tbuckley/cabot-search huggingface dataset:
P16.12 Proangiogenic effect of fibroblast activation protein positive stromal cells derived from human glioblastomas
Authors: E Balaziova, P Vymola, P Hrabal, R Mateu, R Tomas, D Netuka, Z Zemanova, K Svobodova, A Sedo, P Busek
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Increased expression of fibroblast activation protein (FAP) is characteristic for several cancer types including human glioblastomas (GBM). FAP is expressed on both cancer as well as stromal cells which were demonstrated in extracranial tumors to maintain a microenvironment permissive for tumor growth and thus to contribute to tumor progression. FAP is considered a potential diagnostic and therapeutic target and several approaches for its targeting have been recently developed. In this work, we investigated the role of FAP+ stromal cells in glioblastoma angiogenesis. MATERIAL AND METHODS Expression of FAP and other phenotypic markers was assessed by immunocytochemistry and immunohistochemistry. FAP+ stromal cells and primary microvascular endothelial cells were isolated using magnetic activated cell sorting (MACS). Genetic aberrations were assayed by comparative genomic hybridization/single-nucleotide polymorphism analysis. Angiogenesis was evaluated using a 3D spheroid-based sprouting assay and a chorioallantoic membrane assay. A cytokine array was used to analyze soluble mediators released by FAP+ stromal cells. RESULTS FAP+ stromal cells were predominantly localized around activated CD105+ endothelial cells and their quantity positively correlated with glioblastoma vascularization. FAP+ stromal cells derived from human GBMs had a mesenchymal phenotype, were non-tumorigenic and in most cases lacked cytogenetic aberrations characteristic of GBMs. Conditioned media derived from FAP+ stromal cells induced angiogenic sprouting of both macrovascular HUVEC as well as microvascular primary endothelial cells derived from human GBMs. In a chorioallantoic membrane assay, admixture of FAP+ stromal cells to glioma cells was associated with increased angiogenesis and more frequent occurrence of hemorrhages. Cytokine array revealed a significant disbalance between several proangiogenic and antiangiogenic mediators compared to normal pericytes, and an increased Angiopoietin 2/1 ratio in conditioned media from FAP+ stromal cells. CONCLUSION Our results bring new evidence that GBM associated FAP+ stromal cell promote angiogenesis by changing the balance between proangiogenic and antiangiogenic mediators and thus they may contribute to glioblastoma progression. ACKNOWLEDGEMENT Supported by Progres Q28/1LFUK and grant LM2015064 of the EATRIS-CZ and the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).
P14.26 Leptomeningeal Disease Secondary to Melanoma: Diagnosis, Treatment, and Outcomes at a Single Institution between 2013 and 2019
Authors: Y Pina, S Mokhtari, B R Evernden, N D Tran, I Smalley, N I Khushalani, V W Law, J A Puskas, G Caceres, K Smalley, E Peguero, P Forsyth
Journal: Neuro-Oncology (2021)

