tbuckley/cabot-search huggingface dataset:
Factors Contributing to Increases in Diabetes-Related Preventable Hospitalization Costs Among U.S. Adults During 2001–2014
Authors: Sundar S. Shrestha, Ping Zhang, Israel Hora, Linda S. Geiss, Elizabeth T. Luman, Edward W. Gregg
Journal: Diabetes Care (2018)

To examine changes in diabetes-related preventable hospitalization costs and to determine the contribution of each underlying factor to these changes.We used data from the 2001-2014 U.S. National (Nationwide) Inpatient Sample (NIS) for adults (≥18 years old) to estimate the trends in hospitalization costs (2014 USD) in total and by condition (short-term complications, long-term complications, uncontrolled diabetes, and lower-extremity amputation). Using regression and growth models, we estimated the relative contribution of following underlying factors: total number of hospitalizations, rate of hospitalization, the number of people with diabetes, mean cost per admission, length of stay, and cost per day.During 2001-2014, the estimated total cost of diabetes-related preventable hospitalizations increased annually by 1.6% (92.9 million USD; P < 0.001). Of this 1.6% increase, 75% (1.2%) was due to the increase in the number of hospitalizations, which is a result of a 3.8% increase in diabetes population and a 2.6% decrease in the hospitalization rate, and 25% (0.4%) was due to the increase in cost per admission, for a net result of a 1.6% increase in cost per day and a 1.3% decline in mean length of stay. By component, the cost of short-term complications, lower-extremity amputations, and long-term complications increased annually by 4.2, 1.9, and 1.5%, respectively, while the cost of uncontrolled diabetes declined annually by 2.6%.The total cost of diabetes-related preventable hospitalizations had been increasing during 2001-2014, mainly resulting from increases in number of people with diabetes and cost per hospitalization day. The underlying factors identified in our study could lead to efforts that may lower future hospitalization costs.
Зміни рівнів простагландинів у сироватці крові в пацієнтів iз гастроезофагеальною рефлюксною хворобою на фоні цукрового діабету ІІ типу
Authors: Ye.S. Sirchak, M.P. Stan
Journal: GASTROENTEROLOGY (2018)

Актуальність. В основі ураження органів травлення в пацієнтів із цукровим діабетом (ЦД) лежать декілька механізмів: дисфункція вегетативної нервової системи, ангіо­патія, дисрегуляція секреції та інактивація гормонів і інкрементів. Мета дослідження: вивчити особливості зміни рівня простагландинів (Pg) (І2 та F2α) в сироватці крові в пацієнтів iз гастроезофагеальною рефлюксною хворобою (ГЕРХ) на фоні ЦД ІІ типу залежно від порушення індексу маси тіла. Матеріали та методи. Обстежено 54 пацієнти з ЦД ІІ типу та ГЕРХ (І група). У групу порівняння увійшло 22 пацієнти з ГЕРХ (ІІ група). В обстежених хворих визначали показники Pg F2α та 6-кето-простагландину F1α (простациклін крові — Pg I2) в сироватці крові. Результати. Встановлено підвищення рівнів простагландинів в обох групах пацієнтів, але більш виражені зміни спостерігаються в І групi. Звертає на себе увагу більш суттєве зростання концентрації Pg I2 порівняно з показником Pg F2α, особливо в пацієнтів iз ГЕРХ на фоні ЦД ІІ типу (в 3,4 раза проти 2,1 раза в І групi). У пацієнтів iз ГЕРХ встановлено зростання рівня Pg I2 в 2,2 раза, а Pg F2α — лише в 1,6 раза. При поєднанні декількох патологічних станів (ЦД ІІ типу, ГЕРХ, порушення індексу маси тіла) спостерігається більш виражене підвищення концентрації саме простацикліну, що також залежить від тривалості захворювання. Висновки. У пацієнтів iз ГЕРХ встановлено збiльшення рівня простагландинів F2α та I2 в сироватці крові. Поєднання ГЕРХ та ЦД ІІ типу супроводжується більш вираженим зростанням концентрації простагландинів, особливо Pg I2, в сироватці крові. Встановлено залежність між тривалістю ЦД ІІ типу, надмірною вагою тіла та динамікою рівня Pg I2 в сироватці крові в пацієнтів iз ГЕРХ на фоні ЦД ІІ типу.
