tbuckley/cabot-search huggingface dataset:
FRI0030 Cxcl4 and CXCL7 Expression on Macrophages: A Potential Predictor of Disease Outcome in Patients Presenting with Early Synovitis?
Authors: N.J. Adlard, L. Yeo, D.L. Hardie, H. Adams, M. Juarez, C.D. Buckley, K. Raza, A. Filer, D. Scheel-Toellner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Within the context of a comprehensive study of the pathology of the early stages of rheumatoid arthritis (RA) we compared cytokine mRNA expression in the synovium of patients with early inflammatory arthritis who later progressed to rheumatoid arthritis with that of patients with a resolving disease course. Interestingly, we found a trend towards higher expression of platelet related chemokines CXCL4 and CXCL7 mRNA in early RA synovium. <h3>Objectives</h3> To investigate CXCL4 and CXCL7 expression at the protein level and its co-localisation with platelets, macrophages and blood vessels. <h3>Methods</h3> Synovial tissue biopsies were obtained from treatment naïve patients presenting with at least one clinically swollen joint within the first 12 weeks of symptom onset. Patients who went on to develop RA (according to the 1987 ACR criteria) at an 18 month follow-up (n=10), as well as patients whose arthritis spontaneously resolved (n=9) were included. In addition, biopsies collected from longer duration (&gt;12 weeks) treatment naïve RA patients (n=11) and patients with mechanical symptoms undergoing knee arthroscopy without obvious signs of inflammation were included as controls (n=7). Synovial tissue sections were stained with antibodies specific to CXCL4 or CXCL7, CD41, CD68 and vWF using immunofluorescence and staining was quantified using Zeiss imaging software. Specificity of CXCL7 staining was confirmed by blocking with recombinant cytokine. <h3>Results</h3> We observed a statistically significant increase of CXCL4 and CXCL7 protein expression in patients with early RA when compared to early resolvers (CXCL4 p=0.044, CXCL7 p=0.01). This increase reflected a transient stage of early disease, as in treatment-naïve patients with more than 12 weeks disease duration the expression level of these chemokines was found at levels comparable to non-inflamed synovium. Both CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68<sup>+</sup> macrophages within the synovial tissue. However, only staining found outside blood vessels, which co-localised largely with CD68 as a marker for macrophages, differed between synovium from patients with resolving, early and established arthritis (CXCL4 p=0.062, CXCL7 p=0.013). <h3>Conclusions</h3> We have identified two chemokines, CXCL4 and CXCL7, that are expressed at higher levels on macrophages during a transient phase in early RA. Future work will investigate whether these chemokines play a role in disease progression and/or may be used as biomarkers for prediction of disease outcome. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5480
P01.130 Diffusion restriction on MR imaging in the T2 hyperintense, but otherwise normal-appearing white matter of glioblastoma patients treated with TTFields correlates with survival
Authors: J Vymazal, R Zacek, J Sroubek, J Klener, A Rulseh
Journal: Neuro-Oncology (2018)

Based on the positive results of our pilot study that evaluated MR diffusion tensor imaging characteristics in the white matter of 13 subjects with glioblastoma, we aimed to evaluate the prognostic value of diffusion restriction in a new, larger cohort of glioblastoma patients. Thirty-five subjects diagnosed with glioblastoma were treated by surgical resection, radiotherapy, temozolomide and TTFields (Optune®). All subjects were followed by MRI at 1.5 T approximately every two months (total range 160–1810 days) with standard imaging, including diffusion-weighted imaging, until tumor progression. Apparent diffusion coefficient (ADC) maps were calculated using FSL and freehand ROIs were placed on B0 images within the T2 hyperintense white matter (T2HWM) near the resection cavity by a single investigor (AMR), and then projected onto the ADC maps. Additionally, an ROI was similarily placed within the normal-appearing white matter (NAWM). Final values (ADC-ratio) were calculated by dividing ADC in T2HWM by ADC in NAWM. Linear regression slopes (ADC-ratio vs. time) for individual subjects were fitted in R. In 26 subjects a positive slope was observed in ADC-ratio over time, while in the remaining subjects the slope was negative. We found a significant difference between subjects with positive and negative regression slopes in overall survival (OS; hazard ratio = 0.27 [0.1–0.69], log rank p = 0.009) and progression-free survival (PFS; harazd ratio = 0.31 [0.12–0.81], log rank p = 0.02), with positive regression slope associated with more favorable outcome. Our data suggest that increasing ADC in the affected (T2 hyperintense) white matter of glioblastoma patients is favorable, with significantly greater PFS and OS in patients with increasing ADC over time. Changes in ACD likely reflect changes in tumor density in the afftected white matter, with decreasing values (increasing diffusion restriction) corresponding to tumor progression.
Effects of Surface-Active Aerosols and Pulmonary Congestion on Lung Compliance and Resistance
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Exploring the synergistic effects of cabozantinib (cabo) and a programmed cell death protein 1 (PD1) inhibitor in metastatic renal cell carcinoma (mRCC) with artificial intelligence (AI).
Authors: Luis Costa, Daniel Castellano, Javier Puente, Lidia Martin, Urbano Anido, Jessica Gómez, Ignacio Duran
Journal: Journal of Clinical Oncology (2021)

