tbuckley/cabot-search huggingface dataset:
Admissions for neutropenic fever in myelodysplastic syndromes (MDS).
Authors: Ambreen Fatima Ali, Aaron Thomas Gerds, Anjali S. Advani, Sudipto Mukherjee, Ronald M. Sobecks, Mikkael A. Sekeres, Betty Ky Hamilton, Babal Jha, Cameron Beau Hilton, Cassandra M. Kerr, Vera Adema, Madeline Waldron, Caitlin Siebenaller, Yasunobu Nagata, Jaroslaw P. Maciejewski, Aziz Nazha
Journal: Journal of Clinical Oncology (2019)

e18548 Background: MDS are associated with a risk of severe infections due to disease course, patient (pt) age, co-morbidities and treatment. While infection rates have been reported for MDS patients enrolled in clinical trials, the real-world incidence of infections that require hospitalization, and how disease related factors (e.g. genetic mutations) affect the likelihood of infection remain unclear. Methods: Clinical data for MDS pts (per 2016 WHO criteria) diagnosed between 1/2010-12/2016, and treated at the Cleveland Clinic were included. TET2 mutation data obtained by NGS (in the context of genomic panel) was also included. Results: Our dataset included 214 pts of median age 70 years (range 13-99), with 33%, 54%, and 12% having low, intermediate, and high risk MDS according to IPSS-R. Overall, 100 admissions for neutropenic fever were recorded with a median length of stay of 5 days per admission; 63 (29%) pts required at least one admission, and of these 9 (14%) pts required 3 or more (up to 6) admissions. Blood cultures were positive in 17 (27%) pts with common organisms including Staphylococcus (38%), Enterococcus (35%), and Pseudomonas (12%). Urine cultures were positive in 6 (10%) pts, with organisms including E. Coli (50%), Pseudomonas (17%) and Klebsiella (17%). Fungal work up was sent in 18 (29%) pts and was positive in 3 (17%) pts. 13 (21%) pts required ICU transfer, and of those 7 (51%) pts required vasopressor support, and 10 (77%) pts required mechanical ventilation. Median ICU length of stay was 3 days (range 1-26). 13 (21%) pts were discharged on IV antibiotics. Median OS for the entire cohort was 18 months (95% CI 7.9 – 34.7), and median OS for admitted patients was not significantly shorter at 48 or 65 months. The number of admissions for neutropenic fever, length of stay, IPSS-R risk category, TET2 mutation, and ICU transfer did not impact survival. Conclusions: The risk of admission for neutropenic fever was 29% with blood cultures positive in 27% of pts. TET2 mutation status and IPSS-R risk did not impact admission rate, length of stay or ICU transfer.
Successive Norovirus Outbreaks at an Event Center — Nebraska, October–November, 2017
Authors: Rebecca J. Free, Bryan F. Buss, Samir Koirala, Monica Ulses, Anna Carlson, Brianna Loeck, Tom Safranek
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In October 2017, the Nebraska Department of Health and Human Services (NDHHS) was notified by a local health department of a gastrointestinal illness outbreak among attendees of a wedding reception at facility A, an event center. Shortly thereafter, state and local public health officials began receiving reports of similar gastrointestinal illness among attendees of subsequent facility A events. An investigation was initiated to identify cases, establish the cause, assess possible transmission routes, and provide control recommendations. Overall, 159 cases consistent with norovirus infection (three confirmed and 156 probable) were identified among employees of facility A and attendees of nine facility A events during October 27-November 18, 2017. The investigation revealed a public vomiting episode at the facility on October 27 and at least one employee involved with preparing and serving food who returned to work <24 hours after symptom resolution, suggesting that a combination of contaminated environmental surfaces and infected food handlers likely sustained the outbreak. Recommendations regarding sanitation and excluding ill employees were communicated to facility A management. However, facility A performed minimal environmental cleaning and did not exclude ill employees. Consequently, transmission continued. To prevent persistent norovirus outbreaks in similar settings, public health officials should ensure that involved facilities implement a comprehensive prevention strategy as early as possible that includes extensive sanitation and strict exclusion of ill food handlers for at least 48 hours after symptom resolution (1).
