tbuckley/cabot-search huggingface dataset:
68Ga-DOTATATE PET/CT of Ectopic Cushing Syndrome Due to Appendicular Carcinoid
Authors: Chakra Diwaker, Ravi Kumar Shah, Virendra Patil, Swati Jadhav, Anurag Lila, Tushar Bandgar, Nalini Shah
Journal: Clinical Nuclear Medicine (2019)

Abstract Approximately 5% to 15% cases of endogenous Cushing syndrome are due to ectopic adrenocorticotrophic hormone (ACTH)–producing neuroendocrine tumors, which are commonly located in bronchopulmonary system, thymus, and gastrointestinal tract including pancreas. Although carcinoid tumors of the appendix are revealed in 0.3% of patients undergoing routine appendectomy, ACTH-secreting appendicular carcinoid is a rare entity. We present a case of a 22-year-old woman with ectopic ACTH-dependent Cushing syndrome due to an appendicular carcinoid, which was localized with the help of 68 Ga-DOTATATE PET/CT scan.
Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain
Authors: Francesco Maria Petrini, Marko Bumbasirevic, Giacomo Valle, Vladimir Ilic, Pavle Mijović, Paul Čvančara, Federica Barberi, Natalija Katic, Dario Bortolotti, David Andreu, Knut Lechler, Aleksandar Lesic, Sanja Mazic, Bogdan Mijović, David Guiraud, Thomas Stieglitz, Asgeir Alexandersson, Silvestro Micera, Stanisa Raspopovic
Journal: Nature Medicine (2019)
Pensions crisis: government sets out plans to give doctors more flexibility
Authors: Nigel Hawkes
Journal: BMJ (2019)

The government has set out its plans1 to widen the options available in the NHS pension scheme to encourage the most highly paid clinicians not to reduce their hours for tax reasons.

A consultation2 launched on 11 September will allow staff to cut their pension contributions in any given year to avoid breaching Treasury limits and to eliminate “spikes” in contributions caused by promotions or increased earnings, spreading them instead over several years to avoid extra charges.

The Department of Health and Social Care admits that the proposed changes have been forced on it to protect services. The pension and tax rules as they currently exist discourage doctors from taking on extra work for fear of being hit by substantial tax charges.

Matt Hancock, England’s health and social care secretary, said, “Our new plan means every senior clinician will be able to carry out lifesaving work for patients safe in the knowledge that they have …
Retrieved lymph nodes from different anatomic groups in gastric cancer: a proposed optimal number, comparison with other nodal classification strategies and its impact on prognosis
Authors: Siwei Pan, Pengliang Wang, Yanan Xing, Kai Li, Zhenning Wang, Huimian Xu
Journal: Cancer Communications (2019)

