tbuckley/cabot-search huggingface dataset:
Identification of an Autoantigen Demonstrates a Link Between Interstitial Lung Disease and a Defect in Central Tolerance
Authors: Anthony K. Shum, Jason DeVoss, Catherine L. Tan, Yafei Hou, Kellsey Johannes, Clodagh S. O’Gorman, Kirk D. Jones, Etienne B. Sochett, Lawrence Fong, Mark S. Anderson
Journal: Science Translational Medicine (2009)

A defect in immune tolerance to self-antigens may underlie the lung damage that accompanies many autoimmune diseases.
Cyclooxygenase 2 Expression in Rectal Cancer Is of Prognostic Significance in Patients Receiving Preoperative Radiotherapy
Authors: Pieter de Heer, Marleen J.E.M. Gosens, Elza C. de Bruin, N. Geeske Dekker-Ensink, Hein Putter, Corrie A.M. Marijnen, Adriaan J.C. van den Brule, J. Han J.M. van Krieken, Harm J.T. Rutten, Peter J.K. Kuppen, Cornelis J.H. van de Velde
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To determine the effect of cyclooxygenase (COX)-2 expression on clinical behavior in irradiated and nonirradiated rectal carcinomas. Experimental Design: Tumor samples were collected from 1,231 patients of the Dutch TME trial, in which rectal cancer patients were treated with standardized surgery and randomized for preoperative short-term (5 × 5 Gy) radiotherapy or no preoperative radiotherapy. Tissue microarrays were constructed from primary tumor material, and COX-2 expression was assessed by immunohistochemistry. Tumor cell apoptosis was determined by M30 immunostaining. Results: A high level of COX-2 expression after radiotherapy was associated with low levels of tumor cell apoptosis (P = 0.001). COX-2 expression had no significant effect on patient survival or tumor recurrence in nonirradiated tumors. However, in patients receiving preoperative radiotherapy, high level of COX-2 expression was associated with higher incidence of distant recurrences [P = 0.003; hazard ratio (HR), 1.7; 95% confidence interval (95% CI), 1.2-2.5] and shorter disease-free survival (P = 0.002; HR, 1.8; 95% CI, 1.2-2.5) and overall survival (P = 0.009; HR, 1.5; 95% CI, 1.1-2.0), independent of patient age, tumor stage, tumor location, or the presence of tumor cells in the circumferential resection margin. Conclusions: A high level of COX-2 expression after preoperative radiotherapy in resection specimens is associated with apoptosis resistance, high distant recurrence rates, and a poor prognosis in rectal cancer.
Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period
Authors: Fabrice Andre, Khemaies Slimane, Thomas Bachelot, Arianne Dunant, Moise Namer, Alain Barrelier, Omar Kabbaj, Jean Philippe Spano, Hugo Marsiglia, Roman Rouzier, Suzette Delaloge, Marc Spielmann
Journal: Journal of Clinical Oncology (2004)

Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis.A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by chi(2) test, log-rank test, and Cox regression analysis.Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P <.001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P <.001).The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.
Gross hypertrophic pulmonary osteoarthropathy in a 7-year-old child
Authors: N. Barclay, M. Ogbeide, I. A. Grillo
Journal: Thorax (1970)

Hypertrophic pulmonary osteoarthropathy in children is rare and usually associated with an underlying condition. A case of hypertrophic pulmonary osteoarthropathy secondary to a chronic post-measles lung abscess is presented. There was good radiological evidence of an advanced degree of periosteal reaction. This became much more obvious during an exacerbation of the illness. Films taken 10 months after resection of the affected lobe showed almost complete resolution of the bone condition. A feature that is well known in adults, but has not previously been reported in a child, was the exquisite tenderness of the affected bones. The literature is reviewed.
Gastric antral vascular ectasia in systemic sclerosis: complete resolution with methylprednisolone and cyclophosphamide
Authors: A R Lorenzi
Journal: Annals of the Rheumatic Diseases (2001)

