tbuckley/cabot-search huggingface dataset:
Eosinophilic granulomatosis with polyangiitis involving the small intestine: radiographic and endoscopic findings
Authors: Keisuke Kawasaki, Makoto Eizuka, Okinori Murata, Kazuyuki Ishida, Shotaro Nakamura, Tamotsu Sugai, Takayuki Matsumoto
Journal: Endoscopy (2015)

Eosinophilic granulomatosis with polyangiitis (EGPA), previously referred to as Churg–Strauss syndrome, is an eosinophilic vasculitis that involves the lungs, peripheral nerves, and gastrointestinal (GI) tract [1].
Rapid evolution of variants in a rodent multigene family encoding salivary proteins.
Authors: D P Dickinson, L Mirels, L A Tabak, K W Gross
Journal: Molecular Biology and Evolution (1989)

A survey of polypeptides encoded by RNA isolated from the submandibular glands of members of the Muridae (species of Mus and Rattus), in conjunction with cDNA cloning, has identified a class of salivary proteins that we term "spot proteins." Although clearly homologous, these proteins show dramatic differences between species in their polypeptide length. On the basis of the sequence of the corresponding clones, it is inferred that the rat spot 1 protein has a size of 6,370 daltons (Da), whereas that of the inbred mouse spot 1 is 11,603 Da. A second component is expressed in some stocks and strains of Mus, and this spot 2 protein has a size of up to 19,212 Da. The sizes of the corresponding mRNAs show parallel differences, and the variation in the sizes of mRNAs in different species of Mus correlates with the pattern of speciation, the size increasing with increased relatedness to inbred mice. The spot protein sequence comprises three domains: an N-terminal domain rich in hydroxy and acidic amino acids, a central domain consisting of repeats of a 9-amino-acid sequence, and a C-terminal domain that in the mouse is very basic. Variation in the number of repeats largely accounts for the differences in size between the mouse and rat mRNAs and their encoded polypeptides, and the coding sequence appears to have been expanding during speciation in the Muridae. There is extensive divergence in sequence between the mouse and rat mRNAs and their encoded proteins. The pattern of amino acid replacements and nucleotide substitutions is consistent with little, if any, selection constraint on the precise sequence of the spot proteins, suggesting that it is the overall architecture of the molecule, rather than the precise structure, that is important for function. There is strong evidence for a gene conversion event having occurred between the two mouse sequences. Frequent recombination by unequal crossing-over between spot protein coding sequences, if it occurs between active and silent genes, could account not only for the expansion in their size but also for their rapid divergence.
Iodopovidone: An effective agent pleurodesis used through chest tube
Authors: Kotti Amina, Daghfous Hafaoua, Snan Houda, Saad Soumaya, Kahloul Olfa, Tritar Fatma
Journal: European Respiratory Journal (2012)

Background:  Most variety of pleural irritants have been used for pleurodesis, the ideal agent should produce pleurodesis effectively, safely, and in shortest possible time.  Objectif:  Compare efficacy and safety of iodopovidone used through chest tube to other agents used via thoracoscopy.  Patients and methods:  Fifty six patients (35 men and 21 women) with malignant pleural effusion (n=40) or pneumothorax (n=10) aged from 5 to 76 years, were distributed into 2 groups:  - G1: 40 patients treated with injecting iodopovidone 3 successively days (20 ml iodopovidone + 30 ml saline solution) via chest tube  - G2: 16 patients had pleurodesis through thoracoscopy using talc.  Results:  Time to pleurodesis was similar in 2 groups (8+/- 3 vs 6+/- 2 days). As the mean length of hospitalization (31,13 +/- 22 vs 27,4 +/- 15 days) and mean length of drainage (8,8 +/- 6,1 days vs 10,6 +/- 8,1 days), there is no statistically difference in the 2 groups. A complete response with no recurrence was similar in 2 groups obtained in 44 (78,5%) of cases. After instillation of the sclerosing agent, intense cough and dyspnea were noted only in G1 (n= 3), and 2 patients had systemic hypotension and intense pleuritic pain. Local complications were observed in 10 cases (18%) with no statistically difference in 2 groups: pneumothorax (n= 7) and empyema (n= 3). Chest pain evaluated with visual scale measurement after removed tube was similar in 2 groups. As the mean length of follow-up, there is no statistically difference (5 +/- 2.9 and 6,3 +/- 1,8 months).  Conclusion:  Iodopovidone is an effective, safe, cheap, easily available alternative to achieve chemical pleurodesis in cases of recurrent, incapacitating effusions, regardless of etiology.
The use of plasma n-terminal pro B-type natriuretic peptide (proBNP) concentrations in differential diagnosis of comorbidity pulmonary patients
Authors: Perlat Kapisyzi, Dhimitraq Argjiri, Anila Mitre, Jeta Beli, Anila Aliko, Elenka Shehu, Roland Kore, Ylli Vakeflliu, Holta Tafa
Journal: European Respiratory Journal (2011)

