tbuckley/cabot-search huggingface dataset:
Burden of enterotoxigenic Escherichia coli and shigella non-fatal diarrhoeal infections in 79 low-income and lower middle-income countries: a modelling analysis
Authors: John D Anderson, Karoun H Bagamian, Farzana Muhib, Mirna P Amaya, Lindsey A Laytner, Thomas Wierzba, Richard Rheingans
Journal: The Lancet Global Health (2019)

Enterotoxigenic Escherichia coli (ETEC) and shigella are two major pathogens that cause moderate-to-severe diarrhoea in children younger than 5 years. Diarrhoea is associated with an increased risk of stunting, which puts children at risk of death due to other infectious diseases.We modelled ETEC-related and shigella-related mortality and the effect of moderate-to-severe diarrhoea episodes to determine the number of children with stunting due to these infections in 79 low-income and lower middle-income countries. We applied population attributable risk for increased number of deaths due to other infectious diseases in children who are stunted. We calculated 95% uncertainty intervals (UIs) for the point estimates.In children younger than 5 years, we estimate 196 million (95% UI 135-269) episodes of ETEC and shigella diarrhoea occur annually, resulting in 3·5 million (0·8-5·4) cases of moderate-to-severe stunting and 44 400 (29 400-59 800) total ETEC deaths and 63 100 (44 000-81 900) total shigella deaths in 2015. Additional infectious disease mortality due to stunting resulted in increases of 24% (8-34; for ETEC) and 28% (10-39; for shigella) over direct deaths due to diarrhoeal episodes. The distribution of mortality and morbidity varied geographically, with African Region and Eastern Mediterranean Region countries bearing the greatest burden.The expanded effects of non-fatal ETEC and shigella-related diarrhoeal episodes can have lasting consequences. Prevention of these infections could reduce the risk of direct death and stunting and deaths due to other infectious diseases. Understanding the countries and populations with the highest disease risk helps to target interventions for the most vulnerable populations.The Bill & Melinda Gates Foundation.
Targeting the Adenosinergic Axis in the Eμ-TCL1 Chronic Lymphocytic Leukemia Mouse Model Offers Novel Therapeutic Opportunities
Authors: Andrea Papait, Tiziana Vaisitti, Sara Serra, Valentina Audrito, Francesco Tito, Giulia Guerra, Dimitar G Efremov, Silvia Deaglio
Journal: Blood (2018)
Recent trends in age at diagnosis of colon cancer in the United States, 2004-2015, a National Cancer Database study.
Authors: Boone Wilder Goodgame, Jack Virostko, Anna Capasso, Thomas Yankeelov
Journal: Journal of Clinical Oncology (2019)

490 Background: The incidence of colorectal cancer (CRC) in adults younger than age 50 has been increasing in the US since 1970. The US Preventive Services Task Force recommends screening for CRC beginning at age 50, while the American Cancer Society recently revised its guidelines to advise screening at age 45. We analyzed the National Cancer Database (NCDB) from 2004 through 2015 to determine whether the proportion of patients diagnosed younger than 50 has changed during this time. Methods: This was a retrospective study of NCDB data, which includes more than 70 percent of newly diagnosed cancer cases in the US. We examined the proportion of patients diagnosed prior to age 50 as our primary endpoint. We used the Cochran–Armitage test for trend to assess changes in the proportion of cases diagnosed at age &lt; 50 years old as a function of year of diagnosis. Results: We identified 152,749 patients diagnosed under age 50 and 1,033,014 patients diagnosed at age 50 or greater. Over the study period, the proportion of the total number of patients diagnosed with colorectal cancer under age 50 increased (14.3% in 2015 vs. 11.5% in 2004, p &lt; 0.0001). Younger adults with CRC presented with more advanced disease, with 49.9% stage III or IV disease, as compared to 40.0% in those diagnosed over age 50. Both men and women had a rising proportion of cases diagnosed younger than 50 (p &lt; 0.0001) over time. In men, only non-Hispanic whites had an increase in diagnosis at ages less than 50 (p &lt; 0.0001), while in women, all racial and ethnic subgroups had an increase in younger diagnoses over time (p &lt; 0.01). All income quartiles (p &lt; 0.001) demonstrated a proportional increase in younger adults over time, with the highest income quartile having the highest proportion of younger cases. The proportion of younger-onset CRC rose in urban areas (p &lt; 0.001), but did not rise in rural areas. Conclusions: The proportion of persons diagnosed with CRC under age 50 in the US has continued to increase over the past decade. Younger adults presented with more advanced disease, suggesting that screening could improve outcomes.
Role of enterocyte-specific gene polymorphisms in adjuvant treatment for stage III colorectal cancer.
Authors: Mitsukuni Suenaga, Shu Cao, Wu Zhang, Satoshi Matsusaka, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Marta Schirripa, Afsaneh Barzi, Masashi Ueno, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

