tbuckley/cabot-search huggingface dataset:
Exploration of CRISPR/Cas9-based gene editing as therapy for osteoarthritis
Authors: Lan Zhao, Jian Huang, Yunshan Fan, Jun Li, Tianming You, Shisheng He, Guozhi Xiao, Di Chen
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Osteoarthritis (OA) is a painful and debilitating disease and it is associated with aberrant upregulation of multiple factors, including matrix metalloproteinase 13 (MMP13), interleukin-1β (IL-1β) and nerve growth factor (NGF). In this study, we aimed to use the CRISPR/Cas9 technology, a highly efficient gene-editing tool, to study whether the ablation of OA-associated genes has OA-modifying effects. Methods We performed intra-articular injection of adeno-associated virus, which expressed CRISPR/Cas9 components to target each of the genes encoding MMP13, IL-1β and NGF, in a surgically induced OA mouse model. We also tested triple ablations of NGF, MMP13 and IL-1β. Results Loss-of-function of NGF palliates pain but worsens joint damage in the surgically induced OA model. Ablation of MMP13 or IL-1β reduces the expression of cartilage-degrading enzymes and attenuates structural deterioration. Targeting both MMP13 and IL-1β significantly mitigates the adverse effects of NGF blockade on the joints. Conclusions CRISPR-mediated ablation of NGF alleviates OA pain, and deletion of MMP13-1β or IL-1β attenuates structural damage in a post-traumatic OA model. Multiplex ablations of NGF, MMP13 and IL-1β provide benefits on both pain management and joint structure maintenance. Our results suggest that CRISPR-based gene editing is useful for the identification of promising drug targets and the development of feasible therapeutic strategies for OA treatment.
Global collection of “benign” CNS tumors
Authors: Carol Kruchko
Journal: Neuro-Oncology (2019)

CBTRUS data provide the necessary reference data that researchers and clinicians utilize to introduce their manuscripts, often to drive home the importance of their work and the rarity of the tumors they are reporting.We are proud that the January 2019 Supplement 1 of Neuro-Oncology entitled Recent Advances in Meningiomas includes many references to CBTRUS data.In "Challenges and Opportunities in Meningiomas: Recommendations from the International Consortium on Meningiomas, " the introductory manuscript, the reference to CBTRUS data-"Meningiomas are the most common primary intracranial brain tumor"-is especially meaningful, for prior to 2004 the vast majority of these tumors were not included in collection practices in the United States.It was through the passage of Public Law 107-260 mandating the collection of "benign" brain and other CNS tumors (according to ICD-O-3 behavior codes /0 Benign and /1 Uncertain whether benign or malignant 1 ) that these tumors are collected and reported in the United States.Now that there is an International Consortium on Meningiomas, is it time for the World Health Organization to recommend global collection of "benign" CNS tumors?
Redefining Treatment Paradigms in First-line Advanced Non–Small-Cell Lung Cancer
Authors: David F. Heigener, Keith M. Kerr, Gavin M. Laing, Tony S.K. Mok, Fedor V. Moiseyenko, Martin Reck
Journal: Clinical Cancer Research (2019)

Metastatic non-small-cell lung cancer is still a devastating disease; however, treatment options have diversified dramatically in the past two decades. From unselected platinum-based chemotherapy for all patients, several different treatment groups have evolved, that is, those with "druggable" targets, those with a promising immune signature, and those without any predicting factors outlined in this article. Challenge includes the intersections between these groups and the optimal treatment path. These issues will be addressed in this review.
Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells
Authors: Yong-Hee Rhee, Lesly Puspita, Yanuar Alan Sulistio, Seung Won Kim, Vincencius Vidyawan, Rosalie Elvira, Mi-Yoon Chang, Jae-won Shim, Sang-Hun Lee
Journal: Molecular Therapy (2019)

In this study, we found that undifferentiated human pluripotent stem cells (hPSCs; up to 30% of total cells) present in the cultures of neural stem or precursor cells (NPCs) completely disappeared within several days when cultured under neural differentiation culture conditions. Intriguingly, the disappearance of undifferentiated cells was not due to cell death but was instead mediated by neural conversion of hPSCs. Based on these findings, we propose pre-conditioning of donor NPC cultures under terminal differentiation culture conditions as a simple but efficient method of eliminating undifferentiated cells to treat neurologic disorders. In addition, we could establish a new neural differentiation protocol, in which undifferentiated hPSCs co-cultured with NPCs become differentiated neurons or NPCs in an extremely efficient, fast, and reproducible manner across the hESC and human-induced pluripotent stem cell (hiPSC) lines.
TCTAP C-191 A New Insight of In-stent Occlusion Following Subclavian Vein Stenting in Hemodialysis Patients: Intravascular Ultrasound and Angioscopy Findings
Authors: Takamasa Tanaka, Kojiro Miki, Koji Yanaka, Nagataka Yoshihara, Takahiro Imanaka, Hirokuni Akahori, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2019)
Endothelial B2‐receptor overexpression as an alternative animal model for hereditary angioedema
Authors: Camila Lopes Veronez, Sara Maghsodi, Mihail Todiras, Elena Popova, André Felipe Rodrigues, Fatimunnisa Qadri, João Bosco Pesquero, Michael Bader
Journal: Allergy (2019)

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Endovascular Thrombectomy as a Means to Improve Survival in Acute Ischemic Stroke
Authors: Yingfeng Lin, Volker Schulze, Maximilian Brockmeyer, Claudio Parco, Athanasios Karathanos, Yvonne Heinen, Michael Gliem, Hans-Peter Hartung, Gerald Antoch, Sebastian Jander, Bernd Turowski, Stefan Perings, Malte Kelm, Georg Wolff
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. <h3>Objective</h3> To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perform a meta-analysis. <h3>Data Sources</h3> All randomized clinical trials cited for recommendations on EVT vs medical therapy in the latest 2018 American Stroke Association/American Heart Association guidelines. <h3>Study Selection</h3> Ten American Stroke Association/American Heart Association guideline–relevant randomized clinical trials of EVT vs medical therapy were selected for inclusion. Two EVT trials were excluded owing to infrequent use of EVT. <h3>Data Extraction and Synthesis</h3> Data were abstracted by 2 independent investigators and double-checked by 4 others. Singular study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% CIs. <h3>Main Outcomes and Measures</h3> Risk of 90-day mortality and 90-day intracranial hemorrhage was analyzed; sensitivity analyses were performed in early-window EVT trials (which included patients from the onset of symptoms onward) vs late-window EVT trials (which included patients from 6 hours after onset of symptoms onward). <h3>Results</h3> In 10 trials with 2313 patients, EVT significantly reduced the risk for 90-day mortality by 3.7% compared with medical therapy (15.0% vs 18.7%; RR, 0.81; 95% CI, 0.68-0.98;<i>P</i> = .03). Trends were similar in early-window (RR, 0.83; 95% CI, 0.67-1.01;<i>P</i> = .06) and late-window trials only (RR, 0.76; 95% CI, 0.41-1.40;<i>P</i> = .38). There was no difference in the risk for intracranial hemorrhage in EVT vs medical therapy (4.2% vs 4.0%; RR, 1.11; 95% CI, 0.71-1.72;<i>P</i> = .65). Limitations of the studies include trial protocol heterogeneity and bias originating from prematurely terminated trials. <h3>Conclusions and Relevance</h3> This meta-analysis of all evidence on EVT cited in the 2018 American Stroke Association/American Heart Association guidelines shows significant benefits for survival during the first 90 days after acute ischemic stroke compared with medical therapy alone.
Trends in the Proportion of Female Speakers at Medical Conferences in the United States and in Canada, 2007 to 2017
Authors: Shannon M. Ruzycki, Sarah Fletcher, Madalene Earp, Aleem Bharwani, Kirstie C. Lithgow
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Gender equity is a prominent issue in the medical profession. Representation of female physicians at academic meetings has been identified as an important component of gender equity; however, this topic has not been systematically assessed. <h3>Objective</h3> To determine the trend during the last decade in the proportion of speakers who were women at major academic medical conferences held in Canada and in the United States. <h3>Design, Setting, and Participants</h3> A cross-sectional analysis was conducted examining the gender of speakers listed in meeting programs of medical conferences held in Canada and in the United States in 2007 and from 2013 through 2017. Eligible conferences were identified using a sensitive search strategy, and a previously validated tool was used to analyze each meeting speaker list and to assign a proportion of female speakers. Conferences held in English language, hosted in Canada or the United States, and targeted to a physician audience with 100 or more attendees were included. The comparison group was active physicians in Canada and in the United States. <h3>Main Outcomes and Measures</h3> The mean of the proportion of female speakers at each conference per year. <h3>Results</h3> In total, 181 conferences with 701 individual meetings were analyzed, including 100 medical and 81 surgical specialty conferences. The proportion of women ranged from 0% to 82.6% of all speakers. The mean (SD) proportion of female conference speakers for all meetings analyzed significantly increased from 24.6% (14.6%) for 40 meetings in 2007 to 34.1% (15.1%) for 181 meetings in 2017 (<i>P</i> &lt; .001). The mean proportion of female speakers at medical specialty conferences was 9.8% higher (SE, 1.9%;<i>P</i> &lt; .001) than the mean proportion of female speakers at surgical specialty conferences for all years analyzed. The mean proportion of female speakers at conferences was similar to the mean proportion of active female physicians across all specialties in the United States and in Canada for all years analyzed. <h3>Conclusions and Relevance</h3> Although our findings indicate that the proportion of female speakers at medical conferences increased during the last decade, women continue to be underrepresented. Speaker invitation and selection at conferences represent important opportunities to influence gender equity within medicine.
Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children
Authors: Matthew C. Altman, Michelle A. Gill, Elizabeth Whalen, Denise C. Babineau, Baomei Shao, Andrew H. Liu, Brett Jepson, Rebecca S. Gruchalla, George T. O’Connor, Jacqueline A. Pongracic, Carolyn M. Kercsmar, Gurjit K. Khurana Hershey, Edward M. Zoratti, Christine C. Johnson, Stephen J. Teach, Meyer Kattan, Leonard B. Bacharier, Avraham Beigelman, Steve M. Sigelman, Scott Presnell, James E. Gern, Peter J. Gergen, Lisa M. Wheatley, Alkis Togias, William W. Busse, Daniel J. Jackson
Journal: Nature Immunology (2019)
Correction: Coil valve syndrome: a rare complication of percutaneous transhepatic obliteration successfully treated by argon plasma coagulation and double-balloon endoscopy
Authors: Koji Nagaike, Shiro Hayashi, Kengo Nagai, Hirokazu Sasakawa, Kiyonori Yuguchi, Yuichi Yoshida, Masafumi Naito
Journal: Endoscopy (2019)

Correction to: Coil valve syndrome: a rare complication of percutaneous transhepatic obliteration successfully treated by argon plasma coagulation and double-balloon endoscopyEndoscopy eFirstDOI: 10.1055/a-0881-2667
A global scientific strategy to cure hepatitis B
Authors: Peter A Revill, Francis V Chisari, Joan M Block, Maura Dandri, Adam J Gehring, Haitao Guo, Jianming Hu, Anna Kramvis, Pietro Lampertico, Harry L A Janssen, Massimo Levrero, Wenhui Li, T Jake Liang, Seng-Gee Lim, Fengmin Lu, M Capucine Penicaud, John E Tavis, Robert Thimme, Fabien Zoulim, Patrick Arbuthnot, Andre Boonstra, Kyong-Mi Chang, Per-Jei Chen, Dieter Glebe, Luca G. Guidotti, Jacques Fellay, Carlo Ferrari, Louis Jansen, Daryl T Y Lau, Anna S Lok, Mala K Maini, William Mason, Gail Matthews, Dimitrios Paraskevis, Jörg Petersen, Barbara Rehermann, Eui-Cheol Shin, Alex Thompson, Florian van Bömmel, Fu-Sheng Wang, Koichi Watashi, Hung-Chih Yang, Zhenghong Yuan, Man-Fung Yuen, Timothy Block, Veronica Miller, Ulrike Protzer, Christian Bréchot, Stephen Locarnini, Marion G Peters, Raymond F Schinazi
Journal: The Lancet. Gastroenterology & hepatology (2019)
Links in the Chain of Chronic Traumatic Encephalopathy
Authors: Allan H. Ropper
Journal: New England Journal of Medicine (2019)

Medical disorders linked to professional sports attract great public notice. When scholastic and recreational athletics are also implicated in a syndrome, particularly one involving the brain, the worry extends to the risk associated with youth sports. Chronic traumatic encephalopathy (CTE) is such a disorder, and the proponents and skeptics of the validity of the syndrome have had their turns in the medical and popular presses. There is a consensus neuropathological case definition for CTE and an acknowledged pathognomonic pattern of paired helical filaments of tau surrounding small vessels at the depths of cortical sulci.1 The mildest findings are in the . . .
Abstract P214: Anxiety and Depressive Symptoms are Associated with Coronary Artery Calcium. A Cross-sectional Analysis of Elsa-Brasil Baseline Data
Authors: Itamar S Santos, Marcio S Bittencourt, Priscila T Rocco, Alexandre C Pereira, Sandhi M Barreto, André R Brunoni, Alessandra C Goulart, Michael J Blaha, Paulo A Lotufo, Isabela M Bensenor
Journal: Circulation (2016)

Background: Prior mostly smaller studies of the association between symptoms of anxiety or depression and CAC have produced mixed results. Our aim was to investigate whether psychopathological symptoms and diagnoses of anxiety and depression were associated with coronary artery calcium (CAC) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Design: Cross-sectional analysis Methods: We analyzed data from 4,279 ELSA-Brasil subjects (aged 35 to 74 years) from the São Paulo site who underwent CAC score assessment and who were without previous cardiovascular disease at baseline. Prevalent CAC was defined as a CAC score above zero. Anxiety and depressive symptoms were assessed using the Clinical Interview Schedule - Revised (CIS-R). We built binary logistic regression models to determine whether CIS-R scores, anxiety or depression were associated with prevalent CAC. Results: Prevalent CAC was found in 1,211 (28.3%) individuals. After adjustment for age and sex, a direct association between CIS-R scores and prevalent CAC was revealed (odds ratio [OR]:1.12; 95% confidence interval [95%CI]:1.04-1.22). This association persisted after multivariate adjustment for other cardiovascular risk factors (OR:1.11; 95%CI: 1.02-1.20). No independent associations were found for specific diagnoses of anxiety or depression and prevalent CAC. In post-hoc models, we found a significant interaction between age, CIS-R scores, and CAC (p=0.019), suggesting a stronger association in older individuals. Conclusions: Psychopathological symptoms were directly associated with coronary atherosclerosis in the ELSA-Brasil baseline. This association was evident after adjustment for age and sex, persisted in multivariate adjusted models, and seems to be stronger in older individuals.
Hodgkins lymphoma: Clinicopathologic features in paediatric patients presenting at the Komfo Anokye Teaching Hospital-Kumasi.
Authors: Vivian Paintsil, Osei Owusu-Afriyie, Samuel Blay Nguah, Joslin Dogbe, Lawrence Osei-Tutu, Alex Osei-Akoto
Journal: Journal of Clinical Oncology (2015)

e21007 Background: Hodgkin lymphoma (HL) is a distinct primary solid tumour of the immune system with varied histopathologic subtypes. The epidemiology of HL suggests an infectious etiology with Epstein Barr Virus (EBV) in up to 40% of cases and this association is believed to be causal. HL is the fourth commonest cancer seen amongst the paediatric population in the Paediatric Oncology Unit of the Komfo Anokye Teaching Hospital (KATH) but no data exists about it in our environment. The purpose of this study therefore, is to review the demographic profile of paediatric patients with HL, the proportion of patients with B symptoms, histopathologic subtypes, anatomical nodal sites of involvement and stage at presentation. Methods: This is a retrospective study which reviewed the clinical and histopathological features of Hodgkin’s Lymphoma in paediatric patients at Komfo Anokye Teaching Hospital from January 2010 to December, 2014. Results: A total of 14 patient records were reviewed with male: female ratio of 1.8:1 and a median age of 11years (Range; 4years-15years). Nodular sclerosing classic Hodgkin’s lymphoma was the commonest subtype seen in 6(42.9%) and Mixed Cellularity Hodgkin’s lymphoma (21.4%) was the rarest. Nodular predominant HL was seen in 5(35.7%) of patients. Cervical lymphadenopathy (92.9%) was the commonest site of presentation with mediastinal involvement (7.1%) being the least. All the patients presented with fever and weight loss. Over half (57.1%) of the patients presented with night sweats. Majority of patients (64.3%) presented with stage 3 disease whiles four (28.6%) presented with stage 4 disease. Only 1(7.1%) patient presented with a stage 2 disease. Conclusions: Patients were predominantly males with majority presenting with Nodular sclerosing histopathological subtype, cervical lymphadenopathy and B symptoms. Most of the patients presented with advanced disease.
THU-194-Efficacy and safety of glecaprevir/pibrentasvir in patients with HCV genotype 5 or 6 infection: An integrated analysis of phase 2 and 3 studies
Authors: Betty Yao, Tarik Asselah, Linda Fredrick, Gretja Schnell, Kris V. Kowdley, Paul Kwo, Fred Poordad, Kinh Nguyen, Samuel Lee, Federico Mensa
Journal: Journal of Hepatology (2019)
Insulin-like growth factors and sex hormones in tumor tissue in polyneoplasias of female reproductive organs.
Authors: Elena Mikhaylovna Frantsiyants, Tatiana Moiseenko, Marina Ilyinichna Vereskunova, Meri Viktorovich Adamyan, Natalia Viktorovna Chernikova, Viktor Viktorovich Gurnak, Konstantin Pavlovich Boyko
Journal: Journal of Clinical Oncology (2015)

e22244 Background: Higher quantity ofIGF-1R expresses in tumor tissue in breast cancer in comparison with benign tumor or normal breast tissue. At the same time, IGF-1 stimulates proliferation of normal and tumor breast cells. The aim of the study was to analyze levels of sex hormones, synthesis of insulin-like growth factors and their correlation in tissues of malignant and benign tumors in combined breast cancer and uterine myoma (n = 36). Methods: Levels of estrogens and their metabolites 2OHE1 and 16α-OHE1, progesterone, insulin-like growth factors were defined by the ELISA method in tissues of solitary malignant breast tumors (n = 37), uterine myoma (n = 27) and tumors in combined breast cancer and uterine myoma (n = 36). Results: the synchronous process level of IGF-1 in breast and uterine tissues had a negative correlation with content of estradiol (r1= -81, r2= -79; g1,2< 0.05), estrone (r1= -75, r2= -89; g1,2< 0.05), 16ÎÍ1 metabolite (r1= -74, r2= -87; g1,2< 0.05), high positive correlation with content of progesterone (r1= 73, r2= 77; g1,2< 0.05) and 2ÎÍ/16ÎÍ1 ratio (r1= 81, r2= 79; g1,2< 0.05). The opposite relation was registered for levels of IGF-2 and sex hormones in breast and uterine tissues in polyneoplasias: high positive correlation with estradiol synthesis (r1= 79, r2= 80; g1,2< 0.05), estrone (r1= 75, r2= 89; g1,2< 0.05), 16ÎÍ1 (r1= 89, r2= 83; g1,2< 0.05) and negative correlation with production of progesterone (r1= -83, r2= -79; g1,2< 0.05), 2ÎÍ/16ÎÍ1 (r1= -82, r2= -77; g1,2< 0.05). Conclusions: New similar in direction and strength correlations between level of growth factors and certain sex hormones arise in malignant breast tumor combined with benign uterine tumor, in contrast to the solitary processes, which probably plays an important role in pathogenesis of polyneoplasias.
PS-032-Impact of antigen recognition on memory-like HCV-specific CD8+ T-cells
Authors: Nina Hensel, Dominik Wieland, Zuguang Gu, Sagar Sagar, Katharina Jechow, Janine Kemming, Bertram Bengsch, Christoph Neumann-Haefelin, Ralf Bartenschlager, Christian Conrad, Dominic Gruen, Naveed Ishaque, Maike Hofmann, Robert Thimme
Journal: Journal of Hepatology (2019)
Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study
Authors: Mengying Li, Shanshan Li, Jorge E. Chavarro, Audrey J. Gaskins, Sylvia H. Ley, Stefanie N. Hinkle, Xiaobin Wang, Ming Ding, Griffith Bell, Anne A. Bjerregaard, Sjurdur F. Olsen, James L. Mills, Frank B. Hu, Cuilin Zhang
Journal: Diabetes Care (2019)

OBJECTIVE To identify novel modifiable risk factors of gestational diabetes mellitus (GDM) by examining the association between prepregnancy habitual folate intake and GDM risk. RESEARCH DESIGN AND METHODS The study included 14,553 women in the Nurses’ Health Study II who reported at least one singleton pregnancy between the 1991 and 2001 questionnaires. Prepregnancy intakes of total folate, supplemental folate, and food folate were assessed using a food frequency questionnaire administered every 4 years. Incident GDM was ascertained from a self-reported physician diagnosis. Relative risks (RRs) of GDM were estimated using log-binomial models, with adjustment for demographic, lifestyle, and dietary factors. RESULTS Over the study follow-up, 824 incident GDM cases were reported among 20,199 pregnancies. Women with adequate total folate intake (≥400 μg/day) had an RR of GDM of 0.83 (95% CI 0.72, 0,95, P = 0.007) compared with women with inadequate intake (&amp;lt;400 μg/day). This association was entirely driven by supplemental folate intake. The RRs of GDM for 1–399, 400–599, and ≥600 μg/day of supplemental folate intake were 0.83, 0.77, and 0.70, respectively, compared with no supplemental folate intake (Ptrend = 0.002). The association between supplemental folate intake and GDM risk largely persisted after additional adjustment for intake of multivitamins and other micronutrients, as well as among women who likely planned for the pregnancy. CONCLUSIONS Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk.
PS-012-Validation of histologic and non-invasive measures of fibrosis as surrogate end points of disease progression in patients with primary sclerosing cholangitis
Authors: Christopher Bowlus, Mitchell Shiffman, Harry Janssen, Aldo J Montano-Loza, Stephen Caldwell, Velimir Luketic, Xiaomin Lu, Gerald Crans, Chuhan Chung, Mani Subramanian, Robert Myers, Michael P. Manns, Cynthia Levy, Michael Trauner, Zachary Goodman, Andrew Muir
Journal: Journal of Hepatology (2019)