Leptomeningeal disease (LMD) is devastating with a median survival of only 8–10 weeks. LMD affects approximately 5% to 25% of melanoma patients. Its pathophysiology remains unknown and effective treatments are virtually non-existent. The aim was to evaluate demographics, validity of Veridex CellSearch® System (VCS) compared to Gold Standard test (i.e., CSF cytology), risk factors for LMD, and treatment outcomes. A retrospective chart review was performed of subjects with suspected LMD from melanoma enrolled in the MCC 19332/19648 studies between 2013 and 2019 at Moffitt Cancer Center. The patients underwent standard of care with different treatments as deemed appropriate by treating physician. CSF samples were obtained from lumbar punctures, surgeries, and Ommaya reservoir, and sent for analysis. Peripheral blood and CSF were evaluated for detection and quantification of CSF circulating tumor cells (CTCs) with the Veridex CellSearch® System, which is adapted to enumerate CTCs from CSF. More than 100 patient charts were reviewed. Only patients with melanoma as primary tumor (N=48) were included in the analysis, with ages 29–80. N=28 (58%) met criteria for LMD (median age 59, M:F ratio of 3:1). Within the LMD group, n=26 patients had cutaneous melanoma as primary tumor; BRAF mutant n=17 (V600E n=14; G469E n=1). At the time of diagnosis, median KPS score was 70, with most prevalent symptoms of headaches, encephalopathy, focal weakness, and nausea/vomiting. N=20 (71%) patients were diagnosed radiographically and n=5 (18%) with CSF cytology; n=14 (52%) had positive cytology on first LP, n=18 (67%) on first two LPs. From 25 patients with LMD who underwent CellSearch® to quantify CTCs, n=22 (88%) patients had positive CSF CTCs; n=18 (72%) on first sample sent for analysis, n=20 (80%) on first two samples. The sensitivity and specificity of the Veridex CellSearch® System compared to the Gold Standard CSF cytology were analyzed. Survival in months plotted against the percentage of CSF-CTCs showed a significant value of p=0.0377. CSF analysis i.e., inflammatory markers, and treatments pre-/post-LMD diagnosis will be described. Most patient were managed with Ommaya reservoir placement, radiation therapy, immunotherapy, BRAF +/- MEK inhibitors, IT thiotepa, or IT topotecan. The median survival of those with LMD was 3.15 months. Two patients outlived their counterparts by 21.1 and 39.0 months after the LMD diagnosis, one of them is still alive but with a very poor functional status. These results indicate the potential value of the VCS as an additional tool to the gold standard in the diagnosis of LMD in patients with high suspicion of the disease. Future directions involve doing prospective studies to further validate this method, and to better understand this patient population to enhance diagnostic tools and management of LMD.
8 Mechanical and orthopaedic problems
Authors: M TRACHANA, P PRATSIDOU-GERTSI, F PAPADOPOULOU, DE KOLIOUSKAS, A CHRISTODOULOU, J BENIZELOS, F KANAKOUDI-TSAKALIDOU
Journal: Annals of the Rheumatic Diseases (2000)

One of the challenges of paediatric rheumatology is the diagnosis of children with ALL who are referred as possible JIA.We used an internet questionnaire in a retrospective case-control study to obtain predictive factors in 62 children with ALL and 120 children with JIA from 31 international centres.Data analysis was performed using two sided Pearson 2 or Fisher's exact tests.5 shows the results obtained. Results-TableUsing multivariate analysis and regression modelling, we evaluated further several predictive models for ALL.The best were: (a) two of three factors present (1/3 haematological values low, raised lactate dehydrogenase (LDH), night time pain; sensitivity 76%, specificity 86%); (b) blasts + 2 of 3 criteria (1/3 haematological values low, raised LDH, night time pain; sensitivity 81%, specificity 86%).These two models, as well as night time pain and raised LDH, and abnormal x rays by themselves, may be useful in diVerentiating a child with leukaemia from a child with JIA and indicating the need for a bone marrow examination.
Influence of a multidisciplinary program of diet, exercise, and mindfulness on the quality of life of stage IIa-IIb breast cancer survivors.
Authors: J. Vozmediano
Journal: Journal of Clinical Oncology (2021)

193 Background: Integrative oncology has proven to be a useful approach to control cancer symptoms and improve the quality of life (QoL) and overall health of patients, delivering integrated patient care at both physical and emotional levels. The objective of this randomized trial was to evaluate the effects of a triple intervention program on the QoL and lifestyle of women with breast cancer. Methods: Seventy-five survivors of stage IIA-IIB breast cancer were randomized into 2 groups. The intervention group (IG) received a 6-month dietary, exercise, and mindfulness program that was not offered to the control group (CG). Data were gathered at baseline and at 6 months postintervention on QoL and adherence to Mediterranean diet using clinical markers and validated questionnaires. Between-group differences at baseline and 3 months postintervention were analyzed using Student’s t test for related samples and the Wilcoxon and Mann-Whitney U tests. Results: At 6 months postintervention, the IG showed significant improvements versus CG in physical functioning ( p =.027), role functioning ( p =.028), and Mediterranean diet adherence ( p =.02) and a significant reduction in body mass index ( p =.04) and weight ( p =.05), with a mean weight loss of 0.7 kg versus a gain of 0.55 kg by the CG ( p =.05). Dyspnea symptoms were also increased in the CG versus IG ( p =.066). Conclusions: These results demonstrate that an integrative dietary, physical activity, and mindfulness program enhances the QoL and healthy lifestyle of stage IIA-IIB breast cancer survivors. Cancer symptoms may be better managed by the implementation of multimodal rather than isolated interventions. Keywords: integrative oncology, breast cancer, quality of life, diet, exercise, mindfulness. Clinical trial information: NCT04150484.
Racial Inequalities in Drinking Water Lead Exposure: A Wake-Up Call to Protect Patients with End Stage Kidney Disease
Authors: Anne E. Nigra, Ana Navas-Acien
Journal: Journal of the American Society of Nephrology (2021)