Study objective:  The use of plasma proBNP concentrations as a diagnostic tool in differential diagnosis of dyspnea in comorbidity pulmonary patients.   Design:  Observational study.   Setting:  University Hospital of Lung Diseases, Tirana, Albania.   Patients:  67 patients with pleural effusions and 25 patients with dyspnea of unknown etiology were studied.   Intervention:  Plasma proBNP was measured in patients with dyspnea and pleural effusion.   Measurements and results:  Mean age 71±8.9 yr in patients with pleural effusions caused by CHF (n=38), 64±11.6 yr in patients with exudative effusions (n=29) [p 3.1. proBNP plasma level cut-off of 1500 ng/L had a sensitivity of 50%, specificity of 96.5%,PPV of 94%, positive and negative likely-ratio of 14.2 and 0.07 respectively, in the diagnosis of CH.F. Mean plasma proBNP level in comorbidity pulmonary patients with dyspnea was >300 ng/L, adjusting to age, only in 3 of 18 cases aged 50-70 years it was > 900 ng/L.   Conclusions:  The test of plasma proBNP may be one of the first diagnostic tools in comorbidity pulmonary patients with dyspnea and pleural effusions of unknown origin.
Can the qualification of material be estimated by macroscopic appearance of the EBUS-TBNA smear?
Authors: Ayse Güven, Safak Nur Kader, Sevda Sener Comert, Benan Caglayan, Coskun Dogan, Dilek Ece
Journal: European Respiratory Journal (2014)

AIM:  Without on-side pathology it is difficult to decide about the adequacy of the EBUS-TBNA material. But often assistan staff makes a comment about the qualification of material. The aim of the study is to investigate the predictability of qualification of material from the macroscopic appearence of smear material obtained by EBUS-TBNA.   METHOD:  Smear preperations of EBUS-TBNA materials were given points according to the macroscopic appearances from 0 to 5 by the same assitant staff in December 2013. 0 to 2 was accepted as inadequate material whereas 3 to5 was adequate material. All smears for every aspiration was sent to pathology department with different numbers. The same cytopathologist was eximined the smears without knowledge of macroscopic scores. Macroscopic evaluation of smears was compared with cytopathological results. The data obtained was eximined with SPSS 17.0 program and chi-square test.   RESULTS:  110 smears obtained by different aspirations by EBUS included in study. 23(20.9%) of them were accepted macroscopically as inadequate, 87(79.1%)were adequate.There was a statistically signifficance between microscopic evaluation and lymph node reflection of the smear cytopathologically(p=0.01).   CONCLUSION:  With experience and good training, from the macroscopic appearence of smears obtained from EBUS-TBNA it can be estimated if the lymph node is sampled adequately. Nevertheless more studies whith larger series are necessary in this issue.
Abstract 5544: Patient-derived xenograft study reveals the pharmacology and the role of ESR1 gene aberrations in endocrine therapy resistance of ER positive breast cancer
Authors: Triparna Sen, Shunqiang Li, Jieya Shao, Robert Crowder, Robert Kitchens, Matthew J. Ellis
Journal: Cancer Research (2014)

