tbuckley/cabot-search huggingface dataset:
Abstract B21: The gastrointestinal microbiota controls cancer cell intrinsic mechanisms to promote the progression of acute lymphoblastic leukemia
Authors: Wadie Mahauad-Fernandez, Soumaya Zlitni, Ami Bhatt, Dean Felsher
Journal: Cancer Research (2020)

Abstract Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and the second most common acute leukemia in adults. Despite best existing therapy, older children and elderly ALL patients have poor prognoses. Thus, there is a need to identify alternative therapeutics for these patients. There has been controversy about the function of the gut microbiota in cancer, with some reports showing that it supports tumor growth and others showing tumor growth inhibition. Recently, Dr. Melvyn Greaves proposed that ALL development may have a microbial trigger; however, gut microbiota studies in ALL are scarce. Little is known about the role of the gut microbiota in ALL progression and in reshaping cancer cell-intrinsic pathways that are as important as immune responses in the outcome of ALL. Recently, we found that gut microbiota depletion in immunocompromised mice reduces ALL growth by inducing apoptosis and inhibiting proliferation. We show that in immunocompromised microbiome-depleted mice, the rate of ALL tumor growth is reduced compared to microbiome-competent mice. Molecularly, we found that microbiome ablation results in changes in cancer cell-intrinsic pathways of apoptosis and proliferation in these tumors. To further understand how the gut microbiota affects these cancer cell-intrinsic pathways, we have performed RNA sequencing on tumors from microbiome-competent and microbiome-depleted mice accompanied by 16s rRNA sequencing from stool samples and mass spectrometry of blood serum to identify metabolites secreted by the gut microbiota that reach the tumor site, affecting cancer cell growth. Our goal is to define bacterial species and metabolites involved in ALL progression and to mechanistically determine how these bacterial species and metabolites regulate ALL growth via regulation of cancer cell-intrinsic pathways. These data suggest that the gut microbiota may regulate ALL progression in an immune-independent manner via transcriptional changes of cancer cell-autonomous pathways. We envision that the gut microbiota can be reshaped in ALL patients who are elderly, chemo-refractive, and/or immunocompromised to alter cancer cell-intrinsic pathways to treat ALL. The clinical impact of these findings is significant given that ALL patients who are immunocompromised could still benefit from therapeutics aiming at modulating the gut microbiota. Citation Format: Wadie Mahauad-Fernandez, Soumaya Zlitni, Ami Bhatt, Dean Felsher. The gastrointestinal microbiota controls cancer cell intrinsic mechanisms to promote the progression of acute lymphoblastic leukemia [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B21.
Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein
Authors: Holger Fischer, Mohammed Ullah, Cecile C de la Cruz, Thomas Hunsaker, Claudia Senn, Thomas Wirz, Björn Wagner, Dragomir Draganov, Faye Vazvaei, Massimiliano Donzelli, Axel Paehler, Mark Merchant, Li Yu
Journal: Neuro-Oncology (2020)

Studies evaluating the CNS penetration of a novel tyrosine kinase inhibitor, entrectinib, proved challenging, particularly due to discrepancies across earlier experiments regarding P-glycoprotein (P-gp) interaction and brain distribution. To address this question, we used a novel "apical efflux ratio" (AP-ER) model to assess P-gp interaction with entrectinib, crizotinib, and larotrectinib, and compared their brain-penetration properties.
Leaf Tea Dry Fruits Snack Flakes Seeds Candies Chocolate Peanuts Tobacco Tablets Salt Beans Biscuits Puffed Food Granules Potato Chips Pouch Packing Machine
Authors: Haoyuan Quan, Ting Zhang, Hang Xu, Shen Luo, Jun Nie, Xiaoqun Zhu
Journal: Bioactive Materials (2020)
MRG15 orchestrates rhythmic epigenomic remodelling and controls hepatic lipid metabolism
Authors: Yuda Wei, Cheng Tian, Yongxu Zhao, Xiaojian Liu, Feng Liu, Shuang Li, Yanhao Chen, Yan Qiu, Zhuanghui Feng, Lanlan Chen, Tingting Zhou, Xiaoguang Ren, Chengwu Feng, Yan Liu, Wenqiang Yu, Hao Ying, Qiurong Ding
Journal: Nature Metabolism (2020)
Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis
Authors: P. Le Turnier, M. Gregoire, G. Deslandes, K. Lakhal, C. Deschanvres, R. Lecomte, J.-P. Talarmin, V. Dubée, R. Bellouard, D. Boutoille, A.-G. Leroy, B.J. Gaborit, Francois Raffi, David Boutoille, Charlotte Biron, Maeva Lefebvre, Benjamin Jean Gaborit, Paul Le Turnier, Colin Deschanvres, Raphael Lecomte, Marie Chauveau, Nathalie Asseray, Matthieu Gregoire, Ronan Bellouard, Guillaume Deslandes, Eric Dailly, Anne-Gaëlle Leroy, Stéphane Corvec, Pascale Bémer, Jocelyne Caillon, Aurélie Guillouzouic, Karim Lakhal, Raphaël Cinotti, Emmanuel Canet, Cédric Bretonniere, Thomas Guimard, Julia Brochard, Jean Philippe Talarmin, Lydie Katchatourian
Journal: Clinical Microbiology and Infection (2020)
Correction to: MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming
Authors: Yang Liu, Li-Li Lu, Duo Wen, Dong-Li Liu, Li-Li Dong, Dong-Mei Gao, Xin-Yu Bian, Jian Zhou, Jia Fan, Wei-Zhong Wu
Journal: Journal of Hematology & Oncology (2020)

