tbuckley/cabot-search huggingface dataset:
Digital sorting and copy number profiling of purified, PD-L1 positive, Reed Sternberg cells in classical Hodgkin lymphoma.
Authors: Chiara Mangano, Rossana Lanzellotto, Chiara Bolognesi, Claudio Forcato, Alberto Ferrarini, Valentina Del Monaco, Edoardo Petrini, Paola Tononi, Genny Buson, Gianni Medoro, Francesca Fontana, Nicolò Manaresi
Journal: Journal of Clinical Oncology (2017)

7528 Background: Classical Hodgkin Lymphoma (cHL) is one of the disease in which the check-point inhibitors have been demonstrated to be more successful. Lately, it has been reported that in malignant Reed-Sternberg Cells (RSCs), PD-1 ligands (PD-Ls) are overexpressed and that chr.9 amplification correlates with advanced stages of the disease, when the standard therapy have already failed. Unfortunately, the detection of the genetic alterations in RSCs is challenging, as one of the hallmark of cHL is the presence of a small number of malignant cells sparse in an abundant and heterogeneous immune infiltrate. Here we present a method for the isolation and the genetic characterization of purified RSCs, which overcomes the limitations posed by the low-cellularity of cHL biopsies, and could be helpful for earlier detection of genetic alterations and adoption of immunotherapy. Methods: FFPE tissue sections from cHL patients were dissociated down to single-cell suspension and stained using anti-CD30 and anti-PD-L1 antibodies. Beyond the positivity to CD30 and PD-L1, RSCs were selected according to morphological criteria such as cell size and the presence of polylobate nuclei compared to surrounding lymphocytes. Target cells were isolated using the DEPArray™ cell sorter, as single cells or in small pools of cells. Recovered cells were whole genome amplified ( Ampli1™ WGA), and genome-wide copy-number aberrations (CNAs) profiles were obtained using Ampli1™ LowPass kit on IonTorrent platform. Results: After the dissociation, RSCs maintained cell morphology and therefore, we were able to discriminate them from the heterogeneous immune infiltrate. RSCs appeared as large multinucleated cells with a big central nucleolus surrounded by a clear halo; cell diameter and ploidy were computed from the images. Pools of lymphocytes and pools of CD30+/ PD-L1+ RSCs were isolated. Sequencing results confirmed the expected flat profile for lymphocytes, while RSCs showed an aberrant profile with multiple losses and gains. Conclusions: The analysis of purified RSCs, could offer a valuable tool to uncover genetic alterations hidden by cHL immune infiltrate, for earlier adoption of more effective treatment regimens.
PD-L1 expression and survival in patients with non-small cell lung cancer (NSCLC) in Korea.
Authors: Jong-Mu Sun, Wei Zhou, Yoon-La Choi, So-Jung Choi, Se Eun Kim, Zhen Wang, Marisa Dolled-Filhart, Kenneth Emancipator, Russell Weiner, Minjin Park, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Jhingook Kim
Journal: Journal of Clinical Oncology (2014)

