tbuckley/cabot-search huggingface dataset:
Sialic acid–binding immunoglobulin-like lectin (Siglec) 8 in patients with eosinophilic disorders: Receptor expression and targeting using chimeric antibodies
Authors: Fanny Legrand, Yun Cao, Joshua B. Wechsler, Xiang Zhu, Nives Zimmermann, Shakuntala Rampertaap, Joseph Monsale, Kimberly Romito, Bradford A. Youngblood, Emily C. Brock, Michelle A. Makiya, Nenad Tomasevic, Christopher Bebbington, Irina Maric, Dean D. Metcalfe, Bruce S. Bochner, Amy D. Klion
Journal: Journal of Allergy and Clinical Immunology (2018)
Persons of Nonbinary Gender — Awareness, Visibility, and Health Disparities
Authors: Walter Liszewski, J. Klint Peebles, Howa Yeung, Sarah Arron
Journal: New England Journal of Medicine (2018)

As our society’s concept of gender evolves, so does the visibility of contemporary nonbinary people. Yet many members of the medical community may not know how to interact with nonbinary patients respectfully or recognize their unique needs and barriers to care.
Abstract 16723: Aortic Valve Morphology Has an Impact on the Relationship Between Aortic Valve Calcification and Mean Transvalvular Gradient in Women but Not in Men With Aortic Stenosis
Authors: Mylene Shen
Journal: Circulation (2017)

Introduction: The association between aortic valve calcification (AVC) and mean gradient (MG) is different between bicuspid (BAV) and tricuspid (TAV) aortic valve stenosis (AS), especially in young...
Bioassay for monitoring the anti-aging effect of cord blood treatment
Authors: Sang-Hun Bae, Ala Jo, Jae Hyun Park, Chul-Woo Lim, Yuri Choi, Juhyun Oh, Ji-Min Park, TaeHo Kong, Ralph Weissleder, Hakho Lee, Jisook Moon
Journal: Theranostics (2018)

Treating aged animals with plasma of an early developmental stage (e.g, umbilical cord plasma) showed an impressive potential to slow age-associated degradation of neuronal and cognitive functions. Translating such findings to clinical realities, however, requires effective ways for assessing treatment efficacy; ideal methods should be minimally invasive, amenable for serial assays, cost-effective, and quantitative.
Towards Greater Inclusion in Cancer Genomics Studies
Authors: Franklin W. Huang
Journal: Cancer Research (2018)

Abstract The study by Jaratlerdsiri and colleagues represents the first whole-genome sequencing study of prostate cancer from men in sub-Saharan Africa. Preliminary findings include a higher tumor mutation burden in these tumors compared with data from other available prostate cancer cohorts. Although larger studies are needed and greater effort and investment to include patients of African ancestry in cancer genomic studies overall, the findings begin to catalog the diversity of prostate cancer genomics in the African population, which has a high burden of disease and mortality from prostate cancer. See related article by Jaratlerdsiri et al., p. 6736
Cutaneous bacterial sensing through group 2 innate lymphoid cell presentation of endogenous CD1a lipid antigens
Authors: C Hardman, Chen Y-L., M Salimi, R Jarrett, D Johnson, V Jarvinen, R Owens, E Repapi, D Cousins, J Barlow, A McKenzie, G Ogg
Journal: British Journal of Dermatology (2018)
Scaling up a health and nutrition hotline in Malawi: the benefits of multisectoral collaboration
Authors: Carla Blauvelt, Melissa West, Luciana Maxim, Alinafe Kasiya, Isaac Dambula, Upile Kachila, Hope Ngwira, Corinne E Armstrong
Journal: BMJ (2018)

Scaling up a health and nutrition hotline in Malawi: the benefits of multisectoral collaborationCarla Blauvelt and colleagues describe a multisectoral collaboration that enabled the scale up of a health advice telephone service and its transition to government in Malawi• CCPF will be one of the first govern- ment run nationwide health hotlines in Africa when the handover to the Ministry of Health is completed in 2019
Temporal Trends in Unstable Angina Diagnosis Codes for Outpatient Percutaneous Coronary Interventions
Authors: Rishi K. Wadhera, Devraj Sukul, Eric A. Secemsky, Changyu Shen, Hitinder S. Gurm, William E. Boden, Robert W. Yeh
Journal: JAMA Internal Medicine (2018)

