tbuckley/cabot-search huggingface dataset:
ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma
Authors: Congcong Zhang, Michael C. Burger, Lukas Jennewein, Sabrina Genßler, Kurt Schönfeld, Pia Zeiner, Elke Hattingen, Patrick N. Harter, Michel Mittelbronn, Torsten Tonn, Joachim P. Steinbach, Winfried S. Wels
Journal: JNCI Journal of the National Cancer Institute (2015)

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults and currently incurable. To specifically target natural killer (NK) cell activity to GBM, we employed NK-92/5.28.z cells that are continuously expanding human NK cells expressing an ErbB2-specific chimeric antigen receptor (CAR). ErbB2 expression in 56 primary tumors, four primary cell cultures, and seven established cell lines was assessed by immunohistochemistry and flow cytometry. Cell killing activity of NK-92/5.28.z cells was analyzed in in vitro cytotoxicity assays. In vivo antitumor activity was evaluated in NOD-SCID IL2Rγ null (NSG) mice carrying orthotopic human GBM xenografts (6 to 11 mice per group) and C57BL/6 mice carrying subcutaneous and orthotopic ErbB2-expressing murine GBM tumors (5 to 8 mice per group). Statistical tests were two-sided. We found elevated ErbB2 protein expression in 41% of primary GBM samples and in the majority of GBM cell lines investigated. In in vitro assays, NK-92/5.28.z in contrast to untargeted NK-92 cells lysed all ErbB2-positive established and primary GBM cells analyzed. Potent in vivo antitumor activity of NK-92/5.28.z was observed in orthotopic GBM xenograft models in NSG mice, leading to a marked extension of symptom-free survival upon repeated stereotactic injection of CAR NK cells into the tumor area (median survival of 200.5 days upon treatment with NK-92/5.28.z vs 73 days upon treatment with parental NK-92 cells, P < .001). In immunocompetent mice, local therapy with NK-92/5.28.z cells resulted in cures of transplanted syngeneic GBM in four of five mice carrying subcutaneous tumors and five of eight mice carrying intracranial tumors, induction of endogenous antitumor immunity, and long-term protection against tumor rechallenge at distant sites. Our data demonstrate the potential of ErbB2-specific NK-92/5.28.z cells for adoptive immunotherapy of glioblastoma, justifying evaluation of this approach for the treatment of ErbB2-positive GBM in clinical studies.
Bone Marker–Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study
Authors: Noopur Raje, Robert Vescio, Charles W. Montgomery, Ashraf Badros, Nikhil Munshi, Richard Orlowski, Joseph T. Hadala, Ghulam Warsi, Eliza Argonza-Aviles, Solveig G. Ericson, Kenneth C. Anderson
Journal: Clinical Cancer Research (2015)

Zoledronic acid (ZOL) given every 3 to 4 weeks can reduce skeletal-related events (SRE) in patients with bone lesions from multiple myeloma. This study evaluated efficacy and safety of less-frequent ZOL dosing based on bone turnover markers in patients with 1 to 2 years of prior bisphosphonate therapy.Patients received ZOL (4 mg) every 4 or 12 weeks based on urinary N-telopeptide of type 1 collagen (uNTX) levels (every 4 weeks if uNTX ≥50 nmol/mmol creatinine, every 12 weeks if uNTX < 50).Of 121 patients enrolled (mean age, 63.8 years; median follow-up, 21 months), 4 patients started ZOL every 4 weeks and 117 received ZOL every 12 weeks based on uNTX at study entry. All 4 patients who initiated ZOL every 4 weeks switched to every 12 weeks due to decreased uNTX. Thirty-eight of 117 patients who initiated ZOL every 12 weeks switched to ZOL every 4 weeks due to disease progression (n = 20), increased uNTX (n = 14), and SREs (n = 4). Overall SRE incidence was low; 7 (5.8%) and 5 (4.9%) patients experienced an SRE during years 1 and 2, respectively. Mean (SD) SRE rate at year 2 was 0.01 (0.03) per person-year. The 2-year incidence rate for osteonecrosis of jaw was 3.3%. Four deaths were reported, none related to ZOL.Less frequent ZOL dosing (every 12 weeks over 2 years) maintains a low SRE rate and can be safely administered for up to 4 years.
Acute Achilles tendon rupture
Authors: Dishan Singh
Journal: BMJ (2015)