8066 Background: Data are limited on whether programmed cell death ligand-1 (PD-L1) expression is a prognostic factor among patients (pts) with NSCLC. Methods: We evaluated the relationship between PD-L1 expression and overall survival (OS) in 779 NSCLC pts treated at Samsung Medical Center, Seoul, Korea, between 2001 and 2010. Tumor expression of PD-L1 was measured by immunohistochemistry, and PD-L1-positivity was defined as staining in ≥1% of cells. Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis, adjusting for age, gender, smoking, and stage. Results: Median pt age was 64 years (range, 21-86 years), and 74% of pts were male. 49% of pts had adenocarcinoma, 39% squamous cell carcinoma (SCC), and 12% large cell carcinoma or other. Disease stage was I/II in 71% and III/IV in 29%. All pts underwent surgery, and 411 pts received chemotherapy. Median follow-up time was 4.2 years. Overall, 50% of pts were PD-L1-positive. A statistically significant higher prevalence of PD-L1-positivity was observed in males and in pts with SCC or advanced-stage disease (P < 0.001). Overall, PD-L1-positivity was associated with worse OS, with a 5-year OS rate of 55% (95% CI, 50%-60%) for the PD-L1-positive group and 67% (62%-72%) for the PD-L1-negative group (log rank P = 0.02). Further analysis suggested that this association was driven mainly by the pts with adenocarcinoma. The 5-y OS rates for the PD-L1-positive and PD-L1-negative groups were 57% (50%-65%) and 59% (49%-68%), respectively, in SCC pts (log rank P = 0.60), and 52% (42%-61%) and 73% (66%-78%), respectively, in adenocarcinoma pts (log rank P < 0.001; adjusted hazard ratio [AHR] of PD-L1-positive vs PD-L1-negative, 1.47; 95% CI, 1.03-2.11). Similar trends of association between PD-L1-positivity and OS were observed among adenocarcinoma pts who received chemotherapy (log rank P = 0.03; AHR, 1.32; 95% CI, 0.84-2.09) and those who did not (log rank P< 0.01; AHR, 1.88; 95% CI, 1.03-3.43). Conclusions: Based on a preliminary assay and cutoff, our results suggest that PD-L1 expression may be a negative prognostic factor among non-SCC pts with NSCLC, particularly those with adenocarcinoma.
Observed oseltamivir resistance in seasonal influenza viruses in Europe interpretation and potential implications
Authors: A Nicoll, B Ciancio, P Kramarz, None on behalf of the Influenza Project Team
Journal: Eurosurveillance (2008)

In this weeks issue of Eurosurveillance, Zambon and colleagues describe the first findings of the European Union-funded European Surveillance Network for Vigilance Against Viral Resistance (VIRGIL) of some seasonal influenza viral isolates resistant to the antiviral drug oseltamivir in Europe.
Cell biology of spinal cord injury and repair
Authors: Timothy M. O’Shea, Joshua E. Burda, Michael V. Sofroniew
Journal: Journal of Clinical Investigation (2017)

Spinal cord injury (SCI) lesions present diverse challenges for repair strategies. Anatomically complete injuries require restoration of neural connectivity across lesions. Anatomically incomplete injuries may benefit from augmentation of spontaneous circuit reorganization. Here, we review SCI cell biology, which varies considerably across three different lesion-related tissue compartments: (a) non-neural lesion core, (b) astrocyte scar border, and (c) surrounding spared but reactive neural tissue. After SCI, axon growth and circuit reorganization are determined by neuron-cell-autonomous mechanisms and by interactions among neurons, glia, and immune and other cells. These interactions are shaped by both the presence and the absence of growth-modulating molecules, which vary markedly in different lesion compartments. The emerging understanding of how SCI cell biology differs across lesion compartments is fundamental to developing rationally targeted repair strategies.
Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study
Authors: Arpana Agrawal, Elliot C Nelson, Kathleen K Bucholz, Rebecca Tillman, Richard A Grucza, Dixie J Statham, Pamela AF Madden, Nicholas G Martin, Andrew C Heath, Michael T Lynskey
Journal: The Lancet Psychiatry (2017)
Abstract 330: AT1R Conformation Mediates Mechanical Stress-Induced β-Arrestin Signaling
Authors: Wei Tang, Howard A Rockman
Journal: Circulation Research (2012)

Wei Tang1, Howard A. Rockman1,2,3 1Departments of Medicine, 2Departments of Cell Biology, 3Departments of Molecular Genetics and Microbiology, Duke University Medical Center, DUMC 3104, 226 CARL Building, Durham, NC 27710, USA. Introduction: Recent work has shown that mechanical stretch induces β-arrestin-biased Angiotensin II Type 1 Receptor (AT1R) prosurvival cellular signaling. However, the precise molecular details for this are not fully understood. We set out to explore whether the conformation of the AT1R determines stretch-induced cellular signaling and whether this mechanism of stretch-mediated beta-arrestin signaling activates cell cycle progression. Methods: We used HEK 293 cells stably expressing AT1Rs with and without treatment with the nonionic triblock membrane sealant poloxamer 188 (P188). P188 is known to integrate into biological membranes and affect the local microviscosity of the membrane. Mechanical stretch was induced by hypotonic osmotic stress. β-arrestin signaling was examined by the level of phosphorylated ERK (pERK) with and without siRNA targeted to β-arrestin1/2, and cell cycle progression by the level of phosphorylated retinoblastoma (Rb). Results: Both Angiotensin II (AngII) and osmotic stress increased pERK. The increase in pERK by osmotic stress was abrogated in the presence of β-arrestin1/2 siRNA. P188 had no effect on AngII induced pERK, but completely blocked the increase in pERK with osmotic stress. Both AngII and osmotic stress caused the rapid increase phosphorylated Rb at the Ser780 site, which is known to be phosphorylated by cyclin-dependent protein kinase 4. Conclusion: Altering membrane viscosity blocks stretch-induced AT1R signaling indicating a possible role for receptor conformation in stretch-mediated β-arrestin signaling and cell cycle progression. Ongoing studies will directly measure receptor affinity states under ligand-activated vs. mechanical stretch-activated conditions.
Integrin‐Mediated Interactions Control Macrophage Polarization in 3D Hydrogels
Authors: Byung‐Hyun Cha, Su Ryon Shin, Jeroen Leijten, Yi‐Chen Li, Sonali Singh, Julie C. Liu, Nasim Annabi, Reza Abdi, Mehmet R. Dokmeci, Nihal Engin Vrana, Amir M. Ghaemmaghami, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2017)

Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP-1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin-4 (IL-4) induce an anti-inflammatory M2-like phenotype and propagate the effect of IL-4 in induction of M2-like macrophages. Importantly, integrin α2β1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin-mediated 3D microenvironment for biomaterial-based programming.
Defining the role of Lgr5+ stem cells in colorectal cancer: from basic research to clinical applications
Authors: Masayuki Fujii, Toshiro Sato
Journal: Genome Medicine (2017)

Intestinal epithelium is structured by two distinct components: the villi and the crypts. The crypts harbor stem cells expressing Lgr5 and thus have been a representative model to study tissue stem cell functions. Recent advances in organoid technology and analytical modalities have enabled precise characterization of Lgr5+ intestinal stem cells, providing insights into their roles in homeostasis and cancer.
Pregnancy outcomes in women exposed to biologic treatment and affected by chronic arthritis
Authors: C. Bazzani, V. Ramoni, R. Scrivo, M. Biggioggero, M. Nuzzo, M. Filippini, I. Pontikaki, M. Gerosa, M. Mosca, R. Gorla, R. Caporali, R. Cattaneo, P. Meroni, G. Valesini, C. Montecucco, A. Tincani
Journal: Annals of the Rheumatic Diseases (2010)
Ernest George Knox
Authors: Vivien Drake
Journal: BMJ (2017)

Born and brought up in Newcastle upon Tyne, Ernest George Knox (“George”) was awarded a scholarship to Dame Allan’s School, where he also met his future wife, Betty. As teenagers during the war, George and Betty were evacuated to the Lake District. George later navigated many cycling routes and walks in the Lakes, Northumberland, Scotland, and Wales with the aid of a compass, an Ordnance Survey map, a canvas rucksack, and a bar of Kendal mint cake. OS maps were to remain a lifelong source of fascination and a reference …
Influence of Hybridization Upon the Occurrence of Mammary Tumors in Mice
Authors: Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Influence of Hybridization Upon the Occurrence of Mammary Tumors in Mice Get access Howard B. Andervont Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 359–365, https://doi.org/10.1093/jnci/3.4.359 Published: 01 February 1943
Advances and Gaps in Understanding Chronic Traumatic Encephalopathy
Authors: Gil D. Rabinovici
Journal: JAMA (2017)

Traumatic brain injury (TBI) is a major public health concern, affecting an estimated 10 million people worldwide per year and more than 40% of US residents over the course of a lifetime.1,2 Mild TBI, also referred to as concussion, is defined as blunt, nonpenetrating head trauma associated with... Language: en
NHS to stop funding homeopathy and some drugs in targeted savings drive
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The NHS is to stop funding homeopathy and a host of drugs that patients can buy over the counter as part of a major efficiency savings drive.

A public consultation1 launched on 21 July proposes limiting GPs’ prescribing of over-the-counter drugs such as paracetamol and ibuprofen, antifungal treatment, and eczema creams which currently cost the NHS £50m-100m a year (€56m-112m; $65m-130m).

It also proposes limiting prescribing of 18 medicines which are “relatively ineffective, unnecessary, inappropriate, or unsafe for prescription” and cost an estimated £141m a year in total. These include homeopathic remedies, co-proxamol, immediate release fentanyl, and liothyronine.

If taken forward, it will be issued as formal guidance to …
Gender Confirmation Surgery and Terminology in Transgender Health
Authors: Justin D. Arnold
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
Production of Malignancy in Vitro. III. Microcinematographic Equipment
Authors: Earle, Wilton R., Crisp, Laurence R.
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Production of Malignancy in Vitro. III. Microcinematographic Equipment Get access Wilton R. Earle, Wilton R. Earle senior cytologist National Cancer Institute Search for other works by this author on: Oxford Academic PubMed Google Scholar Laurence R. Crisp Laurence R. Crisp associate mechanical engineer National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 2, October 1943, Pages 147–164, https://doi.org/10.1093/jnci/4.2.147 Published: 01 October 1943
Acute Liver Failure Secondary To Hepatic Malignant Infiltration; Clinical Features Enabling Early Identification
Authors: Pablo Solis-Munoz, Vishal C. Patel, Georg Auzinger, Chris Willars, Alberto Quaglia, John B. Karani, Antonio Pagliuca, Nigel Heaton, Julia Wendon, William Bernal
Journal: Hepatology (2013)
The JAK2V617F-bearing vascular niche promotes clonal expansion in myeloproliferative neoplasms
Authors: H Zhan, C H S Lin, Y Segal, K Kaushansky
Journal: Leukemia (2017)

The acquired kinase mutation JAK2V617F plays a central role in myeloproliferative neoplasms (MPNs). However, the mechanisms responsible for the malignant hematopoietic stem/progenitor cell (HSPC) expansion seen in patients with MPNs are not fully understood, limiting the effectiveness of current treatment. Endothelial cells (ECs) are an essential component of the hematopoietic niche, and they have been shown to express the JAK2V617F mutation in patients with MPNs. We show that the JAK2V617F-bearing vascular niche promotes the expansion of the JAK2V617F HSPCs in preference to JAK2WT HSPCs, potentially contributing to poor donor cell engraftment and disease relapse following stem cell transplantation. The expression of Chemokine (C-X-C motif) ligand 12 (CXCL12) and stem cell factor (SCF) were upregulated in JAK2V617F-bearing ECs compared to wild-type ECs, potentially accounting for this observation. We further identify that the thrombopoietin (TPO)/MPL signaling pathway is critical for the altered vascular niche function. A better understanding of how the vascular niche contributes to HSPC expansion and MPN development is essential for the design of more effective therapeutic strategies for patients with MPNs.
The impact of multimodality treatment on outcomes of patients with type II endometrial carcinoma: A single institution experience.
Authors: Shobhana Talukdar, Michelle Jankowski, Rabbie Kriakoss Hanna, Mohamed A. Elshaikh
Journal: Journal of Clinical Oncology (2013)

e16552 Background: To determine the impact of different adjuvant treatment modalities on relapse-free (RFS), disease-specific (DSS) and overall survival (OS) of patients with type II endometrial carcinoma after hysterectomy. Methods: Our prospectively-maintained database of 1605 uterine cancer patients was reviewed for this IRB-approved study. We identified 167 consecutive patients with type II endometrial carcinoma 2009 FIGO stages IA-IIIC2 who underwent hysterectomy between 1991-2012. Recurrence-free survival (RFS), DSS and OS was calculated from the date of hysterectomy using the Kaplan Meier method. Cox regression modeling was used to explore the risks of various factors on recurrence. Results: Median follow-up was 5.4 years. Median age was 65 years. All patients underwent hysterectomy and salpingo-oophorectomy. 95% had peritoneal cytology and 87% underwent lymphadenectomy. 61% were stage I, 11% with stage II and 28% with stage III (including 33 patients with lymph node involvement). There were 60% of patients with uterine serous carcinoma, 22% with clear cell and 18% with a mixed histology. 29% of patients received adjuvant chemoradiotherapy, 25% received either chemotherapy or radiothereapy alone and 21% were managed with close surveillance. 5-year OS, DSS and RFS was 54%, 64% and 54%, respectively. On multivariate analysis and after adjusting for other prognostic factors, multimodality treatment, (p = 0.0076) presence of LVSI (p = 0.0443), lower uterine segment involvement (p = 0.0003) and involvement of lymph nodes (p = 0.001) were the only independent predictors of RFS. These factors in addition to positive peritoneal cytology were also significant predictors of DSS. Age at diagnosis, the presence of LVSI, positive lymph nodes, positive peritoneal cytology and adjuvant multimodality treatment were the only predictors of OS with p = 0.0251, 0.0178, 0.003, 0.0019 and 0.046, respectively. Conclusions: In this hospital-based study, adjuvant radiation treatment combined with chemotherapy was independent predictor of RFS, DSS and OS compared to single modality treatment. These findings need validation from a prospective randomized study.
Efficacy and safety of nintedanib (N) versus sorafenib (S) in Caucasian and Asian patients with advanced hepatocellular carcinoma (HCC): Pooled analysis of two randomized phase II trials.
Authors: Tim Meyer, Daniel H. Palmer, Yee Chao, Caren Choi, Andrzej Deptala, Laetitia Fartoux, Yin-Hsun Feng, Janet Shirley Graham, Julia Hocke, Tae-You Kim, Deng-Yn Lin, Yuk Ting Ma, Markus Peck-Radosavljevic, Paul J. Ross, Baek-Yeol Ryoo, Arne Wenz, Chia-Jui Yen, Arsene-Bienvenu Loembe, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2015)

4074 Background: N is an oral, triple angiokinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor receptors. Two randomized, open-label, Phase II studies evaluated the efficacy and safety of N versus S in patients with advanced HCC in Europe (NCT01004003; 1199.37) and Asia (NCT00987935; 1199.39). Methods: Patients with unresectable, advanced HCC, ECOG-PS ≤ 2, Child–Pugh score A, alanine/aspartate aminotransferase (ALT/AST) ≤ 2 × upper limit of normal and ≥ 1 untreated measurable lesion or previously treated lesion with progression (by RECIST 1.0) were randomized 2:1 to N 200 mg bid or S 400 mg bid continuously in 28-day cycles, until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. The primary endpoint was time to progression (TTP) by independent central review (ICR; RECIST 1.0); secondary endpoints included overall survival (OS) and objective tumor response (OR) by ICR. Results: 188 patients received N (1199.37: n = 62; 1199.39: n = 63) or S (n = 31; n = 32). Main patient demographics/baseline characteristics were balanced between treatments in both trials except for macrovascular invasion (N vs S; 48% vs 31%) in 1199.39. TTP was comparable between N and S (median 3.7 vs 3.9 months; HR 1.31 [95% CI: 0.89–1.91]), as were OS (median 11.4 vs 11.0 months; HR 0.91 [95% CI: 0.65–1.29]) and OR rate (4% vs 5%). The rate of Grade ≥ 3 AEs (62% vs 87%) and AEs leading to dose reduction (19% vs 51%) was lower with N than S; more N-treated patients had AEs leading to drug discontinuation (34% vs 29%). The most frequent ( > 5% of patients in any group; N vs S) Grade ≥ 3 AEs were diarrhea (10% vs 5%), fatigue (7% vs 2%), increased AST (8% vs 13%) and ALT (6% vs 8%), anemia (7% vs 6%), thrombocytopenia (5% vs 8%), skin reaction (1% vs 6%) and hand-foot skin reaction (0 vs 19%). Conclusions: Pooled analysis of two trials in Caucasian and Asian patients showed similar efficacy between N and S. AEs were as expected based on the safety profile of both agents. Further studies of N in patients with advanced HCC are warranted. Clinical trial information: NCT01004003 and NCT00987935.