tbuckley/cabot-search huggingface dataset:
A comparative study on basophil activation test, histamine release assay, and passive sensitization histamine release assay in the diagnosis of peanut allergy
Authors: L. F. Larsen, N. Juel‐Berg, K. S. Hansen, E. N. Clare Mills, R. van Ree, L. K. Poulsen, B. M. Jensen
Journal: Allergy (2017)

Abstract Background Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test ( BAT ), histamine release assay ( HR ), and passive sensitization histamine release assay (passive HR ) in the diagnosis of peanut allergy. Methods BAT , HR , and passive HR were performed on 11 peanut‐allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti‐IgE and tests were performed as follows: BAT — CD 63 upregulation was assessed by flow cytometry; HR —released histamine was quantified by a glass fiber‐based fluorometric method; passive HR —IgE‐stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR . Results CD sens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT , HR , and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). Conclusion BAT displayed a significantly higher CD sens compared to HR and passive HR . The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR .
Bortezomib Based Induction Is Superior to Thalidomide Based Induction in Reducing Early Relapses Following Upfront HDM: an Analysis By the Asian Myeloma Working Group
Authors: Sathish Kumar Gopalakrishnan, Shin-Yeu Ong, Seok Jin Kim, Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Yunxin Chen, Sanjay De Mel, Melissa G. Ooi, Shilpa Surendran, Adeline Lin, Daryl Tan, Brian G M Durie, Wee Joo Chng, Kihyun Kim
Journal: Blood (2016)
Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin
Authors: Elizabeth Sapey, Jaimin M. Patel, Hannah L. Greenwood, Georgia M. Walton, Jon Hazeldine, Charendeep Sadhra, Dhruv Parekh, Rachel C. A. Dancer, Peter Nightingale, Janet M. Lord, David R. Thickett
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro.Objectives: To assess neutrophil migratory accuracy with age during respiratory infections and determine if and how a statin intervention could alter these blunted responses.Methods: The migratory accuracy of blood neutrophils from young (aged <35 yr) and old (aged >60 yr) patients in health and during a lower respiratory tract infection, community-acquired pneumonia, and pneumonia associated with sepsis was assessed with and without simvastatin. In vitro results were confirmed in a double-blind randomized clinical trial in healthy elders. Cell adhesion markers were assessed.Measurements and Main Results: In vitro neutrophil migratory accuracy in the elderly deteriorated as the severity of the infectious pulmonary insult increased, without recovery at 6 weeks. Simvastatin rescued neutrophil migration with age and during mild to moderate infection, at high dose in older adults, but not during more severe sepsis. Confirming in vitro results, high-dose (80-mg) simvastatin improved neutrophil migratory accuracy without impeding other neutrophil functions in a double-blind randomized clinical trial in healthy elders. Simvastatin modified surface adhesion molecule expression and activity, facilitating accurate migration in the elderly.Conclusions: Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events, but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections.Clinical trial registered with www.clinicaltrialsregister.eu (2011-002082-38).
Abstract 257: Berbamine Postconditioning Protects the Heart From Ischemia/Reperfusion Injury Through the Regulation of Autophagy During Reperfusion
Authors: Yanjun Zheng, Xuxia Li, Jinxi Wang, Jiliang Tan, Caimei Zhang, Huangtian Yang
Journal: Circulation Research (2015)

Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern society. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to additional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine, a nature compound of bisbenzylisochinoline alkaloids from Barberry, protects the heart from ischemia/reperfusion (I/R) injury when given before I/R, but it is unknown whether it has cardioprotective effects when given at the onset of reperfusion (postconditioning, PoC), a protocol with more clinical impact. Therefore, the present study was designed to determine whether berbamine PoC (BMPoC) is able to protect the heart from reperfusion injury by using perfused I/R rat hearts and simulated I/R cardiomyocytes. We found that BMPoC added during the first 5-min of reperfusion concentration-dependently improved post-ischemic myocardial function and limited infarcted area. A similar protection was observed in isolated rat cardiomyocytes characterized by the attenuation of I/R-induced depression of cell contraction and loss of mitochondrial membrane potential. Moreover, autophagy (an intracellular bulk degradation process for proteins and organelles) was significantly stimulated by myocardial I/R, but it was suppressed by BMPoC. Next, we examined how berbamine regulates autophagy and found that BMPoC inhibited the expression of beclin 1, a critical regulator for autophagosome initiation. Then, adenoviral overexpression and knockdown of beclin 1 in ventricles conformed its roles in the BMPoC-mediated cardioprotection. Further, Western blot analysis revealed that BMPoC-suppressed beclin 1 expression was mediated via the activation of PI3K/Akt signaling pathway. Our results suggest that BMPoC confers cardioprotection against I/R injury at least in part by the inhibition of beclin1-dependent autophagy through the activation of PI3K/Akt signaling pathway. These findings reveal new roles and mechanisms of berbamine in the cardioprotection against I/R injury.
Efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma analyzed by patient age: A sub-analysis of the CheckMate 040 study
Authors: Ignacio Melero, Anthony El-Khoueiry, Thomas Yau, Chiun Hsu, Masatoshi Kudo, Todd Crocenzi, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore Welling, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Adyb Baakili, Christine dela Cruz, Huanyu Zhao, Bruno Sangro, Tim Meyer
Journal: Annals of Oncology (2017)
Abstract 13: Hippo Signaling Deletion During Heart Failure Reverses Functional Decline
Authors: John Leach, Todd Heallen, Min Zhang, Yuka Morikawa, James Martin
Journal: Circulation Research (2015)

The heart has long been thought of as a static organ incapable of repair. Recent findings have challenged this view of the heart, and have demonstrated that mature cardiomyocytes are capable of re-entering the cell-cycle. However, there is still paucity in understanding endogenous mechanisms preventing cardiomyocyte self-renewal. Our approach is to apply developmental mechanisms of cardiomyocyte cell-cycle control to the damaged heart by altering the Hippo signaling pathway. During development Hippo signaling regulates intrinsic organ size. The core mammalian Hippo pathway includes the Ste20-like serine/threonine kinases Mst1 and Mst2, homologous to the Drosophila Hippo kinase. A subsequent kinase cascade leads to the phosphorylation of the transcription factor Yap. Phosphorylated Yap is sequestered in the cytoplasm, thus preventing transcriptional activity. We previously demonstrated Hippo signaling controls cardiomyocyte proliferation during development to restrain heart size. Additionally, using both the Apex resection (AR) and LAD-ligation (MI) models of cardiac damage, in a Hippo signaling deletion mouse, we demonstrated cardiac regeneration. Indicated by preserved cardiac function and reduced fibrotic scar formation. Additionally, these hearts display cardiomyocyte proliferation as marked by EDU incorporation, pHH3, AurkB, and Ki67 staining. We are taking a new approach to determine the effect of Hippo signaling deletion on the failing heart, by inducing Hippo deletion after fibrotic scar formation has already occurred. To Thus far our results indicate functional recovery of the failing heart only after inducible deletion of Hippo signaling. Consistent with our previous data, preliminary results indicate adult cardiomyocytes after Hippo deletion re-enter the cell cycle. By altering Hippo signaling during heart failure and subsequently inducing cardiomyocyte proliferation we have established recovery of cardiac function. These results will greatly advance strategies to induce cardiac repair.
The false dichotomy of domain-specific versus domain-general cognition
Authors: Ivo Jacobs, Peter Gärdenfors
Journal: Behavioral and Brain Sciences (2017)

Abstract The qualitative division between domain-general and domain-specific cognition is unsubstantiated. The distinction is instead better viewed as opposites on a gradual scale, which has more explanatory power and fits current empirical evidence better. We also argue that causal cognition may be more general than social learning, which it often involves.
Tobacco link with insurance
Authors: C. Siderfin, J. Winn
Journal: BMJ (1998)

Editor—As a general practitioner and a member of the Labour party, I was disappointed by the British government’s controversial plans to exempt Formula One motor racing from the proposed tobacco advertising ban.1 I am, however, heartened by the robust stance of the BMJ and BMA in their continued campaign to reduce the influence of the tobacco companies.2,3

I was thus surprised to discover, through an article in the magazine GP,4 that I was being actively encouraged by BMA Services to invest in a company (Allied Dunbar) entirely owned by the tobacco giant BAT Industries. Fortunately, I learnt of this connection before taking out a life insurance policy with the company. 

