tbuckley/cabot-search huggingface dataset:
Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules
Authors: Pierre P. Massion, Sanja Antic, Sarim Ather, Carlos Arteta, Jan Brabec, Heidi Chen, Jerome Declerck, David Dufek, William Hickes, Timor Kadir, Jonas Kunst, Bennett A. Landman, Reginald F. Munden, Petr Novotny, Heiko Peschl, Lyndsey C. Pickup, Catarina Santos, Gary T. Smith, Ambika Talwar, Fergus Gleeson
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.
Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for esophagogastric junction adenocarcinoma.
Authors: Do Hoon Kim, Eun Jeong Gong, Ji Yong Ahn, Kee Wook Jung, Jeong Hoon Lee, Kee Don Choi, Ho June Song, Gin Hyug Lee, Hwoon-Yong Jung, In-Seob Lee, Beom Su Kim, Moon-Won Yoo, Sung Tae Oh, Jeong Hwan Yook, Byung Sik Kim
Journal: Journal of Clinical Oncology (2017)

144 Background: Endoscopic submucosal dissection (ESD) has been accepted as standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with surgery for adenocarcinoma in the EGJ. Methods: Subjects who underwent ESD or surgery for Siewert type II adenocarcinoma which met absolute and expanded criteria between 2005 and 2010 were eligible for this study. Clinical features and treatment outcomes were retrospectively reviewed using medical records. Results: Among 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range: 13.1-125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for ESD and surgery groups, respectively ( p= 0.376). There was no gastric cancer-related deaths in either groups. Adverse events occurred in 11 patients (13.9%) overall and the incidence of treatment-related adverse events was similar between two groups (10.0% vs. 17.9%, p= 0.308). Conclusions: ESD may be an effective alternative to surgery for the treatment of early gastric cancer in the EGJ, based on comparable long-term outcomes.
Food and soft drink industry has too much influence over US dietary guidelines, report says
Authors: Gareth Iacobucci
Journal: BMJ (2020)

A powerful, industry funded group is playing an “outsized role” in steering the development of new US dietary guidelines and must have its influence curbed to protect public health, a pressure group has urged.

In a report published this week to coincide with Coca-Cola’s annual meeting of shareholders,1 the campaign group Corporate Accountability noted that over half of people appointed to the US 2020 Dietary Guidelines Advisory Committee had ties to the International Life Sciences Institute (ILSI), whose funders include Coke and other global corporations.

ILSI was set up by a Coca-Cola executive 40 years ago in the US and operates throughout the world. It is a not-for-profit organisation and …
Unlocking the Potential of Organ‐on‐Chip Models through Pumpless and Tubeless Microfluidics
Authors: Ludivine C. Delon, Azadeh Nilghaz, Edward Cheah, Clive Prestidge, Benjamin Thierry
Journal: Advanced Healthcare Materials (2020)

Abstract Microfluidic organs‐on‐chips are rapidly being developed toward eliminating the shortcomings of static in vitro models and better addressing basic and translational research questions. A critical aspect is the dynamic culture environment they provide. However, the associated inherent requirement for controlled fluid shear stress (FSS) and therefore the need for precise pumps limits their implementation. To address this issue, here a novel approach to manufacture pumpless and tubeless organs‐on‐chips is reported. It relies on the use of a hydrophilic thread to provide a driving force for the perfusion of the cell culture medium through constant evaporation in the controlled conditions of a cell incubator. Well‐defined and tuneable flow rates can be applied by adjusting the length and/or diameter of the thread. This approach for the preparation of an intestine‐on‐chip model based on the Caco‐2 cell line is validated. Five days culture under 0.02 dyn·cm −2 shear conditions yield monolayers similar to those prepared using a high‐precision peristaltic pump. A pumpless device can also be used to delineate the effect of FSS on the phenotype of adenocarcinomic human alveolar basal epithelial A549 cells. It is anticipated that the pumpless approach will facilitate and herefore increase the use of organs‐on‐chips models in the future.
Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation, T790M, and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy
Authors: Yubo Wang, Nong Yang, Yongchang Zhang, None Li Li, Rui Han, Mengxiao Zhu, Mingxia Feng, Hengyi Chen, Analyn Lizaso, Tian Qin, Xiaoyan Liu, Yong He
Journal: Journal of Thoracic Oncology (2020)
Abstract 13297: The Cardiac Arrest Prediction Model Based on Weather Forecast by Machine Learning
Authors: Takahiro Nakashima, Soshiro Ogata, Teruo Noguchi, Satoshi Yasuda, Yoshio Tahara, Ken Nagao, Kunihiro Nishimura, Hiroshi Nonogi, Koji Iihara, Sunao Kojima
Journal: Circulation (2019)