#### What you need to know While playing tennis, a healthy 35 year old man felt as though he had been hit on the back of the lower leg by his opponent’s racquet. He couldn’t keep playing but could walk. He presents the next day with mild bruising, swelling, and weakness while walking. He can walk on tip toes but Simmonds’ triad (calf squeeze, altered angle of declination, and palpable gap) confirms the diagnosis of a ruptured Achilles tendon. A rupture of the Achilles tendon (fig 1⇓) is a disruption in the conjoined tendon of the gastrocnemius and soleus muscles, usually about 2-6 cm proximal to the tendon insertion into the calcaneus.1 Risk factors include increasing age, Achilles tendonopathy, systemic corticosteroids, previous steroid injections into or around the Achilles tendon, and use of quinolone antibiotics.1 2 Fig 1 On opening the paratenon at surgery, the two ends of a complete transverse rupture of the Achilles tendon, with an intervening gap (arrow), are seen. The plantaris tendon is intact (arrowhead) #### How common is acute Achilles tendon rupture?
Identification of continued challenges and opportunities in oncologists' comprehension of immuno-oncology
Authors: Tara Herrmann, Frieda Pearce, Charlotte Warren, Haleh Kadkhoda, Lianne Wiggins, Andrea Rindo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The treatment of cancer is undergoing a revolution, thanks to new advances in the understanding of the immune system. As part of an ongoing educational curriculum, initial assessment of oncologists' knowledge and practice patterns in the use of immunotherapies identified several
A Crusted Papule in a Premature Neonate
Authors: Cory L. Simpson, Markus D. Boos, Leslie Castelo-Soccio
Journal: JAMA Pediatrics (2015)

A premature male newborn with hemolysis, elevated liver enzymes, and low platelets syndrome, acute respiratory distress, and anemia developed a 0.5-cm, circular, crusted papule with a surrounding rim of erythema on the left hip. What is your diagnosis?
Light-emitting diode fluorescence microscopy for tuberculosis diagnosis: a meta-analysis
Authors: Eva W. Chang, Anne-Laure Page, Maryline Bonnet
Journal: European Respiratory Journal (2015)

Light-emitting diode fluorescence microscopy (LED-FM) is recommended by the World Health Organization to replace conventional Ziehl–Neelsen microscopy for pulmonary tuberculosis diagnosis. Uptake of LED-FM has been slow. One reason is its reported loss of specificity compared with Ziehl–Neelsen microscopy. We aimed to determine the diagnostic accuracy of LED-FM for tuberculosis detection and explore potential factors that might affect its performance. A comprehensive search strategy based on pre-specified criteria was employed to identify eligible studies between January 1, 2000 and April 1, 2014 in 11 databases. Standardised study selection, data extraction and quality assessment were conducted. Pooled sensitivity and specificity of LED-FM using culture as the reference standard were estimated through meta-analyses using a bivariate random-effects model. Investigation of heterogeneity was performed by subgroup analyses. We identified 12 unique studies, half of which were from peripheral healthcare facilities. LED-FM achieved a pooled sensitivity of 66.9% (95% CI 60.5–72.7%) and pooled specificity of 96.8% (95% CI 93.1–98.6%). A pooled sensitivity of 53.0% (95% CI 42.8–63.0%) and pooled specificity of 96.1% (95% CI 86.0–99.0%) were obtained by LED-FM among HIV-infected patients. Study methodology factors and differences in the LED-FM procedure or device could also affect the performance. LED-FM specificity is high and should not be a barrier to device introduction, particularly among peripheral healthcare settings where this technology is meant to be used. Sensitivity is reduced in HIV-infected patients.
Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction
Authors: Meri K Tulic, Mylene Vivinus-Nébot, Akila Rekima, Samara Rabelo Medeiros, Chrystelle Bonnart, Haining Shi, Allan Walker, Raffaella Dainese, Julien Boyer, Nathalie Vergnolle, Thierry Piche, Valérie Verhasselt
Journal: Gut (2015)

Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut.To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation.Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS.HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p<0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-α and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p<0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-α but failed to induce IL-10 secretion (p<0.001).HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.
Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium
Authors: Phillip A Gribble, Eamonn Delahunt, Chris Bleakley, Brian Caulfield, Carrie Docherty, François Fourchet, Daniel Tik-Pui Fong, Jay Hertel, Claire Hiller, Thomas Kaminski, Patrick McKeon, Kathryn Refshauge, Philip van der Wees, Bill Vincenzino, Erik Wikstrom
Journal: British Journal of Sports Medicine (2013)

