tbuckley/cabot-search huggingface dataset:
P-75 Retrospective comparison between FLOT perioperative chemotherapy vs surgery followed by adjuvant chemotherapy: Results from a multicenter analysis
Authors: M. Baleani, A. Bittoni, M. Del Prete, A. Lanese, T. Meletani, E. Giglio, L. Cantini, S. Crocetti, C. Copparoni, A. Lupi, E. Lenci, F. Bini, M. Giulia, F. Pecci, R. Bisonni, P. Alessandroni, F. Graziano, R. Berardi, R. Giampieri
Journal: Annals of Oncology (2020)
P-168 Second-line, anti-VEGF based after first-line, anti-EGFR based treatment in RAS wild-type metastatic colorectal cancer: The multicenter, retrospective, real-life SLAVE study
Authors: A. Parisi, F. Camarda, M. Ribelli, D. Rossini, M. Germani, E. Dell'Aquila, C. Natoli, D. Pietro, D. Corsi, I. Zurlo, P. Lombardi, N. Zanaletti, R. Giampieri, F. Merloni, M. Occhipinti, P. Marchetti, M. Roberto, F. Mazzuca, M. Ghidini, I. Garajová, F. Zoratto, C. Ficorella
Journal: Annals of Oncology (2020)
Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial
Authors: Andrada Seicean, Andrada Samarghitan, Sorana D. Bolboacă, Cristina Pojoga, Ioana Rusu, Daniel Rusu, Zeno Sparchez, Marcel Gheorghiu, Nadim Al Hajjar, Radu Seicean
Journal: Endoscopy (2020)

Abstract Background Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate. Methods This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging. Results 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent. Conclusions The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.
Expression and function of vascular endothelial growth factor receptor–1 in human colon cancer cells
Authors: Fan Fan, Jane S. Wey, Anna Belcheva, Marya F. McCarty, Yan Wu, Daniel J. Hicklin, Lee M. Ellis
Journal: Cancer Research (2004)

4334  Vascular endothelial growth factor (VEGF) has been shown to be associated with tumor angiogenesis and poor prognosis in human colon cancer. VEGF receptor-1 (VEGFR-1/Flt-1) is a high-affinity receptor for VEGF and is typically viewed as being endothelial cell specific. Here we report on the expression and function of VEGFR-1 on colon cancer cell lines. VEGFR-1 was expressed in 7/7 colon cancer cell lines as determined by Western blot analysis. Treatment of the human colon cancer cell line SW480 with VEGF-A (ligand for both VEGFR-1 and VEGFR-2) or VEGF-B (a ligand specific for VEGFR-1) led to activation of Erk 1/2. A blocking antibody to VEGFR-1 (18F1) completely inhibited the ability of VEGF-A and -B to activate Erk 1/2 in SW480 cells. VEGF-A and B did not increase colon cancer cell proliferation as determined by the MTT assay. However, VEGF-A and VEGF-B led to a significant induction of cancer cell motility and invasion through Matrigel. VEGF-A and -B stimulation of colon tumor cells also led to larger and more numerous colonies in soft agar. These data demonstrate that VEGFR-1 is functional on colon cancer cells and may contribute to colon cancer progression.
Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury
Authors: Jun-Jae Chung, Leonard Goldstein, Ying-Jiun J. Chen, Jiyeon Lee, Joshua D. Webster, Merone Roose-Girma, Sharad C. Paudyal, Zora Modrusan, Anwesha Dey, Andrey S. Shaw
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Single-cell transcriptomics techniques have revolutionized the ability to characterize cells from heterogeneous organs like the kidney. Although glomerular disorders are an important cause of CKD, a thorough characterization of the cells in the glomerulus has remained challenging due to the technical difficulties of isolating undamaged cells, especially from glomeruli of diseased animals. This study provides a comprehensive single-cell atlas, based on approximately 75,000 cells, from glomeruli of healthy mice and mice injured in four ways, including all cell types present. The data set will be a valuable resource for generating precise tools to interrogate specific glomerular cell types and in identifying genes involved in the pathogenesis of glomerular diseases. Background The glomerulus is a specialized capillary bed that is involved in urine production and BP control. Glomerular injury is a major cause of CKD, which is epidemic and without therapeutic options. Single-cell transcriptomics has radically improved our ability to characterize complex organs, such as the kidney. Cells of the glomerulus, however, have been largely underrepresented in previous single-cell kidney studies due to their paucity and intractability. Methods Single-cell RNA sequencing comprehensively characterized the types of cells in the glomerulus from healthy mice and from four different disease models (nephrotoxic serum nephritis, diabetes, doxorubicin toxicity, and CD2AP deficiency). Results All cell types in the glomerulus were identified using unsupervised clustering analysis. Novel marker genes and gene signatures of mesangial cells, vascular smooth muscle cells of the afferent and efferent arterioles, parietal epithelial cells, and three types of endothelial cells were identified. Analysis of the disease models revealed cell type–specific and injury type–specific responses in the glomerulus, including acute activation of the Hippo pathway in podocytes after nephrotoxic immune injury. Conditional deletion of YAP or TAZ resulted in more severe and prolonged proteinuria in response to injury, as well as worse glomerulosclerosis. Conclusions Generation of comprehensive high-resolution, single-cell transcriptomic profiles of the glomerulus from healthy and injured mice provides resources to identify novel disease-related genes and pathways.
P-144 Infigratinib versus gemcitabine plus cisplatin as first-line therapy in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: phase 3 PROOF trial
Authors: G. Abou-Alfa, I. Borbath, A. Cohn, L. Goyal, A. Lamarca, T. Macarulla, D. Oh, S. Roychowdhury, S. Sadeghi, R. Shroff, M. Howland, A. Li, T. Cho, A. Pande, M. Javle
Journal: Annals of Oncology (2020)
The N-linked glycan structures of HSP96 are a determinant of its biochemical function
Authors: Robert Suriano, Devyani Chaudhuri, Salil Ghosh, Badithe T. Ashok, Asesh Banerjee, Abraham Mittelman, Raj K. Tiwari
Journal: Cancer Research (2006)