Abstract Background: The study of estrogen-receptor-positive patient-derived xenografts (PDXs) from patients with disease progression despite endocrine therapy has revealed recurrent ESR1 mutation, gene amplification and ESR1 gene translocations as likely drivers of resistance. We addressed this hypothesis further using pharmacological and genetic approaches in the PDX system. Methodology: ER positive PDXs that harbored one of four recurrent ligand binding domain (LBD) mutations (Y537S/N/C and D538G) as well as a ESR1/YAP1 translocation were studied in parallel with T47D and MCF7 cells expressing these mutants through lentivirus constructs. Single cell suspensions generated from PDX models were using for in vitro experiments using with a panel of endocrine inhibitors and ESR1 shRNA constructs. In vitro effects were confirmed using in vivo tumor response. Results: Cell suspensions from ER+ PDX models in short-term culture successfully reproduced the endocrine therapy resistant phenotypes exhibited by the donor patient, thereby facilitating drugs screens designed to identify new endocrine approaches for ESR1 mutant breast cancer using authentic models rather than an exclusive reliance on models derived by transfection of mutant constructs into standard indicator cell lines. We were also able to demonstrate that that lentivirus-driven shRNA mediated knockdown of ESR1-YAP1 caused inhibition of PDX tumor growth in in vivo and reduced cell growth in vitro, confirming that this chimeric protein is a driver of estradiol-independent growth. Conclusion: ER+ PDX can be manipulated in vitro and in vivo to successfully model ESR1 mutation and gene-rearrangement driven endocrine therapy resistance. PDX studies complement standard ectopic expression systems for the study of ESR1 mutation-driven resistance and, we hypothesize, will provide pharmacological data that will predict the activity of pharmacological agents designed to improve outcomes for patients with ESR1 mutant driven endocrine therapy resistance. Citation Format: Triparna Sen, Shunqiang Li, Jieya Shao, Robert Crowder, Robert Kitchens, Matthew J. Ellis. Patient-derived xenograft study reveals the pharmacology and the role of ESR1 gene aberrations in endocrine therapy resistance of ER positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5544. doi:10.1158/1538-7445.AM2014-5544
Neoadjuvant chemotherapy for adult osteosarcoma: Results of long term follow-up
Authors: M. A. Lowery, K. Cadoo, A. Treacy, M. Walsh, B. Hurson, P. Dervan, D. N. Carney
Journal: Journal of Clinical Oncology (2008)

10543 Background: Neoadjuvant and adjuvant chemotherapy for treatment of osteosarcoma has significantly improved survival rates and rates of limb sparing surgery in the adult population. We present results of 65 adult patients with metastatic and nonmetastatic osteosarcoma treated at our institution over the last 21 years, with median follow-up of 8 years (range 1 to 21 years). Methods: All patients > 14 years treated for osteosarcoma at our institution were identified from the institutional histology database & records reviewed. Results: 80% of patients were male, with a median age of 20 years at diagnosis (range 14 to 71). The site of primary was the femur in 36 patients (55%), the tibia in 11 patients (17%), the humerus in 5 patients (8%); other sites included the ulna, scapula, maxilla, pelvis & calcaneum. 58 patients (89%) had neo-adjuvant chemotherapy with combination of cisplatin / doxorubicin alternating with high-dose methotrexate. 27 patients (42%) had tumour necrosis > 80% and received the same treatment postoperatively. Patients with poor tumour necrosis received VP16/ifosfamide postoperatively. 47 patients (72%) had limb sparing surgery. 8 patients (12%) developed local recurrence at a median time of 18 months (2 to 72). Of these, 3 patients (37%) went on to develop distant metastases. 11 patients in total (17%) developed distant metastases at a median time of 24 months (range: 12 to 48 months). 7 patients underwent resection of pulmonary metastases, of these 3 (43%) were alive and disease free at last follow-up. 56 patients (86%) had localised disease at presentation. Of these patients, 41 (73%) were alive and disease free at last follow-up. 8 patients (12%) had metastatic disease at presentation; of these 2 (25%) were alive and disease free at last follow-up. There was one treatment-related death; no cases of doxorubicin induced cardiomyopathy were identified. Conclusions: At a median follow-up of 8 years, no cases of local or distant recurrence were identified beyond 6 years. With pre- and postoperative chemotherapy, a cure rate of >70% for adult patients with localised disease was confirmed with long term follow-up. The combination of aggressive chemotherapy and surgical resection of metastatic disease resulted in a long term survival rate of 25% for patients presenting with distant metastases. No significant financial relationships to disclose.
Phase 1 study of MEDI4736, an anti-PD-L1 antibody, in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma.
Authors: Michael S. Gordon, Jose Lutzky, Donald P. Lawrence, Keith W. Orford, Andy Blake-Haskins, Alessandra Di Pietro, Paul B. Robbins, Mohammed M. Dar, Antoni Ribas
Journal: Journal of Clinical Oncology (2014)

