tbuckley/cabot-search huggingface dataset:
Diabetes, cardiovascular disease, and chronic kidney disease in South Asia: current status and future directions
Authors: Anoop Misra, Nikhil Tandon, Shah Ebrahim, Naveed Sattar, Dewan Alam, Usha Shrivastava, K M Venkat Narayan, Tazeen H Jafar
Journal: BMJ (2017)

South Asians are more susceptible to diabetes and cardiovascular diseases and have worse outcomes than other ethnicities, say <b>Anoop Misra, Tazeen Jafar, and colleagues</b>. They call for urgent action to provide screening and treatment, complemented by population level lifestyle modifications.
Hospitalizations for Crohn’s Disease — United States, 2003–2013
Authors: Christopher A. Malarcher, Anne G. Wheaton, Yong Liu, Sujay F. Greenlund, Suraj J. Greenlund, Hua Lu, Janet B. Croft
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In 2009, an estimated 565,000 Americans had Crohn's disease (1), an inflammatory bowel disorder that can affect any part of the gastrointestinal tract. Symptoms include persistent diarrhea, abdominal cramps and pain, constipation leading to bowel obstruction, and rectal bleeding.* Symptoms sometimes intensify in severity and require hospitalization and surgeries of the small intestine, colon, or rectum (2). Hospital discharge data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) were used to estimate U.S. hospitalizations† for Crohn's disease as both the first-listed and any-listed§ discharge diagnosis and common surgical procedures during hospitalizations with Crohn's disease as first-listed diagnosis from 2003 to 2013, the most recent decade of data. Despite new therapies that were expected to improve remission and reduce hospitalizations, estimated numbers (and age-adjusted rates per 100,000 U.S. population) of hospitalizations for Crohn's disease as the first-listed diagnosis did not change significantly from 2003 to 2013. The proportion of these hospitalizations during which small bowel resection was performed decreased from 4.9% in 2003 to 3.9% in 2013 (p<0.05); however, colorectal resection and fistula repair rates remained stable. Hospital stays for any-listed Crohn's disease increased from >120,000 (44.2 per 100,000) in 2003 to >196,000 (59.7 per 100,000) in 2013 (p<0.05). Patient education initiatives should focus on increasing awareness of exacerbating factors and medication compliance to prevent hospitalizations.
Contents, Vol. 39, 1983
Authors: Marcia Pavlou, Dusan Stefoski, William W. Weddington, Jr., Arcangelo Calobrisi, Yoshihide Nakai, Tomoko Araki, Susumu Takahashi, Akira Shimada, Tetsuya Nakagawa, R.A. Pierloot
Journal: Psychotherapy and Psychosomatics (1983)

dos age and for added warnings and precautions.
An <i>Ex Vivo</i> Platform for the Prediction of Clinical Response in Multiple Myeloma
Authors: Ariosto Silva, Maria C. Silva, Praneeth Sudalagunta, Allison Distler, Timothy Jacobson, Aunshka Collins, Tuan Nguyen, Jinming Song, Dung-Tsa Chen, Lu Chen, Christopher Cubitt, Rachid Baz, Lia Perez, Dmitri Rebatchouk, William Dalton, James Greene, Robert Gatenby, Robert Gillies, Eduardo Sontag, Mark B. Meads, Kenneth H. Shain
Journal: Cancer Research (2017)

Abstract Multiple myeloma remains treatable but incurable. Despite a growing armamentarium of effective agents, choice of therapy, especially in relapse, still relies almost exclusively on clinical acumen. We have developed a system, Ex vivo Mathematical Myeloma Advisor (EMMA), consisting of patient-specific mathematical models parameterized by an ex vivo assay that reverse engineers the intensity and heterogeneity of chemosensitivity of primary cells from multiple myeloma patients, allowing us to predict clinical response to up to 31 drugs within 5 days after bone marrow biopsy. From a cohort of 52 multiple myeloma patients, EMMA correctly classified 96% as responders/nonresponders and correctly classified 79% according to International Myeloma Working Group stratification of level of response. We also observed a significant correlation between predicted and actual tumor burden measurements (Pearson r = 0.5658, P &amp;lt; 0.0001). Preliminary estimates indicate that, among the patients enrolled in this study, 60% were treated with at least one ineffective agent from their therapy combination regimen, whereas 30% would have responded better if treated with another available drug or combination. Two in silico clinical trials with experimental agents ricolinostat and venetoclax, in a cohort of 19 multiple myeloma patient samples, yielded consistent results with recent phase I/II trials, suggesting that EMMA is a feasible platform for estimating clinical efficacy of drugs and inclusion criteria screening. This unique platform, specifically designed to predict therapeutic response in multiple myeloma patients within a clinically actionable time frame, has shown high predictive accuracy in patients treated with combinations of different classes of drugs. The accuracy, reproducibility, short turnaround time, and high-throughput potential of this platform demonstrate EMMA's promise as a decision support system for therapeutic management of multiple myeloma. Cancer Res; 77(12); 3336–51. ©2017 AACR.
Should we intubate patients during cardiopulmonary resuscitation?
Authors: Carl L Gwinnutt
Journal: BMJ (2017)