A case of severe, transfusion dependent anaemia in a 72 year old woman, which on endoscopy was found to be due to gastric antral vascular ectasia (GAVE), is reported. Repeated endoscopic sclerotherapy was ineffective. She subsequently developed Raynaud9s phenomenon and on further investigation was found to have classical systemic sclerosis with lung involvement. Treatment with pulses of intravenous methylprednisolone and cyclophosphamide resulted in significant improvement in her pulmonary function tests and skin score. Coincidentally, her haemoglobin stabilised and further endoscopic examinations were normal. This is the first report of cyclophosphamide and methylprednisolone leading to complete and sustained resolution of GAVE in association with systemic sclerosis.
Restricted Clonal Expression of IL-2 By Naive T Cells Reflects Differential Dynamic Interactions with Dendritic Cells
Authors: Vincent Hurez, Arman Saparov, Albert Tousson, Michael J. Fuller, Takekazu Kubo, James Oliver, Benjamin T. Weaver, Casey T. Weaver
Journal: The Journal of Experimental Medicine (2003)

Limited frequencies of T cells express IL-2 in primary antigenic responses, despite activation marker expression and proliferation by most clonal members. To define the basis for restricted IL-2 expression, a videomicroscopic system and IL-2 reporter transgenic model were used to characterize dendritic cell (DC)-T cell interactions. T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2. Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression. Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Authors: Rebecca C Coll, Avril A B Robertson, Jae Jin Chae, Sarah C Higgins, Raúl Muñoz-Planillo, Marco C Inserra, Irina Vetter, Lara S Dungan, Brian G Monks, Andrea Stutz, Daniel E Croker, Mark S Butler, Moritz Haneklaus, Caroline E Sutton, Gabriel Núñez, Eicke Latz, Daniel L Kastner, Kingston H G Mills, Seth L Masters, Kate Schroder, Matthew A Cooper, Luke A J O'Neill
Journal: Nature Medicine (2015)
Bilateral Pneumothoraces After Resuscitation With Esophageal Airway
Authors: Michael G. Sarr
Journal: JAMA (1980)

To the Editor.—  Use of the esophageal obturator airway, generally by the emergency medical technician (EMT), has proved to be a safe, facile, and effective means of ventilation in emergencies. 1 However, it is not without complications, as reported by Carlson et al (241:1154, 1979). A case seen recently adds another possible complication. A middle-aged man apparently had a cardiac arrest at home. Initial resuscitation by the EMT during transport included ventilation using an esophageal obturator airway. On arrival at the emergency room, the patient had massive subcutaneous emphysema of the entire torso, which had developed en route. Attempts at rapid resuscitation proved futile. Postmortem chest roentgenogram minutes later disclosed not only mediastinal emphysema, but also massive bilateral pneumothoraces.  Although an autopsy was not granted, this case most likely demonstrates one complication of the use of the esophageal airway, ie, esophageal disruption. Positive-pressure mask ventilation probably led to mediastinal emphysema,
Salt Lake City, Andre Agassi and Irene Davis: BJSM's letter from the Americas...
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2011)

Warm upwhether to accept a runner-up cheque for $1100.He needed the money, but taking it would mean losing his amateur status...He rang his dad for advice.'What the hell do you mean?Take the money'.Andre countered, 'If I take the money Dad, there's no turning back.I'm pro.'...His dad acted as if there was a bad connection.'You've dropped out of school!You have an eighth-grade education.What are your choices?What the hell
Neoplastic Diseases (Tumor Chemotherapy)
Authors: R. Lee Clark, Wataru W. Sutow
Journal: Annual Review of Medicine (1959)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
A clinically relevant SCID-hu in vivo model of human multiple myeloma
Authors: Pierfrancesco Tassone, Paola Neri, Daniel R. Carrasco, Renate Burger, Victor S. Goldmacher, Robert Fram, Vidit Munshi, Masood A. Shammas, Laurence Catley, Gary S. Jacob, Salvatore Venuta, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Tumor Necrosis Factor-α–Converting Enzyme (ADAM17) Mediates GPIbα Shedding From Platelets In Vitro and In Vivo
Authors: Wolfgang Bergmeier, Crystal L. Piffath, Guiying Cheng, Vandana S. Dole, Yuhua Zhang, Ulrich H. von Andrian, Denisa D. Wagner
Journal: Circulation Research (2004)