Abstract Background The optimal number of retrieved lymph nodes (LNs) in gastric cancer (GC) is still debatable and previous studies proposing new classification alternatives mostly focused on the number of retrieved LNs without proper consideration on the anatomic nodal groups’ location. Here, we assessed the impact of retrieved LNs from different nodal location groups on the survival of GC patients. Methods Stage I–III gastric cancer patients who had radical gastrectomy were investigated. LN grouping was determined according to the 13th edition of the JCGC. The optimal cut‐off values of retrieved LNs in different LN groups (Group 1 and 2) were calculated, based on which a proposed nodal classification (rN) simultaneously accounting the optimal number and location of retrieved LNs was proposed. The performance of rN was then compared to that of LN ratio, log‐odds of metastatic LNs (LODDs) and the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) N classification. Results The optimal cut‐off values for Group 1 and 2 were 13 and 9, respectively. The 5‐year overall survival (OS) was higher for patients in retrieved Group 1 LNs &gt; 13 (vs. Group 1 LNs ≤ 13, 63.2% vs. 57.9%, P = 0.005) and retrieved Group 2 LNs &gt; 9 (vs. Group 2 LNs ≤ 9, 72.5% vs. 60.7%, P = 0.009). Patients staged as pN0–3b were sub classified using this Group 1 and 2 nodal analogy. The OS of pN0–N2 patients in retrieved Group 1 LNs &gt; 13 or Group 2 LNs &gt; 9 were superior to those in retrieved Group 1 LNs ≤ 13 and Group 2 LNs ≤ 9 (All P &lt; 0.05); except for pN3 patients. The rN classification was formulated and demonstrated better 5‐year OS prognostication performance as compared to the LNR, LODDs, and the 8th UICC/AJCC N staging system. Conclusions The retrieval of &gt; 13 and &gt; 9 LNs for Group 1 and Group 2, respectively, could represent an alternative lymph node retrieval approach in radical gastrectomy for more precise survival prognostication and minimizing staging migration, especially if &gt; 16 LNs is found to be difficult.
EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma
Authors: Carina Venter, Matthew Greenhawt, Rosan W. Meyer, Carlo Agostoni, Imke Reese, George du Toit, Mary Feeney, Kate Maslin, Bright I. Nwaru, Caroline Roduit, Eva Untersmayr, Berber Vlieg‐Boerstra, Isabella Pali‐Schöll, Graham C. Roberts, Peter Smith, Cezmi A. Akdis, Ioana Agache, Miriam Ben‐Adallah, Stephan Bischoff, Remo Frei, Holger Garn, Kate Grimshaw, Karin Hoffmann‐Sommergruber, Nonhlanhla Lunjani, Antonella Muraro, Lars K. Poulsen, Harald Renz, Milena Sokolowska, Catherine Stanton, Liam O'Mahony
Journal: Allergy (2019)

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.
What Does Reduced FDG Uptake Mean in High-Grade Gliomas?
Authors: Caroline Bund, Benoît Lhermitte, A. Ercument Cicek, Elisa Ruhland, François Proust, Izzie Jacques Namer
Journal: Clinical Nuclear Medicine (2019)

As well as in many others cancers, FDG uptake is correlated with the degree of malignancy in gliomas, that is, commonly high FDG uptake in high-grade gliomas. However, in clinical practice, it is not uncommon to observe high-grade gliomas with low FDG uptake. Our aim was to explore the tumor metabolism in 2 populations of high-grade gliomas presenting high or low FDG uptake.High-resolution magic-angle spinning nuclear magnetic resonance spectroscopy was realized on tissue samples from 7 high-grade glioma patients with high FDG uptake and 5 high-grade glioma patients with low FDG uptake. Tumor metabolomics was evaluated from 42 quantified metabolites and compared by network analysis.Whether originating from astrocytes or oligodendrocytes, the high-grade gliomas with low FDG avidity represent a subgroup of high-grade gliomas presenting common characteristics: low aspartate, glutamate, and creatine levels, which are probably related to the impaired electron transport chain in mitochondria; high serine/glycine metabolism and so one-carbon metabolism; low glycerophosphocholine-phosphocholine ratio in membrane metabolism, which is associated with tumor aggressiveness; and finally negative MGMT methylation status.It seems imperative to identify this subgroup of high-grade gliomas with low FDG avidity, which is especially aggressive. Their identification could be important for early detection for a possible personalized treatment, such as antifolate treatment.
TGFβ signaling in germinal center B cells promotes the transition from light zone to dark zone
Authors: Anne R. Albright, Juraj Kabat, Moyi Li, Fiona Raso, Andrea Reboldi, Jagan R. Muppidi
Journal: The Journal of Experimental Medicine (2019)

B cells in germinal centers (GCs) cycle between light zone (LZ) and dark zone (DZ). The cues in the GC microenvironment that regulate the transition from LZ to DZ have not been well characterized. In Peyer’s patches (PPs), transforming growth factor-β (TGFβ) promotes IgA induction in activated B cells that can then differentiate into GC B cells. We show here that TGFβ signaling occurs in B cells in GCs and is distinct from signaling that occurs in activated B cells in PPs. Whereas in activated B cells TGFβ signaling is required for IgA induction, in the GC it was instead required for the transition from LZ to DZ. In the absence of TGFβ signaling, there was an accumulation of LZ GC B cells and reduced antibody affinity maturation likely due to reduced activation of Foxo1. This work identifies TGFβ as a microenvironmental cue that is critical for GC homeostasis and function.
de Winter Electrocardiogram Pattern—An Unusual ST-Segment Elevation Myocardial Infarction Equivalent Pattern
Authors: Wei-Wei Xu, Liang Lu, Mei-Juan Jin
Journal: JAMA Internal Medicine (2019)

