tbuckley/cabot-search huggingface dataset:
Abstract 370: Delivery of CPR in Patients With Single and Biventricular Cardiac Disease
Authors: Todd Sweberg, Heather Griffis, Priscilla Yu, Ivie Esangbedo, Kelly Bora, Dana E Niles, Xuemei Zhang, Richard Hanna, Vinay M Nadkarni, Tia T Raymond
Journal: Circulation (2019)

Introduction: Diminished survival after cardiopulmonary resuscitation (CPR) has been shown in patients with congenital heart disease (CHD) and single ventricle (SV) anatomy compared to biventricular anatomy (BV). The role guideline-compliant CPR plays in SV outcomes is unknown. Hypothesis: During pediatric in-hospital cardiac arrest (IHCA), there will be a difference in CPR delivery and outcomes of patients with SV compared to BV anatomy. Methods: Prospective observational cohort from 12 pediRES-Q sites of IHCA in children ≤ 18 years with CPR quality metric data (chest compression (CC) rate, depth, and fraction (CCF)) (Zoll R-Series, Chelmsford, MA). We compared 60-sec CC epoch compliance with 2015 American Heart Association guideline targets defined as: CC rate 100-120/min; depth ≥4.0 cm in &lt;1 yo, ≥5 to ≤6 cm in 1-&lt;18 yo; and CCF ≥0.80. Total guideline compliance was defined as a CC event with ≥ 60% epochs meeting all targets. Metric summaries were reported as median [IQR] and compliance as frequency (%). Differences were assessed using Wilcoxon rank-sum and Fishers exact tests, respectively. Logistic regression assessed for associations with outcomes, including anatomy and proportion of guideline-compliant CPR. Results: From 10/2015 to 3/2019, we analyzed 82 events (&gt; 5 epochs) in patients with CHD. Thirty-seven percent had SV anatomy and more SV patients were post-operative (70% vs 2%). There were no differences in time to first epinephrine dose (1 vs 2 min), shockable rhythm (7% vs 6%), or need for ECMO (27% vs 23%). Total guideline compliance across all ages was not different (SV 10.0% vs BV 5.8%, P=0.67) and not associated with ROSC or survival to hospital discharge (SHD). There was a 75% lower adjusted odds of SHD in 1-&lt;8 yo vs &lt;1 yo. Conclusion: There were no meaningful differences in resuscitative practice or delivery of guideline-compliant CPR in those with SV versus BV anatomy. Guideline-compliant CPR was not associated with outcomes regardless of cardiac anatomy.
Differential expression of HOX genes in primary glioblastomas and glioblastoma cell lines
Authors: Rana Abdel-Fattah, Aizhen Xiao, Beatriz M Lopes, Isa Hussaini
Journal: Cancer Research (2006)