<i>Anisakis</i> is a major cause of anaphylaxis in seaside areas: An epidemiological study in Japan
Authors: Ryo Morishima, Shinji Motojima, Daiki Tsuneishi, Takeshi Kimura, Tamao Nakashita, Junmei Fudouji, Shigeki Ichikawa, Hiroaki Ito, Hiroshi Nishino
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Galectins role as predictive markers for anti-PD-1-based immunotherapy in non-small cell lung cancer.
Authors: Carlo Capalbo, Marco Filetti, Giorgia Scafetta, Paolo Marchetti, Armando Bartolazzi
Journal: Journal of Clinical Oncology (2019)

111 Background: Checkpoint inhibitor-based immunotherapy is opening a promising scenario in oncology with objective responses registered in several tumors. However reliable predictive markers of tumor responsiveness are still lacking. These markers need to be urgently identified for a better selection of patients candidate to immunotherapy. In NSCLC setting, the pleiotropic molecules Galectin 1 and 3 regulate apoptosis and tumor immune-escape and are in the right position to play as predictive marker in anti-PD1 based immunotherapy. Methods: 27 consecutive patients with non small cell lung cancer (NSCLC) stage IV, treatment-naive, selected on the basis of PD-L1 tumor proportion score (TPS) ≥ 50 % were considered for immunotherapy with anti PD-1 antibodies as a first-line treatment. Patients assessments were conducted at baseline and after 3 cycles of therapy (week 12) and classified according to immune-related response criteria (iRECIST). Immunohistochemical analysis was performed on primary tumor biopsies before treatment in order to evaluate Gal-1 and Gal-3 expression both in cancer cells and tumor interstitium. Tumors were grouped in 2 different classes depending on the expression level of these molecules. Results: In our preliminary data there seems to be a strong correlation between the responses to anti-PD-1 treatment and a low-intermediate expression of intratumoral Gal-3 and interstitial Gal-1. In fact, all patients in the intratumoral Gal-3 low-intermediate expression group had an excellent response to immunotherapic treatment (10/10 patients), while 15/17 patients with high intracellular Gal-3 expression had clinical and radiographic progression of the disease after only three cycles of treatment, despite the high expression of PD-L1. In contrast, 8/11 patients with a low-intermediate interstitial expression of Gal-1 had an excellent response to treatment, whereas in the group with high interstitial expression of Gal-1, the response rate was drastically lower (5/15 patients). Conclusions: The expression of interstitial Gal-1 protein and intratumoral Gal-3 protein appear to be a good candidates as predictive markers of response to immunotherapy.
Are Atherogenic Lipoprotein Phenotype and Inflammation Indicative of Plaque Phenotype and Clinical Stability in Coronary Artery Disease?
Authors: Katharina Lechner, Martin Halle
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Germline Variants in Highly Selected Patients With Prostate Cancer
Authors: Samantha Greenberg, Jonathan Tward, Brock O’Neil
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Investigating the tumor-immune microenvironment in an autochthonous murine model of cholangiocarcinoma.