This case report presents the electrocardiographic findings of a man in his 60s with no history of cardiovascular disease who presented to the emergency department with chest pain of 1 hour’s duration.
<i>Notes from the Field:</i> Interventions to Reduce Measles Virus Exposures in Outpatient Health Care Facilities — New York City, 2018
Authors: Karen A. Alroy, Neil M. Vora, Robert J. Arciuolo, Mekete Asfaw, Beth M. Isaac, Martha Iwamoto, Antonine Jean, Denise H. Benkel, Kathleen Blaney, Bindy Crouch, Anita Geevarughese, Krishika A. Graham, Maura Lash, Demetre Daskalakis, Jane R. Zucker, Jennifer B. Rosen
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
Macrophage miR-34a Is a Key Regulator of Cholesterol Efflux and Atherosclerosis
Authors: Yanyong Xu, Yang Xu, Yingdong Zhu, Huihui Sun, Cody Juguilon, Feng Li, Daping Fan, Liya Yin, Yanqiao Zhang
Journal: Molecular Therapy (2019)

Macrophages play a crucial role in the pathogenesis of atherosclerosis, but the molecular mechanisms remain poorly understood. Here we show that microRNA-34a (miR-34a) is a key regulator of macrophage cholesterol efflux and reverse cholesterol transport by modulating ATP-binding cassette transporters ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1). miR-34a also regulates M1 and M2 macrophage polarization via liver X receptor α. Furthermore, global loss of miR-34a reduces intestinal cholesterol or fat absorption by inhibiting cytochrome P450 enzymes CYP7A1 and sterol 12α-hydroxylase (CYP8B1). Consistent with these findings, macrophage-selective or global ablation of miR-34a markedly inhibits the development of atherosclerosis. Finally, therapeutic inhibition of miR-34a promotes atherosclerosis regression and reverses diet-induced metabolic disorders. Our studies outline a central role of miR-34a in regulating macrophage cholesterol efflux, inflammation, and atherosclerosis, suggesting that miR-34a is a promising target for treatment of cardiometabolic diseases.
Decreased expression of mitochondrial miR-5787 contributes to chemoresistance by reprogramming glucose metabolism and inhibiting MT-CO3 translation
Authors: Weixiong Chen, Peng Wang, Yingjuan Lu, Tingting Jin, Xinyuan Lei, Mo Liu, Peilin Zhuang, Junkun Liao, Zhaoyu Lin, Bowen Li, Yu Peng, Guokai Pan, Xiaobin Lv, Hanqing Zhang, Zhanpeng Ou, Shule Xie, Xinyu Lin, Sheng Sun, Soldano Ferrone, Bakhos A. Tannous, Yi Ruan, Jinsong Li, Song Fan
Journal: Theranostics (2019)