Chronic lead exposure in public drinking water remains a persistent environmental injustice that disproportionately affects Black communities across the United States. In this issue of JASN , Danzinger et al. [1][1] evaluated the association of public drinking water lead exposures with serum
CHEERS to You on a Well-done Cost-effectiveness Analysis of Prehospital Plasma for Helicopter Resuscitation of Patients With Traumatic Shock
Authors: Stephanie M. Armocida, Bryan A. Cotton, Elliott R. Haut
Journal: JAMA Surgery (2021)

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 Journals 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
CHANGES IN LIPOPROTEIN PARTICLE NUMBER WITH EZETIMIBE/SIMVASTATIN COADMINISTERED WITH EXTENDED-RELEASE NIACIN IN PATIENTS WITH TYPE II HYPERLIPIDEMIA
Authors: Anh Le, Ran Jin, Andrew Tershakovec, David Neff, Joanne Tomassini, James Otvos, Peter Wilson
Journal: Journal of the American College of Cardiology (2012)
Audio Interview: New Evidence on SARS-CoV-2 Vaccine Boosters
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

New Evidence on SARS-CoV-2 Vaccine Boosters In this audio interview conducted on September 14, 2021, the editors discuss new studies that measure the effectiveness of booster doses in raising antib...
Intracellular hydroxyproline imprinting following resolution of bleomycin-induced pulmonary fibrosis
Authors: Shengren Song, Zhenli Fu, Ruijuan Guan, Jie Zhao, Penghui Yang, Yang Li, Hang Yin, Yunxin Lai, Gencheng Gong, Simin Zhao, Jiangtian Yu, Xiaomin Peng, Ying He, Yumei Luo, Nanshan Zhong, Jin Su
Journal: European Respiratory Journal (2021)