Introduction: Cardiovascular events is the leading cause of out-of-hospital cardiac arrest (OHCA). Previous studies showed the association between weather condition and the occurrence of cardiovasc...
A Novel Role for Bronchial MicroRNAs and Long Noncoding RNAs in Asthma Remission
Authors: Ilse M. Boudewijn, Mirjam P. Roffel, Cornelis J. Vermeulen, Martijn C. Nawijn, Klaas Kok, M. Martijn Terpstra, Gerard H. Koppelman, Victor Guryev, Maarten van den Berge
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells
Authors: Samantha A. Swenson, Tyler J. Gilbreath, Heather Vahle, R. Willow Hynes-Smith, Jared H. Graham, Henry C.-H. Law, Catalina Amador, Nicholas T. Woods, Michael R. Green, Shannon M. Buckley
Journal: Blood (2020)
Abstract 16078: Novel Myl2 Variant Identified Through Exome Sequencing of an Autosomal Recessive Form of Hypertrophic Cardiomyopathy
Authors: Sathiyanarayanan Manivannan, Sihem Darouich, Aida Masmoudi, David Gordon, Gloria Zender, Sara Fitzgerald-Butt, Imeni Lariani, Kim McBride, Peter White, Maher Kharrat, Vidu Garg
Journal: Circulation (2018)

Massively parallel sequencing technologies have allowed for the discovery of disease-causing mutations in children with rare diseases. Here, we report a consanguineous family in which four children...
Ingestion of Caustic Substances
Authors: Robert S. Hoffman, Michele M. Burns, Sophie Gosselin
Journal: New England Journal of Medicine (2020)

Acids and alkalis can cause tissue damage on contact. Accidental and intentional ingestions of caustic materials in adults and children are a worldwide health issue. Acids act in part by denaturing proteins, and alkalis by saponifying fats. Approaches to management are outlined.
Cullin-RING Ligase 5: Functional characterization and its role in human cancers
Authors: Yongchao Zhao, Xiufang Xiong, Yi Sun
Journal: Seminars in Cancer Biology (2020)

Cullin-RING ligase 5 (CRL5) is a multi-protein complex and consists of a scaffold protien cullin 5, a RING protein RBX2 (also known as ROC2 or SAG), adaptor proteins Elongin B/C, and a substrate receptor protein SOCS. Through targeting a variety of substrates for proteasomal degradation or modulating various protein-protein interactions, CRL5 is involved in regulation of many biological processes, such as cytokine signal transduction, inflammation, viral infection, and oncogenesis. As many substrates of CRL5 are well-known oncoproteins or tumor suppressors, abnormal regulation of CRL5 is commonly found in human cancers. In this review, we first briefly introduce each of CRL5 components, and then discuss the biological processes regulated by four members of SOCS-box-containing substrate receptor family through substrate degradation. We next describe how CRL5 is hijacked by a variety of viral proteins to degrade host anti-viral proteins, which facilitates virus infection. We further discuss the regulation of CUL5 and its various roles in human cancers, acting as either a tumor suppressor or an oncoprotein in a context-dependent manner. Finally, we propose novel insights for future perspectives on the validation of cullin5 and other CRL5 components as potential targets, and possible targeting strategies to discover CRL5 inhibitors for anti-cancer and anti-virus therapies.
AML-Associated Somatic Mutations Can be Detected in Stem and Progenitor Populations in Patients with Antecedent Multiple Myeloma Years before Onset of Therapy-Related Transformation
Authors: Ashwin Sridharan, Carolina D. Schinke, George Georgiev, Mariana Da Silva Ferreira, Kith Pradhan, Yu Xia, Maya Panjikaran, Gregory Sims, Chirag Bhagat, Armin Graber, Christoph Heuck, Daisy Alapat, Niels Weinhold, Sarah K Johnson, Bart Barlogie, Gareth J. Morgan, Ulrich G. Steidl, Britta Will, Amit Verma
Journal: Blood (2017)
YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition
Authors: Jaffer A Ajani, Yan Xu, Longfei Huo, Ruiping Wang, Yuan Li, Ying Wang, Melissa Pool Pizzi, Ailing Scott, Kazuto Harada, Lang Ma, Xiaodan Yao, Jiankang Jin, Wei Zhao, Xiaochuan Dong, Brian D Badgwell, Namita Shanbhag, Ghia Tatlonghari, Jeannelyn Santiano Estrella, Sinchita Roy-Chowdhuri, Makoto Kobayashi, Jody V Vykoukal, Samir M Hanash, George Adrian Calin, Guang Peng, Ju-Seog Lee, Randy L Johnson, Zhenning Wang, Linghua Wang, Shumei Song
Journal: Gut (2020)

Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target.Patient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases.YAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1high PC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1high PC cells especially in combination with cytotoxics in vivo PDX model.YAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.
Consistent Physical Activity and Future Neurocognitive Problems in Adult Survivors of Childhood Cancers: A Report From the Childhood Cancer Survivor Study
Authors: Emily Barlow-Krelina, Yan Chen, Yutaka Yasui, Christine Till, Todd M. Gibson, Kirsten K. Ness, Wendy M. Leisenring, Rebecca M. Howell, Paul C. Nathan, Kevin C. Oeffinger, Leslie L. Robison, Gregory T. Armstrong, Kevin R. Krull, Kim Edelstein
Journal: Journal of Clinical Oncology (2020)

PURPOSE To investigate longitudinal associations between physical activity (PA) and neurocognitive problems in adult survivors of childhood cancer. METHODS A total of 12,123 5-year survivors diagnosed between 1970 and 1999 (median [range] age at diagnosis, 7 [0-21] years, time since diagnosis at baseline, 16 [6-30] years) and 720 siblings self-reported PA and neurocognitive problems. PA was collected at baseline, and PA and neurocognitive data were obtained 7 (1-12) years and 12 (9-14) years later. PA consistency was defined as any combination of ≥ 75 minutes of vigorous or 150 minutes of moderate activity per week on all surveys. Multiple linear regressions, conducted separately for CNS and non-CNS survivors, identified associations between PA consistency and neurocognitive outcomes (expected mean, 50; standard deviation [SD], 10). Mediating effects of body mass index (BMI) and chronic health conditions (CHCs) were evaluated. RESULTS Survivors were less likely than siblings to report consistent PA (28.1% v 33.6%) and more likely to report problems in Task Efficiency (T-scores mean ± SD: siblings, 50.0 ± 0.4; CNS, 61.4 ± 0.4; non-CNS, 53.3 ± 0.3), Emotion Regulation (siblings, 51.4 ± 0.4; CNS, 54.5 ± 0.3; non-CNS 53.4 ± 0.2), and Memory (siblings, 50.8 ± 0.4; CNS, 58.9 ± 0.4; non-CNS, 53.5 ± 0.2; all P &lt; .001). Survivors of CNS cancers (52.8 ± 0.3) also reported poorer Organization than siblings (49.9 ± 0.4; P &lt; .001). After adjusting for age at diagnosis, age at questionnaire, emotional distress, and cancer treatment exposures, consistent PA was associated with fewer neurocognitive problems compared with consistent inactivity for both CNS and non-CNS groups (T-score differences ranging from −7.9 to −2.2) and larger neurocognitive improvements over time (−6.0 to −2.5), all P ≤ .01. BMI and severe CHCs partially mediated the PA-neurocognitive associations, but the mediation effects were small (change in β ≤ 0.4). CONCLUSION Adult survivors of childhood cancer who report more consistent PA have fewer neurocognitive problems and larger improvements in these concerns many years after treatment.
Organic osmolytes increase expression of specific tight junction proteins in skin and alter barrier function in keratinocytes*
Authors: C. El‐Chami, A.R. Foster, C. Johnson, R.P. Clausen, P. Cornwell, I.S. Haslam, M.C. Steward, R.E.B. Watson, H.S. Young, C.A. O'Neill
Journal: British Journal of Dermatology (2020)

The epidermal barrier is important for water conservation, failure of which is evident in dry-skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs, which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact.We aimed to characterize osmolyte transporters in skin and keratinocytes, and, using transporter inhibitors, to investigate whether osmolytes can modify TJs. Such modification would suggest a possible link between intracellular and extracellular mechanisms of water regulation in skin.Immunostaining and quantitative polymerase chain reaction of organic osmolyte-treated organ-cultured skin were used to identify changes to organic osmolyte transporters, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture.Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudin-1, claudin-4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro.Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasizes a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterized by skin barrier dysfunction.
Imaging neoangiogenesis in rheumatoid arthritis (INIRA): whole-body synovial uptake of a <sup>99m</sup>Tc-labelled RGD peptide is highly correlated with power Doppler ultrasound
Authors: Laura Attipoe, Khaldoun Chaabo, Julekha Wajed, Fahim-Ul Hassan, Dharsene Shivapatham, Matthew Morrison, Jim Ballinger, Gary Cook, Andrew P Cope, Toby Garrood
Journal: Annals of the Rheumatic Diseases (2020)

Ultrasound (US) is superior to clinical examination in detecting synovitis in patients with rheumatoid arthritis (RA).1 It is dynamic, relatively cheap and can be used in the clinic. However, it is time consuming and impractical to image large numbers of joints. There is no consensus on the minimum US joint count required to adequately reflect the burden of disease activity. MRI has similar sensitivity to US for detecting synovitis but again is time consuming, expensive and may not be tolerated by some patients. Both modalities require expertise to interpret the images. Three-phase bone scintigraphy has good sensitivity, but due to lower specificity, it is not routinely used to detect synovitis.2