TPS9108 Background: Greater understanding of tumor immunology in melanoma has led to the development of targeted treatments with improved outcomes in patients (pts) with metastatic melanoma (MM). Dabrafenib, a V600E BRAF inhibitor, combined with trametinib, a MEK inhibitor, resulted in high response rates, progression-free survival (PFS) of 9.4 mo in BRAF mutation-positive melanoma and is now an FDA-approved combination. Adding an immunomodulator may further improve outcomes. MEDI4736, a highly potent anti-PD-L1 antibody, showed clinical activity in a phase 1 study of pts with solid tumors including MM and is being evaluated in combination with dabrafenib/trametinib or trametinib alone in BRAF mutation-positive or BRAFmutation-negative melanoma. Methods: This global, multicenter, open-label phase 1b study (NCT02027961) is enrolling adults with unresectable or MM and ECOG performance status 0-1 into 3 cohorts. In cohort A, BRAF V600E or V600K mutation-positive (BRAF-MP) pts receive dabrafenib orally (PO) twice daily, trametinib PO once daily (QD) and MEDI4736 intravenously (IV) every 2 wks (q2w), given concomitantly followed by continued dabrafenib/trametinib until progressive disease (PD). In cohorts B and C, BRAF V600E or V600K mutation-negative (BRAF-WT) pts receive trametinib PO QD and MEDI4736 IV q2w according to 2 different treatment schedules until PD. Primary objectives are determination of maximum tolerated dose (dose-limiting toxicity) and safety profile (adverse events, laboratory evaluations, physical exams, echocardiograms/electrocardiograms) of MEDI4736 in combination with dabrafenib/trametinib or trametinib alone. Secondary objectives include antitumor activity (objective response based on RECIST, duration of response, PFS, and overall survival), pharmacokinetic profile, and immunogenicity of the combination. Exploratory objectives include biomarkers, patient-reported outcomes, and tumor growth parameters. Recruitment is ongoing (target: 69 pts). Clinical trial information: NCT02027961.
Broad-Spectrum Antifungal Prophylaxis in Patients With Cancer at High Risk for Invasive Mold Infections: Point
Authors: Antonio V. Gonzalez, Andrew J. Ullmann, Nikolaos G. Almyroudis, Brahm H. Segal
Journal: Journal of the National Comprehensive Cancer Network (2008)

Invasive fungal infections (IFIs) are a leading cause of infection-related mortality in patients with acute leukemia and prolonged neutropenia and in allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD). Although invasive candidiasis was the principal IFI predating fluconazole prophylaxis, invasive aspergillosis and other mold infections now cause most deaths from fungal infection in this patient population. The availability of broad-spectrum antifungal agents that can be safely administered over prolonged periods has stimulated interest in using mold-active prophylactic agents early as prophylaxis rather than later as therapy for suspected or documented IFIs. Two recent, prospective, randomized trials have shown a clear benefit of posaconazole prophylaxis in patients with myelodysplastic syndrome and acute mye-logenous leukemia with prolonged neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the peer-reviewed published database on the strategy of preemptive antifungal therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal prophylaxis is used initially and modifications are triggered by a combination of laboratory markers and chest CT scans, is currently limited to an open-label feasibility study. Does sufficient evidence currently exist that the net benefit of the preemptive approach is at least on a par with posaconazole prophylaxis in the specific patient groups that were studied? The authors believe not and that more research is needed before the pre-emptive strategy can be recommended.
High Local Recurrence Risk After Breast-Conserving Therapy in Node-Negative Premenopausal Breast Cancer Patients Is Greatly Reduced by One Course of Perioperative Chemotherapy: A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study
Authors: Paula H. M. Elkhuizen, Henk-Jan van Slooten, Pieter C. Clahsen, Jo Hermans, Cornelis J. H. van de Velde, Lambert C. J. M. van den Broek, Marc J. van de Vijver
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Patients with invasive breast cancer may develop a local recurrence (LR) after breast-conserving therapy (BCT). Younger age has been found to be an independent risk factor for LR. Within a group of premenopausal node-negative breast cancer patients, we studied risk factors for LR and the effect of perioperative chemotherapy (PeCT) on LR. PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare surgery followed by one course of PeCT (fluorouracil, doxorubicin, and cyclophosphamide) with surgery alone. From patients treated on this trial, we selected premenopausal patients with node-negative breast cancer who were treated with BCT to examine whether histologic characteristics and the expression of various proteins (estrogen receptor, progesterone receptor, p53, Ki-67, bcl-2, CD31, c-erbB-2/neu) are risk factors for subsequent LR. Also, the effect of one course of PeCT on the LR risk (LRR) was studied. RESULTS: Using multivariate analysis, age younger than 43 years (relative risk [RR], 2.75; 95% confidence interval [CI], 1.46 to 5.18; P = .002), multifocal growth (RR, 3.34; 95% CI, 1.27 to 8.77; P = .014), and elevated levels of p53 (RR, 2.14; 95% CI, 1.13 to 4.05; P = .02) were associated with higher LRR. Also, PeCT was found to reduce LRR by more than 50% (RR, 0.47; 95% CI, 0.25 to 0.86; P = .02). Patients younger than 43 years who received PeCT achieved similar LR rates as those of patients younger than 43 years who were treated with BCT alone. CONCLUSION: In premenopausal node-negative patients, age younger than 43 years is the most important risk factor for LR after BCT; this risk is greatly reduced by one course of PeCT. The main reason for administering systemic adjuvant treatment is to improve overall survival. The important reduction of LR after BCT is an additional reason for considering systemic treatment in young node-negative patients with breast cancer.
Exercise-induced loss of forced expiratory volume in 1 second in firefighters
Authors: Claudia Gregoriano, Nebal Abu Hussein, Sabrina Maier, Stefanie Zogg, Daniela Margelli Hartmann, David Miedinger, Jörg Daniel Leuppi
Journal: European Respiratory Journal (2013)