Background Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to reconsider the importance of the choice of animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution. Methods This study aimed to follow the dynamic fibrotic features of bleomycin-treated mouse lungs over extended durations through a combination of the latest technologies (micro-computed tomography imaging and histological detection of degraded collagens) and traditional methods. In addition, we also applied immunohistochemistry to explore the distribution of all hydroxyproline-containing molecules. Results As determined by classical biochemical methods, total lung hydroxyproline contents reached a peak at 4 weeks after bleomycin injury and maintained a steady high level thereafter until the end of the experiments (16 weeks). This result seemed to partially contradict with the changes of other fibrosis evaluation parameters, which indicated a gradual degradation of collagens and a recovery of lung aeration after the fibrosis peak. This inconsistency was well reconciled by our data from immunostaining against hydroxyproline and fluorescent peptide staining against degraded collagen, together showing large amounts of hydroxyproline-rich degraded collagen fragments detained and enriched within the intracellular regions at 10 or 16 weeks rather than at 4 weeks after bleomycin treatment. Conclusions Our present data not only offer respiratory researchers a new perspective towards the resolution nature of mouse lung fibrosis, but also remind them to be cautious when using the hydroxyproline content assay to evaluate the severity of fibrosis.
Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design
Authors: Haiying Qin, Lila Yang, John A Chukinas, Nirali N Shah, Samiksha Tarun, Marie Pouzolles, Christopher D Chien, Lisa M Niswander, Anthony R Welch, Naomi A Taylor, Sarah K Tasian, Terry J Fry
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Successful development of chimeric antigen receptor (CAR) T cell immunotherapy for children and adults with relapsed/refractory acute myeloid leukemia (AML) is highly desired given their poor clinical prognosis and frequent inability to achieve cure with conventional chemotherapy. Initial experiences with CD19 CAR T cell immunotherapy for patients with B-cell malignancies highlighted the critical impact of intracellular costimulatory domain selection (CD28 vs 4-1BB (CD137)) on CAR T cell expansion and in vivo persistence that may impact clinical outcomes. However, the impact of costimulatory domains on the efficacy of myeloid antigen-directed CAR T cell immunotherapy remains unknown. Methods In this preclinical study, we developed six CAR constructs targeting CD33, a highly expressed and validated AML target, comprised of one of three single-chain variable fragments with CD3ζ and either CD28 or 4-1BB costimulatory domains. We systematically compared the preclinical in vitro and in vivo efficacy of T cells lentivirally transduced with CD33 CAR constructs (CD33CARTs) against human AML. Results We observed potent in vitro cytokine production and cytotoxicity of CD33CARTs incubated with human CD33+ AML cell lines, as well as robust in vivo antileukemia activity in cell line and childhood AML patient-derived xenograft (PDX) models. Gemtuzumab-based CD33CARTs were unexpectedly toxic in vivo in animal models despite observed in vitro anti-leukemia activity. CD28-based CD33CARTs consistently induced more robust inhibition of leukemia proliferation in AML cell line and PDX models than did 4-1BB-based CD33CARTs. A ‘best-in-class’ lintuzumab-CD28/CD3ζ CAR construct was thus selected for clinical translation. Conclusions CD33 is a critical antigen for potential immunotherapeutic targeting in patients with AML. Based on this rigorous preclinical evaluation, our validated clinical grade lintuzumab-CD28/CD3ζ CD33CART immunotherapy is now under evaluation in a first-in-child/first-in-human phase 1 clinical trial for children and adolescents/young adults with relapsed/refractory AML. Trial registration number clinicaltrials.gov; NCT03971799 .
Ninth international congress on peer review and scientific publication—call for abstracts
Authors: John P A Ioannidis, Michael Berkwits, Annette Flanagin, Fiona Godlee, Theodora Bloom
Journal: BMJ (2021)

In 2019, before the covid-19 pandemic, we highlighted the unprecedented promise and peril surrounding the quantity, quality, and integrity of scientific research. 1 The pandemic has been a crash test for scientific publishing, emphasising the great successes and failures, and the promise and perils of current systems.In 2020 because of the pandemic, we announced a postponement of the ninth international congress on peer review and scientific publication.We now confirm plans to hold the meeting on 8-10 September 2022 and announce the official call for abstracts.The aim of the congress is to encourage research into the quality and credibility of peer review and scientific publication and to further the evidence base on which scientists can improve the conduct, reporting, and dissemination of scientific research.As with the previous eight congresses, 2 the ninth will feature three days of presentations of original research about processes, policies, problems, and innovations related to peer review, scientific publication, and research dissemination.Participants will include editors and publishers of scientific peer reviewed journals, researchers, funders, bibliometric and informatics experts, information innovators, librarians, journalists, policy makers, ethicists, scientific information producers and disseminators, and anyone interested in the progress of the scientific information enterprise and the quality of scientific evidence.The congress embraces a wide range of disciplines, including (but not limited to) biomedicine, health and life sciences, applied sciences, basic sciences, physical and chemical sciences,
A Supramolecular Nanomedicine Based on Bendamustine and MDM2‐Targeted D‐peptide Inhibitor for Breast Cancer Therapy
Authors: Yunjiang Zhou, Yaxin Chen, Xing Huang, Yingying Tan, Rong Hu, Chong Li, Miao‐Miao Niu
Journal: Advanced Healthcare Materials (2021)