While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.
Does Initial Staging or Tumor Histology Better Identify Asymptomatic Brain Metastases in Patients with Non–small Cell Lung Cancer?
Authors: Ann A. Shi, Subba R. Digumarthy, Jennifer S. Temel, Elkan F. Halpern, Landon B. Kuester, Suzanne L. Aquino
Journal: Journal of Thoracic Oncology (2006)
A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure
Authors: Marc Moss, Amy Nordon-Craft, Dan Malone, David Van Pelt, Stephen K. Frankel, Mary Laird Warner, Wendy Kriekels, Monica McNulty, Diane L. Fairclough, Margaret Schenkman
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Early physical therapy (PT) interventions may benefit patients with acute respiratory failure by preventing or attenuating neuromuscular weakness. However, the optimal dosage of these interventions is currently unknown.To determine whether an intensive PT program significantly improves long-term physical functional performance compared with a standard-of-care PT program.Patients who required mechanical ventilation for at least 4 days were eligible. Enrolled patients were randomized to receive PT for up to 4 weeks delivered in an intensive or standard-of-care manner. Physical functional performance was assessed at 1, 3, and 6 months in survivors who were not currently in an acute or long-term care facility. The primary outcome was the Continuous Scale Physical Functional Performance Test short form (CS-PFP-10) score at 1 month.A total of 120 patients were enrolled from five hospitals. Patients in the intensive PT group received 12.4 ± 6.5 sessions for a total of 408 ± 261 minutes compared with only 6.1 ± 3.8 sessions for 86 ± 63 minutes in the standard-of-care group (P < 0.001 for both analyses). Physical function assessments were available for 86% of patients at 1 month, for 76% at 3 months, and for 60% at 6 months. In both groups, physical function was reduced yet significantly improved over time between 1, 3, and 6 months. When we compared the two interventions, we found no differences in the total CS-PFP-10 scores at all three time points (P = 0.73, 0.29, and 0.43, respectively) or in the total CS-PFP-10 score trajectory (P = 0.71).An intensive PT program did not improve long-term physical functional performance compared with a standard-of-care program. Clinical trial registered with www.clinicaltrials.gov (NCT01058421).
Comparison of Skin Toxic Effects Associated With Gefitinib, Erlotinib, or Afatinib Treatment for Non–Small Cell Lung Cancer
Authors: Kai-Lung Chen, Chia-Chi Lin, Yung-Tsu Cho, Che-Wen Yang, Yi-Shuan Sheen, Hsiao-En Tsai, Chia-Yu Chu
Journal: JAMA Dermatology (2015)

Comparison of Skin Toxic Effects AssociatedWith Gefitinib, Erlotinib, or Afatinib Treatment for Non-Small Cell Lung Cancer Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used to treat non-small cell lung cancer.Four major skin toxic effects with different incidences have been reported from clinical studies, including acneiform eruption (60%-94%), pruritus (16%-60%), xerosis (4%-38%), and paronychia (6%-12%). 1,2However, a direct comparison of the incidences and severities of the 4 types of skin toxic effects for 3 different EGFR-TKIs in the same patient cohort has been lacking to date.
Interleukin-1 synergizes with granulocyte-macrophage colony-stimulating factor on granulocytic colony formation by intermediate production of granulocyte colony-stimulating factor
Authors: MR Schaafsma, JH Falkenburg, N Duinkerken, J Van Damme, BW Altrock, R Willemze, WE Fibbe
Journal: Blood (1989)
Nutrient Regulation: Conjugated Linoleic Acid's Inflammatory and Browning Properties in Adipose Tissue
Authors: Wan Shen, Michael K. McIntosh
Journal: Annual Review of Nutrition (2016)