4780  Autologous HSP96 is being evaluated as a multivalent peptide cancer vaccine. The ability of HSP96 to act as a peptide chaperone forms the basis for its use as a multivalent biological cancer vaccine. Internalization of HSP96/peptide complex occurs through cell surface receptors, such as CD91 resulting in cross presentation of cancer specific antigenic peptides and elicitation of tumor specific cytotoxic T lymphocytes (CTLs). HSP96 is a glycoprotein containing two known N-linked glycan structures and four more potential N-linked glycosylation sites. However, the role of these glycosyl moieties, if any, on the structure and function of HSP96 is currently unknown. We discovered that purified HSP96, from various human and rat prostate tumors have significant differences in glycosylation patterns which is correlated with cell specific phenotype and removal of glycosyl moieties modulates peptide binding affinity. We demonstrated these effects using glycosylated and unglycosylated purified HSP96 and VSV-8 peptide (RGYVYQGL). These results for the first time implicate glycans as signatorial elements of tissue derived HSP96 that modulate its peptide chaperoning and binding ability. Other functions of HSP96 such as the integral ATPase activity and cell surface receptor mediated endocytosis may also be dependent on glycan structures. These studies are intended to define the structural components that determine the pleomorphic functions of HSP96 based cancer vaccines.
P-139 Comparison of cost-effectiveness of anti-epidermal growth factor receptor monoclonal antibody and anti-vascular endothelial growth factor monoclonal antibody in K-RAS WT, RAS WT, and RAS WT left-sided metastatic colorectal cancer
Authors: S. Lee, C. Chiang, K. Lam, V. Lee, I. Wong, S. Chan, H. Choi
Journal: Annals of Oncology (2020)
The Associations of Interstitial Lung Abnormalities with Cancer Diagnoses and Mortality
Authors: Gisli T. Axelsson, Rachel K. Putman, Thor Aspelund, Elias F. Gudmundsson, Tomayuki Hida, Tetsuro Araki, Mizuki Nishino, Hiroto Hatabu, Vilmundur Gudnason, Gary M. Hunninghake, Gunnar Gudmundsson
Journal: European Respiratory Journal (2020)