Intubation should remain the standard while we wait for randomised trials

As a trainee anaesthetist in the early 1980s, attendance at a “cardiac arrest” was frequent. My role was to intubate and ventilate the patient’s lungs with the highest possible concentration of oxygen. Other members of the team would insert a central line; attach an electrocardiogram monitor; give calcium, sodium bicarbonate, and intra-cardiac adrenaline; and defibrillate the patient, often in this sequence. Little attention was paid to chest compressions, a task usually delegated to the most junior person, often a student.

Over the years, most of these interventions have been abandoned as research has clarified which ones are associated with improved outcomes—namely good quality chest compressions and early defibrillation when the rhythm is ventricular fibrillation or ventricular tachycardia. So why are we still intubating patients’ tracheas as part of their management during cardiopulmonary resuscitation?

Perhaps the strongest reasons are the well known benefits of intubation during general anaesthesia—including effective ventilation in patients with poor pulmonary …
Experience and Outcomes of Hepatitis C Treatment in a Cohort of Homeless and Marginally Housed Adults
Authors: Joshua A. Barocas, Marguerite Beiser, Casey León, Jessie M. Gaeta, James J. O’Connell, Benjamin P. Linas
Journal: JAMA Internal Medicine (2017)

This study describes the experience and virologic outcomes in a cohort of hepatitis C virus–infected homeless and marginally housed adults who were provided access to community-based treatment programs.
Comparison of Bleeding Tools in a Cohort of Pediatric Patients with ITP: Data from the Pediatric ITP Consortium of North America ICON1 Study
Authors: Breakey R. Vicky, Rachael F Grace, Carolyn M. Bennett, Jenny M. Despotovic, Jennifer A Rothman, Yves D. Pastore, Ellis J Neufeld, Robert J. Klaassen, Michele Lambert, James B. Bussel, George R. Buchanan, Melissa J. Rose, Amy E. Geddis, Kristin Shimano, Kerry Hege, Kristina M. Haley, Adonis Lorenzana, Alexis A. Thompson, Michael Jeng, Shelley E. Crary, Michelle Neier, Travis Brown, Peter Forbes, Cindy Neunert
Journal: Blood (2016)
Circulating Microparticles As Predictive Biomarkers of Acute Graft Versus Host Disease
Authors: Thiago Xavier Carneiro, Daniella Gregolin Marrese, Melina Gonçalves dos Santos, Matheus Vescovi Gonçalves, Yana Sarkis Novis, Edgar Gil Rizzatti, Vanderson Rocha, Alex Freire Sandes, Celso Arrais Rodrigues
Journal: Blood (2016)
Bortezomib and interferon alpha-2b in metastatic melanoma.
Authors: Joseph Markowitz, Eric A Luedke, Valerie P Grignol, Erinn Hade, Bonnie K. Paul, Bethany L. Mundy-Bosse, Thao-Vi Dao, Sri Vidya Kondalasula, Gregory B. Lesinski, Thomas Olencki, Kari Lynn Kendra, William Edgar Carson
Journal: Journal of Clinical Oncology (2013)