1746  Abstract HOX genes are a large family of regulatory genes implicated in the control of developmental processes. HOX genes are involved in malignant transformation and progression of different types of tumors. Despite intensive efforts to delineate the expression profiles of HOX genes in other cell types, nothing is known regarding the global expression profile of these genes in normal human astrocytes and astrocytomas. In the present study, we have analyzed the expression profile of the 39 class I HOX genes in normal human astrocytes (NHA and E6/E7), two well established glioblastoma cell lines (U-87 MG and U-1242-MG) as well as neoplastic (WHO grades II/III and IV) and non-neoplastic (temporal lobe) patient specimens. RT-PCR, quantitative real-time PCR, immunocytochemistry and Western blot analyses revealed a differential expression of 9 HOX genes (A6, A7, A9, A13, B13, D4, D9, D10 and D13) in normal human astrocytes from cell lines and non-neoplastic patient specimens. Our data show that HOX genes are differentially expressed in neoplastic and non-neoplastic astrocytes and multiple HOX genes are overexpressed in malignant astrocytes from cell lines and patients specimens. The differential expression of HOX genes in normal and neoplastic astrocytes suggests a role of these genes in brain tumorigenesis.
Genomic Analysis of European Drosophila melanogaster Populations Reveals Longitudinal Structure, Continent-Wide Selection, and Previously Unknown DNA Viruses
Authors: Martin Kapun, Maite G Barrón, Fabian Staubach, Darren J Obbard, R Axel W Wiberg, Jorge Vieira, Clément Goubert, Omar Rota-Stabelli, Maaria Kankare, María Bogaerts-Márquez, Annabelle Haudry, Lena Waidele, Iryna Kozeretska, Elena G Pasyukova, Volker Loeschcke, Marta Pascual, Cristina P Vieira, Svitlana Serga, Catherine Montchamp-Moreau, Jessica Abbott, Patricia Gibert, Damiano Porcelli, Nico Posnien, Alejandro Sánchez-Gracia, Sonja Grath, Élio Sucena, Alan O Bergland, Maria Pilar Garcia Guerreiro, Banu Sebnem Onder, Eliza Argyridou, Lain Guio, Mads Fristrup Schou, Bart Deplancke, Cristina Vieira, Michael G Ritchie, Bas J Zwaan, Eran Tauber, Dorcas J Orengo, Eva Puerma, Montserrat Aguadé, Paul Schmidt, John Parsch, Andrea J Betancourt, Thomas Flatt, Josefa González
Journal: Molecular Biology and Evolution (2020)

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatiotemporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterize variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Authors: Hang Zhou, Julia M. Sealock, Sandra Sanchez-Roige, Toni-Kim Clarke, Daniel F. Levey, Zhongshan Cheng, Boyang Li, Renato Polimanti, Rachel L. Kember, Rachel Vickers Smith, Johan H. Thygesen, Marsha Y. Morgan, Stephen R. Atkinson, Mark R. Thursz, Mette Nyegaard, Manuel Mattheisen, Anders D. Børglum, Emma C. Johnson, Amy C. Justice, Abraham A. Palmer, Andrew McQuillin, Lea K. Davis, Howard J. Edenberg, Arpana Agrawal, Henry R. Kranzler, Joel Gelernter
Journal: Nature Neuroscience (2020)
What can the world learn from New Zealand on climate?
Authors: Jocelyn Timperley
Journal: The Lancet Planetary Health (2020)

nz/ climate-change/climate-changeand-government/emissionsreduction-targets/ about-our-emissions What can the world learn from New Zealand on climate?New Zealand is often seen as a climate leader on the international stage, but the reality of its action so far is complex.New Zealand was lauded last year for its strong ambition when it passed a bill to reach net zero emissions by 2050, and its electricity has been largely renewable for decades.However, the country has stalled on action to cut emissions in other major emitting sectors such as transport and agriculture, instead using commercial forestry offsets to meet climate goals."The reality is that for whatever reason, nothing much had been achieved over the previous 20 or 30 years", says Professor James Renwick, a climate scientist at Victoria University of Wellington and member of the Climate Change Commission, an independent body set up to advise the government on how to meet its 2050 goal.Renwick says he would like to think New Zealand could become a world leader in green technology, green policy, and green economics."We're not really seeing it at all yet, but there's no reason why New Zealand couldn't be", he says.
Procedural Skills of Practicing Nephrologists
Authors: Thomas G. Tape
Journal: Annals of Internal Medicine (1990)

Objective: To determine which procedures nephrologists do in practice, where they learned the procedures, and how much training they recommend to achieve and maintain clinical competence in each. Design: Mailed survey. Participants: A random sample of 700 members of the American College of Physicians who were identified as practicing nephrologists; 516 (74%) responded. Results: Acute peritoneal dialysis, acute hemodialysis, continuous arteriovenous hemofiltration, and percutaneous renal biopsy were done by 95%, 97%, 87%, and 91% of the respondents, respectively. Except for hemofiltration, procedures were learned by most respondents during fellowship training. Compared with general internists, fewer nephrologists did most of the 19 general procedures included in the survey. The number of nephrology procedures done during the past year varied considerably among respondents, as did the minimum number of procedures they recommended for achieving and maintaining competence. Neither the variation in number of procedures done nor recommendations regarding certification were explained by differences in practice characteristics. Median recommendations remained relatively constant among subgroups. Conclusions: Nearly all nephrologists do the four nephrology procedures included in the survey. Their opinions about the training needed for competence help to better define requirements for training programs. More attention should be focused on training and certifying practicing nephrologists in procedures learned after formal fellowship training.
Careful consideration of the bleeding caused by transbronchial lung cryobiopsies
Authors: Arnaud Bourdin, Micaela Romagnoli, Anne Sophie Gamez, Kheira Hireche, Jean Philippe Berthet, Jean Pierre Mallet, Isabelle Vachier, Stefano Nava, Paul Reynaud, Nicolas Molinari, Carey Suehs
Journal: European Respiratory Journal (2020)