Re: Friederike Haidl, David Pfister, Axel Heidenreich. Re: Prostatic Artery Embolization in the Treatment of Localized Prostate Cancer: A Bicentric Prospective Proof-of-Concept Study of 12 Patients. Mordasini L, Hechelhammer L, Diener PA, et al. J Vasc Interv Radiol 2018;29:589–97. Eur Urol 2018;74:525–6
Authors: Alessia Cimadamore, Marina Scarpelli, Matteo Santoni, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2018)
Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG
Authors: Jessica L. Brady, Michael S. Binkley, Carla Hajj, Monica Chelius, Karen Chau, Alex Balogh, Mario Levis, Andrea Riccardo Filippi, Michael Jones, Michael Mac Manus, Andrew Wirth, Masahiko Oguchi, Anders Krog Vistisen, Therese Youssef Andraos, Andrea K. Ng, Berthe M. P. Aleman, Seo Hee Choi, Youlia Kirova, Sara Hardy, Gabriele Reinartz, Hans T. Eich, Scott V. Bratman, Louis S. Constine, Chang-Ok Suh, Bouthaina Dabaja, Tarec C. El-Galaly, David C. Hodgson, Umberto Ricardi, Joachim Yahalom, Richard T. Hoppe, N. George Mikhaeel
Journal: Blood (2018)
Single Agent Oral Selinexor Demonstrates Deep and Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both GCB and Non-GCB Subtypes: The Phase 2b Sadal Study
Authors: Marie Maerevoet, Joost Vermaat, Miguel A. Canales, René-Olivier Casasnovas, Eric Van Den Neste, Andre Goy, Brian T. Hill, Catherine Thieblemont, Maria De Fatima De La Cruz, Federica Cavallo, George Follows, Sylvain Choquet, Ronit Gurion, Reda Bouabdallah, Ulrich Jaeger, Agnes Nagy, John Kuruvilla, Krzysztof Warzocha, Nagesh Kalakonda, Paolo Caimi, Sameer Bakhshi, Matthew Ku, Nada Hamad, Hendrik Veelken, Ewa Matczak, Xiwen Ma, Jean-Richard Saint-Martin, Jatin J. Shah, Michael G. Kauffman, Sharon Shacham, Josée M Zijlstra
Journal: Blood (2018)
Long‐term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa: a strategy to reduce side‐effects, improving patients’ compliance
Authors: C. Marasca, A. Masarà, M.C. Annunziata, V. Bettoli, M.A. Luciano, G. Fabbrocini
Journal: British Journal of Dermatology (2018)

Linked Article: Albrecht et al. Br J Dermatol 2019;180:749–755.
Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics
Authors: Svenja Siemer, Dana Westmeier, Matthias Barz, Jonas Eckrich, Désirée Wünsch, Christof Seckert, Christian Thyssen, Oliver Schilling, Mike Hasenberg, Chengfang Pang, Dominic Docter, Shirley K. Knauer, Roland H. Stauber, Sebastian Strieth
Journal: Biomaterials (2018)
Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years
Authors: Rosalyn Hithersay, Carla M. Startin, Sarah Hamburg, Kin Y. Mok, John Hardy, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Dean Nizetic, André Strydom
Journal: JAMA Neurology (2018)

This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS).
Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis
Authors: Diane C. Saunders, Marcela Brissova, Neil Phillips, Shristi Shrestha, John T. Walker, Radhika Aramandla, Greg Poffenberger, David K. Flaherty, Kevin P. Weller, Julie Pelletier, Tracy Cooper, Matt T. Goff, John Virostko, Alena Shostak, E. Danielle Dean, Dale L. Greiner, Leonard D. Shultz, Nripesh Prasad, Shawn E. Levy, Robert H. Carnahan, Chunhua Dai, Jean Sévigny, Alvin C. Powers
Journal: Cell Metabolism (2018)
Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity
Authors: Scott R. Walsh, Donald Bastin, Lan Chen, Andrew Nguyen, Christopher J. Storbeck, Charles Lefebvre, David Stojdl, Jonathan L. Bramson, John C. Bell, Yonghong Wan
Journal: Journal of Clinical Investigation (2018)

Despite its success in treating melanoma and hematological malignancies, adoptive cell therapy (ACT) has had only limited effects in solid tumors. This is due in part to a lack of specific antigen targets, poor trafficking and infiltration, and immunosuppression in the tumor microenvironment. In this study, we combined ACT with oncolytic virus vaccines (OVVs) to drive expansion and tumor infiltration of transferred antigen-specific T cells and demonstrated that the combination is highly potent for the eradication of established solid tumors. Consistent with other successful immunotherapies, this approach elicited severe autoimmune consequences when the antigen targeted was a self-protein. However, modulation of IFN-α/-β signaling, either by functional blockade or rational selection of an OVV backbone, ameliorated autoimmune side effects without compromising antitumor efficacy. Our study uncovers a pathogenic role for IFN-α/-β in facilitating autoimmune toxicity during cancer immunotherapy and presents a safe and powerful combinatorial regimen with immediate translational applications.
Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: a matched case-control study
Authors: Farah Naz Qamar, Mohammad Tahir Yousafzai, Muhammad Khalid, Abdul Momin Kazi, Heeramani Lohana, Sultan Karim, Ayub Khan, Aneeta Hotwani, Shahida Qureshi, Furqan Kabir, Fatima Aziz, Naveed Masood Memon, Mudassar Hussain Domki, Rumina Hasan
Journal: The Lancet Infectious Diseases (2018)
Epigenetic Hallmarks of Fetal Early Atherosclerotic Lesions in Humans
Authors: Filomena de Nigris, Francesco Cacciatore, Francesco P. Mancini, Dino F. Vitale, Gelsomina Mansueto, Francesco P. D’Armiento, Concetta Schiano, Andrea Soricelli, Claudio Napoli
Journal: JAMA Cardiology (2018)

Although increasingly strong evidence suggests a role of maternal total cholesterol and low-density lipoprotein cholesterol (LDLC) levels during pregnancy as a risk factor for atherosclerotic disease in the offspring, the underlying mechanisms need to be clarified for future clinical applications.To test whether epigenetic signatures characterize early fetal atherogenesis associated with maternal hypercholesterolemia and to provide a quantitative estimate of the contribution of maternal cholesterol level to fetal lesion size.This autopsy study analyzed 78 human fetal aorta autopsy samples from the Division of Human Pathology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. Maternal levels of total cholesterol, LDLC, high-density lipoprotein cholesterol (HDLC), triglycerides, and glucose and body mass index (BMI) were determined during hospitalization owing to spontaneous fetal death. Data were collected and immediately processed and analyzed to prevent degradation from January 1, 2011, through November 30, 2016.Results of DNA methylation and messenger RNA levels of the following genes involved in cholesterol metabolism were assessed: superoxide dismutase 2 (SOD2), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein 2 (SREBP2), liver X receptor α (LXRα), and adenosine triphosphate-binding cassette transporter 1 (ABCA1).Among the 78 fetal samples included in the analysis (59% male; mean [SD] fetal age, 25 [3] weeks), maternal cholesterol level explained a significant proportion of the fetal aortic lesion variance in multivariate analysis (61%; P = .001) independently by the effect of levels of HDLC, triglycerides, and glucose and BMI. Moreover, maternal total cholesterol and LDLC levels were positively associated with methylation of SREBP2 in fetal aortas (Pearson correlation, 0.488 and 0.503, respectively), whereas in univariate analysis, they were inversely correlated with SREBP2 messenger RNA levels in fetal aortas (Pearson correlation, -0.534 and -0.671, respectively). Epivariations of genes controlling cholesterol metabolism in cholesterol-treated human aortic endothelial cells were also observed.The present study provides a stringent quantitative estimate of the magnitude of the association of maternal cholesterol levels during pregnancy with fetal aortic lesions and reveals the epigenetic response of fetal aortic SREBP2 to maternal cholesterol level. The role of maternal cholesterol level during pregnancy and epigenetic signature in offspring in cardiovascular primary prevention warrants further long-term causal relationship studies.