550 Background: Enterocyte subtype of the Colorectal Cancer (CRC) Assigner classifier is known as favorable to oxaliplatin-based adjuvant treatment for stage III CRC. We previously reported potential predictive value of single nucleotide polymorphisms (SNPs) in enterocyte-related genes in metastatic CRC (Suenaga, ASCO2018). In this study, we examined clinical significance of MS4A12 and CDX2 SNPs in adjuvant treatment (AT) for Stage III CRC. Methods: 350 patients with Stage III CRC were included in this study: 274 received AT (discovery cohort: median age = 62, median follow-up = 59.9 months) and 76 received surgery alone (control: median age = 75, median follow-up = 58.0 months). 68 and 206 patients received FOLFOX and oral fluoriopyrimidine, respectively. SNPs were analyzed by PCR-based direct sequencing. Disease-free survival and overall survival (OS) were analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression. Results: In discovery cohort, the G/G variant in MS4A12 rs4939378 was associated with lower 5-y survival rate than any A allele in uni- and multi-variate analyses (70% vs 90%, univariate: HR 2.29, 95% CI: 1.03-5.06, P = 0.035; multivariable: HR 2.58, 95% CI: 1.15-5.76, P = 0.021). Patients with the G/G variant in CDX2 rs3812863 had better OS than those with any A, though not significant in multivariable analysis (5 y-survival rate: 95% vs 82%, univariate: HR 0.34, 95% CI: 0.12-0.97, P = 0.034; multivariable: HR 0.39, 95% CI: 0.13-1.11, P = 0.078). There was no significance in the control, and significant interaction was observed between MS4A12 genotypes and groups (interaction P = 0.007). In addition, there was no interaction between MS4A12 rs4939378 and FOLFOX vs oral fluoropyrimidine. Conclusions: Our findings suggest that MS4A12 and CDX2 gene polymorphisms may predict outcome in patients with Stage III CRC. However, clinical significance of the SNPs for oxaliplatin seems to differ depending on tumor stage. Further research and validation study are warranted to explore the association of the SNPs with carcinogenesis or cancer progression.
Follow‐up, 18 months off house dust mite immunotherapy, of a randomized controlled study on the primary prevention of atopy
Authors: Cherry Alviani, Graham Roberts, Helen Moyses, Sarah Pearson, Maria Larsson, Zaraquiza Zolkipli, Louise J. Michaelis, Ramesh Kurukulaaratchy, Syed Hasan Arshad
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
AML-Fated Clones Arise in Stem and Progenitor Cells in Myelofibrosis Patients Several Years Prior to AML Diagnosis
Authors: Jenny M. Ho, Jessie James Franco Medeiros, Michelle Chan-Seng-Yue, Lauren Hummel, Andrea Arruda, Amanda Mitchell, Caroline J McNamara, James Kennedy, Anne Tierens, Hubert Tsui, Mark D. Minden, Vikas Gupta, John E. Dick
Journal: Blood (2018)
Dissecting Ex Vivo Expansion of Mobilized Peripheral Blood Hematopoietic Stem and Progenitor Cells By Single Cell RNA Sequencing
Authors: Matteo Maria Naldini, Gabriele Casirati, Erika Zonari, Giacomo Desantis, Andrea Cammarata, Stefano Beretta, Ivan Merelli, Fabio Ciceri, Bernhard Gentner
Journal: Blood (2018)
Antibody deficiency in patients taking clozapine
Authors: Mark J Ponsford, Stephen Jolles
Journal: BMJ (2019)