Interaction of the platelet receptor glycoprotein (GP) Ib-V-IX with von Willebrand factor exposed at a site of vascular injury is an essential step in the initiation of a hemostatic plug. Proteolytic cleavage (shedding) of the GPIbalpha subunit was first described >25 years ago, the protease mediating this event as well as its physiological function, however, have not been elucidated. We reported recently that shedding of GPIbalpha induced by platelet storage or mitochondrial injury involves a platelet-derived metalloproteinase(s). Here we show that GPIbalpha shedding in response to mitochondrial injury or physiological activation is inhibited in platelets obtained from chimeric mice, which express inactive tumor necrosis factor-alpha converting enzyme (TACE(DeltaZn/DeltaZn)) in blood cells only. Shedding was also inhibited in mouse and human platelets in the presence of 2 potent TACE inhibitors: TAP1 and TMI-1. Our data further suggest that TACE is important in the regulation of GPIbalpha expression in vivo because we observed an approximately 90% reduction in soluble GPIbalpha (glycocalicin) in plasma of TACE(DeltaZn/DeltaZn) chimeras as well as significantly increased levels of GPIbalpha on circulating platelets. In contrast, shedding of P-selectin from activated platelets was not affected by the mutation in TACE. Damaged TACE(DeltaZn/DeltaZn) platelets were further characterized by a markedly improved post-transfusion recovery and hemostatic function in mice. In conclusion, our data demonstrate that TACE is expressed in platelets and that it is the key enzyme mediating shedding of GPIbalpha.
Mothers’ Functioning and Children’s Symptoms 5 Years After a SCUD Missile Attack
Authors: Nathaniel Laor, Leo Wolmer, Donald J. Cohen
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors assessed the long-term consequences of the SCUD missile attack in Israel on children as a function of their mothers' psychological functioning, family cohesion, and the event itself. METHOD: Five years after the Gulf War, the authors assessed the internalizing, externalizing, stress, and posttraumatic symptoms of 81 children aged 8–10 years whose homes were damaged in the SCUD missile attack, as well as general and posttraumatic symptoms, defensive style, and object relations in their mothers. RESULTS: There was a significant decrease in severity in most symptom domains and an increase in avoidant symptoms in the children. Greater severity of symptoms was associated with being displaced, living in a family with inadequate cohesion, and having a mother with poor psychological functioning. The association between the symptoms of children and mothers was stronger among the younger children. Posttraumatic symptoms increased in one-third of the children and decreased in one-third over the last 30 months of the study. Severe posttraumatic symptoms were reported in 8% of the children. CONCLUSIONS: Despite a continuous decrease in symptom severity, risk factors identified shortly after the Gulf War continued to exert their influence on children 5 years after the traumatic exposure.
Transcriptional Output of the Salvador/Warts/Hippo Pathway Is Controlled in Distinct Fashions in <i>Drosophila melanogaster</i> and Mammalian Cell Lines
Authors: Xiaomeng Zhang, Claire C. Milton, Patrick O. Humbert, Kieran F. Harvey
Journal: Cancer Research (2009)

