tbuckley/cabot-search huggingface dataset:
Synergistic antitumor efficacy and altered gene expression signature in breast cancer cells treated with immunotoxins and cyclosporin A
Authors: O. Fodstad, Y. Xi, K. Risberg, J. Ju, Y. G. Anderson
Journal: Journal of Clinical Oncology (2007)

13505 Background: Immunotoxins (ITs) has shown limited clinical success related to liver toxicity and development of anti-IT antibodies. To delay the immune response we tested combinations of ITs and the Cyclosporin A (CsA). we have shown that one IT, currently in a phase I/II clinical trial, acts by inducing apoptosis and protein synthesis inhibition, but gene expression analysis of IT treated cells has never been reported. Hence, we also studied changes in gene expression induced by ITs alone and the effects of adding (CsA) on both treatment efficacy and gene expression signature. Methods: Human MA-11 breast cancer cells were treated in vitro with antiEGFR- and antiEPCAM-based ITs alone and in combinations with CsA. Therapeutic efficay was assessed by MTS cell viability assay. Total RNA from untreated and treated cells was isolated and CodeLink Uniset Human 20 k Oligo Bioarray (GE Healthcare, Amersham Biosciences, NJ), containing approximately 20,289 gene probes, was used to generate gene expression profiles. Gene expression analysis was carried out using GeneSpring software version 7.2 using One-way ANOVA with p&lt;0.05. Comparisons of gene list across different groups were performed using Venn Diagrams. Results: Combination therapy produced remarkable synergistic effects in MA-11 cells in vitro and in metastasis models in vivo. Moreover, in conventional rats receiving repeated injections of ITs and CsA the formation of anti-IT antibodies was virtually abrogated. Changes in gene expression profiles induced by the ITs alone and in combination with CsA were evaluated to elucidate the underlying molecular mechanisms for the synergistic effects. The ITs each induced specific changes in expression of some apoptosis-related genes but also fogenes in pathways unrelated to apoptosis and protein synthesis. The addition of CsA induced up- or down-regulation of a number of interesting non-immune-associated genes Conclusions: Important shortcomings for successful clinical use of ITs may be overcome by combination therapy with CsA. The possibility for further improvement is provided by results of gene profiling studies identifying therapy-induced genes belonging to different cell signaling pathways. No significant financial relationships to disclose.
Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up
Authors: Panagiotis Baliakas, Bianca Tesi, Ulla Wartiovaara-Kautto, Asbjørg Stray-Pedersen, Lone Smidstrup Friis, Ingunn Dybedal, Randi Hovland, Kirsi Jahnukainen, Klas Raaschou-Jensen, Per Ljungman, Cecilie F. Rustad, Charlotte K. Lautrup, Outi Kilpivaara, Astrid Olsnes Kittang, Kirsten Grønbæk, Jörg Cammenga, Eva Hellström-Lindberg, Mette K. Andersen
Journal: HemaSphere (2019)

Abstract Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.
Impact of the Oncology Care Model (OCM) on pain management: A retrospective cohort analysis.
Authors: Aaron Ciner, Jacqueline Norrell, Renee Kurz, Ann W. Silk
Journal: Journal of Clinical Oncology (2019)