336 Background: Nonclinical and clinical data suggest that cabo with a PD1 inhibitor provides synergistic antitumor activity in patients with mRCC, possibly by a cabo-induced switch to an immunopermissive tumor microenvironment. We used a complementary, unbiased, AI approach to gain a holistic view of the complex interplay between multiple pathways, cells and molecules and identify the mechanisms that may underpin this synergism. Methods: Biological targets associated with mRCC pathophysiology or drug actions were identified from proteomic, genomic and transcriptomic databases and literature. Using systems- and AI-based technology, the data were integrated using machine learning into mathematical models of the human mRCC protein network topology. The combined effects of cabo and a PD1 inhibitor on biological targets were simulated assuming target receptors were fully activated or fully inhibited. Relevant effects on known cancer processes (e.g. angiogenesis, metastasis, cell proliferation, immune evasion) were identified using artificial neural networks. Biologically plausible synergistic mechanisms were described with sampling methods. Results: Inhibition of VEGF/VEGFR and GAS6/TAMR axes by cabo enhanced the known effects of PD1 inhibitors on immune evasion mechanisms by modulating multiple humoral and cellular components of the innate and adaptive immune responses (Table). PD1 inhibitors further enhanced the anti-angiogenic and tumor pro-apoptotic effects of cabo by modulating pro- and anti-angiogenic factors and T cell cytotoxicity. Conclusions: These data provide a mechanistic rationale and further support for the beneficial combination of cabo and a PD1 inhibitor and may guide future nonclinical and clinical research. [Table: see text]
Dermatology
Authors: Jeffrey S, Dover
Journal: JAMA (1990)

In the treatment of benign vascular anomalies, the distinct advantages of the 577-nm pulsed dye laser over other treatment modalities, especially the extremely low risk of scarring, have enabled this laser to become the treatment of choice for many port-wine stains and telangiectasia in adults. More important, it is the treatment of choice for port-wine stains in children—an entity for which previously there existed no reasonably effective treatment. Of 36 port-wine stains treated in children with the pulsed dye laser, 34 cleared completely without adverse effect, while only 2 developed atrophic scarring.<sup>1</sup>By treating port-wine stains in early childhood (as early as 3 weeks of age), the psychological burden on the family and the child may be alleviated. Based on the same concept of producing preferential injury to skin structures by using brief and selectively absorbed laser pulses, pigmented skin structures rather than vascular structures can be selectively damaged.
Ten-year follow-up results of balloon mitral commissurotomy in children and adolescents Habib Gamra, Fethi Betbout, Faouzi Maatouk, Khaldoun Ben Hamda, Mohamed Abdellaoui, Zohra Dridi, Taoufik Hendiri, Sonia Hammami, Hatem Boughanmi, Mohamed Ben Farhat. Cardiology Department - University Hospital, Monastir, Tunisia
Journal: Journal of the American College of Cardiology (2001)
Endogenous Estrogens and Breast Cancer Risk: The Case for Prospective Cohort Studies
Authors: Paolo G. Toniolo
Journal: Environmental Health Perspectives (1997)