BMA Services provides independent financial advice to members of the BMA and their families. All financial products are vetted by BMA Services, and policies are recommended to their clients from a shortlist of financial institutions, the “best advice panel,” which is reviewed every six months. Allied Dunbar and Zurich Life are two companies on the panel. BAT Industries have owned Allied Dunbar since the mid-1980s and it is considering a merger with Zurich Life.4 BMA Services is jointly owned by the BMA and Jardine Insurance Brokers, each of which receives 50% of the profits. It would therefore seem that it is not only the Labour party that has benefited from tobacco industry money. 

In this day of ethical investment, representatives of BMA Services should at the very least have a duty to disclose all important ethical or material facts about the companies they are advising their clients to invest in. A proverb states: “He who lives in a glass house should not throw stones.” Perhaps the BMA should consider whether Allied Dunbar (and Zurich Life if the proposed merger goes ahead) should remain on the list of companies recommended by BMA Services.
Risk of subsequent breast cancer after radiotherapy according to hormone-receptor status: A nested case-control study in the Childhood Cancer Survivor Study (CCSS).
Authors: Lindsay M. Morton, Lene Veiga, Rochelle E. Curtis, Diana Withrow, Peter Inskip, Kevin C. Oeffinger, Chaya S. Moskowitz, Joseph Neglia, Lucie Marie Turcotte, Rebecca M. Howell, Rita Weathers, Susan A Smith, Tara O. Henderson, Wendy M. Leisenring, John Whitton, Todd M. Gibson, Leslie L. Robison, Gregory T. Armstrong, Amy Berrington De Gonzalez
Journal: Journal of Clinical Oncology (2017)

10520 Background: Survivors of childhood cancer have a high absolute risk of subsequent breast cancer after chest-directed radiotherapy; however, it is not known if this risk differs by hormone-receptor status and radiation to the ovaries. Methods: We conducted a nested case-control study within the CCSS of 282 five-year survivors of childhood cancer with subsequent breast cancer and 1202 matched controls. Radiation dose to the location of the breast tumor (or corresponding location for controls) and mean dose to the ovaries were estimated from treatment records for each patient. Risk of radiation-related breast cancer was measured with the Excess Odds Ratio per Gray (EOR/Gy) and corresponding 95% confidence interval (CI), derived from conditional logistic regression. Results: The median age at subsequent breast cancer diagnosis was 39 years (range 21-58). Although 87% of cases and 70% of controls received radiotherapy, breast doses were higher in cases than controls (61% vs 24% breast dose &gt; 10Gy), whereas ovarian doses were lower (7% vs 13% ovary dose &gt; 5Gy). In the subset of cases (n = 159) with currently available estrogen receptor (ER) status (76% cases ER+, 24% cases ER-), there was a linear dose-response relation with radiation dose to the breast that was similar for ER+ (EOR/Gy = 0.51; 95%CI: 0.19-1.34) and ER- breast tumors (EOR/Gy = 0.41; 95%CI: 0.05-2.88). If the patient received an ovarian dose &gt; 5Gy, this dose-response was significantly reduced for ER+ tumors but not for ER- tumors. Conclusions: Preliminary analyses demonstrate that radiation exposure to the breast to treat childhood cancer results in an increased risk of both ER+ and ER- breast cancers. The novel finding that only the risk of ER+ breast cancer is lowered if the ovaries are also exposed is consistent with known differences by hormone receptor status in the biological mechanisms of breast carcinogenesis.
Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin-like function
Authors: Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J. Müller, Charles T. Esmon, Peter P. Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Journal: Blood (2017)
Single-cell sorting and recovery of pure tumor cell populations to enable molecular sequence analysis of tumor tissue specimens limited by size and or tumor content.
Authors: Valeria Sero, Claudio Forcato, Chiara Bolognesi, Genny Buson, Paola Tononi, Giulio Signorini, Francesca Fontana, Gianni Medoro, Nicolò Manaresi, Farideh Z. Bischoff
Journal: Journal of Clinical Oncology (2016)