MicroRNAs (miRNAs) have been recently found in the mitochondria, and were named "mitomiRs", but their function has remained elusive.Here, we aimed to assess the presence and function(s) of mitomiRs in tongue squamous cell carcinoma (TSCC).Methods: miRNA microarray was performed in paired TSCC cell lines, Cal27 and its chemoresistant counterpart, Cal27-re.Decreased expression of mitomiRs in chemoresistant cells was characterized.The functions of mitomiRs were investigated by a series of in vitro and in vivo experiments.Results: Differential microarray analysis identified downregulation of mitomiR-5787 in Cal27-re cells.We knocked down mitomiR-5787 in parental cells and upregulated its expression in cisplatin-resistant cells.The sensitivity of TSCC cells to cisplatin was regulated by miR-5787.The glucose metabolism assay suggested that reduced expression of miR-5787 changed the balance of glucose metabolism by shifting it from oxidative phosphorylation to aerobic glycolysis.Xenograft experiments in BALB/c-nu mice further verified the in vitro results.Reduced expression of miR-5787 contributes to chemoresistance in TSCC cells by inhibiting the translation of mitochondrial cytochrome c oxidase subunit 3 (MT-CO3).The prognostic analysis of 126 TSCC patients showed that the patients with low expression of miR-5787 and/or MT-CO3 had poor cisplatin sensitivity and prognosis.Conclusions: Mitochondrial miR-5787 could regulate cisplatin resistance of TSCC cells and affect oxidative phosphorylation and aerobic glycolysis.Downregulation of miR-5787 inhibited the translation of MT-CO3 to regulate cisplatin resistance of TSCC.Mitochondrial miR-5787 and MT-CO3 can be used as predictive biomarkers or therapeutic targets for cisplatin chemotherapy resistance.
Copy number gain of ZEB1 mediates a double-negative feedback loop with miR-33a-5p that regulates EMT and bone metastasis of prostate cancer dependent on TGF-β signaling
Authors: Yuhu Dai, Zhengquan Wu, Chuandong Lang, Xin Zhang, Shaofu He, Qing Yang, Wei Guo, Yingrong Lai, Hong Du, Xinsheng Peng, Dong Ren
Journal: Theranostics (2019)

Background: The reciprocal repressive loop between ZEB1 and miRNAs has been extensively reported to play an important role in tumor progression and metastasis of various human tumor types. The aim of this study was to elucidate the role and the underlying mechanism of the double-negative feedback loop between ZEB1and miR-33a-5p in bone metastasis of prostate cancer (PCa). Methods: miR-33a-5p expression was examined in 40 bone metastatic and 165 non-bone metastatic PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-33a-5p expression and clinicopathological characteristics, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-33a-5p in bone metastasis of PCa were investigated both by EMT and the Transwell assay in vitro, and by a mouse model of left cardiac ventricle inoculation in vivo. siRNA library, real-time PCR and chromatin immunoprecipitation (ChIP) were used to identify the underlying mechanism responsible for the decreased expression of miR-33a-5p in PCa. Bioinformatics analysis, Western blotting and luciferase reporter analysis were employed to examine the relationship between miR-33a-5p and its potential targets. Clinical correlation of miR-33a-5p with its targets was examined in human PCa tissues and primary PCa cells. Results: miR-33a-5p expression was downregulated in PCa tissues with bone metastasis and bone-derived cells, and low expression of miR-33a-5p strongly and positively correlated with advanced clinicopathological characteristics, and shorter overall and bone metastasis-free survival in PCa patients. Upregulating miR-33a-5p inhibited, while silencing miR-33a-5p promoted EMT, invasion and migration of PCa cells. Importantly, upregulating miR-33a-5p significantly repressed bone metastasis of PC-3 cells in vivo. Our results further revealed that recurrent ZEB1 upregulation induced by copy number gains transcriptionally inhibited miR-33a-5p expression, contributing to the reduced expression of miR-33a-5p in bone metastatic PCa tissues. In turn, miR-33a-5p formed a double negative feedback loop with ZEB1 in target-independent manner, which was dependent on TGF-β signaling. Finally, the clinical negative correlations of miR-33a-5p with ZEB1 expression and TGF-β signaling activity were demonstrated in PCa tissues and primary PCa cells. Conclusion: Our findings elucidated that copy number gains of ZEB1-triggered a TGF-β signaling-dependent miR-33a-5p-mediated negative feedback loop was highly relevant to the bone metastasis of PCa.
Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment
Authors: Michael Fehlings, Suchit Jhunjhunwala, Marcin Kowanetz, William E. O’Gorman, Priti S. Hegde, Hermi Sumatoh, Boon Heng Lee, Alessandra Nardin, Etienne Becht, Susan Flynn, Marcus Ballinger, Evan W. Newell, Mahesh Yadav
Journal: Journal for ImmunoTherapy of Cancer (2019)