It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu.Nearly all the epidemiological studies conducted in the 1970s and 1980s were hospital-based case-control studies in which specimen sampling was performed well after the clinical appearance of the disease.Early prospective cohort studies also had limitations in their small sample sizes or short follow-up periods.However, more recent case-control studies nested within large cohorts, such as the New York University Women's Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are generating new data indicating that increased levels of estrone, estradiol and bioavailable estradiol, as well as their androgenic precursors, may be associated with a 4-to 6-fold increase in the risk of postmenopausal breast cancer.Further new evidence, which complements and expands the observations from the latter studies, shows that women with the thickest bone density, which may be a surrogate for cumulated exposure to hormones, experience severalfold increased risk of subsequent breast cancer as compared to women with thin bones.These data suggests that endogenous sex hormones are a key factor in the etiology of postmenopausal breast cancer.New prospective cohort studies should be conducted to examine the role of endogenous sex hormones in blood and urine samples obtained early in the natural history of breast cancer jointly with an assessment of bone density and of other important risk factors, such as mammographic density, physical activity, body weight, and markers of individual susceptibility, which may confer increased risk through an effect on the metabolism of endogenous hormones or through specific metabolic responses to Western lifestyle and diet.
A multicenter analysis of the role of prophylactic transfusion of blood products in patients with cirrhosis and esophageal varices undergoing endoscopic band ligation
Authors: Annabel Blasi, Salvador Machlab, Raquel Risco, Joao Pedro Costa-Freixas, Geovanny Hernández Cely, Diana Horta, Alex Bofill, Pablo Ruiz-Ramirez, Joaquim Profitos, Josep Marti Sanahuja, Alejandro Fernandez Simon, Mercedes Vergara Gómez, Jordi Sánchez-Delgado, Andres Cardenas
Journal: Journal of Hepatology (2020)
Withdrawing Care
Authors: David K. P. Lee
Journal: JAMA (1994)

<h3>Objective.</h3> —To describe the process and outcomes of withdrawing life-sustaining interventions in a medical intensive care unit (MICU). <h3>Design.</h3> —Retrospective case series. <h3>Setting.</h3> —Medical intensive care unit in a community teaching hospital. <h3>Patients.</h3> —Consecutive series of 28 patients in whom mechanical ventilation, dialysis, and/or vasopressors were withdrawn. We distinguished physiological, neurological, and functional rationales for care withdrawal. <h3>Main Outcome Measures.</h3> —Duration of discussions, MICU length of stay, and hospital survival. <h3>Results.</h3> —Mean ±SD Acute Physiology and Chronic Health Evaluation (APACHE II) score was 27.1 ±7.3 on MICU admission, and average ±SD predicted hospital mortality was 61%±22%. Discussions leading to withdrawal of care occurred over an average ±SD of 5.2±5.5 days, with decisions achieved soonest in cases with poor neurological prognosis. Average ±SD MICU length of stay was 1.4±1.8 days following a decision to withdraw MICU care, and only four patients received more than 48 hours of additional MICU care. Four patients were discharged alive from the hospital. <h3>Conclusions.</h3> —Patients and their surrogates willingly considered outcomes in addition to mortality when considering withdrawal of life-sustaining interventions. Finding an accommodation between physician judgments and patient preferences took time and effort but was an effective means of limiting ineffective life-sustaining efforts. Withdrawing futile or unwanted care was not always fatal. (<i>JAMA</i>. 1994;271:1358-1361)
DECEITFUL TRADEMARKS LOSE THEIR PROTECTION.
Journal: JAMA (1903)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Acute malnutrition and high childhood mortality related to diarrhea. Lessons from the 1991 Kurdish refugee crisis
Authors: R. Yip
Journal: JAMA (1993)