6][7][8] Various mechanisms have been proposed for the rise in pneumonia, including sedation, sialorrhoea and aspiration, agranulocytosis, and smoking. 9 10Following the introduction of calculated globulin screening in Wales, 11 we found a novel and striking association between use of the antipsychotic clozapine and antibody deficiency. 12Patients taking clozapine follow an intensive regimen of blood testing for the rare risk of agranulocytosis (with cumulative incidence of <1% cases), but antibody testing is not included in existing clozapine monitoring programmes.We urge consideration of this potential mechanistic explanation as a modifiable risk factor for the higher rates of pneumonia and sepsis related mortality reported in this vulnerable cohort.
The New Possibility of Lymphoscintigraphy to Guide a Clinical Treatment for Lymphedema in Patient With Breast Cancer
Authors: Kwan Sik Seo, Minseok Suh, Sunmok Hong, Gi Jeong Cheon, Shi-Uk Lee, Gwang Pyo Jung
Journal: Clinical Nuclear Medicine (2019)

Lymphedema is a chronic disease that occurs frequently after breast cancer treatment. For the treatment of lymphedema, surgical approach such as vascularized lymph node transfer and super-microscopic lymphovenous anastomosis surgery is well established. Complex decongestive therapy (CDT) and sympathetic ganglion block (SGB) are two non-surgical therapeutic options. This study aimed to evaluate the effectiveness of lymphoscintigraphy in guiding the selection of the optimal non-surgical treatment in lymphedema.A total of 81 lymphedema patients who underwent lymphoscintigraphy and were treated with CDT or SGB were retrospectively evaluated. The parameters for the lymphoscintigraphic findings included the extent of dermal backflow (small extent/large extent groups), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized groups). The change in the circumferential difference between the two sides of the body at the upper arm and forearm was used as the clinical outcome variable. Paired comparison and group comparison analysis were conducted.Of 81 patients, 41 received CDT and 40 received SGB. There were no significant differences in demographic data between the CDT and SGB groups. Both CDT and SGB had a significant therapeutic effect. Upper arm edema was more significantly reduced after SGB than after CDT in the small extent group (P = 0.004), the forearm-restricted pattern group (P = 0.002), and the non-visualized group (P = 0.018). In the other groups, SGB and CDT showed comparable therapeutic effects without statistical differences.SGB was found to have a better therapeutic effect in the lymphedema patients with specific lymphoscintigraphic findings compared with CDT. Lymphoscintigraphy may be helpful in selecting the appropriate approach to lymphedema treatment. Further well-designed prospective studies are warranted to validate the findings of this study.
10-Day Low Dose Decitabine Regimen for Elderly Acute Myeloid Leukemia Patient Maintenance Treatment
Authors: Jia Liu, Kong Peiyan, Li Gao, Cheng Zhang, Yao Liu, Hongju Yan, Lidan Zhu, Shichun Gao, Gao Lei, Defu Zeng, Xi Zhang
Journal: Blood (2018)
l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease
Authors: Ali Canbay, Jan-Peter Sowa
Journal: Drugs (2019)

l-ornithine l-aspartate (LOLA) has been known as an effective ammonia-lowering agent for more than 50 years with good evidence in hepatic encephalopathy. Administration of LOLA removes ammonia via two distinct mechanisms: by synthesis of urea and by the synthesis of glutamine via the enzyme glutamine synthetase. While LOLA has been used in cirrhosis and acute liver injury settings, it is less clear if LOLA could be used in non-alcoholic fatty liver disease (NAFLD). NAFLD and the progressive form non-alcoholic steatohepatitis (NASH) are currently the leading causes of chronic liver disease worldwide, with roughly 25% of the world population affected by NAFLD. Consequences of NASH are end-stage liver disease and cardiovascular morbidity and mortality. As the basis for NAFLD is excess calorie uptake and excess adipose tissue mass, the conservative therapeutic approach is weight loss by intense lifestyle change. However, no pharmacological treatment options are currently approved. LOLA is being investigated as a pharmacological tool to ameliorate liver injury in NAFLD on the basis that it lowers liver ammonia concentrations and supplies anti-oxidative glutamine and glutathione. Indirect hepatoprotective effects currently under investigation could also be beneficial.
Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study
Authors: Tyler S. Kaster, Jonathan Downar, Fidel Vila-Rodriguez, Kevin E. Thorpe, Kfir Feffer, Yoshihiro Noda, Peter Giacobbe, Yuliya Knyahnytska, Sidney H. Kennedy, Raymond W. Lam, Zafiris J. Daskalakis, Daniel M. Blumberger
Journal: American Journal of Psychiatry (2019)