An increased incidence of lung cancer is well known among patients with idiopathic pulmonary fibrosis. It is not known whether interstitial lung abnormalities, i.e. early fibrotic changes of the lung, are a risk factor for lung cancer in the general population. The study's objective was to assess whether interstitial lung abnormalities were associated with diagnoses of, and mortality from, lung cancer and other cancers. Data from the AGES-Reykjavik study, a cohort of 5764 older Icelandic adults, were used. Outcome data were ascertained from electronic medical records. Gray's tests, Cox proportional hazards models and proportional subdistribution hazards models were used to analyse associations of interstitial lung abnormalities with lung cancer diagnoses and lung cancer mortality as well as diagnoses and mortality from all cancers. There was a greater cumulative incidence of lung cancer diagnoses (p&lt;0.001) and lung cancer mortality (p&lt;0.001) in participants with interstitial lung abnormalities than in others. Interstitial lung abnormalities were associated with an increased hazard of lung cancer diagnosis (hazard ratio 2.77) and lung cancer mortality (hazard ratio 2.89) in adjusted Cox models. Associations of interstitial lung abnormalities with all cancers were found in models including lung cancers but not in models excluding lung cancers. People with interstitial lung abnormalities are at increased risk of lung cancer and lung cancer mortality, but not of other cancers. This implies that an association between fibrotic and neoplastic diseases of the lung exists from the early stages of lung fibrosis and suggests that interstitial lung abnormalities could be considered as a risk factor in lung cancer screening efforts.
Association of Positive Affect Instability With All-Cause Mortality in Older Adults in England
Authors: Anthony D. Ong, Andrew Steptoe
Journal: JAMA Network Open (2020)

<h3>Importance</h3> There is increasing recognition that positive affective states have a protective association for all-cause mortality. However, positive states of happiness and excitement vary over time, and little is known about the association of fluctuations in positive affect with survival. <h3>Objective</h3> To investigate the association of positive affect instability, conceptualized as fluctuations in momentary positive affect, with mortality in a population-based sample of older adults in England. <h3>Design, Setting, and Participants</h3> This survey study used data from a longitudinal survey collected in wave 2 (2004) of the English Longitudinal Study of Ageing, a nationally representative sample of older men and women living in England, with follow-up continuing until March 2018. Participants included people aged 50 years or older at recruitment. Data were analyzed from September 2019 to April 2020. <h3>Main Outcomes and Measures</h3> The main outcome was all-cause mortality. Positive and negative affect were measured at 4 time points over the course of 1 day: soon after waking, 30 minutes after waking, at 7:00pm, and at bedtime. <h3>Results</h3> Data were analyzed from 3834 participants (mean [SD] age at baseline, 64.0 [7.4] years; 2082 [54.3%] women) with a mean (SD) follow-up of 12.25 (2.60) years. Adjusting for demographic characteristics, baseline illness, health behaviors, and mean level and instability in negative affect, Cox proportional hazards regression showed that high positive affect instability was associated with greater mortality, with a hazard ratio of 1.25 (95% CI, 1.04-1.49;<i>P</i> = .02). Associations did not differ by age, suggesting that the increased mortality risk associated with high positive affect instability was not restricted to older ages. <h3>Conclusion and Relevance</h3> These findings suggest that temporal fluctuations in positive affect were associated with mortality risk in older adults. These findings illustrate the value of incorporating dynamic assessments of positive affect in distal health outcomes such as mortality.
Emerging pharmacological therapies for ARDS: COVID-19 and beyond
Authors: Shahd Horie, Bairbre McNicholas, Emanuele Rezoagli, Tài Pham, Ger Curley, Danny McAuley, Cecilia O’Kane, Alistair Nichol, Claudia dos Santos, Patricia R. M. Rocco, Giacomo Bellani, John G. Laffey
Journal: Intensive Care Medicine (2020)

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.
SO-12 Multicentre validation of an immune-inflammation-based nomogram to predict survival in western resectable gastroesophageal adenocarcinoma: The NOMOGAST
Authors: M. Salati, L. Marcheselli, N. De Ruvo, G. Esposito, S. Fenocchi, G. Cucciarrè, F. Serra, N. Cautero, F. Cabry, R. Gelmini, G. Vittimberga, G. Radi, L. Solaini, P. Morgagni, G. Ercolani, M. Ghidini, G. Grizzi, M. Ratti, F. Gelsomino, G. Luppi, M. Dominici, A. Spallanzani
Journal: Annals of Oncology (2020)
Differential expression of connexins in melanoma and adjacent epidermis
Authors: Nikolas K. Haass, Johanna M. Brandner, Patricia A. Brafford, Ewa Wladykowski, Steven Kazianis, Keiran S. Smalley, Ingrid Moll, Meenhard Herlyn
Journal: Cancer Research (2004)