<h3>Objective.</h3> —To determine the extent, major causes, and contributory factors of high rates of morbidity and mortality among children at mountain camps along the Turkey-Iraq border during the 1991 Kurdish refugee crisis. <h3>Design.</h3> —A cross-sectional rapid nutrition survey among children and a retrospective mortality survey covering a 2-month period from the onset of the crisis. <h3>Population Studied.</h3> —Households of Kurdish refugees at resettlement camp 1 near Zakho in northern Iraq. <h3>Main Outcome Measures.</h3> —Prevalence of wasting (low weight-for-height) and mean weight-for-height status, prevalence of diarrhea, and crude and age-specific mortality rates. <h3>Results.</h3> —Weight-for-height measurements indicated that children under 2 years of age had suffered significant (<i>P</i>&lt;.001) recent malnutrition. The elevated prevalence of wasting and the reduced mean weight-for-height status in this group indicated generalized weight loss. This weight loss was likely the result of the high rates of diarrhea, which still affected 50% of the younger children at the time of survey. The crude mortality rate for all ages was 8.9 per 1000 per month (expected rate, 0.6 per 1000); two thirds of the deaths occurred among children aged 5 years or younger, and half among infants younger than 1 year. An estimated 12% of all infants died during the first 2 months of the crisis. Most deaths were due to diarrhea, dehydration, and resulting malnutrition. <h3>Conclusions.</h3> —The high rates of malnutrition and mortality related to diarrhea in infants and younger children of Kurdish refugees took place rapidly despite prompt relief efforts and a previously healthy population. This experience underscores the need for early and aggressive public health management of sanitation, water sources, and diarrhea control programs to augment the traditional focus on food and medical relief during the emergency phase of a refugee crisis. (<i>JAMA</i>. 1993;270:587-590)
Hyperthermia of arterial stented segments by magnetic force: A new method to eliminate intimal hyperplasia Christodoulos Stefanadis, Konstantinos Toutouzas, Eleftherios Tsiamis, Charalambos Vlachopoulos, Dorothea Tsekoura, Pavlos Toutouzas. Hippokration Hospital, Athens
Journal: Journal of the American College of Cardiology (2001)
One-Year Follow-Up of the Phagocytic Activity of Leukocytes after Exposure of Rats to Asbestos and Basalt Fibers
Authors: Marta Hurbankova
Journal: Environmental Health Perspectives (1994)

The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats.Asbestos and basalt fibers differed in their effects on the parameters stud- ied.Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase 1, followed by the suppression of the parameters in the chronic phase I1.Exposure to asbestos and basalt fibers led, in phase I1, to impairment of the phagocytic activity of granulocytes.Asbestos fibers also significantly decreased phagocytic activity of monocytes.Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase 11. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers.-
Identification of a lung cancer growth factor, LASEP1, as a serological and prognostic biomarker and a therapeutic target.
Authors: Atsushi Takano, Yusuke Nakamura, Yataro Daigo
Journal: Journal of Clinical Oncology (2014)

11036 Background: Cancer-specific oncoantigens could be ideal targets for the development of novel diagnostic/prognostic biomarkers and/or therapies. Methods: To identify new oncoantigens, we screened up-regulated genes that encode secreted protein in 120 cases of non-small cell lung cancers (NSCLCs) by means of cDNA microarray containing 27,648 genes and examined clinicopathological significance of their protein expression by tissue microarray covering 374 NSCLCs. We further examined their growth/invasion effect on cancer cells by siRNA and Matrigel invasion assays. We also measured their protein concentration in serum by ELISA. Results: We identified LASEP1 (Lung cancer Associated Serum Protein 1) as a candidate secreted protein. Immunohistochemical staining confirmed that positive staining of LASEP1 was observed in 210 (56%) of 374 NSCLCs. Multivariate analysis revealed that high level of LASEP1 expression was associated with poor prognosis for NSCLCs patients. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 lung cancers, while 4 (3.9%) of 102 healthy volunteers were falsely diagnosed. Furthermore, suppression of LASEP1 by siRNAs inhibited the growth of cancer cell through a significant increase in the number of cells at the G1 phase. In addition exogenous LASEP1 expression enhanced the growth and the cell mobility in vitro. LASEP1 interacts with its 50-kDa receptor (LASEPR) on the surface of cancer cells. siRNAs for LASEPR also inhibited the growth of cancer cells. The LASEP1-LASEPR interaction promoted the cell growth in an autocrine manner. The growth activity of the LASEP1-positive cells was neutralized by addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media. The systemic administration of the anti-LASEP1 antibody to tumor-implanted mice significantly suppressed tumor growth without any adverse events. By gene expression analysis using microarray to determine down-stream genes of LASEP1, we identified WHSC1 encoding an oncogenic histone methyltransferase as a LASEP1-target gene. Conclusions: LASEP1 was suggested to be a good candidate for the development of biomarkers and therapeutic target for lung cancer.
&lt;emph type="ital"&gt;Pümpfrage&lt;/emph&gt; Redivivus
Authors: Brandon Stone
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal