tbuckley/cabot-search huggingface dataset:
Quantitative immunohistochemical analysis of VEGF expression on a pancreatic cancer tissue microarray
Authors: Harry H. Yoon, Gina G. Chung, Malini Harigopal, Lori A. Charette, Maciej P. Zerkowski, Laurie Thomas, Saritha Salikooti, John J. Chang, David L. Rimm, Barbara A. Burtness
Journal: Cancer Research (2004)

424  Immunohistochemical measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer have typically been qualitative or semi-quantitative. Furthermore, VEGF levels in primary versus metastatic sites are not well characterized. We have recently developed a set of algorithms called automated quantitative analysis (AQUA) that can assess tissue microarrays (TMA) using fluorescent tags to define tumors, localize sub-cellular compartments, and grade intensity of specific markers on a continuous scale. Our purpose was to use AQUA to compare VEGF levels on a pancreatic cancer TMA containing tumors removed from pancreas and metastatic sites. TMAs were constructed by arraying 1.5-mm cores from 80 cases of pancreatic adenocarcinoma (1996-2002) obtained from the archives of the Yale Dept. of Pathology. Fourteen normal pancreatic cores served as controls. Staining for AQUA is similar to standard immunohistochemistry and involves antigen retrieval and application of primary antibodies, but with epifluorescence detection. Slides are then counterstained with DAPI for nuclear and cytokeratin for membrane visualization. Primary antibodies used were VEGF specific for isoforms 165, 189, and 206 (BD Pharmingen) and cytokeratin (DAKO). Of the 80 cases on the TMA, 58 were evaluable, of which 35, 9, and 14 were from pancreas, liver, and other intraabdominal contiguous or metastatic sites, respectively. Mean VEGF expression of malignant tissue (score 32.8) was similar to that of normal pancreatic tissue (score 29.9; p=0.43 two-tailed student’s t-test). Mean VEGF expression in extratumoral, stromal compartments, however, was lower in malignant spots (score 6.9) compared to normal pancreas (score 17.6; p=0.00042). VEGF expression among the different cancer sites did not differ significantly with the exception of pancreas (score 33.5) compared to non-hepatic contiguous or metastatic sites (score 26.3; p=0.038). In conclusion, VEGF expression was similar in normal pancreatic and malignant tissue as measured by quantitative immunohistochemistry. Stromal VEGF expression however, appeared to be lower in malignant tissue than in normal pancreas, and tumor expression of VEGF was lower in non-hepatic contiguous or metastatic sites compared with primary pancreatic cancers. Further evaluation will be performed on an expanded cohort of patients and correlated with clinical outcome.
334MO Haemoglobin, body mass index and age as risk-factors for paclitaxel- and oxaliplatin-induced peripheral neuropathy
Authors: D. Mizrahi, S.B. Park, T. Li, H. Timmins, T. Trinh, K. Au, E. Battaglini, D. Wyld, R. Henderson, P. Grimison, H. Ke, J. Marker, B. Wall, D. Goldstein
Journal: Annals of Oncology (2020)
Impact of systemic factors in shaping the periodontal microbiome
Authors: Flavia Teles, Yu Wang, George Hajishengallis, Hatice Hasturk, Julie T. Marchesan
Journal: Periodontology 2000 (2020)