<b>Lung surface photos show wounds/haemorrhages caused by transbronchial lung cryobiopsy (TBLC). TBLC bleeding can extensively soil airways with consequences for lung function, stressing the need for bleeding prevention and more research <i>via</i> registries.</b>https://bit.ly/34wWAeR
Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness
Authors: Haiquan Lu, Yangyiran Xie, Linh Tran, Jie Lan, Yongkang Yang, Naveena L. Murugan, Ru Wang, Yueyang J. Wang, Gregg L. Semenza
Journal: Journal of Clinical Investigation (2020)

Breast cancer stem cells (BCSCs) play a critical role in cancer recurrence and metastasis. Chemotherapy induces BCSC specification through increased expression of pluripotency factors, but how their expression is regulated is not fully understood. Here, we delineate a pathway controlled by hypoxia-inducible factor 1 (HIF-1) that epigenetically activates pluripotency factor gene transcription in response to chemotherapy. Paclitaxel induces HIF-1-dependent expression of S100A10, which forms a complex with ANXA2 that interacts with histone chaperone SPT6 and histone demethylase KDM6A. S100A10, ANXA2, SPT6, and KDM6A are recruited to OCT4 binding sites and KDM6A erases H3K27me3 chromatin marks, facilitating transcription of genes encoding the pluripotency factors NANOG, SOX2, and KLF4, which along with OCT4 are responsible for BCSC specification. Silencing of S100A10, ANXA2, SPT6, or KDM6A expression blocks chemotherapy-induced enrichment of BCSCs, impairs tumor initiation, and increases time to tumor recurrence after chemotherapy is discontinued. Pharmacological inhibition of KDM6A also impairs chemotherapy-induced BCSC enrichment. These results suggest that targeting HIF-1/S100A10-dependent and KDM6A-mediated epigenetic activation of pluripotency factor gene expression in combination with chemotherapy may block BCSC enrichment and improve clinical outcome.
The Factor V Leiden variant and risk of chronic thromboembolic pulmonary hypertension
Authors: Mark W. Dodson, Kelli Sumner, Jadyn Carlsen, Meghan M. Cirulis, Emily L. Wilson, Abhishek Gadre, Timothy M. Fernandes, Lynette M. Brown, D. Hunter Best, C. Gregory Elliott
Journal: European Respiratory Journal (2020)

<b>The Factor V Leiden variant is identified significantly less frequently among CTEPH patients who had their first venous thromboembolism prior to 50 years of age than among similar patients with acute pulmonary embolism who did not develop CTEPH</b>https://bit.ly/2W6qoLK
Persistence and Drivers of High-Cost Status Among Dual-Eligible Medicare and Medicaid Beneficiaries
Authors: Jose F. Figueroa, Zoe Lyon, Xiner Zhou, David C. Grabowski, Ashish K. Jha
Journal: Annals of Internal Medicine (2018)

People who are dually eligible for Medicare and Medicaid often have complex health needs that make their care particularly expensive, but little is known about the drivers of spending in this popul...
Associations between commute mode and cardiovascular disease, cancer, and all-cause mortality, and cancer incidence, using linked Census data over 25 years in England and Wales: a cohort study
Authors: Richard Patterson, Jenna Panter, Eszter P Vamos, Steven Cummins, Christopher Millett, Anthony A Laverty
Journal: The Lancet Planetary Health (2020)

BackgroundActive travel is increasingly recognised as an important source of physical activity. We aimed to describe associations between commute mode and cardiovascular disease, cancer, and all-cause mortality.MethodsWe analysed data from the Office for National Statistics Longitudinal Study of England and Wales (ONS-LS), which linked data from the Census of England and Wales (henceforth referred to as the Census) for 1991, 2001, and 2011 to mortality and cancer registrations. The cohort included individuals traced in the ONS-LS who were economically active (ie, aged ≥16 years, not retired from work, and not a full-time carer). Commuting by private motorised transport, public transport, walking, and cycling were compared in terms of all-cause mortality, cancer mortality, cardiovascular disease mortality, and cancer incidence, using Cox proportional-hazards models with time-varying covariates. Models were adjusted for age, sex, housing tenure, marital status, ethnicity, university education, car access, population density, socioeconomic classification, Carstairs index quintile, long-term illness, and year entered the study, and were additionally stratified by socioeconomic group.FindingsBetween the 1991 Census and the 2011 Census, 784 677 individuals contributed data for at least one Census, of whom 394 746 were included in the ONS-LS and were considered to be economically active working-age individuals. 13 983 people died, 3172 from cardiovascular disease and 6509 from cancer, and there were 20 980 incident cancer cases. In adjusted models, compared with commuting by private motorised vehicle, bicycle commuting was associated with a 20% reduced rate of all-cause mortality (hazard ratio [HR] 0·80, 95% CI 0·73–0·89), a 24% decreased rate of cardiovascular disease mortality (0·76, 0·61–0·93), a 16% lower rate of cancer mortality (0·84, 0·73–0·98), and an 11% reduced rate of incident cancer (0·89, 0·82–0·97). Compared with commuting by private motorised vehicle, rail commuters had a 10% lower rate of all-cause mortality (HR 0·90, 95% CI 0·83–0·97) and a 21% decreased rate of cardiovascular disease mortality (0·79, 0·67–0·94), in addition to a 12% reduced rate of incident cancer (0·88, 0·83–0·94). Walk commuting was associated with 7% lower cancer incidence (HR 0·93, 95% CI 0·89–0·97) Stratified analyses did not indicate differences in associations between socioeconomic groups.InterpretationOur findings augment existing evidence for the beneficial health effects of physically active commute modes, particularly cycling and train use, and suggest that all socioeconomic groups could benefit.FundingNational Institute for Health Research.
Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
Authors: Mayilaadumveettil Nishana, Caryn Ha, Javier Rodriguez-Hernaez, Ali Ranjbaran, Erica Chio, Elphege P. Nora, Sana B. Badri, Andreas Kloetgen, Benoit G. Bruneau, Aristotelis Tsirigos, Jane A. Skok
Journal: Genome biology (2020)

Abstract Background Ubiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL, is normally only present in the testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription. Results We demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem, we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C, and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites to regulate transcription, chromatin looping, and insulation. Conclusion This study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.
A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease
Authors: Verena Petzer, Piotr Tymoszuk, Malte Asshoff, Joana Carvalho, Jonathan Papworth, Cecilia Deantonio, Luke Bayliss, Matthew Stephen Wake, Markus Seifert, Natascha Brigo, Lara Valente de Souza, Richard Hilbe, Philipp Grubwieser, Egon Demetz, Stefanie Dichtl, Chiara Volani, Sylvia Berger, Felix Böhm, Alexander Hoffmann, Christa Pfeifhofer-Obermair, Laura von Raffay, Sieghart Sopper, Stephanie Arndt, Anja Bosserhoff, Léon Kautz, Prunelle Perrier, Manfred Nairz, Dominik Wolf, Guenter Weiss, Volker Germaschewski, Igor Theurl
Journal: Blood (2020)
Dendritic cells co-cultured with opsonized tumor cells provide T cell-mediated protective and therapeutic immunity against B cell lymphoma in vivo
Authors: Briana Jill Williams, Nikolay Korokhov, Susan Boling, Linda Li, J. Michael Mathis, David T. Curiel
Journal: Cancer Research (2005)