2769   Under normal homeostasis, melanocyte growth is controlled by the surrounding keratinocytes through a complex system of paracrine growth factors and cell-cell adhesion molecules. Disruption of this balance can alter the expression of cell-cell adhesion and cell-cell communication molecules and thus lead to development of melanoma. Gap junctional intercellular communication (GJIC) plays an important role in maintaining tissue homeostasis and is thus a critical factor in the life and death balance of cells. In the skin GJIC is likely to be involved in the regulation of keratinocyte growth, differentiation and migration as well as in keratinocyte-melanocyte interactions. Ten of the 21 connexins are expressed in human skin. Changes in connexin expression, in particular loss of Connexin (Cx) 43, may result in a reduction or a loss of gap junctional activity, which is thought to contribute to tumor progression. Using microarrays and RT-PCR we show that Cx43 is not expressed in 14 of the 28 investigated melanoma cell lines and only weakly in the other 14, but is highly expressed in melanocytes, keratinocytes, fibroblasts and endothelial cells. On the other hand, Cx32 is expressed in 24/28 melanoma cell lines and –at a lower level –in all melanocytes, but not in keratinocytes, fibroblasts and endothelial cells. Cx26 is weakly expressed in 12/28 melanoma cell lines. In contrast, Cx30 is only weakly expressed in 3/28 melanoma cell lines. These three cell lines were also positive for Cx43 and Cx26 and were derived from metastases of the same patient.Using immunofluorescence on human tissue sections, we did not detect Cx43, Cx26 and Cx30 in melanoma (n=8). However, we show an induction of Cx26 and Cx30 in the epidermis adjacent to melanoma, while both are not detectable in the epidermis adjacent to benign non-epithelial skin tumors (melanocytic nevi and angioma). As the expression patterns of Cx26 and Cx30 are not identical with CK6, a marker for hyperproliferation, and CK17, a marker of trauma, we suggest that the induction of these gap junctional proteins is not a reflection of reactive hyperproliferative or traumatized epidermis. We instead discuss the putative roles of these gap junctional proteins in tumor progression.
Health Policy and Privacy Challenges Associated With Digital Technology
Authors: David Grande, Xochitl Luna Marti, Rachel Feuerstein-Simon, Raina M. Merchant, David A. Asch, Ashley Lewson, Carolyn C. Cannuscio
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Digital technology is part of everyday life. Digital interactions generate large amounts of data that can reveal information about the health of individual consumers (the digital health footprint). <h3>Objective</h3> Τo describe health privacy challenges associated with digital technology. <h3>Design, Setting, and Participants</h3> For this qualitative study, In-depth, semistructured, qualitative interviews were conducted with 26 key experts from diverse fields in the US between January 1 and July 31, 2018. Open-ended questions and hypothetical scenarios were used to identify sources of digital information that contribute to consumers' health-relevant digital footprints and challenges for health privacy. Participants also completed a survey instrument on which they rated the health relatedness of digital data sources. <h3>Main Outcomes and Measures</h3> Health policy challenges associated with digital technology based on qualitative responses to expert interviews. <h3>Results</h3> Although experts' ratings of digital data sources suggested a possible distinction between health and nonhealth data, qualitative interviews uniformly indicated that all data can be health data, particularly when aggregated across sources and time. Five key characteristics of the digital health footprint were associated with health privacy policy challenges: invisibility (people are unaware of how their data are tracked), inaccuracy (data in the digital health footprint can be inaccurate), immortality (data have no expiration date and are aggregated over time), marketability (data have immense commercial value and are frequently bought and sold), and identifiability (individuals can be readily reidentified and anonymity is nearly impossible to achieve). There are virtually no regulatory structures in the US to protect health privacy in the context of the digital health footprint. <h3>Conclusions and Relevance</h3> The findings suggest that a sector-specific approach to digital technology privacy in the US may be associated with inadequate health privacy protections.
Precision metabolome reprogramming for imprecision therapeutics in retinitis pigmentosa
Authors: Salvatore Caruso, Joseph Ryu, Peter M.J. Quinn, Stephen H. Tsang
Journal: Journal of Clinical Investigation (2020)

Retinitis pigmentosa (RP), the most common form of rod-cone dystrophy, is caused by greater than 3100 mutations in more than 71 genes, many of which are preferentially expressed in rod photoreceptors. Cone death generally follows rod loss regardless of the underlying pathogenic mutation. Preventing the secondary loss of cone photoreceptors would preserve central visual acuity and substantially improve patients' quality of life. In this issue of the JCI, Wang et al. demonstrate that adeno-associated virus-mediated overexpression of TGF-β1 promoted cone survival and function in 3 distinct RP models with rod-specific mutations. TGF-β1 induces microglia to metabolically tune from a glycolytic phenotype (M1) to an oxidative phenotype (M2), which associates with neuroprotection and the antiinflammatory ecosystem. Consolidating the results of this study with our current understanding of how TGF-β1 regulates microglia polarization, we highlight cell-specific metabolome reprogramming as a promising non-gene-specific therapeutic avenue for inherited retinal degenerations.