e20018 Background: Preclinical studies revealed that bortezomib and interferon-α (IFN-α ) induce synergistic apoptosis in human melanoma cells. Combined treatment with bortezomib and IFN-α led to significant survival increases in a melanoma murine model. A phase I study is presented to determine the safety, tolerability and dose-limiting toxicity of bortezomib when administered in combination with interferon-alpha-2b (IFN-α) to patients with metastatic melanoma. Methods: Metastatic melanoma patients with ECOG status ≤ 2 were treated on a 5 week cycle. IFN-α (5 MU/m 2 ) was administered subcutaneously (s.c.) on days 1, 3, and 5 of week one. During weeks 2-4 bortezomib was administered intravenously on day 1 along with IFNEα (5 MU/m 2 s.c.) on days 1, 3, and 5. There was no treatment during week 5. After the first cycle, bortezomib was administered intravenously on day 1 of the weekly cycle along with IFNEα on days 1, 3, and 5. Bortezomib does levels were 1.0, 1.3, or 1.6 mg/m 2 to cohorts of three patients. Results: 16 patients (8 men, 8 women, median age 58.5 (34-82) years) were treated. The most common metastatic disease sites included the lung, subcutaneous nodules, lymph nodes, and soft tissue. Other sites included: brain, skin, viscera, and bone. Grade 3 toxicities most frequently included fatigue, vomiting, and diarrhea. Syncope, depression, hypokalemia, motor neuropathy, and dyspnea were also observed. Grade 4 toxicities included fatigue and lymphopenia. There were 1 PR, 7 SD, and 8 PD. Median PFS and OS were 2.5 months (95% CI: 1.4-3.7) and 10.3 months (95% CI: 5.5-12.8), respectively. Bortezomib did not limit the ability of IFN-α to induce STAT1 phosphorylation in PBMCs. Levels of proEangiogenic cytokines (VEGF and IL-8) were higher in melanoma patients than in normal controls. Levels of VEGF, IL-8 and IL-6 all decreased during week 2 in the patient who experienced a PR. Bioplex cytokine analysis revealed decreases in IL-8 and VEGF in melanoma patients. Conclusions: Bortezomib and IFN-α represents a novel immune based treatment for melanoma. This combination reduces levels of pro-angiogenic factors in melanoma patients, is generally well tolerated, and can be safely administered to melanoma patients including those patients with treated CNS metastases. Clinical trial information: NCT01462773.
Neurocognitive Sequelae in Adult Childhood Leukemia Survivors Related to Levels of Phosphorylated Tau
Authors: Iris Elens, Sabine Deprez, Marina Danckaerts, Patricia Bijttebier, Veerle Labarque, Anne Uyttebroeck, Stefaan Van Gool, Rudi D’Hooge, Jurgen Lemiere
Journal: JNCI Journal of the National Cancer Institute (2017)

Central nervous system–directed prophylactic chemotherapy increases survival in childhood leukemia, but possible late neurocognitive sequelae remain a concern. We compared intellectual performance (WAIS IV), memory (AVLT), and executive functioning (ANT) between adult leukemia survivors (n = 31) and control individuals (n = 35). In survivors, cerebrospinal fluid (CSF) levels of phosphorylated Tau (p-Tau) during treatment and total intrathecal methotrexate dose correlated with adult intellectual performance (Pearson's and Spearman's coefficients, respectively). Long-term memory and attentional control, both maturing before survivors' mean age at diagnosis, were unaffected (P > .05 on all four subtests), in contrast to cognitive flexibility and information processing (P < .05 for eight of the subtests), which mature during adolescence. CSF p-Tau and methotrexate dose negatively correlated with intellectual performance (r = −0.414, P = .04 and r = −0.484, P = .007, respectively), but not with each other (r = 0.219, P = .29). These data identify CSF p-Tau as a predictor of late neurocognitive sequelae (in addition to methotrexate dose). Early identification of children at risk could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.
Decellularized Plants: Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture (Adv. Healthcare Mater. 8/2017)
Authors: Gianluca Fontana, Joshua Gershlak, Michal Adamski, Jae-Sung Lee, Shion Matsumoto, Hau D. Le, Bernard Binder, John Wirth, Glenn Gaudette, William L. Murphy
Journal: Advanced Healthcare Materials (2017)

In article number 1601225, human dermal fibroblasts seeded on a decellularized parsley stem are described by William L. Murphy and co-workers. Plant tissues can be decellularized and biofunctionalized to allow adhesion of human cells. These adaptable scaffolds possess elevated hydrophilicity and excellent water transport abilities innate of plant tissues. These scaffolds were shown to enable efficient expansion of human cells for prolonged periods of culture.
Characterization of CG-781, a potent histone deacetylase inhibitor, as a cancer therapeutic
Authors: Z. Alexander Cao, Kathryn E. Bass, Anthony Neri, Sriram Balasubramanian, Cindy Brown, Gail Siu, Ling Leung, Jack R. Davis, Steve Capaldi, Dewi Ngadimo, Erik Verner, Joseph J. Buggy, Stacie A. Dalrymple
Journal: Cancer Research (2005)