4221  Therapeutic vaccines targeting the tumor-specific immunoglobulin expressed by B cell lymphoma (idiotype, Id) have shown promise in early clinical studies. However, patient-specific Id vaccines limit the host’s anti-tumor response to a single antigenic target and require complex procedures for production. Recent studies have shown that in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells is augmented in the presence of anti-tumor antibodies. We asked if DCs loaded with phagocytosed killed lymphoma cells in the presence of a tumor-specific antibody could provide protective anti-tumor immunity in vivo. Irradiated 38C13 murine lymphoma cells were co-cultured with bone marrow derived DCs (ratio 3:1) in the presence or absence of a tumor-specific monoclonal antibody (murine anti-38C13 Id). Groups of 12 mice were immunized with 2 biweekly subcutaneous injections of either DCs co-cultured with irradiated tumor cells, DCs alone, or irradiated tumor cells alone. Two weeks after the second vaccination, mice were challenged subcutaneously with a lethal tumor inoculum. The majority of mice vaccinated with DCs co-cultured with antibody-coated tumor cells were protected from tumor challenge (mean of 60% long-term survival in 6 experiments, range 33-83%). In contrast, no long-term survivors were observed among mice receiving DCs alone or irradiated tumor cells alone. Following tumor challenge, tumor-free survival was observed in only 29% of mice given DCs co-cultured with tumor cells, compared to 59% survival when co-cultures included the opsonizing antibody (p=0.013). In a therapeutic model, pre-existing tumor could be eradicated from mice treated with chemotherapy before vaccination. To investigate whether protective immunity was directed against Id versus other lymphoma tumor antigens, vaccinated mice were challenged with an Id-negative variant of 38C13, V2. While Id protein vaccination failed to protect against V2, vaccination with DCs cultured with antibody-coated 38C13 cells provided protection against lethal challenges of both 38C13 (72%) and the V2 variant (67%, p=0.62), indicating that additional non-Id tumor antigens are targets of the protective immunity. No anti-tumor antibodies were detected in animals vaccinated with DCs cultured with antibody-coated 38C13 cells. In vivo depletion experiments revealed a critical role for effector CD8+ T cells in mediating tumor protection (p=0.0001 vs. control), with CD4+ T cells playing a lesser role (p=0.047 vs. control), suggesting that sustained T cell help facilitates anti-tumor effector function. These results show that the protective immunity against 38C13 lymphoma following vaccination with DCs loaded with opsonized apoptotic tumor cells is T cell-mediated. Further studies are underway using anti-CD20 antibodies for opsonizing tumor cells.
We must screen refugees to ensure no one is left behind: a case study of Malaysia
Authors: Yen Jun Wong, Shaun Wen Huey Lee
Journal: European Respiratory Journal (2020)

The United Nation High Commission for Refugees (UNHCR) estimates that there are approximately 25.9 million refugees worldwide [1]. The adverse living conditions, poor nutrition, low health literacy as well as physical and mental stress encountered by refugees increases the risk of these underprivileged individuals acquiring communicable diseases such as hepatitis, parasitic disease, and respiratory infections including tuberculosis (TB) [2]. As such, rapid diagnosis and appropriate treatment among all refugees for active TB as a strategy to control TB should be a global priority to achieve the United Nations Sustainable Development Goals on ending the TB epidemic by 2030, which is aligned with the World Health Organization (WHO) End TB Strategy [3]. Mandatory screening for tuberculosis should be considered for refugees upon their arrival in Malaysia <https://bit.ly/3at5uMV>
178P Risks of distant metastasis of different breast cancer subtypes after surgery: A cohort study in indigenous Indonesian population
Authors: H.L. Sakti, W.S. Avanti, L. Choridah, E.K.D. Dwianingsih, W.A. Harahap, T. Aryandono, S.L. Anwar
Journal: Annals of Oncology (2020)