Obesity is the most widespread nutritional disease in the United States. Developing effective and safe strategies to manage excess body weight is therefore of paramount importance. One potential strategy to reduce obesity is to consume conjugated linoleic acid (CLA) supplements containing isomers cis-9, trans-11 and trans-10, cis-12, or trans-10, cis-12 alone. Proposed antiobesity mechanisms of CLA include regulation of (a) adipogenesis, (b) lipid metabolism, (c) inflammation, (d) adipocyte apoptosis, (e) browning or beiging of adipose tissue, and (f) energy metabolism. However, causality of CLA-mediated responses to body fat loss, particularly the linkage between inflammation, thermogenesis, and energy metabolism, is unclear. This review examines whether CLA's antiobesity properties are due to inflammatory signaling and considers CLA's linkage with lipogenesis, lipolysis, thermogenesis, and browning of white and brown adipose tissue. We propose a series of questions and studies to interrogate the role of the sympathetic nervous system in mediating CLA's antiobesity properties.
POPDC1S201F causes muscular dystrophy and arrhythmia by affecting protein trafficking
Authors: Roland F.R. Schindler, Chiara Scotton, Jianguo Zhang, Chiara Passarelli, Beatriz Ortiz-Bonnin, Subreena Simrick, Thorsten Schwerte, Kar-Lai Poon, Mingyan Fang, Susanne Rinné, Alexander Froese, Viacheslav O. Nikolaev, Christiane Grunert, Thomas Müller, Giorgio Tasca, Padmini Sarathchandra, Fabrizio Drago, Bruno Dallapiccola, Claudio Rapezzi, Eloisa Arbustini, Francesca Romana Di Raimo, Marcella Neri, Rita Selvatici, Francesca Gualandi, Fabiana Fattori, Antonello Pietrangelo, Wenyan Li, Hui Jiang, Xun Xu, Enrico Bertini, Niels Decher, Jun Wang, Thomas Brand, Alessandra Ferlini
Journal: Journal of Clinical Investigation (2015)

The Popeye domain–containing 1 (POPDC1) gene encodes a plasma membrane–localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1S201F displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1S201F and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1S201F in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1S191F) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.
Chronic spontaneous urticaria and internal parasites - a systematic review
Authors: P. Kolkhir, G. Balakirski, H. F. Merk, O. Olisova, M. Maurer
Journal: Allergy (2015)

Abstract Chronic spontaneous urticaria ( CSU ) is defined as persistent wheals, angioedema, or both lasting for &gt;6 weeks due to known or unknown causes. Some epidemiological studies and case reports suggest that internal parasite infections ( PI ) can cause CSU . Here, we provide a systematic overview of published findings on the prevalence and relevance of PI in CSU and we discuss possible pathomechanisms. The prevalence of PI in CSU was investigated by 39 independent studies and comorbidity reportedly ranged from 0 to 75.4% (two‐thirds of these studies reported infection rates of 10% or less). The prevalence of PI in adult and pediatric CSU patients ranged from 0% to 75.4% and from 0% to 37.8%, respectively. CSU patients were more often diagnosed with protozoa and had a significantly higher risk of toxocariasis seropositivity and Anisakis simplex sensitization when compared to healthy controls. Patients with chronic urticaria more frequently had seropositivity of fasciolosis, Anisakis simplex sensitization, and the presence of Blastocystis hominis allele 34 ( ST 3) as compared with control subjects. In 21 studies, efficacy of treatment with antiparasitic drugs ranged from 0 to 100% (35.7% of 269 CSU patients benefitted). In 9 (42.8%) of 21 studies, more than 50% of efficacy was observed. The reported rate of urticaria comorbidity in PI patients in 18 independent studies is 1–66.7%. Urticaria including CSU might be a quite common symptom of strongyloidiasis and blastocystosis. Pathogenic mechanisms in CSU due to PI may include specific IgE, Th2 cytokine skewing, eosinophils, activation of the complement, and the coagulation systems.
Appropriate Screening for Substance Use vs Disorder—Reply
Authors: Quyen Q. Tiet, Rudolf H. Moos, Susan M. Frayne
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine 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 Internal Medicine journal
A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study
Authors: A C Rawstron, C Fazi, A Agathangelidis, N Villamor, R Letestu, J Nomdedeu, C Palacio, O Stehlikova, K-A Kreuzer, S Liptrot, D O'Brien, R M de Tute, I Marinov, M Hauwel, M Spacek, J Dobber, A P Kater, P Gambell, A Soosapilla, G Lozanski, G Brachtl, K Lin, J Boysen, C Hanson, J L Jorgensen, M Stetler-Stevenson, C Yuan, H E Broome, L Rassenti, F Craig, J Delgado, C Moreno, F Bosch, A Egle, M Doubek, S Pospisilova, S Mulligan, D Westerman, C M Sanders, R Emerson, H S Robins, I Kirsch, T Shanafelt, A Pettitt, T J Kipps, W G Wierda, F Cymbalista, M Hallek, P Hillmen, E Montserrat, P Ghia
Journal: Leukemia (2015)

In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10−5). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10−4) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10−6). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.