1801  Histone acetylation is one mechanism by which chromatin structure and its transcription is regulated. Transcriptionally active chromatin regions are associated with hyperacetylated histones and transcriptionally silent chromatin regions are associated with hypoacetylated histones. Histone deacetylases (HDACs) and histone acetyltransferases thus play a crucial role in regulating chromatin structure and gene expression. One of the hallmarks of human neoplasia is aberrant gene expression (the activation of genes for proliferation and the silencing of tumor suppressors). Because of its role(s) in chromatin remodeling and transcriptional regulation, HDAC inhibitors are being evaluated as anti-cancer therapeutics. Here we present data on CG-781 on its activities as an HDAC inhibitor and as an anti-cancer agent. CG-781 has displayed potent activity against recombinant human HDAC enzymes in vitro. It has exhibited sub-μM growth-inhibitory activities in vitro against an array of human cancer cell lines. Examination of CG-781 in vivo has revealed significant anti-tumor activity against different tumor xenografts. Statistically significant tumor growth inhibition at 80+% and 40+% has been achieved with CG-781 against HCT 116 & DLD-1 respectively. Anti-tumor activity was observed with different pre-clinical dosing regimens, and also with either intravenous or intraperitoneal delivery. Pharmacodynamic evaluation of circulating blood cells and tumor samples revealed that protein acetylation correlates with drug exposure. Gene expression profiling over various doses and timepoints has identified a robust set of genes whose expression in tumors is affected by treatment with CG-781. Similar analysis of whole blood samples from the same mice has also provided a set of marker genes that track with efficacy. Continued analysis and validation of target genes regulated by CG-781 could provide greater insight into the mechanism of action for CG-781 and potentially facilitate its clinical application.
A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients
Authors: Lingjian Yang, Janet Taylor, Amanda Eustace, Joely J. Irlam, Helen Denley, Peter J. Hoskin, Jan Alsner, Francesca M. Buffa, Adrian L. Harris, Ananya Choudhury, Catharine M.L. West
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Hypoxia modification improves overall survival in muscle-invasive bladder cancer patients who undergo radiotherapy. There is evidence that hypoxic tumors benefit most from hypoxia modification. The study aimed to identify or derive a hypoxia gene signature that predicts benefit from hypoxia-modifying treatment in bladder cancer. Experimental Design: Published hypoxia signatures were tested and a new one derived by analyzing bladder cancer transcriptomic data from public databases. Tumor samples were available from the BCON phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Gene expression data were generated for 151 tumors using Affymetrix Human 1.0 Exon ST arrays and used for independent validation. Results: A 24-gene signature was derived, which was prognostic in four of six independent surgical cohorts (n = 679; meta HR, 2.32; 95% CI, 1.73–3.12; P &amp;lt; 0.0001). The signature was also prognostic in BCON patients receiving radiotherapy alone (n = 75; HR for local relapse-free survival, 2.37; 95% CI, 1.26–4.47; P = 0.0076). The signature predicted benefit from CON (n = 76; HR, 0.47; 95% CI, 0.26–0.86; P = 0.015). Prognostic significance (P = 0.017) and predictive significance (P = 0.058) remained after adjusting for clinicopathologic variables. A test for interaction between hypoxia status and treatment arms was significant (P = 0.0094). Conclusions: A 24-gene hypoxia signature has strong and independent prognostic and predictive value for muscle-invasive bladder cancer patients. The signature can aid identification of patients likely to benefit from the addition of carbogen and nicotinamide to radiotherapy. Clin Cancer Res; 23(16); 4761–8. ©2017 AACR.
Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology
Authors: Steven M. Walker, Laura A. Knight, Andrena M. McCavigan, Gemma E. Logan, Viktor Berge, Amir Sherif, Hardev Pandha, Anne Y. Warren, Catherine Davidson, Adam Uprichard, Jaine K. Blayney, Bethanie Price, Gera L. Jellema, Christopher J. Steele, Aud Svindland, Simon S. McDade, Christopher G. Eden, Chris Foster, Ian G. Mills, David E. Neal, Malcolm D. Mason, Elaine W. Kay, David J. Waugh, D. Paul Harkin, R. William Watson, Noel W. Clarke, Richard D. Kennedy
Journal: European Urology (2017)