86 Background: Pain is a common symptom among patients with cancer and impacts performance status and quality of life. The OCM was implemented at Rutgers Cancer Institute of New Jersey (RCINJ) in July 2016 with the goal of improving many quality metrics in cancer care including documentation of pain and a plan of care for pain. Hypothesis: Documentation of pain and a plan of care for pain improved after implementation of the OCM at RCINJ. Improved documentation would correlate with a decrease in reported quantitative pain scores. Methods: Data from patients enrolled in OCM during its first year of implementation (post OCM) was compared to data from a control cohort the preceding year (pre OCM). The initial progress note and EMR flowsheet in each year were reviewed to determine pain documentation. For patients reporting a pain score ≥ 1 on a 0-10 scale, the association between documentation of a plan of care and improvement in quantitative pain score on a subsequent visit was analyzed using Chi square testing. Results: A total of 260 patient charts were analyzed. A quantitative pain score was documented in 99% of patients in the pre OCM group and 100% in the post OCM group. For those with a pain score ≥ 1, documentation of a plan of care increased from 43% to 55% after OCM implementation. Patients whose charts contained documented plans of care for pain were less likely to have decreased pain scores at a subsequent visit (51% vs 76%). Conclusions: (1) Documentation of a quantitative pain score was completed in nearly all patients before and after the implementation of OCM. (2) There was a non-statistically significant increase in documentation of plan of care for pain after OCM implementation. (3) Documentation of a plan of care was not associated with a decreased pain score at a subsequent visit. This may be the result of small sample size or related to progressive cancer-related pain or inadequate pain intervention. [Table: see text]
Clinical Implications of TP53 Mutations and p53 Dysfunction in Patients with Myelodysplastic Syndrome (MDS). a Study from the Italian MDS Clinical Network
Authors: Marianna Rossi, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Laura Giordano, Marta Ubezio, Erica Travaglino, Lucio Morabito, Chiara Milanesi, Elena Saba, Lorenza Borin, Massimo Bernardi, Valeria Santini, Maria Teresa Voso, Susanna Fenu, Attilio Orazi, Armando Santoro, Andrea Bacigalupo, Alessandro Rambaldi, Matteo Giovanni Della Porta
Journal: Blood (2017)
Event-Free Survival As a Surrogate for Overall Survival in Relapsed DLBCL after Autologous Transplant: A Subgroup Analysis of LY.12 and Coral
Authors: Sarit Assouline, Shen Li, Christian Gisselbrecht, Patrick Fogarty, Annette E. Hay, Eric Van Den Neste, Lois E. Shepherd, Norbert Schmitz, Tara Baetz, Armand Keating, Sue Robinson, Matthew D. Seftel, Caterina Stelitano, Marina S. Djurfeldt, Ralph Meyer, Bingshu E. Chen, Michael Crump
Journal: Blood (2019)
Distinct molecular profile of IRF4-rearranged large B-cell lymphoma
Authors: Joan Enric Ramis-Zaldivar, Blanca Gonzalez-Farré, Olga Balagué, Verónica Celis, Ferran Nadeu, Julia Salmerón-Villalobos, Mara Andrés, Idoia Martin-Guerrero, Marta Garrido-Pontnou, Ayman Gaafar, Mariona Suñol, Carmen Bárcena, Federico Garcia-Bragado, Maitane Andión, Daniel Azorín, Itziar Astigarraga, Maria Sagaseta de Ilurdoz, Constantino Sábado, Soledad Gallego, Jaime Verdú-Amorós, Rafael Fernandez-Delgado, Vanesa Perez, Gustavo Tapia, Anna Mozos, Montserrat Torrent, Palma Solano-Páez, Alfredo Rivas-Delgado, Ivan Dlouhy, Guillem Clot, Anna Enjuanes, Armando López-Guillermo, Pallavi Galera, Matthew J. Oberley, Alanna Maguire, Colleen Ramsower, Lisa M. Rimsza, Leticia Quintanilla-Martinez, Elaine S. Jaffe, Elías Campo, Itziar Salaverria
Journal: Blood (2019)
Macrophage‐derived progranulin promotes allergen‐induced airway inflammation
Authors: Jun‐Pyo Choi, So Young Park, Keun‐Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk‐Soo Kwon, Tae‐Bum Kim, Hae‐Sim Park, Hee‐Bom Moon, Woo‐Jung Song, You Sook Cho
Journal: Allergy (2019)

Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, and we investigated the role of PGRN in allergic airway inflammation.Production of PGRN and various type 2 cytokines was evaluated in mouse airways exposed to house dust mite allergen, and main cellular sources of these molecules were investigated using macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage-derived PGRN-deficient mice and NKT cell knockout mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation.PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN-induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRN-deficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period.The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
Olaparib maintenance therapy in patients (pts) with a BRCA1 and/or BRCA2 mutation (BRCAm) and newly diagnosed advanced ovarian cancer (OC): SOLO1 China cohort
Authors: L. Wu, J. Zhu, R. Yin, X. Wu, G. Lou, J. Wang, Y. Gao, B. Kong, X. Lu, Q. Zhou, Y. Wang, Y. Chen, W. Lu, W. Li, Y. Cheng, J. Liu, X. Ma, J. Zhang
Journal: Annals of Oncology (2019)
Acute care and hydration due to chemotherapy-induced nausea and vomiting (CINV) among patients receiving NEPA prophylaxis for anthracycline + cyclophosphamide (AC).
Authors: Eric Roeland, Rudolph M. Navari, Kathryn Jean Ruddy, Thomas William LeBlanc, Rebecca Anne Clark-Snow, Rita S. Wickham, Gary Binder, William L. Bailey, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2019)