Authors: Booyeon Julia Han, Luis I. Ruffolo, Katherine M. Jackson, Brian A. Belt, Nathania Figueroa, Joseph D. Murphy, David Linehan, Peter A. Prieto
Journal: Journal of Clinical Oncology (2019)

53 Background: Cholangiocarcinoma (CCA) is the most common liver malignancy within the biliary tree with increasing incidence and poor survival. Although surgical resection can be curative, prognosis remains abysmal with high rates of unresectability and recurrence, and new systemic therapies are needed. CCA tumors are characterized by an abundant inflammatory immune cell infiltrate, yet little is known about the immune dynamics underlying the disease. Here, we present a preclinical murine model of CCA for identifying potential targets susceptible to immune-based therapies. Methods: Mice with targeted activation of Kras G12D and loss of p53 (Kras-p53 -/- ) in the liver were exposed to 5-Diethoxycarbonyl-1.4-dihydrocollidine for 4 weeks to induce spontaneous CCA tumorigenesis. Immunohistochemistry staining was performed for mouse and human CCA. Immune compartments (bone marrow, spleen, peripheral blood, tumor draining and non-draining lymph nodes, and CCA tumor) of mice were processed for CyTOF analysis. In vitro assays of isolated myeloid leukocytes were performed to demonstrate function. Results: Tumor associated neutrophils (TANs) and tumor associated macrophages (TAMs) were present in high levels in human CCA tumors and the murine model. CyTOF analysis demonstrated mobilization of TANs, TAMs, and CCR2 + inflammatory monocytes into the tumor. The checkpoint marker PD-1 was upregulated on CD8 + and CD4 + T cells and associated with PD-L1 + TANs, TAMs, monocytes, and dendritic cells. The immunosuppressive tumor microenvironment was also characterized by TAMs expressing IL-10, TGFβ, and arginase 1; regulatory B cells expressing IL-10 and TGFβ; and Gata3 + T H 2 cells. Isolated myeloid leukocytes suppressed T cell proliferation and induced invasive migration. Conclusions: Kras-p53 -/- mice developed CCA tumors histologically similar to human disease: the data portray immunosuppressive cells in the tumor microenvironment, a possible obstacle for an effective anti-tumor response. Understanding the immune dynamics of immunosuppressive populations within the tumor microenvironment will be key to mount a potent therapeutic response for durable remission and improved survival.
Analysis of regulatory T cells in patients of NSCLC with malignant pleural effusion.
Authors: Prabhat Singh Malik, Vinod Raina, Amar Singh, Dipendrea Kumar Mitra
Journal: Journal of Clinical Oncology (2012)

e17511 Background: Enrichment of regulatory T (Treg) cells at the affected anatomic site in cancer may suppress the anti-tumor immune response influencing the cancer progression. Understanding of the clinical relevance of Treg mediated suppression of anti-tumor immune response and mechanisms underlying their preferential trafficking to the affected anatomic site is still limited. The aim of this study was to enumerate the frequencies of Treg cells in malignant pleural effusion and peripheral blood of patients with advanced NSCLC and it’s trend after treatment. Methods: Treg frequencies were evaluated in pleural effusion and peripheral blood of the patients with advanced NSCLC (n=27) using flowcytometry and compared with peripheral blood of age and sex matched healthy controls (n=15) and tubercular pleural effusions (n=10). The Treg cells were characterized as CD4+CD25+Foxp3+ T cells gated on CD4+CD25+ T cells. We assessed the effect of treatment response on Treg frequency. We have also looked for the expression of chemokine receptors CCR4 and CCR6 on the Tregs in pleural effusion and peripheral blood of the patients. Results: Compared to healthy controls, frequency of CD4+CD25+Foxp3+ Tregs was significantly increased in peripheral blood of patients with NSCLC (p=0.0036). In pleural effusion of patients, Treg frequency was higher than their corresponding peripheral blood (p=0.025). As compared to tubercular pleural effusion Treg frequency was higher in malignant effusion (p&lt;0.0001). We had 12 patients who completed treatment and in whom response evaluation was available. Treg frequency reduced at the time of response (PR or SD) and increased again at disease progression. Surface expression of CCR4 and CCR6 was higher on Treg cells as compared to non Treg CD4 cells among the patients (p=0.0001; p=0.001 respectively). However, there was no difference in expression of these chemokine receptors on Tregs in pleural fluid and peripheral blood. Conclusions: Tregs are increased in patients of NSCLC, both at disease site and in systemic circulation. This increase may be chemokine receptors mediated. Treg frequency changes with treatment and response. Modulation of Tregs may have therapeutic implication in the management of advanced NSCLC.