Integrin αvβ3 is a cell adhesion molecule upregulated on activated vascular endothelial cells in neoangiogenesis. It is overexpressed in the inflamed synovium and on activated cells such as osteoclasts.3 99mTc-maraciclatide (Serac Healthcare) is a radiolabelled tracer containing the RGD tripeptide motif which binds with high affinity to αv …
Accumulation of natriuretic peptides is associated with protein energy wasting and activation of browning in white adipose tissue in chronic kidney disease
Authors: Mathilde Luce, Christophe Barba, Dan Yi, Anne Mey, Damien Roussel, Emilie Bres, Bérengère Benoit, Myriam Pastural, Samuel Granjon, Jean Christophe Szelag, Maurice Laville, Walid Arkouche, Anais Bouchara, Elsa Nyam, Denis Fouque, Christophe O. Soulage, Laetitia Koppe
Journal: Kidney International (2020)
Targeting Endoglin-Expressing Regulatory T Cells in the Tumor Microenvironment Enhances the Effect of PD1 Checkpoint Inhibitor Immunotherapy
Authors: Mark J.A. Schoonderwoerd, Maaike F.M. Koops, Ricardo A. Angela, Bryan Koolmoes, Melpomeni Toitou, Madelon Paauwe, Marieke C. Barnhoorn, Yingmiao Liu, Cornelis F.M. Sier, James C.H. Hardwick, Andrew B. Nixon, Charles P. Theuer, Marieke F. Fransen, Lukas J.A.C. Hawinkels
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Endoglin is a coreceptor for TGFβ ligands that is highly expressed on proliferating endothelial cells and other cells in the tumor microenvironment. Clinical studies have noted increased programmed cell death (PD)-1 expression on cytotoxic T cells in the peripheral blood of patients with cancer treated with TRC105, an endoglin-targeting antibody. In this study, we investigated the combination of endoglin antibodies (TRC105 and M1043) with an anti-PD1 antibody. Experimental Design: The combination anti-endoglin/anti-PD1 antibodies was tested in four preclinical mouse models representing different stages of cancer development. To investigate the underlying mechanism, Fc-receptor–knockout mice were used complemented with depletion of multiple immune subsets in mice. Tumor growth and the composition of immune infiltrate were analyzed by flow cytometry. Finally, human colorectal cancer specimens were analyzed for presence of endoglin-expressing regulatory T cells (Treg). Results: In all models, the combination of endoglin antibody and PD1 inhibition produced durable tumor responses, leading to complete regressions in 30% to 40% of the mice. These effects were dependent on the presence of Fcγ receptors, indicating the involvement of antibody-dependent cytotoxic responses and the presence of CD8+ cytotoxic T cells and CD4+ Th cells. Interestingly, treatment with the endoglin antibody, TRC105, significantly decreased the number of intratumoral Tregs. Endoglin-expressing Tregs were also detected in human colorectal cancer specimens. Conclusions: Taken together, these data provide a rationale for combining TRC105 and anti-PD1 therapy and provide additional evidence of endoglin's immunomodulatory role.
Covid-19: Care home deaths in England and Wales rise sharply
Authors: Adrian O’Dowd
Journal: BMJ (2020)

Every year, pediatric urinary tract infections (UTI) account for 1.5 million clinician visits in the US alone. Up to 50% of infants with UTI develop a kidney infection (acute pyelonephritis, APN). Despite antibiotic therapy, 15% of children with APN develop renal scarring, which is associated with deterioration in kidney function. Here, we determined the contribution of macrophages and neutrophils to bacterial clearance and the development of kidney fibrosis during experimental APN. Female C3H/HeOuJ mice were treated, via retro-orbital, with one of the following antibodies: isotype IgG (control), anti-Ly6G (depletes neutrophils), anti-CD115 (depletes monocytes), and anti-GR1 (depletes monocytes and neutrophils). After cell depletion, the animals were transurethrally infected with UPEC. Ascending UTI was evaluated via biophotonic imaging. The dynamics of monocytes and neutrophils were determined by flow cytometry. Histopathological scores were performed by H&amp;E and Sirius-Red stainings. Transcriptomic analyses of kidneys were performed using TaqMan Arrays. Our data indicate that neutrophils are required for bacterial clearance, while macrophages promote inflammation in the infected urinary tract. However, the absence of neutrophils results in increased macrophage infiltration and exaggerated macrophage-dependent inflammatory responses in the bladder and kidney. Also, our results demonstrate that macrophage-dependent inflammation during APN, leads to renal scarring and renal functional impairment. These findings uncover a role for the neutrophil-macrophage imbalance in promoting kidney fibrosis during APN. This knowledge will be helpful to develop novel therapies to prevent post-APN scarring in children.