112 Background: In the US, the CMS OP-35 oncology outcome measure deems 30-day post-chemotherapy acute care involving nausea and emesis (NV) or 8 other toxicities as avoidable, with studies showing 15% of &gt; 2500 patients receiving anthracycline + cyclophosphamide (AC)-based chemotherapy had avoidable acute care, of which 32% involved NV. Our aim was to evaluate resource use (emergency department [ED] visits, inpatient admissions [IP], or hydration) in a prospective trial of women with breast cancer who received combination netupitant/palonosetron (NEPA) + dexamethasone (DEX) for CINV prophylaxis for AC-based chemotherapy. Methods: Women initiating AC received oral or IV NEPA + DEX. Pre-specified endpoints included safety, complete response, acute care (ED/IP), unplanned IV hydrations (as determined by investigator), days of CINV, and ≥3 days of CINV. We defined CINV as emesis or rescue drug use up to 5 days after AC, and defined concomitant ED/IP or hydrations in the same period as CINV-related. We limited our analysis to the first 2 cycles, the median duration in the NEPA study. Results: 402 patients received ≥1 cycle of AC and 391 completed 2 cycles. Nine patients had IP (none CINV-related), and 5 patients had a total of 6 ED visits (1 CINV-related). Three patients had a CINV-related unplanned hydration. Patients had ≥1 day of CINV in 172 of 793 cycles (21.7%); of these, the majority had symptom duration for 1-2 days, while 78 (9.8%) had ≥3 days of CINV in a cycle. Conclusions: In this prospective CINV prophylaxis study in women receiving AC chemotherapy, &lt; 1% of women receiving NEPA + DEX required acute care for CINV and &lt; 1% required unplanned hydrations for CINV. These rates are below previously reported CINV-related acute care rates for AC suggesting NEPA may help avoid CINV-related acute care. Clinical trial information: NCT03403712.
An Anti-Opioid System, Courtesy of a Worm Model
Authors: Brigitte L. Kieffer
Journal: New England Journal of Medicine (2019)

A forward genetic screen using the worm Caenorhabditis elegans implicated the G protein–coupled receptor 139 in suppressing signaling by the mu opioid receptor. Further experiments in mouse models suggest that antagonizing this receptor could enhance the analgesic efficacy of medicinal opioids.
Suppression of angiogenesis and tumor growth by selective inhibition of Angiopoietin-2
Authors: Jonathan D. Oliner, Hosung Min, Juan Leal, Dongyin Yu, Shashirekha Rao, Edward You, Xiu Tang, Haejin Kim, Susanne Meyer, Seong Joon Han, Nessa Hawkins, Robert Rosenfeld, Elyse Davy, Kevin C. Graham, Frederick Jacobsen, Shirley Steavenson, Joanne Ho, Qing Chen, Thomas Hartmann, Mark Michaels, Michael Kelley, Luke Li, Karen Sitney, Frank Martin, Ji-Rong Sun
Journal: Cancer Research (2005)