The rule of 10s versus the rule of 2s: High complication rates after conventional excision with postoperative margin assessment of specialty site versus trunk and proximal extremity melanomas
Authors: Alexandra K. Rzepecki, Charles D. Hwang, Jeremy R. Etzkorn, Thuzar M. Shin, Joseph F. Sobanko, Nicole M. Howe, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2018)
Metastatic lung cancer induced by the cooperation ofp53 and K-ras mutations in mice
Authors: Shuling Zheng, Clifton Stephens, Guillermina Lozano
Journal: Cancer Research (2004)

5568  Lung cancer is a worldwide devastating disease with a five-year survival of only 5-10%. Many mouse models have been developed to study the pathophysiology of lung cancer. A recently developed mouse model is that the proto-oncogene K-ras is spontaneously activated at codon 12 due to a latent allele placed at the endogenous locus ( K-rasLA1). All K-rasLA1/+ mice develop lung cancer at about one year of age. K-rasLA1/+ mice on a 129/Sv background have a slightly better survival. This somatic activation of K-ras mimics the spontaneous mutation of K-ras occurring in human cancer, but its infrequent metastasis does not manifest human lung cancer well. A mouse model for hereditary Li-Fraumeni syndrome harbors a mutant p53 with a missense mutation at codon 172 generated by homologous recombination (p53R172HΔg). This mutant p53 allele induces highly metastatic osteosarcomas and carcinomas in heterozygous mice, representing a gain-of-function allele. Given that K-ras mutations are frequently associated with p53 mutations in lung cancer, we hypothesized that mice with both p53 and ras mutations might develop metastatic lung cancer. 129/SvEv inbred p53R172HΔg/+ mice were crossed with K-rasLA1/+ mice to generate double heterozygous mice and three groups of control mice. Mice were monitored for survival and tumor formation. All animals showing obvious tumors or other signs of distress were sacrificed and subjected to full necropsy. Tumors and metastases were morphologically diagnosed by a pathologist. At one year of age, about 90% of double heterozygous mice had died while only 50% of K-rasLA1/+ or 20% of p53R172HΔg/+ mice had died. Double heterozygous mice had a significantly reduced life span and all developed lung tumors, which could be diagnosed by micro-CT scanning in live mice. Since many mice developed multiple primary tumors, immunohistochemical staining of surfactant protein C further identified and confirmed the diagnosis of metastases from lung cancer. Metastases were found in about 30% of lung carcinomas and about 35% of all types of carcinomas. Moreover, double heterozygous mice had a broader tumor spectrum and different tumor frequencies when compared with parental strains. This mouse model has two major molecular alterations common in lung cancer and develops lung cancer with metastasis. The occurrence of metastases and change of tumor incidences demonstrate the cooperation of mutant p53 and K-ras in vivo. This mouse model better recapitulates human lung cancer and will be very useful for testing novel therapeutic interventions.