An amendment to this paper has been published and can be accessed via the original article.
Immune responses in the lungs of patients with tuberculous pleural effusion without parenchymal tuberculosis
Authors: Won-Il Choi
Journal: European Respiratory Journal (2012)

Background:   Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. Because most studies of TPE focused on the pleural space, little information regarding lung parenchyma is available. We therefore aimed to investigate immune responses in the lung parenchyma of TPE patients without active parenchymal tuberculosis.    Methods:   Patients with any evidence of active parenchymal tuberculosis, either from radiologic or bacteriologic evaluation, were excluded. Bronchoalveolar lavage fluid (BALF) was collected from 10 newly diagnosed, untreated, HIV-negative TPE patients and 10 healthy controls. We analyzed T-lymphocyte subpopulations and measured 10 cytokines in BALF. Cytokine levels in BALF were standardised using urea.    Results:   The concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and the CD4+/CD8+ ratio of T-lymphocytes were significantly higher in TPE patients without active parenchymal tuberculosis than in the controls. Of the cytokines measured in BALF, VEGF showed the highest concentration. No difference was observed in T-helper type 2 cytokines between the 2 groups.    Conclusion:   There were significant immune responses and increases in IFN-γ, TNF-α, and VEGF in the lung parenchyma of TPE patients without active parenchymal tuberculosis. This result suggests that TPE may induce a significant immune response in lung parenchyma.
Abstract 13: Economic Impact of Moderate-vigorous Physical Activity Among Those with and without Established Cardiovascular Disease: 2012 Medical Expenditure Panel Survey
Authors: Javier Valero-Elizondo, Joseph A Salami, Chukwuemeka U Osondu, Adnan Younus, Alejandro Arrieta, Erica S Spatz, Jamal S Rana, Salim S Virani, Ron Blankstein, Michael J Blaha, Emir Veledar, Khurram Nasir
Journal: Circulation (2016)

Background: Physical activity (PA) is an established factor for favorable cardiovascular disease (CVD) outcomes and quality of life. However, to date little is available on PA’s independent impact on healthcare cost. In this study, we aimed to estimate this effect on medical expenditure from a nationally representative cohort with and without CVD. Methods: The 2012 Medical Expenditure Panel Survey data was analyzed. Our study population was limited to non-institutionalized adults ≥ 40 years of age. Variables of interest were CVD (coronary artery disease, stroke, heart failure, dysrhythmias or peripheral artery disease), modifiable risk factors (MRF; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity), and PA (dichotomous variable: defined as moderate-vigorous exercise of ≥ 30 minutes, 5 times/week). Two-part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita, taking into consideration the survey’s complex design. Results: Our final study sample consisted of 15,651 surveyed individuals (mean age: 58.5 ± 12 years, 46% male). Overall, 46% engaged in at least moderate exercise, translating to 21 million physically active adults in the U.S. Of those with CVD, 34% reported PA, vs. 47% without CVD. In those without CVD, a higher prevalence of PA was noted with lower MRF burden (≥ 3: 35%, 2: 44%, 0-1: 53%). Generally, participants reporting moderate-vigorous PA incurred significantly lower healthcare costs, seen both in those with and without CVD. Among those without CVD, those engaged in moderate-vigorous PA with 0-1 &amp; ≥ 3 MRF had $1,038 &amp; $1,785 less healthcare expenditure, respectively, than their less physically active counterparts. Conclusion: In addition to tremendously improving CVD risk, moderate-vigorous PA is also associated with significantly less healthcare spending. Our findings further reinforce the importance of physical activity in health promotion and CVD prevention.
OC-072 The Microaerophilic Microbiota of De-Novo Paediatric Inflammatory Bowel Disease: the Biscuit Study
Authors: R Hansen, S Berry, I Mukhopadhya, J Thomson, K Saunders, C Nicholl, M Bisset, R Russell, E El-Omar, G Hold
Journal: Gut (2013)