e13003 Background: Often, the amount of tumor tissue needed for clinical determination of patient’ mutation status exceeds what is actually available. Macrodissected FFPE tumor specimens can be small, difficult to recover and/or remain compromised by low tumor content. Though the less invasive fine needle aspiration (FNA) procedure yields cells with good quality, tumor cell frequency is often also very low. We have previously reported the utility of the DEPArray in overcoming intracellular tumor heterogeneity, which limits downstream analysis. Here, we demonstrate 100% efficiency in recovering pure tumor cell populations from tumor-derived macrodissected FFPE and FNA using the DEPArray platform. Methods: FFPE macrodissected sections and FNA (n = 14) originating from prostate, breast, pancreatic and lung tumors were evaluated. Each was processed using a disassociation and staining procedure followed by DEPArray sorting based on cytokeratin (Ker), vimentin (Vim) and nuclear staining. The recovered cells were directly lysed in the collection tube prior to PCR-based target enrichment for next generation sequencing using Ion AmpliSeq CHPv2. Results: DEPArray analysis allowed identification of well separated cell populations, including tumor and stromal cells in all 14 samples analyzed. Among the macrodissected samples, the tumor cell content ranged from 4% to 54% (mean of 23%), demonstrating an unexpected low frequency of tumor cells after macrodissection. Among the FNA specimens analyzed, only 21% (4.3% to 42.7% range) of the total (mean of 6335) cells analyzed were of tumor origin. For subsequent NGS analysis, groups of pure tumor and stromal cells (mean 174 cells, range from 37 to 280) were recovered. Among the tumor cells isolated, we observed non-synonymous somatic variants and LOH events for different genes that could not be evaluated as well in matched-unsorted samples. Conclusions: DEPArray can be used to isolate pure tumor cells from heterogeneous patient samples limited in tumor content that were obtained through routine procedures such as macrodissected FFPE and FNA, making them now suitable for comprehensive downstream molecular analysis.
Abstract 353: Sunitinib Induces Endoplasmic Reticulum Stress in Cardiomyocytes
Authors: Meredith L Rees, Heinrich Taegtmeyer
Journal: Circulation Research (2012)

Introduction: Chemotherapy-induced cardiac toxicities are the main obstacle for effective treatment of cancer, particularly in patients with pre-existing heart disease. This often results in premature termination of cancer treatment. Prominent among these agents is sunitinib (Sutent), which causes cardiac dysfunction in nearly 20% of cancer patients. It has recently been suggested that cardiac microvascular dysfunction, particularly loss of pericyte coverage, underlies sunitinib-induced cardiac dysfunction. However the exact mechanisms of sunitinib-induced cardiotoxicites are still unknown. Results: Neonatal rat ventricular myocytes were treated with increasing concentrations (100nM-5uM) of sunitinib. Irrespective of the dose, there was a significant increase in markers of ER stress (Grp78, Grp 94, Erp72 and phospo/total-eIF2a) after 24 hours of treatment. The ER stress inducer thapsigargin was used as a positive control. Concordant with an increase in ER stress was the activation of mTOR in sunitinib (but not thapsigargin) treated NRVMs, suggesting a possible role of mTOR-mediated proteotoxicity in sunitinib-induced cardiac dysfunction. Protein synthesis, evaluated by 14 C-phenylalanine incorporation into proteins, was moderately elevated in cells treated with sunitinib. Conclusions: In addition to impairment of angiogenesis and pericyte loss, sunitinib induces mTOR activation and ER stress. We propose that the cardiac myocyte secretes paracrine factors that stabilize the cardiac microcirculation. This process is disrupted by sunitinib and ultimately leads to heart failure.
Accuracy of Referring Provider and Endoscopist Impressions of Colonoscopy Indication
Authors: Mariam Naveed, Meredith Clary, Chul Ahn, Nisa Kubiliun, Deepak Agrawal, Byron Cryer, Caitlin Murphy, Amit G. Singal
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Referring provider and endoscopist impressions of colonoscopy indication are used for clinical care, reimbursement, and quality reporting decisions; however, the accuracy of these impressions is unknown. This study assessed the sensitivity, specificity, positive and negative predictive value, and overall accuracy of methods to classify colonoscopy indication, including referring provider impression, endoscopist impression, and administrative algorithm compared with gold standard chart review. Methods: We randomly sampled 400 patients undergoing a colonoscopy at a Veterans Affairs health system between January 2010 and December 2010. Referring provider and endoscopist impressions of colonoscopy indication were compared with gold-standard chart review. Indications were classified into 4 mutually exclusive categories: diagnostic, surveillance, high-risk screening, or average-risk screening. Results: Of 400 colonoscopies, 26% were performed for average-risk screening, 7% for high-risk screening, 26% for surveillance, and 41% for diagnostic indications. Accuracy of referring provider and endoscopist impressions of colonoscopy indication were 87% and 84%, respectively, which were significantly higher than that of the administrative algorithm (45%; P<.001 for both). There was substantial agreement between endoscopist and referring provider impressions (κ=0.76). All 3 methods showed high sensitivity (>90%) for determining screening (vs nonscreening) indication, but specificity of the administrative algorithm was lower (40.3%) compared with referring provider (93.7%) and endoscopist (84.0%) impressions. Accuracy of endoscopist, but not referring provider, impression was lower in patients with a family history of colon cancer than in those without (65% vs 84%; P=.001). Conclusions: Referring provider and endoscopist impressions of colonoscopy indication are both accurate and may be useful data to incorporate into algorithms classifying colonoscopy indication.
Prediction of pathological response to neoadjuvant treatment in rectal cancer with a two-protein immunohistochemical score derived from stromal gene-profiling
Authors: S. Gonçalves-Ribeiro, R. Sanz-Pamplona, A. Vidal, X. Sanjuan, N. Guillen Díaz-Maroto, A. Soriano, J. Guardiola, N. Albert, M. Martínez-Villacampa, I. López, C. Santos, J. Serra-Musach, R. Salazar, G. Capellà, A. Villanueva, D.G. Molleví
Journal: Annals of Oncology (2017)
Multiple Endocrine Neoplasia and Hyperparathyroid-Jaw Tumor Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood
Authors: Jonathan D. Wasserman, Gail E. Tomlinson, Harriet Druker, Junne Kamihara, Wendy K. Kohlmann, Christian P. Kratz, Katherine L. Nathanson, Kristian W. Pajtler, Andreu Parareda, Surya P. Rednam, Lisa J. States, Anita Villani, Michael F. Walsh, Kristin Zelley, Joshua D. Schiffman
Journal: Clinical Cancer Research (2017)

Abstract Children and adolescents who present with neuroendocrine tumors are at extremely high likelihood of having an underlying germline predisposition for the multiple endocrine neoplasia (MEN) syndromes, including MEN1, MEN2A and MEN2B, MEN4, and hyperparathyroid-jaw tumor (HPT-JT) syndromes. Each of these autosomal dominant syndromes results from a specific germline mutation in unique genes: MEN1 is due to pathogenic MEN1 variants (11q13), MEN2A and MEN2B are due to pathogenic RET variants (10q11.21), MEN4 is due to pathogenic CDKN1B variants (12p13.1), and the HPT-JT syndrome is due to pathogenic CDC73 variants (1q25). Although each of these genetic syndromes share the presence of neuroendocrine tumors, each syndrome has a slightly different tumor spectrum with specific surveillance recommendations based upon tumor penetrance, including the age and location for which specific tumor types most commonly present. Although the recommended surveillance strategies for each syndrome contain similar approaches, important differences do exist among them. Therefore, it is important for caregivers of children and adolescents with these syndromes to become familiar with the unique diagnostic criteria for each syndrome, and also to be aware of the specific tumor screening and prophylactic surgery recommendations for each syndrome. Clin Cancer Res; 23(13); e123–e32. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.