Assembly of a pan-genome from deep sequencing of 910 humans of African descent
Authors: Rachel M. Sherman, Juliet Forman, Valentin Antonescu, Daniela Puiu, Michelle Daya, Nicholas Rafaels, Meher Preethi Boorgula, Sameer Chavan, Candelaria Vergara, Victor E. Ortega, Albert M. Levin, Celeste Eng, Maria Yazdanbakhsh, James G. Wilson, Javier Marrugo, Leslie A. Lange, L. Keoki Williams, Harold Watson, Lorraine B. Ware, Christopher O. Olopade, Olufunmilayo Olopade, Ricardo R. Oliveira, Carole Ober, Dan L. Nicolae, Deborah A. Meyers, Alvaro Mayorga, Jennifer Knight-Madden, Tina Hartert, Nadia N. Hansel, Marilyn G. Foreman, Jean G. Ford, Mezbah U. Faruque, Georgia M. Dunston, Luis Caraballo, Esteban G. Burchard, Eugene R. Bleecker, Maria I. Araujo, Edwin F. Herrera-Paz, Monica Campbell, Cassandra Foster, Margaret A. Taub, Terri H. Beaty, Ingo Ruczinski, Rasika A. Mathias, Kathleen C. Barnes, Steven L. Salzberg
Journal: Nature Genetics (2018)

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.
Data Access and Interactive Visualization of Whole Genome Sequence of Sickle Cell Patients within the St. Jude Cloud
Authors: Lance E. Palmer, Xin Zhou, Clay McLeod, Evadnie Rampersaud, Jeremie H. Estepp, Xing Tang, Jian Wang, Edgar Siosan, J. Robert Michael, Kirby Birch, Jason R Hodges, Martha Villavicencio, Michael Rusch, Scott Newman, Heather Mulder, John Easton, Keith Perry, James R. Downing, Jane S. Hankins, Gang Wu, Jinghui Zhang, Mitchell J. Weiss
Journal: Blood (2018)
Abstract 17065: Serum Triglyceride Predicts First Cardiovascular Events in Diabetic Patients With Hypercholesterolemia and Retinopathy: A Post-hoc Analysis of a Randomised Controlled Trial
Authors: Akihiro Nomura, Masa-aki Kawashiri, Hayato Tada, Masakazu Yamagishi, Issei Komuro, Hiroshi Ito
Journal: Circulation (2017)

Introduction: Low-density lipoprotein (LDL) cholesterol predicts cardiovascular events in patients with diabetes mellitus. However, it is uncertain whether serum triglyceride level is also associat...
The Wilms’ tumor suppressor protein1 activates anti-proliferative and apoptotic pathways resulting in growth arrest and apoptosis in a cellular system
Authors: Debra J. Birn-Morrison, Jacqueline M. Mason, Milton A. English, Windy Berkofsky-Fessler, Jonathan D. Licht
Journal: Cancer Research (2004)

1787  The Wilms’ tumor suppressor protein (WT1), a transcription factor critical for normal kidney development, is mutated in 10-15% of Wilms’ tumors. Genetic data originally identified WT1 as a tumor suppressor and experiments in vitro showed that the protein plays a role in both growth suppression and apoptosis. We recently established a tetracycline-repressible system for expressing wild-type and tumor-derived mutant WT1 proteins in Saos2 cells. Wild-type, but not mutant, WT1 blocks cellular proliferation, DNA synthesis and rapidly induces apoptosis. Caspases 8 and 9 are cleaved, indicating that both intrinsic and extrinsic apoptotic pathways are activated. Using microarray analysis, we defined two sets of genes involved in growth control and apoptosis, respectively. Mutant WT1 protein does not induce expression of any of these genes. The genes that comprise the apoptotic subset are Bak, Bik, Foxo1, Fas ligand and Akt. Foxo1 mediates programmed cell death by inducing the transcription of Fas ligand. Foxo1 is inactivated by AKT-dependent phosphorylation, which promotes the nuclear export of Foxo1. In our system, Foxo1 and Fas ligand are induced whereas AKT is inhibited. WT1 may reset the threshold for apoptosis in two ways, by activating the transcription of pro-apoptotic Bcl-2 family members and by activating the synthesis of Fas ligand. One of the genes involved in growth control is MKP3, a dual-specificity phosphatase that specifically dephosphorylates activated ERK1/2 and down-regulates Ras-mediated growth factor signaling. This correlates with our recent study demonstrating that WT1 directly activates Sprouty1, another Ras/MAPK inhibitor, and may explain why WT1 prevents cellular transformation by activated Ras. The gene array data is confirmed by real time PCR analysis. Bak, Foxo1 and MKP3 are rapidly induced upon WT1 expression, indicating that they are probably directly regulated by WT1. In support of this, the Bak, Foxo1 and MKP3 promoters are activated by WT1 in transient transfection assays. As predicted, WT1 induction leads to decreased phosphorylation of ERK1/2 and decreased expression and phosphorylation of Akt. Altogether, by demonstrating that WT1 activates intrinsic and extrinsic apoptotic signals through Bak and Foxo1, and blocks the Ras/MAPK pathway through MKP3 and Sprouty1, we have defined a novel mechanism by which WT1 can limit growth.