<h3>Introduction</h3> Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study etiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; <i>Helicobacter</i> and <i>Campylobacter</i> are previously implicated in IBD pathogenesis. The aim of the study was to assess these and other microaerophilic bacteria in de-novo paediatric IBD. <h3>Methods</h3> 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and <i>Sutterella wadsworthensis</i>. <h3>Results</h3> 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was <i>S. wadsworthensis</i> (32 distinct isolates). Unusual <i>Campylobacter</i> were isolated from 8 subjects (including 3 <i>C. concisus</i>, 1 <i>C. curvus</i>, 1 <i>C. lari</i>, 1 <i>C. rectus</i>, 3 <i>C. showae</i>). No <i>Helicobacter</i> were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (<i>Helicobacter</i> 11% vs. 12%, p = 1.00; <i>Campylobacter</i> 75% vs. 76%, p = 1.00; <i>S. wadsworthensis</i> 82% vs. 71%, p = 0.312). <h3>Conclusion</h3> This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. <i>Campylobacter</i> appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. <i>S. wadsworthensis</i> appears to be a common commensal. <i>Helicobacter</i> species are relatively rare in the paediatric colon. <h3>Disclosure of Interest</h3> None Declared
Developmental Outcomes Among Young Children With Congenital Zika Syndrome in Brazil
Authors: Anne C. Wheeler, Danielle Toth, Ty Ridenour, Lucélia Lima Nóbrega, Raíne Borba Firmino, Claudia Marques da Silva, Pollyanna Carvalho, Douglas Marques, Katherine Okoniewski, Liana O. Ventura, Donald B. Bailey, Camila V. Ventura
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Although birth defects in children with congenital Zika syndrome (CZS) are expected to result in significant intellectual disabilities, the extent of delay and profiles of development have yet to be fully described. <h3>Objectives</h3> To describe the neurodevelopmental profiles of children with CZS and to test whether prenatal and postpartum characteristics were associated with the severity of developmental delays. <h3>Design, Setting, and Participants</h3> This is a case series of the trajectories of developmental, behavioral, and medical needs of 121 young children with CZS who were assessed at a specialized rehabilitation center in Recife, Brazil, beginning in January 2018 as part of 5-year longitudinal study. Children were included if they had serologic confirmation of Zika virus and met clinical criteria accompanied by parental report of suspected exposure to Zika virus during pregnancy. <h3>Exposures</h3> Prenatal Zika virus exposure. <h3>Main Outcomes and Measures</h3> The Brazilian version of the Bayley Scales of Infant and Toddler Development, Third Edition, was administered by trained assessors as part of an initial comprehensive assessment battery. Caregiver interviews and medical record reviews were conducted to gather basic demographic information and medical comorbidities. Linear regression was used to identify potential factors for development. <h3>Results</h3> The sample included 121 young children (mean [SD] age, 31.2 [1.9] months; 61 [50.4%] girls). At age approximately 2.5 years, nearly all children in this sample demonstrated profound developmental delays across all domains of functioning, with a mean (SD) developmental age equivalent to approximately 2 to 4 months (eg, cognitive domain, 2.24 [3.09] months; fine motor subscale, 2.15 [2.93] months; expressive language subscale, 2.30 [2.52] months). A relative strength was found in receptive language, with scores on this scale significantly higher than most other domains (eg, cognition:<i>t</i> = 3.73;<i>P</i> &lt; .001; fine motor:<i>t</i> = 6.99;<i>P</i> &lt; .001). Head circumference at birth was the single strongest factor associated with outcomes across all developmental domains (eg, cognitive: β = 1.41; SE, 0.67;<i>P</i> = .04; fine motor: β = 1.36; SE, 0.49;<i>P</i> = .007). <h3>Conclusions and Relevance</h3> The findings of this study provide important information regarding the severity of disability that these children and their families will experience. The findings also establish an initial point from which to monitor developmental trajectories, medical comorbidities (eg, seizures), effectiveness of interventions, and cumulative consequences on families.
Strict Preanalytical Oral Glucose Tolerance Test Blood Sample Handling Is Essential for Diagnosing Gestational Diabetes Mellitus
Authors: Julia M. Potter, Peter E. Hickman, Carmen Oakman, Catherine Woods, Christopher J. Nolan
Journal: Diabetes Care (2020)