Nivolumab-Associated Giant Cell Arteritis With Scalp Necrosis
Authors: Alexander Kreuter, Bijan Koushk-Jalali, Antonino Cusenza, Frank Oellig, Christian Tigges
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma
Authors: Tabea C. Froehlich, Karin Müller-Decker, Jana D. Braun, Thomas Albrecht, Anne Schroeder, Karsten Gülow, Sergij Goerdt, Peter H. Krammer, Jan P. Nicolay
Journal: Blood (2019)
Codelivery of paclitaxel and temozolomide through a photopolymerizable hydrogel prevents glioblastoma recurrence after surgical resection
Authors: Mengnan Zhao, Elia Bozzato, Nicolas Joudiou, Sina Ghiassinejad, Fabienne Danhier, Bernard Gallez, Véronique Préat
Journal: Journal of Controlled Release (2019)
PTEN/PI3K signaling in cancer and the response to cytokines: From growth factors to immune actors.
Authors: Sanjay Chandrasekaran, Maiko Sasaki, Brian Paul Pollack
Journal: Journal of Clinical Oncology (2019)

35 Background: The PTEN/PIK3 pathway plays an important role in the cellular response to growth factors and aberrant activation of PI3K signaling is a hallmark of many forms of cancer. While the role of PI3K signaling has been well studied in the context of growth factor biology, its role in the cellular response to cytokines such as interferons (IFNs) is less well understood. We examined the impact of PI3K activation on interferon signaling pathways using an in vitro experimental model system. Methods: Cultured human HCT 116 colorectal carcinoma cells and isogenic PTEN (-/-) cells were treated with escalating doses of IFNg, IFNa2b, and IFNl. IFN response was evaluated by measuring MHC Class I and Class II mRNA levels and cell surface expression via RT-PCR and flow cytometry, respectively. Western blots for total AKT, phospho-AKT (pAKT), PTEN, STAT1, and pSTAT1 were performed. Corroborating pharmacologic studies were performed using cultured HPV-negative SqCC/Y1 oSCC cells treated with IFN and the PTEN inhibitor VO-OHpic and AKT activator SC79. Clinical correlates utilizing immunohistochemistry (IHC) on human head and neck cancers were conducted. Results: PTEN (-/-) cells expressed lower basal levels of MHC I and the induction by IFNs were likewise attenuated. Dramatically, PTEN knockout reduced IFN-g- induced surface expression of MHC II by &gt; 50%. Corresponding reductions in MHC I/II mRNA were seen. IHC in patient biopsy samples showed an inverse relationship between phospho-AKT and MHC I expression. We identified a potential explanation of this effect wherein PTEN/PIK3 signaling implicates STAT1, a downstream target of IFN signaling. PTEN inhibition consistently modulated total and phosphorylated levels of STAT1 protein. Conclusions: Much remains unknown about the link between growth factor pathways and the tumor immune response. We demonstrate using an in vitro model that genetic and pharmacologic activation of the PI3K pathway attenuates the immune response to IFNs and represses MHC induction and expression. We present a novel mechanism for explaining this phenomenon linking the PTEN/PIK3 and STAT1 pathways. Further characterization of this interaction in in vitro models is necessary.