Search trends are only proxies for engagement, and sentinel surveillance (such as surveys) will clarify these early findings.However, our findings demonstrate the power of grassroots movements to respond to large-scale public health crises.These results suggest that #MeToo may have reduced the stigma of sexual harassment and/or assault as more seek help. 5 Public health investments in preventing sexual harassment and/or assault is disproportionately small compared with the scale of the problem, 6 in part because the problem is hidden from the public.With millions more persons than ever voicing their needs months after #MeToo began, public health leaders should respond by investing in enhanced prevention training and improving resources for survivors.
Abstract 19827: Hematopoietic PI3-Kinase δ-Deficiency Aggravates Atherosclerosis through Impairment of Regulatory T Cells
Authors: Mario Zierden, Christopher Millarg, Marius Vantler, Eva Berghausen, Stephan Baldus, Stephan Rosenkranz
Journal: Circulation (2017)

Although macrophages outnumber other leukocytes in atherosclerotic lesions, T-helper 1 (Th1) cells and regulatory T cells (Tregs) can shape the course of disease by possessing inflammatory and regu...
<i>Cis</i>-Acting <i>circ-CTNNB1</i> Promotes β-Catenin Signaling and Cancer Progression via DDX3-Mediated Transactivation of YY1
Authors: Feng Yang, Erhu Fang, Hong Mei, Yajun Chen, Huanhuan Li, Dan Li, Huajie Song, Jianqun Wang, Mei Hong, Wenjing Xiao, Xiaojing Wang, Kai Huang, Liduan Zheng, Qiangsong Tong
Journal: Cancer Research (2018)

Circular RNAs (circRNA), a subclass of noncoding RNA characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNA in regulating Wnt/β-catenin signaling and cancer progression remain elusive. Here, we screen cis-acting circRNA generated by β-catenin (CTNNB1)/transcription factor 7-like 2 genes and identify one intronic circRNA derived from CTNNB1 (circ-CTNNB1) as a novel driver of cancer progression. Circ-CTNNB1 was predominantly expressed in the nucleus, upregulated in cancer tissues and cell lines, and associated with unfavorable outcomes in patients with cancer. Circ-CTNNB1 promoted β-catenin activation, growth, invasion, and metastasis in cancer cells. Circ-CTNNB1 bound DEAD-box polypeptide 3 (DDX3) to facilitate its physical interaction with transcription factor Yin Yang 1 (YY1), resulting in the transactivation of YY1 and transcriptional alteration of downstream genes associated with β-catenin activation and cancer progression. Preclinically, administration of lentivirus-mediated short hairpin RNA targeting circ-CTNNB1 or a cell-penetrating inhibitory peptide blocking the circ-CTNNB1-DDX3 interaction inhibited downstream gene expression, tumorigenesis, and aggressiveness in cancer cells. Taken together, these results demonstrate cis-acting circ-CTNNB1 as a mediator of β-catenin signaling and cancer progression through DDX3-mediated transactivation of YY1. SIGNIFICANCE: These findings reveal the oncogenic functions of a cis-acting circular RNA in β-catenin activation and cancer progression, with potential value as a therapeutic target for human cancers.
Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: A randomized, controlled trial
Authors: Youhei Miyauchi, Katsunori Furukawa, Daisuke Suzuki, Hideyuki Yoshitomi, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
Journal: International Journal of Surgery (2018)
Ibrutinib Treatment Improves T-Cell Proliferative Ability and Effector Function in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) Patients
Authors: Isabelle G. Solman, Marlene Taylor, Hana You, Susan M. O'Brien, Stephen P. Mulligan, John C. Byrd, James P. Dean, Danelle F. James, Ann Mongan
Journal: Blood (2018)
P023 Factors Associated With Administration of Subsequent Cytotoxic Chemotherapy after Nivolumab in Patients With Advanced NSCLC
Authors: H. Jo, H. Horinouchi, R. Higashiyama, N. Tamura, S. Yagishita, Y. Matsumoto, S. Murakami, Y. Goto, S. Kanda, Y. Fujiwara, N. Yamamoto, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
Abstract 19486: Unique Upregulation of Phosphodiesterase 1 in Single Ventricle Congenital Heart Disease
Authors: Stephanie J Nakano, Karin Nunley, Penny Nelson, Anastacia M Garcia, Brian L Stauffer, Carmen C Sucharov, Shelley D Miyamoto
Journal: Circulation (2017)