4662  In the classical pathway of Nuclear Factor-kappa B (NF-κB) activation, NF-κB subunits are sequestered in the cytoplasm by the Inhibitor of Kappa B (IKB) and released to the nucleus when IKB is phosphorylated by the Inhibitor of Kappa B kinase (IKK) complex. The IKK complex consists of the regulatory IKKγ subunit, along with a dimer of IKKα subunits, IKKβ subunits, or both an IKKα and IKKβ subunit. In this study, our lab showed that IKKα specific induction of NF-κB translocation to the nucleus promoted a pro-angiogenic phenotype in endothelial cells (ECs) in vitro and in vivo through the classical NF-κB signaling pathway. IKKα expression, but not IKKβ expression, increased cell motility and tube formation in endothelial cells (ECs). This pro-angiogenic phenotype could be blocked with the co-expression of IKB, demonstrating that IKKα induction of NF-κB translocation was through the classical pathway. We also found that IKKα activation had a pro-angiogenic effect in vivo. We subcutaneously injected Rag-1 mice with matrigel containing Lewis Lung Carcinoma (LLC) cells alone or LLC cells mixed with either IKKα-expressing or GFP-expressing ECs. Tumor size was measured daily, and tissue was harvested for analysis. We found that LLC cells mixed with IKKα-expressing ECs formed palpable tumors earlier than control tumors and tumors containing IKKα-expressing ECs initially grew much larger than controls. The vascular density was significantly higher, and there were fewer hypoxic regions in tumors containing IKKα-expressing ECs than in control tumors. Tumor cell growth was significantly higher and apoptosis was significantly lower in these tumors compared to control tumors. The data demonstrates that IKKα activation in ECs plays an important role in tumor angiogenesis. IKKα-expressing ECs induced a pro-angiogenic phenotype in ECs in vitro and increased the levels of tumor angiogenesis as demonstrated by an increase vascular density in tumor tissue. The increase in tumor angiogenesis promoted cell growth and lowered the levels of apoptosis in tumor tissue. Thus the expression and activation of IKKα provide potential new targets for anti-angiogenic cancer therapies.
Effect of Cognitive Aids on Adherence to Best Practice in the Treatment of Deteriorating Surgical Patients
Authors: Lena Koers, Maartje van Haperen, Clemens G. F. Meijer, Suzanne B. E. van Wandelen, Elbert Waller, Dave Dongelmans, Marja A. Boermeester, Jeroen Hermanides, Benedikt Preckel
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Failure to rescue causes significant morbidity and mortality in the surgical population. Human error is often the underlying cause of failure to rescue. Human error can be reduced by the use of cognitive aids. <h3>Objectives</h3> To test the effectiveness of cognitive aids on adherence to best practice in the management of deteriorating postoperative surgical ward patients. <h3>Design, Setting, and Participants</h3> Randomized clinical trial in a simulation setting. Surgical teams consisted of 1 surgeon and 2 nurses from a surgical ward from 4 different hospitals in Amsterdam, the Netherlands. Data were analyzed between February 2, 2017, and December 18, 2018. <h3>Interventions</h3> The teams were randomized to manage 3 simulated deteriorating patient scenarios with or without the use of cognitive aids. <h3>Main Outcomes and Measures</h3> The primary outcome of the study was failure to adhere to best practice, expressed as the percentage of omitted critical management steps. The secondary outcome of the study was the perceived usability of the cognitive aids. <h3>Results</h3> Of the total participants, 93 were women and 51 were men. Twenty-five surgical teams performed 75 patient scenarios with cognitive aids, and 25 teams performed 75 patient scenarios without cognitive aids. Using the cognitive aids resulted in a reduction of omitted critical management steps from 33% to 10%, which is a 70% (<i>P</i> &lt; .001) reduction. This effect remained significant (odds ratio, 0.63; 95% CI, −0.228 to −0.061;<i>P</i> = .001) in a multivariate analysis. Overall usability (scale of 0-10) of the cognitive aids was scored at a median of 8.7 (interquartile range, 8-9). <h3>Conclusions and Relevance</h3> Failure to comply with best practice management of postoperative complications is associated with worse outcomes. In this simulation study, adherence to best practice in the management of postoperative complications improves significantly by the use of cognitive aids. Cognitive aids for deteriorating surgical patients therefore have the potential to reduce failure to rescue and improve patient outcome. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT03812861
Doctors criticise Indian government’s advice to delay oxytocin at childbirth
Authors: Ganapati Mudur
Journal: BMJ (2019)

Doctors and maternal health experts have questioned the scientific rationale and ethics of an Indian health ministry announcement that calls on obstetric staff to delay giving oxytocin to women after childbirth until the uterus has expelled the placenta.

The experts have emphasised that the advice deviates from World Health Organization guidelines practised worldwide, including in India. These recommend that oxytocin should be administered within a minute of birth to lower the risk of postpartum haemorrhage.

The health ministry included its suggestion on oxytocin in an advisory notice sent to health officials throughout India on 6 November, primarily recommending delayed cord clamping, a practice widely accepted to be beneficial to newborns.