Abstract Since 2010, next‐generation sequencing platforms have laid the foundation to an exciting phase of discovery in oral microbiology as it relates to oral and systemic health and disease. Next‐generation sequencing has allowed large‐scale oral microbial surveys, based on informative marker genes, such as 16S ribosomal RNA, community gene inventories (metagenomics), and functional analyses (metatranscriptomics), to be undertaken. More specifically, the availability of next‐generation sequencing has also paved the way for studying, in greater depth and breadth, the effect of systemic factors on the periodontal microbiome. It was natural to investigate systemic diseases, such as diabetes, in such studies, along with systemic conditions or states, , pregnancy, menopause, stress, rheumatoid arthritis, and systemic lupus erythematosus. In addition, in recent years, the relevance of systemic “variables” (ie, factors that are not necessarily diseases or conditions, but may modulate the periodontal microbiome) has been explored in detail. These include ethnicity and genetics. In the present manuscript, we describe and elaborate on the new and confirmatory findings unveiled by next‐generation sequencing as it pertains to systemic factors that may shape the periodontal microbiome. We also explore the systemic and mechanistic basis for such modulation and highlight the importance of those relationships in the management and treatment of patients.
14980 Safety and clinical outcomes of the 1064-nm neodymium-doped yttrium aluminum garnet laser combined with topical antifungal agents for onychomycosis in patients with diabetes mellitus
Authors: Jong-Kil Seo, Dong Hye Suh, Hyun-Joo Kim, None Ye-Jin, Hyo-Eun Kwon, Hye-Jin Ahn, Ki-Heon Jeong, Mu-Hyoung Lee, Min Kyung Shin
Journal: Journal of the American Academy of Dermatology (2020)
Radionuclide Imaging in the Diagnosis of Transthyretin Cardiac Amyloidosis
Authors: Patrícia Rodrigues, André Dias Frias, Patrícia Gouveia, Maria Trêpa, Marta Fontes Oliveira, Ricardo Costa, Hipólito Reis, Inês Amorim, Paulo Palma, Henrique Cyrne Carvalho, Severo Torres
Journal: JACC. Cardiovascular imaging (2020)
African malaria deaths set to dwarf covid-19 fatalities as pandemic hits control efforts, WHO warns
Authors: Owen Dyer
Journal: BMJ (2020)

Excess malaria deaths caused by pandemic driven shortfalls in prevention and treatment efforts will probably dwarf direct deaths from covid-19 in sub-Saharan Africa, the World Health Organization has warned.

Progress against malaria—dramatic in the first decade of this century—had already stalled since 2016 as foreign donors drifted away. But 2020 is likely to be the first year in decades to see an increase in deaths, WHO warned in its 2020 World Malaria Report.1

About 1.5 billion malaria cases and 7.6 million deaths have been averted since 2000, WHO estimates. But annual case numbers in sub-Saharan Africa have been unchanged since 2016 at about 230 million, and this year the region will fall far short of milestones …
Donor Characteristics and Regional Differences in the Utilization of HCV-Positive Donors in Liver Transplantation
Authors: Ben L. Da, Ghideon Ezaz, Tatyana Kushner, James Crismale, Gaurav Kakked, Ahmet Gurakar, Douglas Dieterich, Thomas D. Schiano, Behnam Saberi
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Increased utilization of hepatitis C virus (HCV)–positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear. <h3>Objective</h3> To characterize HCV-positive donors and the allografts that come from them. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age &lt;18 years) recipients were excluded. <h3>Main Outcomes and Measures</h3> The primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed. <h3>Results</h3> Of 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab–positive donors were HCV NAT positive. HCV Ab–positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab–negative donors. These findings were even more pronounced in HCV Ab–positive /NAT–positive compared with HCV Ab–positive/NAT–negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab–positive donors, accounting for 64.4% of all HCV Ab–positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab–positive donors (18.7%). The use of HCV Ab–positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT–positive donors. <h3>Conclusions and Relevance</h3> In this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.
Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2–negative advanced breast cancer: final overall survival results from SOLAR-1
Authors: F. André, E.M. Ciruelos, D. Juric, S. Loibl, M. Campone, I.A. Mayer, G. Rubovszky, T. Yamashita, B. Kaufman, Y.-S. Lu, K. Inoue, Z. Pápai, M. Takahashi, F. Ghaznawi, D. Mills, M. Kaper, M. Miller, P.F. Conte, H. Iwata, H.S. Rugo
Journal: Annals of Oncology (2020)

Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC.Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a one-sided stratified log-rank test was carried out with an O'Brien-Fleming efficacy boundary of P ≤ 0.0161.In the PIK3CA-mutated cohort (n = 341), median OS [95% confidence interval (CI)] was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant [hazard ratio (HR) = 0.86 (95% CI, 0.64-1.15; P = 0.15)]. OS results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively [HR = 0.68 (0.46-1.00)]. Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively [HR = 0.72 (0.54-0.95)]. No new safety signals were observed with longer follow-up.Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment of patients with PIK3CA-mutated, HR+, HER2- ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation. CLINICALTRIALS.NCT02437318.
Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension
Authors: Katharina Wöran, Georg Semmler, Mathias Jachs, Benedikt Simbrunner, David Josef Maria Bauer, Teresa Binter, Katharina Pomej, Albert Friedrich Stättermayer, Philipp Schwabl, Theresa Bucsics, Rafael Paternostro, Katharina Lampichler, Matthias Pinter, Michael Trauner, Mattias Mandorfer, Judith Stift, Thomas Reiberger, Bernhard Scheiner
Journal: Clinical Gastroenterology and Hepatology (2020)
17021 The patient-reported burden of atopic dermatitis and its association with itch: Observations from the upadacitinib phase 2b randomized, placebo-controlled trial in moderate to severe atopic dermatitis
Authors: Jonathan I. Silverberg, Brian Calimlim, Henrique D. Teixeira, Meijing Wu, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2020)
Poverty and Targeted Immunotherapy: Survival in Children’s Oncology Group Clinical Trials for High-Risk Neuroblastoma
Authors: Kira Bona, Yimei Li, Lena E Winestone, Kelly D Getz, Yuan-Shung Huang, Brian T Fisher, Ami V Desai, Troy Richardson, Matt Hall, Arlene Naranjo, Tara O Henderson, Richard Aplenc, Rochelle Bagatell
Journal: JNCI Journal of the National Cancer Institute (2020)

Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials.We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided.In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group.Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.
Advances in the diagnosis and management of gastroesophageal reflux disease
Authors: David A Katzka, Peter J Kahrilas
Journal: BMJ (2020)

Abstract Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett’s esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of Helicobacter pylori. Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
The effectiveness of a video-based smoking cessation intervention focusing on maternal and child health to help Chinese expectant fathers quit smoking: an open-label, single-blind, three-arm, randomised controlled trial
Authors: Wei Xia, William Ho Cheung Li, Wenzhi Cai, Peige Song, Xiaoyu Zhou, Katherine Ka Wai Lam, Laurie Long Kwan Ho, Chunxian Zeng, Ka Yan Ho
Journal: The Lancet (2020)
180P Real-world (RW) treatment (tx) patterns and outcomes in patients (pts) from Taiwan and Singapore with intermediate and advanced hepatocellular carcinoma (HCC)
Authors: S.P. Choo, S.K. Mhatre, A. Ferro, R. Machado, D.H-C. Liu, N. Irahara, V.E. Gaillard, Y-Y. Shao
Journal: Annals of Oncology (2020)
An Adenosine-Independent Index of Stenosis Severity From Coronary Wave–Intensity Analysis: A New Paradigm in Coronary Physiology for the Cath Lab?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Morton J. Kern
Journal: Journal of the American College of Cardiology (2012)
The Molecular Determinants of Thermoadaptation:<i>Methanococcales</i>as a Case Study
Authors: Michel Lecocq, Mathieu Groussin, Manolo Gouy, Céline Brochier-Armanet
Journal: Molecular Biology and Evolution (2020)

Previous reports have shown that environmental temperature impacts proteome evolution in Bacteria and Archaea. However, it is unknown whether thermoadaptation mainly occurs via the sequential accumulation of substitutions, massive horizontal gene transfers, or both. Measuring the real contribution of amino acid substitution to thermoadaptation is challenging, because of confounding environmental and genetic factors (e.g., pH, salinity, genomic G + C content) that also affect proteome evolution. Here, using Methanococcales, a major archaeal lineage, as a study model, we show that optimal growth temperature is the major factor affecting variations in amino acid frequencies of proteomes. By combining phylogenomic and ancestral sequence reconstruction approaches, we disclose a sequential substitutional scheme in which lysine plays a central role by fine tuning the pool of arginine, serine, threonine, glutamine, and asparagine, whose frequencies are strongly correlated with optimal growth temperature. Finally, we show that colonization to new thermal niches is not associated with high amounts of horizontal gene transfers. Altogether, although the acquisition of a few key proteins through horizontal gene transfer may have favored thermoadaptation in Methanococcales, our findings support sequential amino acid substitutions as the main factor driving thermoadaptation.
16007 Ixekizumab demonstrated longer medication persistence than other biologics in the treatment of psoriasis patients: Results from IBM MarketScan databases
Authors: Andrew Blauvelt, Craig L. Leonardi, Mark Lebwohl, Baojin Zhu, William Malatestinic, Joe Eastman Eastman, Jiaying Guo, David Shrom, Mwangi J. Murage, Russel Burge
Journal: Journal of the American Academy of Dermatology (2020)
Preliminary study on modelling, fabrication by photo-chemical etching and in vivo testing of biodegradable magnesium AZ31 stents
Authors: Bala Subramanya Pavan Kumar Kandala, Guangqi Zhang, Capucine LCorriveau, Mark Paquin, Madeleine Chagnon, Dana Begun, Vesselin Shanov
Journal: Bioactive Materials (2020)