Introduction: In pediatric patients with single ventricle congenital heart disease (SV), the molecular mechanisms of maladaptive myocardial remodeling leading to SV failure are poorly understood. P...
Association of Serum Cholesterol Efflux Capacity With Mortality in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Maryse Guerin, Johanne Silvain, Julie Gall, Maryam Darabi, Myriam Berthet, Eric Frisdal, Marie Hauguel-Moreau, Michel Zeitouni, Mathieu Kerneis, Benoit Lattuca, Delphine Brugier, Jean-Philippe Collet, Philippe Lesnik, Gilles Montalescot
Journal: Journal of the American College of Cardiology (2018)
Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases
Authors: Jessica J. Lin, Ginger Y. Jiang, Nencyben Joshipura, Jennifer Ackil, Subba R. Digumarthy, Sandra P. Rincon, Beow Y. Yeap, Justin F. Gainor, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2018)
Expression of Bcl-2 family genes during cisplatin induced apoptosis in mesothelioma cells
Authors: Michael Garlepp, Natalia Popowicz, Simon Fox
Journal: Cancer Research (2007)

3585  Malignant mesothelioma (MM) is highly resistant to drug therapy. Since many cytotoxic agents exert their effect by induction of apoptosis we investigated the genetic control of key regulators of the mitochondrial apoptotic pathway, the Bcl-2 protein family, during cisplatin induced apoptosis in MM. Gene expression was assayed in four representative human MM cell lines (ONE58, JU77, NO36, LO68) using conventional and real-time RT-PCR. The expression and subcellular localisation of p53 was determined by fluorescence microscopy. All four MM cell lines constitutively expressed Bcl-2, Bcl-xL, Bax, Bak, NOXA and PUMA as demonstrated by RT-PCR. Cells were exposed to cisplatin at concentrations of 0-100μg/ml and apoptosis/cytotoxicity was assessed by MTT and JC-1 mitochondrial depolarization assays. Sensitivity to cisplatin as reflected in the IC50 ranged from 1.13±0.2 μg/ml (JU77) to 3.72±1.3 μg/ml (ONE58). Mitochondrial depolarization indicated an active role for the mitochondria during cisplatin induced apoptosis. Cisplatin induction of gene expression was examined in the JU77 and ONE58 at their respective IC50. There were significant differences in the magnitude and timing of transcriptional responses. Bak was a transcriptional target of cisplatin in both cell lines, although maximal upregulation was seen at 1h in JU77 compared to 6h in ONE58. In JU77 Bcl-xL and NOXA mRNAs were also upregulated at 1 hr, but Bax mRNA was not. In contrast, in ONE58 Bcl-xL was essentially unchanged while both Bax and NOXA were upregulated. In ONE58 basal p53 levels were significantly elevated in comparison to JU77. In response to cisplatin p53 levels increased in JU77 but not ONE58. These findings indicate that pro-apoptotic Bak gene expression was a significant target of cisplatin in both JU77 and ONE58. Changes in anti-apoptotic Bcl-xL expression may play a role in the resistance of JU77 but did not appear to be a factor in ONE58. These results provide insights into apoptotic mechanisms in MM cells after exposure to cytotoxic drugs.
The Antibody Response to <i>Plasmodium falciparum</i>: Cues for Vaccine Design and the Discovery of Receptor-Based Antibodies
Authors: Joshua Tan, Luca Piccoli, Antonio Lanzavecchia
Journal: Annual Review of Immunology (2018)

Plasmodium falciparum remains a serious public health problem and a continuous challenge for the immune system due to the complexity and diversity of the pathogen. Recent advances from several laboratories in the characterization of the antibody response to the parasite have led to the identification of critical targets for protection and revealed a new mechanism of diversification based on the insertion of host receptors into immunoglobulin genes, leading to the production of receptor-based antibodies. These advances have opened new possibilities for vaccine design and passive antibody therapies to provide sterilizing immunity and control blood-stage parasites.
NHS in England balances books, but local deficits mean worse care in some areas, says report
Authors: Nigel Hawkes
Journal: BMJ (2018)

The NHS in England balanced its books in 2017-18, but appearances can be deceptive, says the parliamentary Public Accounts Committee in its review of the NHS’s accounts.1

Striking the balance required some creative accounting, such as using money from the Sustainability and Transformation Fund to meet winter pressures, and the overall picture of stability conceals some local variation that could be affecting the care of patients.