Abstract Bendamustine (BEN) is a FDA‐approved bifunctional DNA‐alkylating chemotherapy drug, but it suffers from short half‐life, instability, and poor biocompatibility in the clinical application. Due to unique biostability of d ‐amino acid‐containing peptides (D‐peptides), constructing D‐peptide‐small molecule drug conjugates is emerging as a promising strategy for cancer therapy. Here, a high‐affinity MDM2‐targeted D‐peptide (peptide 5) is discovered by applying structure‐based drug design (SBDD). Taking the advantages of d ‐amino acids, a novel self‐assembling D‐peptide‐small molecule drug conjugate (BEN‐FF‐peptide 5) is developed by simultaneously conjugating small molecule drug BEN and peptide 5 to the self‐assembling peptide. In vitro results demonstrate that BEN‐FF‐peptide 5 exhibits superior cellular uptake ability, good biostability in human serum and strong inhibitory effect on the growth of human breast cancer (MCF‐7) cells. In vivo study reveals that BEN‐FF‐peptide 5 significantly inhibits the growth of MCF‐7 cells‐derived xenograft in nude mice with no obvious side effects. This work provides a useful strategy to construct D‐peptide‐small molecule drug conjugates for high‐efficacy and low‐toxicity cancer therapy.
Response by Reynolds et al to Letters Regarding Article, “Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of Myocardial Infarction With Nonobstructive Coronary Arteries in Women”
Authors: Harmony R. Reynolds, Raymond Y. Kwong, Akiko Maehara, Nathaniel R. Smilowitz
Journal: Circulation (2021)
Relation of ABO blood group with survival in covid-19 patients admitted in hospital central de la defensa, Madrid, Spain
Authors: M. T. Calderon-Lopez, A. M. Sologuren-Sanchez-Ferragut, L. Romeralo-Calvo, Y. Paredes-Munoz, C. Rojo-Vidal, S. Haro-Canada, E. Toledo-Hernandez, M. J. Contreras-Agudo, S. Gomez-Arevalillo, S. F. P. D. Guzman, C. Gonzalez-Haro, A. Matilla-Garcia
Journal: HemaSphere (2021)

Background: There are some papers reporting a possible link between blood group type and susceptibility to SARS-CoV2 (COVID-19) infection and perhaps even with mortality. They describe a higher risk to develop COVID-19 in individuals with blood type A, whereas those with blood type O would have a lower susceptibility to COVID-19 infection. Aims: To describe the distribution of the blood groups among the COVID-19 patients admitted in our hospital during the worse pandemic months in our country (March to May) and their relation with survival. Methods: From March1st to May 31st1299 Covid-19 patients were admitted in our hospital (a 520-bed institution);a27% died. We had the blood group testing performed in297 out of the1299 patients. Those records were in our blood bank software (Delphy.) because of a previous transfusion or a transfusion during the COVID-19 hospitalization. We examined the ABO types among these patients and we compared this data with the frequency observed in the Spanish healthy population according to the Red Cross records of blood donors. Statistical study was performed using the Chi square test (χ2) and Kaplan-Meier survival curves, by SPSS software. Results: In the297 COVID-19 patients admitted in our Hospital with ABO blood type recorded, the 55.2% were men, 44.8% women;median age was 79 (21-103). We found a higher percentage of blood type A and a lower of O among the COVID-19 patients, compared with the prevalence of those blood groups in Spanish healthy population, but that difference was not statistically significant. Regarding survival curves among different blood groups, we found a decreased mortality in patients with O blood type (25.2%) compared with the rest of groups (34.5%). That difference was close to be statistically significant (p 0.08), showing a clear tendency that could be maybe significant with a bigger group of patients. Summary/Conclusion: The distribution of the blood group in COVID-19 admitted patients in our hospital is similar to data already published: a higher rate of COVID-19 infection in patients with blood type A and a lower rate of type O. We also found lower mortality in our patients with O blood type;with a special signification when we compare O with the rest of blood groups together. There are some literature describing that anti-A antibodies could be protective against COVID-19 infection;this could explain the tendency we found of better survival in patients with O blood type.
Methodological Rigor in Preclinical Cardiovascular Research: Contemporary Performance of AHA Scientific Publications
Authors: Richard G. Jung, Cameron Stotts, Dwipen Makwana, Pouya Motazedian, Pietro Di Santo, Cheng-Yee Goh, Louis Verreault-Julien, Trevor Simard, F. Daniel Ramirez, Benjamin Hibbert
Journal: Circulation Research (2021)