There is strong evidence that immunotherapy-mediated tumor rejection can be driven by tumor-specific CD8+ T cells reinvigorated to recognize neoantigens derived from tumor somatic mutations. Thus, the frequencies or characteristics of tumor-reactive, mutation-specific CD8+ T cells could be used as biomarkers of an anti-tumor response. However, such neoantigen-specific T cells are difficult to reliably identify due to their low frequency in peripheral blood and wide range of potential epitope specificities.Peripheral blood mononuclear cells (PBMC) from 14 non-small cell lung cancer (NSCLC) patients were collected pre- and post-treatment with the anti-PD-L1 antibody atezolizumab. Using whole exome sequencing and RNA sequencing we identified tumor neoantigens that are predicted to bind to major histocompatibility complex class I (MHC-I) and utilized mass cytometry, together with cellular 'barcoding', to profile immune cells from patients with objective response to therapy (n = 8) and those with progressive disease (n = 6). In parallel, a highly-multiplexed combinatorial tetramer staining was used to screen antigen-specific CD8+ T cells in peripheral blood for 782 candidate tumor neoantigens and 71 known viral-derived control peptide epitopes across all patient samples.No significant treatment- or response associated phenotypic difference were measured in bulk CD8+ T cells. Multiplexed peptide-MHC multimer staining detected 20 different neoantigen-specific T cell populations, as well as T cells specific for viral control antigens. Not only were neoantigen-specific T cells more frequently detected in responding patients, their phenotypes were also almost entirely distinct. Neoantigen-specific T cells from responder patients typically showed a differentiated effector phenotype, most like Cytomegalovirus (CMV) and some types of Epstein-Barr virus (EBV)-specific CD8+ T cells. In contrast, more memory-like phenotypic profiles were observed for neoantigen-specific CD8+ T cells from patients with progressive disease.This study demonstrates that neoantigen-specific T cells can be detected in peripheral blood in non-small cell lung cancer (NSCLC) patients during anti-PD-L1 therapy. Patients with an objective response had an enrichment of neoantigen-reactive T cells and these cells showed a phenotype that differed from patients without a response. These findings suggest the ex vivo identification, characterization, and longitudinal follow-up of rare tumor-specific differentiated effector neoantigen-specific T cells may be useful in predicting response to checkpoint blockade.POPLAR trial NCT01903993 .
Ascending Aortic Length and Risk of Aortic Adverse Events
Authors: Jinlin Wu, Mohammad A. Zafar, Yupeng Li, Ayman Saeyeldin, Yan Huang, Rui Zhao, Juntao Qiu, Maryam Tanweer, Mohamed Abdelbaky, Anton Gryaznov, Joelle Buntin, Bulat A. Ziganshin, Sandip K. Mukherjee, John A. Rizzo, Cuntao Yu, John A. Elefteriades
Journal: Journal of the American College of Cardiology (2019)
Abstract 15057: Clinical Profile and 12-Month Prognosis of Miocardial Infarction With Non Obstructive Coronary Arteries According to Definitions of 2016 ESC Position Paper
Authors: David Galan Gil, Javier Lopez Pais, Barbara Izquierdo Coronel, Maria Jesus Espinosa Pascual, Blanca Alcon Duran, Paula Awamleh Garcia, Alfonso Fraile Sanz, Joaquin Jesus Alonso Martin
Journal: Circulation (2018)

Introduction: An standardized definition of myocardial infarction with non-obstructive coronary arteries has recently been published by the European Society of Cardiology. The aim of this study is ...
2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure
Authors: Steven M. Hollenberg, Lynne Warner Stevenson, Tariq Ahmad, Vaibhav J. Amin, Biykem Bozkurt, Javed Butler, Leslie L. Davis, Mark H. Drazner, James N. Kirkpatrick, Pamela N. Peterson, Brent N. Reed, Christopher L. Roy, Alan B. Storrow
Journal: Journal of the American College of Cardiology (2019)