The Department of Health and Social Care spent £120.7bn (€134bn; $153bn) on running costs and £5.2bn on capital spending in 2017-18. Both budgets were underspent, as it had been allocated £121.3bn for running and £5.6bn for capital costs.

Failing to stay within budget is a capital offence in Whitehall, so the department’s civil servants will …
Collagen density regulates the activity of tumor-infiltrating T cells
Authors: Dorota E. Kuczek, Anne Mette H. Larsen, Marie-Louise Thorseth, Marco Carretta, Adrija Kalvisa, Majken S. Siersbæk, Ana Micaela C. Simões, Anne Roslind, Lars H. Engelholm, Elfriede Noessner, Marco Donia, Inge Marie Svane, Per thor Straten, Lars Grøntved, Daniel H. Madsen
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Tumor progression is accompanied by dramatic remodeling of the surrounding extracellular matrix leading to the formation of a tumor-specific ECM, which is often more collagen-rich and of increased stiffness. The altered ECM of the tumor supports cancer growth and metastasis, but it is unknown if this effect involves modulation of T cell activity. To investigate if a high-density tumor-specific ECM could influence the ability of T cells to kill cancer cells, we here studied how T cells respond to 3D culture in different collagen densities. <h3>Methods</h3> T cells cultured in 3D conditions surrounded by a high or low collagen density were imaged using confocal fluorescent microscopy. The effects of the different collagen densities on T cell proliferation, survival, and differentiation were examined using flow cytometry. Cancer cell proliferation in similar 3D conditions was also measured. Triple-negative breast cancer specimens were analyzed for the number of infiltrating CD8+ T cells and for the collagen density. Whole-transcriptome analyses were applied to investigate in detail the effects of collagen density on T cells. Computational analyses were used to identify transcription factors involved in the collagen density-induced gene regulation. Observed changes were confirmed by qRT-PCR analysis. <h3>Results</h3> T cell proliferation was significantly reduced in a high-density matrix compared to a low-density matrix and prolonged culture in a high-density matrix led to a higher ratio of CD4+ to CD8+ T cells. The proliferation of cancer cells was unaffected by the surrounding collagen-density. Consistently, we observed a reduction in the number of infiltrating CD8+ T-cells in mammary tumors with high collagen-density indicating that collagen-density has a role in regulating T cell abundance in human breast cancer. Whole-transcriptome analysis of 3D-cultured T cells revealed that a high-density matrix induces downregulation of cytotoxic activity markers and upregulation of regulatory T cell markers. These transcriptional changes were predicted to involve autocrine TGF-β signaling and they were accompanied by an impaired ability of tumor-infiltrating T cells to kill autologous cancer cells. <h3>Conclusions</h3> Our study identifies a new immune modulatory mechanism, which could be essential for suppression of T cell activity in the tumor microenvironment.
Abstract 21209: Prevalence and Clinical Outcome of Thrombus Detected on Transvenous Leads at the Time of Lead Extraction
Authors: Gordon Ho, Ishan Mehta, Timothy T Maus, Swapnil Khoche, Jonathan C Hsu, Travis L Pollema, Ulrika Birgersdotter-Green, Gert V Pretorius
Journal: Circulation (2017)