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics.This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics.Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory.Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.
Would Bone Marrow be Associated with Superior Outcomes Compared with Peripheral Blood for Male Recipients with Female Donors in HLA-Matched Related Transplantation?
Authors: Hideki Nakasone, Koji Kawamura, Kimikazu Yakushijin, Akihito Shinohara, Heiwa Kanamori, Kazuteru Ohashi, Takahiro Fukuda, Naoyuki Uchida, Hirohisa Nakamae, Junya Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshihiro Inamoto, Sachiko Seo, Fumihiko Kimura, Masao Ogata
Journal: Blood (2018)
Abstract 16189: 99mTc-duramycin Imaging Detects Cancer Therapy Related Cardiac Dysfunction Before a Decrease in Lvef
Authors: Takehiro Nakahara, Artiom D Petrov, Takashi Tanimoto, Nezam Haider, Navneet Narula, Farhan Chaudhry, Jeffrey A Mattis, Koon Y Pak, Gagan Sahni, Amy Tiersten, Aarti Bhardwaj, Partho P Sengupta, Marc R Dweck, Harry W Strauss, Jagat Narula
Journal: Circulation (2016)

Background: Although the remission rate of cancer has increased, cardiotoxicity due to cancer therapy remains a major problem. Detection of cardiotoxicity prior to a decrease in left ventricular fu...
Durability of Transcatheter and Surgical Bioprosthetic Aortic Valves in Patients at Lower Surgical Risk
Authors: Lars Søndergaard, Nikolaj Ihlemann, Davide Capodanno, Troels H. Jørgensen, Henrik Nissen, Bo Juel Kjeldsen, Yanping Chang, Daniel Andreas Steinbrüchel, Peter Skov Olsen, Anna Sonia Petronio, Hans Gustav Hørsted Thyregod
Journal: Journal of the American College of Cardiology (2019)
Abstract 11820: NG2+ Cells Protect Against Cardiac Remodeling and Failure After Myocardial Infarction in Mice
Authors: Joost Offerhaus, Peter Rainer, Peter Andersen, Djahida Bedja, Dong I Lee, Lincoln Shenje, Oscar H Cingolani
Journal: Circulation (2015)