OBJECTIVE Preanalytical processing of blood samples can affect plasma glucose measurement because ongoing glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined. RESEARCH DESIGN AND METHODS All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation). RESULTS A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P &amp;lt; 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887). CONCLUSIONS The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.
Adult diffuse glioma GWAS by molecular subtype identifies variants in<i>D2HGDH</i>and<i>FAM20C</i>
Authors: Jeanette E Eckel-Passow, Kristen L Drucker, Thomas M Kollmeyer, Matt L Kosel, Paul A Decker, Annette M Molinaro, Terri Rice, Corinne E Praska, Lauren Clark, Alissa Caron, Alexej Abyzov, Anthony Batzler, Jun S Song, Melike Pekmezci, Helen M Hansen, Lucie S McCoy, Paige M Bracci, Joseph Wiemels, John K Wiencke, Stephen Francis, Terry C Burns, Caterina Giannini, Daniel H Lachance, Margaret Wrensch, Robert B Jenkins
Journal: Neuro-Oncology (2020)

Abstract Background Twenty-five germline variants are associated with adult diffuse glioma, and some of these variants have been shown to be associated with particular subtypes of glioma. We hypothesized that additional germline variants could be identified if a genome-wide association study (GWAS) were performed by molecular subtype. Methods A total of 1320 glioma cases and 1889 controls were used in the discovery set and 799 glioma cases and 808 controls in the validation set. Glioma cases were classified into molecular subtypes based on combinations of isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation, and 1p/19q codeletion. Logistic regression was applied to the discovery and validation sets to test for associations of variants with each of the subtypes. A meta-analysis was subsequently performed using a genome-wide P-value threshold of 5 × 10−8. Results Nine variants in or near D-2-hydroxyglutarate dehydrogenase (D2HGDH) on chromosome 2 were genome-wide significant in IDH-mutated glioma (most significant was rs5839764, meta P = 2.82 × 10−10). Further stratifying by 1p/19q codeletion status, one variant in D2HGDH was genome-wide significant in IDH-mutated non-codeleted glioma (rs1106639, meta P = 4.96 × 10−8). Further stratifying by TERT mutation, one variant near FAM20C (family with sequence similarity 20, member C) on chromosome 7 was genome-wide significant in gliomas that have IDH mutation, TERT mutation, and 1p/19q codeletion (rs111976262, meta P = 9.56 × 10−9). Thirty-six variants in or near GMEB2 on chromosome 20 near regulator of telomere elongation helicase 1 (RTEL1) were genome-wide significant in IDH wild-type glioma (most significant was rs4809313, meta P = 2.60 × 10−10). Conclusions Performing a GWAS by molecular subtype identified 2 new regions and a candidate independent region near RTEL1, which were associated with specific glioma molecular subtypes.
Dissecting RoomDiseases of the breastWestern Medicine, Jay R Harris, Mark E Lippman, Monica Morrow, Samuel Hellman (Eds.), Lippincott-Raven, Philadelphia, New York (1996), Pp 1047. $165., ISBN: 0-397-51470-0
Authors: Jayant S Vaidya
Journal: The Lancet (1996)
Response to: ‘JAK inhibitors as promising agents for refractory Takayasu arteritis’ by Watanabe
Authors: Shun Tanimura, Hiroyuki Nakamura, Tetsuya Horita
Journal: Annals of the Rheumatic Diseases (2020)

Response to: 'JAK inhibitors as promising agents for refractory Takayasu arteritis' by WatanabeWe thank Watanabe for his interest in our case report showing that tofacitinib, a janus kinase (JAK) inhibitor, successfully induced a remission of Takayasu arteritis (TAK) complicated by ulcerative colitis (UC) 1 and for providing some meaningful comments to supplement our discussion. 2Watanabe wonders if JAK inhibitors can be effective in TAK patients without UC.In addition, he is concerned that types of JAK inhibitors may affect the efficiency in treating TAK.We agree that the issues should be evaluated in a large-scale case series and clinical study.According to a limited number of case reports, JAK inhibitors were effective in TAK regardless of coexisting UC and types of JAK inhibitors.Sato et al reported a similar case of TAK with UC successfully treated with tofacitinib (JAK1/JAK3 inhibitor). 3On the other hand, Régnier et al reported that ruxolitinib or baricitinib (JAK1/JAK2 inhibitors) clinically improved TAK without UC in three patients. 4They also demonstrated that the improvement was along with decrease of Th1/Th17-related cytokines and correction of effector/regulatory T-cell imbalance.However, as suggested by Watanabe, JAK inhibitors could modulate innate immunity composed of macrophages and natural killer cells in TAK.For the management of refractory TAK, EULAR recommends considering tumour necrosis factor (TNF) inhibitor or tocilizumab, 5 although the evidence for TNF inhibitor depends on only open-label studies, 6 and a randomised controlled trial of tocilizumab failed to achieve its primary endpoint. 7Tocilizumab rapidly normalises IL-6-driven serum inflammatory markers despite sustained vessel inflammation. 1 8It can be confusing when the disease activity of TAK is correctly assessed.Thus, additional treatment options with clear evidence have been desired for TAK.To conclude, we believe that further studies should be conducted in refractory TAK for evaluating the efficacy and safety of JAK inhibitors as a promising agent.