The Salvador/Warts/Hippo (SWH) pathway is an important modulator of organ size, and deregulation of pathway activity can lead to cancer. Several SWH pathway components are mutated or expressed at altered levels in different human tumors including NF2, LATS1, LATS2, SAV1, and YAP. The SWH pathway regulates tissue growth by restricting the activity of the transcriptional coactivator protein known as Yorkie (Yki) in Drosophila melanogaster and Yes-associated protein (YAP) in mammals. Yki/YAP drives tissue growth in partnership with the Scalloped (Sd)/TEAD1-4 transcription factors. Yki/YAP also possesses two WW domains, which contact several proteins that have been suggested to either promote or inhibit the ability of Yki to induce transcription. To investigate the regulatory role of the Yki/YAP WW domains, we analyzed the functional consequence of mutating these domains. WW domain mutant YAP promoted transformation and migration of breast epithelial cells with increased potency, suggesting that WW domains mediate the inhibitory regulation of YAP in these cells. By contrast, the WW domains were required for YAP to promote NIH-3T3 cell transformation and for the ability of Yki to drive tissue growth in D. melanogaster and optimally activate Sd. This shows that Yki/YAP WW domains have distinct regulatory roles in different cell types and implies the existence of proteins that promote tissue growth in collaboration with Yki and Sd.
Rheumatoid arthritis secondary non-responders to TNF can attain an efficacious and safe response by switching to certolizumab pegol: a phase IV, randomised, multicentre, double-blind, 12-week study, followed by a 12-week open-label phase
Authors: Michael H Schiff, Johannes von Kempis, Ronald Goldblum, John R Tesser, Ruediger B Mueller
Journal: Annals of the Rheumatic Diseases (2014)

To study the efficacy and safety of certolizumab pegol (CZP) in patients with active rheumatoid arthritis (RA) who had discontinued an initially effective TNF inhibitor (TNF-IR).A randomised 12-week double-blind trial with CZP (n=27) or placebo (n=10) followed by an open-label 12 week extension period with CZP.Baseline characteristics of the 2 groups were similar. ACR20 response (primary end point) at week 12 was achieved in 61.5%, and none of CZP and placebo-treated patients, respectively. Weeks 12-24 showed a maximum effect for CZP at 12 weeks, and that placebo patients switched blindly to CZP attained similar results seen with CZP in weeks 0-12. Since this result was highly significant, study inclusion was terminated after entry of 33.6% of the originally planned 102 patients. Adverse events occurred in 16/27 (59.3%) CZP subjects and 4/10 (40%) placebo subjects. There were no serious adverse events, neoplasms, opportunistic, or serious infections.This first, prospective, blinded trial of CZP in secondary TNF-IR shows that the ACR20 response rate observed with CZP was higher than that reported in most previous studies of TNF-IR. Additionally, CZP demonstrated good safety and tolerability. This study supports the use of CZP in RA patients who are secondary non-responders to anti-TNF therapies.
Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors.
Authors: M Roach, D R Gandara, H S Yuo, P S Swift, S Kroll, D C Shrieve, W M Wara, L Margolis, T L Phillips
Journal: Journal of Clinical Oncology (1995)

To identify factors associated with radiation pneumonitis (RP) resulting from combined modality therapy (CMT) for lung cancer.Series published before 1994 that used CMT for the treatment of lung cancer and explicitly reported the incidence of RP are the basis for this analysis. Factors evaluated included the radiation dose per fraction (Fx), total radiation dose, fractionation scheme (split v continuous), type of chemotherapy and intended dose-intensity, overall treatment time, histology (small-cell lung cancer [SCLC] v non-small-cell lung cancer [NSCLC]), and treatment schedule (concurrent v induction, sequential, or alternating CMT).Twenty-four series, including 27 treatment groups and 1,911 assessable patients, met our criteria for inclusion in this analysis. The median total dose of radiation used in the trials analyzed was 50 Gy (range, 25 to 63 Gy). The median daily Fx used was 2.0 Gy (range, 1.5 to 4.0 Gy). Nineteen series included 22 treatment groups and 1,745 patients treated with single daily fractions. Among these patients, 136 received a daily Fx greater than 2.67 Gy. Five series used twice-daily radiotherapy and included 166 patients (Fx, 1.5 to 1.7 Gy). The incidence of RP was 7.8%. In a multivariate analysis, only daily Fx, number of daily fractions, and total dose were associated with the risk of RP (P < .0001, P < .018, and P < .003, respectively).In this analysis, the use of Fx greater than 2.67 Gy was the most significant factor associated with an increased risk of RP. High total dose also appears to be associated with an increased risk, but twice-daily irradiation seems to reduce the risk expected if the same total daily dose is given as a single fraction. High-Fx radiotherapy should be avoided in patients who receive CMT with curative intent.
Vascular Endothelial Growth Factor Concentration as a Predictive Marker: Ready for Primetime?
Authors: Peter A. Kavsak, Hal Hirte, Sebastien J. Hotte
Journal: Clinical Cancer Research (2010)