Background: In fire brigade environments working with self-contained breathing apparatus (SCBA) might cause bronchoconstriction in firefighters, because of inhalation of dry and cool air delivered by SCBA.  Aims: To investigate the loss in forced expiratory volume in 1 second (FEV1) after exercise with SCBA.  Methods: A prospective study of firefighters assigned to work with SCBA was carried out in Basel. Participants completed questionnaires on respiratory symptoms. Firefighters of the University Hospital Basel were exercise-challenged by climbing up 46 floors of a tower wearing SCBA. Prior to the exercise, exhaled nitric oxide (FeNO) and FEV1 were measured. Upon arrival on the top, FEV1 was assessed every minute during a 10-min period.  Results: 18 firefighters aged 27 to 53 (89% male, age 42.7±7.1yrs) participated in this study. Complete data were available from 13 participants. 8 subjects (62%) were non-smoker and 3 (23%) had an established diagnosis of asthma. Mean FeNO was 13.9±4.6ppb. No participant exceeded the threshold of 25ppb. Mean baseline FEV1 was 3.8± 0.6l/min. 8 individuals (62%) showed a significant drop in FEV1 after this exercise challenge test: 5 individuals (39%) had loss of >10%, 1 (8%) >15% and 2 (15%) >20% in FEV1 after exercise. Participants with and without a significant drop had a mean FeNO of 16±5 and 12±3ppb, respectively (p=ns). All individuals with loss of >15% were current or ex-smoker. 2 out of 3 asthmatics had a significant drop in FEV1 after exercise.  Conclusion: Current and ex-smokers or asthmatics were more likely to have significant loss in FEV1 post exercise with SCBA. Moreover, individuals with significant loss in FEV1 tended to have higher pre-exercise FeNO values.
Abstract 11232: Assessment of Diffuse Myocardial Fibrosis With Native T1 Values on Cardiovascular Magnetic Resonance and Its Relationship With Myocardial Function in Asymptomatic Aortic Stenosis Patients
Authors: Seung-Pyo Lee, Whal Lee, Eun-Ah Park, Hyung-Kwan Kim, Yong-Jin Kim, Dae-Won Sohn
Journal: Circulation (2014)

Introduction: Aortic stenosis (AS) typically provokes diffuse myocardial fibrosis (DMF). Methods to evaluate DMF using cardiovascular magnetic resonance (CMR) are yet to be made easier and validated for wide clinical use. Hypothesis: To test whether T1 mapping, without the use of gadolinium contrast, may be useful for assessment of DMF and whether it correlates with subclinical myocardial dysfunction in asymptomatic AS patients. Methods: 80 asymptomatic patients with moderate or severe AS and normal LVEF and 15 sex-matched control subjects were prospectively enrolled. Patients underwent 2D-echocardiography, speckle tracking imaging and CMR in a 3.0T scanner including mapping of T1 relaxation time with modified Look-Locker Inversion-recovery (MOLLI) sequence. Patients were divided into three groups according to the native T1 value. Results: Native T1 values correlated well with the degree of DMF on intraoperative myocardial biopsy specimens (r=0.777, p-value&lt;0.001) and differed significantly between AS and control subjects (1208±45 vs. 1169±21(msec), p-value&lt;0.001). LV volumes and mass were significantly different between the tertiles (80.8±10.3 vs. 93.4±23.1 vs. 121.5±37.9(mL/m2), 78.0±18.3 vs. 93.4±29.7 vs. 121.1±44.3(g/m2) for LV end-diastolic volume index and LV mass index, all p-value&lt;0.001) as well as the degree of AS severity (0.55±0.14 vs. 0.46±0.12 vs. 0.45±0.13(cm2/m2), p-value=0.008 for indexed aortic valve area on echocardiography). Native T1 significantly correlated with global longitudinal strain by 2D-speckle trackle imaging (r=0.598, p-value&lt;0.001), e’ velocity (r=-0.437, p-value&lt;0.001) and indexed left atrial volume (r=0.475, p-value&lt;0.001). Conclusion: Native T1 value using MOLLI sequence in asymptomatic AS patients enables noninvasive, simple quantification of DMF and correlates well with subclinical LV systolic and diastolic dysfunction.