Gene Family Evolution in the Pea Aphid Based on Chromosome-Level Genome Assembly
Authors: Yiyuan Li, Hyunjin Park, Thomas E Smith, Nancy A Moran
Journal: Molecular Biology and Evolution (2019)

Genome structural variations, including duplications, deletions, insertions, and inversions, are central in the evolution of eukaryotic genomes. However, structural variations present challenges for high-quality genome assembly, hampering efforts to understand the evolution of gene families and genome architecture. An example is the genome of the pea aphid (Acyrthosiphon pisum) for which the current assembly is composed of thousands of short scaffolds, many of which are known to be misassembled. Here, we present an improved version of the A. pisum genome based on the use of two long-range proximity ligation methods. The new assembly contains four long scaffolds (40-170 Mb), corresponding to the three autosomes and the X chromosome of A. pisum, and encompassing 86% of the new assembly. Assembly accuracy is supported by several quality assessments. Using this assembly, we identify the chromosomal locations and relative ages of duplication events, and the locations of horizontally acquired genes. The improved assembly illuminates the mode of gene family evolution by providing proximity information between paralogs. By estimating nucleotide polymorphism and coverage depth from resequencing data, we determined that many short scaffolds not assembling to chromosomes represent hemizygous regions, which are especially frequent on the highly repetitive X chromosome. Aligning the X-linked aphicarus region, responsible for male wing dimorphism, to the new assembly revealed a 50-kb deletion that cosegregates with the winged male phenotype in some clones. These results show that long-range scaffolding methods can substantially improve assemblies of repetitive genomes and facilitate study of gene family evolution and structural variation.
Time from randomization to first subsequent induction/salvage therapy (ST) in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) treated with inotuzumab ozogamicin (InO) in the phase 3 INO-VATE trial.
Authors: Elias Jabbour, Matthias Stelljes, Anjali S. Advani, Daniel J. DeAngelo, Tao Wang, Alexander Neuhof, Erik Vandendries, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2019)

7025 Background: Additional salvage regimens are burdensome for R/R ALL patients (pts) due to therapy-associated toxicities, which may affect quality of life with poor efficacy. In INO-VATE (Kantarjian et al, NEJM 2016), pts receiving InO vs standard chemotherapy (SC) had significantly greater remission rates and longer overall survival; after study treatment discontinuation, overall fewer STs (mainly burdensome chemotherapies) were used in the InO group vs SC. Methods: Study design was published. Adults with CD22+ ALL who were due to receive 1st or 2nd salvage treatment were randomized 1:1 to InO (n = 164) or SC (n = 162). Time to the first ST (TST) was time from randomization to the start of the first ST. Pts who did not receive any ST were censored. Data cutoff: Jan 4, 2017. Results: Fewer InO pts had ST vs SC pts (Table). Among the censored pts, 83/108 (76.9%) in the InO vs 54/69 (78.3%) in the SC group died, 23/108 (21.3%) vs 5/69 (7.2%) were alive at the end of the study, and 2/108 (1.9%) vs 10/69 (14.5%) were no longer being followed for survival. TST was longer in pts receiving InO vs SC. Overall median (95% CI) TST was 18.8 (14.7–NA) vs 3.9 (2.4–5.1) months; hazard ratio (HR) = 0.34, 97.5% CI: 0.23–0.49, 1-sided P&lt; 0.0001. For pts (InO: 85, SC: 126) who never received hematopoietic stem cell transplantation (HSCT) on study, fewer InO pts had ST vs SC pts; TST was significantly longer in InO vs SC. For pts (InO: 70, SC: 18) who had HSCT directly after salvage, TST was extended in InO vs SC. Conclusions: In this study, treatment with InO provided the benefit of extended TST, effectively allowing patients a longer time period until an ST was needed in both patients who proceeded to as well as those who did not proceed to HSCT. Clinical trial information: NCT01564784. [Table: see text]
Nourishing the gut microbiota: The potential of prebiotics in microbiota-gut-brain axis research
Authors: Boushra Dalile, Kristin Verbeke, Lukas Van Oudenhove, Bram Vervliet
Journal: Behavioral and Brain Sciences (2019)

Abstract Dietary fiber and prebiotics consistently modulate microbiota composition and function and hence may constitute a powerful tool in microbiota-gut-brain axis research. However, this is largely ignored in Hooks et al.’s analysis, which highlights the limitations of probiotics in establishing microbiome-mediated effects on neurobehavioral functioning and neglects discussing the potential of prebiotics in warranting the microbiota's role in such effects.