Introduction: Myocardial infarction kills cells, leading to cardiac remodeling (CR) and heart failure. Pericytes are microvascular mural cells that have been recently shown to have plasticity and cardiac regenerative potential, and also to interfere with CR, yet different niches present in cardiac tissue together with many cell markers that characterize resident pericytes have raised interrogate regarding their cell-specific differentiation capabilities. NG2 is a cell trans-membrane proteoglycan receptor and the most robust marker for pericytes. NG2 is normally present in embryonic cardiac myocytes, but in the adult heart its expression is only limited to pericytes and pericyte-like cells. Hypothesis: NG2+ cells are protective after myocardial infarction in the adult heart. Methods: Myocardial infarction (MI) was performed by coronary artery ligation in double transgenic mice (NG2cre-Z/EG) that express NG2-GFP under cre-lox technology, in mice lacking NG2 (NG2 -/-), and in wilt type littermate controls (WT). Cardiac histology was performed using Masson staining for fibrosis (Optical) and immunohistochemistry (Confocal) microscopy. Cardiac function was assessed by fractional shortening (FS) determined by echocardiography. Results: 7 days after MI, NG2 positive cardiac myocytes were seen in the double transgenic mice (co-staining with alpha-sarcomeric actinin) more abundantly in the infarct border zone (confocal microscopy), as opposed to those subjected to sham MI, in which NG2+ cells were mainly limited to pericytes (192 ± 26 vs 1730 ± 290 NG2+ve cardiac myocytes/cm2; p &lt;0.001). Cardiac function deteriorated more after 4 weeks in NG2-/- compared to WT (FS = 21 ± 2.1 vs. 12.5 ± 1.1 %, WT and NG2 -/- respectively; p &lt; 0.001). Histologic examination of cardiac tissue revealed more interstitial fibrosis in the NG2-/- hearts (1.1 ± 0.2 vs 2.3 ± 0.3 %, WT and NG2-/-), seen mainly in the remote infarct zone. Quantitative analysis (qPCR) in different progenitor cell lines also revealed co-expression of NG2 with ISL-1, a robust cardiac stem cell marker. Conclusions: Our findings indicate that NG2+ cells play a key role in post-MI cardiac remodeling, and suggest a potential therapeutic role of resident NG2+ cells in HF.
Real-Life Data on the Outcome of Daratumomab-Refractory Myeloma Patients: Multi-Center Experience
Authors: Noam Benyamini, Adir S, Moshe E. Gatt, Yael C Cohen, Irit Avivi, Svetlana Trestman, Olga Shvetz, Tamar Tadmor, Najib Dally, Yevgeny Chober, Hila Magen, Chezi Ganzel, Osnat Jarchowcky Dolberg, Celia Suriu, Noa Lavi
Journal: Blood (2018)
Transgender Identity and Experiences of Violence Victimization, Substance Use, Suicide Risk, and Sexual Risk Behaviors Among High School Students — 19 States and Large Urban School Districts, 2017
Authors: Michelle M. Johns, Richard Lowry, Jack Andrzejewski, Lisa C. Barrios, Zewditu Demissie, Timothy McManus, Catherine N. Rasberry, Leah Robin, J. Michael Underwood
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Transgender youths (those whose gender identity* does not align with their sex†) experience disparities in violence victimization, substance use, suicide risk, and sexual risk compared with their cisgender peers (those whose gender identity does align with their sex) (1-3). Yet few large-scale assessments of these disparities among high school students exist. The Youth Risk Behavior Survey (YRBS) is conducted biennially among local, state, and nationally representative samples of U.S. high school students in grades 9-12. In 2017, 10 states (Colorado, Delaware, Hawaii, Maine, Maryland, Massachusetts, Michigan, Rhode Island, Vermont, Wisconsin) and nine large urban school districts (Boston, Broward County, Cleveland, Detroit, District of Columbia, Los Angeles, New York City, San Diego, San Francisco) piloted a measure of transgender identity. Using pooled data from these 19 sites, the prevalence of transgender identity was assessed, and relationships between transgender identity and violence victimization, substance use, suicide risk, and sexual risk behaviors were evaluated using logistic regression. Compared with cisgender males and cisgender females, transgender students were more likely to report violence victimization, substance use, and suicide risk, and, although more likely to report some sexual risk behaviors, were also more likely to be tested for human immunodeficiency virus (HIV) infection. These findings indicate a need for intervention efforts to improve health outcomes among transgender youths.
Abstract 20209: Risk Factors for 'Microsize' versus Usual Myocardial Infarctions in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Zaid I Al Marzooq, Lisandro D Colantonio, Peter M Okin, Joshua S Richman, Todd M Brown, Emily B Levitan, Joanna Bryan, Monika M Safford
Journal: Circulation (2017)

Introduction: Increasingly sensitive troponin assays allow detection of very small elevations of troponin. Microsize MI is a recently described phenomenon consisting of events that meet rigorous criteria for MI, but with very low peak troponin elevations (<0.05 ng/mL). Emerging evidence shows that these events are common and carry increased risk of all-cause mortality, but risk factors for microsize vs. usual MI have not been examined. Objectives: To compare risk factors for microsize vs. usual MIs in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort (n=30,239). Methods: Among 24,470 REGARDS participants free of coronary heart disease at baseline, heart-related hospitalizations were expert adjudicated for MI using published guidelines. MIs were classified as microsize MI (peak troponin <0.5 ng/ml) or usual MI (peak troponin ≥0.5 ng/ml). Competing risk analyses assessed associations between baseline risk factors and incident microsize vs. usual MI. Results: The 891 inclu...
Assessment of the Genomic Landscape of Intermediate Risk Acute Myeloid Leukemia As Defined By 2010 ELN Risk Classification
Authors: Ekaterina Panina, Frank G. Rücker, Lars Bullinger, Anna Dolnik, Julia Herzig, Tamara J. Blätte, Verena I. Gaidzik, Peter Paschka, Maria-Veronica Teleanu, Nikolaus Jahn, Laura K. Schmalbrock, Daniela Weber, Lena Kubanek, Thomas Kindler, Jörg Westermann, Michael Lubbert, Helmut R. Salih, Felicitas Thol, Michael Heuser, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2018)
PARP Inhibitors and Parkinson’s Disease
Authors: Abby L. Olsen, Mel B. Feany
Journal: New England Journal of Medicine (2019)

A recent study implicates the enzyme poly(adenosine 5′-diphosphate-ribose) polymerase 1 (PARP1) as a mediator of neuronal cell death in Parkinson’s disease. The findings also provide support for a class of FDA-approved drugs that inhibit PARP1, currently used in the treatment of certain breast and ovarian cancers, as candidate drugs for Parkinson’s disease.