“Prophylactic oxytocin should not be administered immediately after birth . . . but only after the delivery of placenta,” it said, citing two …
Drug shortages are fuelling patient complaints, doctors warn
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Worsening drug shortages are prompting frustrated patients to file complaints against their GPs, doctors have told The BMJ .

Warnings over medicine supplies have intensified in recent months, with reports of unprecedented shortages of drugs such as hormone replacement therapy, antihypertensives, and antidepressants. Last month the government introduced serious shortage protocols for the antidepressant fluoxetine, to allow pharmacists to supply an alternative strength or form of the drug because of shortages.1 Brexit is not viewed as the cause of what is a longstanding issue, but it is thought to be exacerbating the problem.23

Sally Johnston, a GP in Hampshire and chair of Hampshire and Isle of Wight Local Medical Committee, told The BMJ that she …
Longitudinal Assessment of Circulating Tumor Mutational Burden Using a Next-Generation Sequencing Cancer Gene Panel: A Potential Biomarker of Response to Programmed Cell Death 1 (PD-1) Blockade in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma
Authors: Martina Di Trani, Ettore Rizzo, Silvia Locatelli, Fabrizio Marino, Vanessa Cristaldi, Valeria Spina, Alessio Bruscaggin, Federica De Paoli, Giuseppa Careddu, Marcello Rodari, Margarita Kirienko, Eleonora Calabretta, Massimo Magagnoli, Lucia Morello, Francesca Ricci, Arturo Chiti, Armando Santoro, Stefan Hohaus, Davide Rossi, Carmelo Carlo-Stella
Journal: Blood (2019)
Re: Vincent Misrai, Enrique Rijo, Kevin C. Zorn, Nicolas Barry-Delongchamps, Aurelien Descazeaud. Waterjet Ablation Therapy for Treating Benign Prostatic Obstruction in Patients with Small- to Medium-size Glands: 12-month Results of the First French Aquablation Clinical Registry. Eur Urol 2019;76:667–75
Authors: Sheng Hu, Xiaobo Zhang, Xiong Chen, Dongjie Li
Journal: European Urology (2019)
PATTERNS OF ALCOHOL USE AFTER EARLY LIVER TRANSPLANTATION (LT) FOR ALCOHOLIC HEPATITIS (AH): IMPLICATIONS FOR SELECTION AND MONITORING
Authors: Gene Y. Im, Brian Lee, Ann Lazar, Michael R. Lucey, Ethan M. Weinberg, Hyosun Helen Han, Haripriya Maddur, R. M. Ghobrial, George Therapondos, Christine Hsu, Oren K. Fix, Sheila L. Eswaran, Kirti Shetty, Neha R. Jakhete, David W. Victor, David P. Foley, Neil Mehta, Lisanne Dinges, Mary E. Rinella, Thomas D. Schiano, Sander S. Florman, Constance Mobley, Norah Terrault, John P. Rice
Journal: Hepatology (2019)
Genetic Landscapes Reveal How Human Genetic Diversity Aligns with Geography
Authors: Benjamin M Peter, Desislava Petkova, John Novembre
Journal: Molecular Biology and Evolution (2019)

Abstract Geographic patterns in human genetic diversity carry footprints of population history and provide insights for genetic medicine and its application across human populations. Summarizing and visually representing these patterns of diversity has been a persistent goal for human geneticists, and has revealed that genetic differentiation is frequently correlated with geographic distance. However, most analytical methods to represent population structure do not incorporate geography directly, and it must be considered post hoc alongside a visual summary of the genetic structure. Here, we estimate “effective migration” surfaces to visualize how human genetic diversity is geographically structured. The results reveal local patterns of differentiation in detail and emphasize that while genetic similarity generally decays with geographic distance, the relationship is often subtly distorted. Overall, the visualizations provide a new perspective on genetics and geography in humans and insight to the geographic distribution of human genetic variation.
Allergen‐specific immunotherapy boosts allergen‐specific IgD production in house dust mite‐sensitized asthmatic patients
Authors: Tadech Boonpiyathad, Panitan Pradubpongsa, Wat Mitthamsiri, Pattraporn Satitsuksanoa, Alain Jacquet, Atik Sangasapaviliya
Journal: Allergy (2019)

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