To the Editors:  The article by Hanrahan et al. in the May issue of  Clinical Cancer Research  (1) describes the clinical utility of baseline vascular endothelial growth factor (VEGF) to identify subjects who may benefit from treatment with vandetanib (a VEGF receptor/epidermal growth factor receptor/RET inhibitor; ref. 1). However, important issues, such as preanalytic, analytic, and postanalytic interpretation for VEGF concentrations, need to be addressed before a VEGF cutoff can be “applied to clinical practice” as the authors conclude.  First, an important preanalytic issue is the choice of sample type (e.g., matrix). Hanrahan and colleagues indicate that sample type (serum versus EDTA plasma) is a major factor in the concentrations observed, which cannot be easily extrapolated when considering reference intervals and cutoffs. For example, despite using the matrix-specific cutoffs in their study groups (e.g., study groups 3, 6, and 7), only the low VEGF group in study groups 3 and 6 (both with EDTA plasma) had significant lower hazard ratios ( P    Second, the analytic performance of the VEGF assay was not reported; only the limit of detection and analytic range were stated. Without knowledge of the precision across the analytic range, it cannot be assumed that adequate performance was obtained at the different cutoffs used in the study.  Third, the cutoffs chosen are likely inappropriate. The population where the cutoffs are derived is not characterized (e.g., sex, age, and biochemical indices not provided) and the sample size is too small ( n  = 37; ref. 1). Minimally, 120 healthy individuals are required to establish a reference interval, and more if subgrouping is required (3). This type of reference interval study has previously been done for VEGF in EDTA plasma ( n  = 304 children;  n  = 540 adults), which showed that VEGF concentrations are age dependent, with positive associations existing with platelet count, alanine aminotransferase, and oral contraceptive use (4). Unfortunately, Hanrahan et al. (1) did not include these important covariates in their models.  We believe that future prospective studies assessing VEGF measurement should incorporate these important preanalytic, analytic, and postanalytic issues.  Disclosure of Potential Conflicts of Interest  P. Kavsak, commercial research grant and honoraria, Beckman Coulter; commercial research support, Randox Ltd.
Nutritional aspects of women strength athletes
Authors: J S Volek, C E Forsythe, W J Kraemer
Journal: British Journal of Sports Medicine (2006)

Strength training elicits sports related and health benefits for both men and women. Although sexual dimorphism is observed in exercise metabolism, there is little information outlining the specific nutritional needs of women strength athletes. Many women athletes restrict energy intake, specifically fat consumption, in order to modify body composition, but this nutritional practice is often counter-productive. Compared to men, women appear to be less reliant on glycogen during exercise and less responsive to carbohydrate mediated glycogen synthesis during recovery. Female strength athletes may require more protein than their sedentary and endurance training counterparts to attain positive nitrogen balance and promote protein synthesis. Therefore, women strength athletes should put less emphasis on a very high carbohydrate intake and more emphasis on quality protein and fat consumption in the context of energy balance to enhance adaptations to training and improve general health. Attention to timing of nutrient ingestion, macronutrient quality, and dietary supplementation (for example, creatine) are briefly discussed as important components of a nutritionally adequate and effective strength training diet for women.