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.
Epidemiology of stage IV breast cancer patients: A review of the National Cancer Database.
Authors: Jessica Gries, Van T.H. Do, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2014)

e12523 Background: Breast Cancer is the second most common cancer and cancer-related death in women in the United States (CA Cancer J Clin. 2013 Jan;63(1):11-30. Epub 2013 Jan 17.). Breast cancer patients tend to have distinctive characteristics that change as the cancer progresses to Stage IV, especially in race and socioeconomic status. This is the largest epidemiological study to determine factors associated with patients presenting with Stage IV breast cancer. Methods: A population-based study using the National Cancer Database (2000-2011), which contains 70% of cancer diagnoses from 1,658 American College of Surgeons Accredited-Hospitals across the United States. From 2000-2011, 2,294,058 women were diagnosed with Breast Cancer, and Stage IV represented 3.56% (81,618) of the total patient population. Stage IV Breast Cancer was compared to all stages using the Chi square test. Results: There was an increased incidence of Stage IV Breast Cancer in Black, No Insurance, Medicaid, Medicare, Lower Educated, and Lower Household Income patients (Table). While White females incidence decreased to 74% in Stage IV to 80% in earlier stages, Black females increased to 17% when compared to 10% all stages. There was no significant difference in Age Group, Hispanics, Distance Travelled, and Charlson comorbidity score. Conclusions: This study emphasizes the differences in race, insurance, education, and income in regards to incidence of Stage IV Breast Cancer. These factors influence the occurrence of a more aggressive stage of the disease. Defining characteristics of Stage IV Breast Cancer patients may help provide better treatment and prevention of Stage IV disease for women of varying racial and socioeconomic backgrounds. Epidemiology of stage IV breast cancer patients. Stage IV (%) All stages (%) Race/ethnicity* White 74 80 Black 17 10 Hispanic 5 5 Insurance* None 6 2 Medicaid 10 5 Medicare 39 35 Private 40 54 Education* % without HS degree (Lower value means more education) > 31% 16 11 23-30.9% 17 15 18-22% 16 15 12-17.9% 23 24 < 12% 24 30 Household income* (per year) < $28,000 12 8 $28,000 - 32,999 13 11 $33,000 - 38,999 17 16 $39,000 - 48,999 23 23 > $49,000 31 37 * p-value < .0001.
Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial
Authors: Thomas Van Stappen, Niels Vande Casteele, Gert Van Assche, Marc Ferrante, Séverine Vermeire, Ann Gils
Journal: Gut (2017)

Objective To evaluate the clinical relevance of antidrug antibodies (ADAs) measured using a drug-tolerant assay in a post hoc analysis of the Trough Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled trial. Design ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who presented with an infliximab TC &lt;3 µg/mL at screening, were reanalysed after optimisation and at the end of the study using a drug-tolerant ADA assay. Patients underwent dose escalation to achieve therapeutic TCs between 3 µg/mL and 7 µg/mL prior to randomisation. Patients were grouped into quartiles (Q1–4) according to ADA concentration at screening. Results Using a drug-tolerant assay, the immunogenicity detection rate increased from 21% (drug-sensitive assay) to 63% at screening, from 0% to 51% after optimisation and from 3% to 42% at the end of TAXIT. Patients in ADA Q4 required a higher cumulative infliximab dose (2390 (880–2998) mg) to achieve target TCs, resulting in a higher drug cost (€10 712 (4120–13 596)) compared with ADA-negative patients (€2060 (1648–3296)) and patients in ADA Q1/Q2 (€2060 (1648–4120)/€2060 (1751–3296), p&lt;0.001). However, all but one patient belonging to ADA Q4 were also ADA-positive using a drug-sensitive assay. Conclusions Upon dose intensification, low concentration ADAs, not detectable using a drug-sensitive assay, disappear in more than half of the patients over time and are clinically non-relevant. In contrast, high concentration ADAs which are typically also detected in a drug-sensitive assay, persist over time and necessitate a higher cumulative dose and drug cost. In the latter group, proactive drug switching may be more cost-efficient. Clinical Trials Register 2011-002061-38; Post-results.