Magnesium metal (Mg) is a promising material for stent applications due to its biocompatibility and ability to be resorbed by the body. Manufacturing of stents by laser cutting has become an industry standard. Our alternative approach uses photo-chemical etching to transfer a pattern of the stent onto a Mg sheet. In this study, we present three stages of creating and validating a stent prototype, which includes design and simulation using finite element analysis (FEA), followed by fabrication based on AZ31 alloy and, finally, in vivo testing in peripheral arteries of domestic pigs. Due to the preliminary character of this study, only six stents were implanted in two domestic farm pigs weighing 25–28 kg and they were evaluated after 28 days, with an interim follow-up on day 14. The left and right superficial femoral, the left iliac, and the right renal artery were selected for this study. The diameters of the stented artery segments were evaluated at the time of implantation, on day 14 and then, finally, on day 28, by quantitative vessel analysis (QVA) using fluoroscopic imaging. Optical Coherence Tomography (OCT) imaging displayed some malposition, breaks, stacking, and protrusion into the lumen at the proximal, distal, and mid-sections of the stented arteries. The stents degraded with time, but simultaneously became embedded in the intima. After 28 days, the animals were euthanized, and explanted vessels were fixed for micro-CT imaging and histology studies. Micro-CT imaging revealed stent morphological and volumetric changes due to the in-body degradation. An in vivo corrosion rate of 0.75 mm/year was obtained by the CT evaluation. The histology suggested no-life threatening effects, although moderate injury, inflammation, and endothelialization scores were observed.
Compassionate use of delamanid in adults and children for drug-resistant tuberculosis: 5-year update
Authors: Sambuddha Ghosh, Lusine Breitscheidel, Natasa Lazarevic, Alexandra Martin, Jeffrey Hafkin, Norbert Hittel
Journal: European Respiratory Journal (2020)

Background Although delamanid has been approved for the treatment of multidrug-resistant TB (MDR-TB) in numerous regions, in areas where it is not yet registered it can be accessed as part of salvage therapy (in particular for those patients with limited treatment options) via the Otsuka compassionate use programme. Here we present the analysis of interim treatment outcomes by 24 weeks of more than 200 MDR-TB patients globally who received delamanid under this programme. Methods We evaluated treatment efficacy with respect to culture negativity at 24 weeks, as well as the safety profile of delamanid, in an MDR-TB patient cohort treated under compassionate use between 2014 and 2019. Results Among patients who received delamanid as part of a multidrug regimen, 123 (61%) out of 202 had extensively drug-resistant TB (XDR-TB), 66 (33%) out of 202 had HIV co-infection and 34 (17%) out of 202 were children aged between 6 and 17 years. Of those patients who were culture positive at delamanid treatment initiation and who completed 24 weeks of delamanid treatment in combination with other anti-tuberculosis (TB) drugs, culture negativity was achieved in 116 (79%) out of 147 cases. The corresponding rates of culture negativity for patients with XDR-TB and HIV co-infection, as well as the paediatric subgroup were 69 (77%) out of 90, 44 (92%) out of 48 and 20 (80%) out of 25, respectively. QT interval prolongation was the most frequently observed serious adverse event and was reported in 8% of patients receiving delamanid. Overall, treatment safety outcomes did not reveal any new or unidentified risks. Conclusions The use of delamanid combined with other active drugs has the potential to achieve high rates of culture negativity in difficult-to-treat drug-resistant TB cases, with a favourable safety profile.