Introduction: The prevalence and clinical significance of incidental thrombus formation on transvenous leads is not well characterized. We performed a prospective cohort study of patients referred for transvenous lead extraction to evaluate the prevalence and short term major clinical outcomes of thrombus detected on transvenous leads. Hypothesis: Thrombus incidentally detected on transvenous leads is not associated with major adverse clinical outcomes. Methods: Consecutive patients referred for transvenous lead extraction for non-infectious indications such as lead malfunction were enrolled. Routine pre-operative trans-esophageal echocardiograms were performed prospectively for all patients, focusing on all transvenous leads from the superior vena cava to endocardial insertion points to examine for thrombus. Clinical endpoints of mortality and cardiovascular morbidity (symptomatic pulmonary embolism, myocardial infarction or cerebrovascular accident) were assessed at minimum 1 month follow-up clinic visit or phone call. Results: Out of 166 patients referred for lead extraction, 111 patients had non-infectious indications and were included in the analysis. Lead thrombi were detected in 22 patients (20%). Baseline characteristics including age (65±13 vs 61±16 yrs, p=0.9) and age of implanted leads (99±68 vs 88±57 months, p=0.5) were similar between patients with and without lead thrombi. There were no deaths, myocardial infarction, pulmonary embolism, nor stroke in patients with thrombi. Median length of follow up was 9 months. Conclusions: Incidental thrombi on transvenous leads are commonly found in patients referred for transvenous lead extraction and are rarely associated with short-term major adverse outcomes. Careful extraction of leads with small incidentally detected thrombi can be performed without major clinical sequelae. Larger studies are needed to further assess the long term clinical significance of lead thrombi.
Methotrexate-associated Lymphoproliferative Disorder with Diffuse Ground-Glass Opacities
Authors: Kazuo Tsuchiya, Yuzo Suzuki, Hideki Yasui, Hironao Hozumi, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Satoshi Baba, Takafumi Suda
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Abstract 19021: Coarctation of the Aorta and Late Hypertension in Survivors May be the Consequence of Common Gene Mutations
Authors: Melissa G Lee, Priscilla R Prestes, Enzo Porello, Gavin Lambert, Igor E Konstantinov, Fadi J Charchar, Yves d'Udekem
Journal: Circulation (2017)

Introduction: There is a high prevalence of hypertension late after coarctation repair but its exact mechanism is unknown. Importantly, the genetic predisposition to both coarctation and the development of late hypertension in these patients is not well explored. This study aims to investigate genetic mutations in known cardiovascular genes in coarctation patients with and without late hypertension. Methods: Nineteen patients (male 42%, 8/19) aged ≥18 years with a coarctation repair underwent 24-hour blood pressure monitoring and venipuncture for DNA extraction. Blood samples were analyzed using the TruSight Cardio Sequencing Panel (Illumina) in the MiSeq Sequencer which sequences 174 genes involved in cardiovascular disease. Reads were aligned to the human genome version hg19, detected using SamTools 1.2 and annotated on SnpEff. Hypertension was defined as mean 24-hour systolic blood pressure ≥135 mmHg or diastolic blood pressure ≥85 mmHg. Results: After a mean follow-up of 26 ± 5 years, hypertension was...
Residual Risk After Tetralogy of Fallot Repair
Authors: Roger Andrew de Freitas
Journal: JAMA Cardiology (2018)

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AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) Vs Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Authors: John P. Leonard, Marek Trněný, Koji Izutsu, Nathan H. Fowler, Xiaonan Hong, Jun Zhu, Huilai Zhang, Fritz Offner, Adriana Scheliga, Grzegorz S. Nowakowski, Antonio Pinto, Francesca Re, Laura Maria Fogliatto, Phillip Scheinberg, Ian W. Flinn, Cláudia Moreira, David Liu, Stacey Kalambakas, Pierre Fustier, Chengqing Wu, John G. Gribben
Journal: Blood (2018)
PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia
Authors: Andrew Chase, Andrea Pellagatti, Shalini Singh, Joannah Score, William J. Tapper, Feng Lin, Yvette Hoade, Catherine Bryant, Nicola Trim, Bon Ham Yip, Katerina Zoi, Chiara Rasi, Lars A. Forsberg, Jan P. Dumanski, Jacqueline Boultwood, Nicholas C. P. Cross
Journal: Leukemia (2018)
Cyclin-Dependent Kinase Inhibitor–Associated Thromboembolism
Authors: Sven R. Olson, Thomas G. DeLoughery, Joseph J. Shatzel
Journal: JAMA Oncology (2018)

This Viewpoint analyzes data on the thrombotic risk associated with cyclin-dependent kinase inhibitors and notes the need for additional research on the thrombotic risk of these drugs, the influence of combined drug therapy on thrombotic risk, and patient selection.