol 2020;77:420–33
Authors: Stephen B. Williams, Peter C. Black, Lars Dyrskjøt, Roland Seiler, Bernd Schmitz-Dräger, Roman Nawroth, Tilman Todenhöfer, Ashish M. Kamat, Peter J. Goebell
Journal: European Urology (2019)
PATIENT SELECTION, REGION AND TREATING PHYSICIAN ARE RELATED TO ESTIMATES OF ORAL ANTICOAGULATION USE IN ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Miney Paquette, Opeyemi Fadahunsi, Mei Wang, Jeff S. Healey, Ratika Parkash, Sarah Quayyum, Maheer Khan, Robby Nieuwlaat
Journal: Journal of the American College of Cardiology (2020)
INTENSITY OF LIPID LOWERING THERAPY AND LDL-C LEVELS AFTER 12 MONTHS IN PATIENTS WITH POLYVASCULAR DISEASE—INSIGHTS FROM THE GOULD REGISTRY
Authors: Ben Peterson, Deepak Bhatt, Christie M. Ballantyne, James de Lemos, Robert S. Rosenson, Katherine Mues, Mary Elliott-Davey, Shushama Alam, Yuyin Liu, Mikhail Kosiborod, Christopher P. Cannon
Journal: Journal of the American College of Cardiology (2020)
Prognostic model for overall survival in patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy.
Authors: Matt D. Galsky, Susanne Krege, Chia-Chi Lin, Noah M. Hahn, Thorsten Ecke, Erin L. Moshier, Guru Sonpavde, James H. Godbold, William K. Oh, Aristotelis Bamias
Journal: Journal of Clinical Oncology (2012)

4524 Background: Patients with metastatic urothelial cancer (UC) treated with cisplatin-based chemotherapy have heterogeneous clinical outcomes. Pretreatment prognostic variables have previously been defined (Bajorin, JCO, 1999) but have not been extensively validated or expanded upon. Methods: Pretreatment clinical parameters from 400 international patients with metastatic UC treated on phase II and III first-line clinical trials with cisplatin-based chemotherapy from 11/1997 to 10/2011 were evaluated (cisplatin + gemcitabine +/- paclitaxel or +/- antiangiogenic agent = 235; MVAC = 83; cisplatin + 5FU +/- paclitaxel = 79). Parameters were subjected to multivariable regression analysis to determine which patient characteristics had independent prognostic significance for survival. Results: Complete data were available on 361 patients, median survival was 13.9 months (95% CI 12.4, 16.5); 247 have died. In multivariable analysis, ECOG performance status (≥1), visceral metastases (lung, liver, bone), and white blood count (WBC, continuous variable) were significantly associated with poor survival (P &lt; .05), whereas perioperative chemotherapy, hemoglobin, platelets, creatinine clearance, site of primary tumor, and number of metastatic sites were not (Table). The cut-off for WBC was established at 10. Median survival times for patients with 0, 1, 2, or 3 risk factors were 26.9, 16.8, 12.8, 9.7 months (log rank p value &lt; 0.0001). When subjected to internal validation, the model achieved a bootstrap-corrected c-index of 0.60. External validation is ongoing utilizing data from a phase III trial (n=186) of MVAC versus docetaxel plus cisplatin. Conclusions: A model derived from pretreatment parameters from an international cohort of patients was constructed that confirmed, and expanded upon, known prognostic factors in metastatic UC. This model may be useful for patient counseling and clinical trial design. Better predictions require the identification of additional factors that affect survival. [Table: see text]
Secondary primary cancer in the long-term survivors with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer
Authors: N. Takigawa, Y. Segawa, K. Kiura, M. Tabata, H. Ueoka, T. Yonei, T. Shibayama, I. Takata, K. Matsuo, M. Tanimoto
Journal: Journal of Clinical Oncology (2006)

7147 Background: Although concurrent chemoradiotherapy (CT/RT) is associated with increased survival for patients (pts) with locally advanced non-small cell lung cancer (NSCLC), long-outcomes beyond 5 years have not been fully analyzed. Methods: Between 1994 and 1999, we conducted two phase II studies examining concurrent CT/RT for treatment of surgically unresectable stage IIIA or IIIB NSCLC. One regimen consisted of three cycles of 5-fluorouracil 500mg/m 2 and cisplatin 20mg/m 2 , days 1–5, every 4 weeks and concurrent hyperfractionated thoracic RT (1.25Gy twice daily, total 62.5–70Gy) [FP-TRT] (Segawa et al. BJC 82, 2000). The other consisted of docetaxel 40mg/m 2 and cisplatin 40mg/m 2 , days 1, 8, 29 and 36 and concurrent thoracic RT (2Gy daily, total 60Gy) [DP-TRT] (Kiura et al. BJC 89, 2003). Long-term data is presented. Results: In 50 pts treated with FP-TRT, the median survival time (MST) was 1.6 years (yr; 95% confidential interval [CI]: 0.91 - 2.25 yr) by a median follow-up time of 10.4 yr and the actual 5 yr-survival rate was 30%. In 15 long-term survivors, 3 and 2 pts died due to primary NSCLC and secondary primary cancer (SPC), respectively, 1 was lost to follow-up, and 9 are still alive. In 42 pts treated with DP-TRT, the MST was 2.1 yr (95% CI: 0.82 - 2.48 yr) by a median follow-up time of 6.3 yr and the actual 5 yr-survival rate was 31%. In 13 long-term survivors, 1 pt died due to primary NSCLC, 1 died due to SPC, 1 was lost to follow-up, and 10 are still alive. Overall, 7 of 92 pts enrolled in these studies developed SPCs (2 NSCLC, 1 small cell lung cancer, 2 esophageal cancers, 2 gall bladder cancers) although no pts developed leukemia or myelodysplastic syndrome. An observed incidence rate of SPCs was 2356.1/100,000 (95% CI: 947.6 - 4856.0). Cumulative incidence was 5.8% (standard error [SE] 4.0%) at 5 yr, 10.0% (SE 5.6%) at 8 yr and 60.8% (SE 18.9%) at 10 yr. The median time from the beginning of CT/RT to the diagnosis of SPC was 9.6 yr (95% CI: 8.1 - 11.1 yr). Conclusions: Approximately 30% of pts survived more than 5 years after concurrent CT/RT, however, they were still at risk of dying from primary NSCLC. Occurrence of SPC in long-term survivors should be concerned in follow-up. No significant financial relationships to disclose.
CORONARY PERFUSION PRESSURE GRADIENT IS ASSOCIATED WITH INCREASED ADVERSE OUTCOMES IN PATIENTS WITH ADVANCED HEART FAILURE
Authors: Christiana Jeukeng, Sula Mazimba, Kenneth C. Bilchick, Khadijah Breathett, Sami Ibrahim, Victor Mwansa, Nishaki Mehta, Younghoon Kwon, Comfort Elumogo, Laja Olusola, Mwennya Mubanga
Journal: Journal of the American College of Cardiology (2020)