FRI0507 The prevalence of latent tuberculosis infection in indian patients of takayasu arteritis
Authors: N.V. Negalur, G. Ekbote, D. Tanna, N. Mendiratta, R. Gupta, A. Bhan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Studies have shown a correlation between Tuberculosis (TB) and Takayasu arteritis (TA). Some even postulate that infection with TB is required for the initiation of aortoarteritis. Hence, this project was undertaken to find an association of TB and TA by studying the prevalence of Latent Tuberculosis Infection (LTBI) in Indian TA patients. <h3>Objectives</h3> To study the prevalence of LTBI in Indian TA patients and see whether LTBI is more in these patients as compared to the historical cohort (40% in Indian population). <h3>Methods</h3> This was a cross sectional observational study. All consecutive patients with TA (satisfying the ACR 1990 criteria) were included prospectively from a period of May 2016 to December 2017. Their clinical, laboratory and radiological data were collected after obtaining informed consent. Patients were divided into groups based on the angiographic classification. LTBI was assessed by the Mantoux test and Quantiferon TB Gold test. Mantoux test (MT) was done with 5TU and results were read after 48–72 hours. An induration more than 10 mm was considered positive. Quantiferon TB Gold assay (QTB) was done by ELISA technique and (patient minus control) value &gt;0.35 IU/ml was considered positive. A positive result of MT and /or QTB was considered positive for LTBI. Chest X-ray was included to access evidence of past or active TB lesions. Active infection was defined as clinical and microbiological and /or radiological evidence of TB. The study was approved by the Ethics committee of Medanta hospital. <h3>Results</h3> Out of 66 consecutive TA patients, 46 patients had tests available for LTBI and these were included in the analysis. The mean age of the cohort was 34.9 years with a median disease duration of 24 months. Males consisted of 11 patients whereas females formed the majority i.e. 35 patients (M: F= 1: 3.1). Angiographic Type V (54.3%) was the commonest in the cohort followed by Type IIB (17.3%), Type IV, I, IIA and III (15.2%, 8.6%, 2.1% and 2.1% respectively). LTBI positivity was present in 32.6% of the cohort; with 5 patients (10.8%) having both tests positive. 6 patients were MT positive without being QTB positive and 4 patients were only QTB positive. Eight patients had history of Tuberculosis out of which 1 was diagnosed with TB and TA simultaneously. Four patients were diagnosed as TA during the course of Anti tubercular treatment (ATT) between 4 to 6 months, whereas the rest were diagnosed after ATT completion. The mean duration of Anti tubercular treatment was 8 months. Koch's contact was seen in 7 patients. <h3>Conclusions</h3> The prevalence of LTBI in Indian Takayasu patients was 32.6%, which was not higher than the population prevalence (40% in the historical cohort). However, a larger cohort and further association studies are needed for the relationship between TA and Tuberculosis. <h3>Disclosure of Interest</h3> None declared