tbuckley/cabot-search huggingface dataset:
Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer
Authors: Edmund K. Moon, Raghuveer Ranganathan, Evgeniy Eruslanov, Soyeon Kim, Kheng Newick, Shaun O'Brien, Albert Lo, Xiaojun Liu, Yangbing Zhao, Steven M. Albelda
Journal: Clinical Cancer Research (2015)

Tumor-infiltrating lymphocytes (TILs) become hypofunctional, although the mechanisms are not clear. Our goal was to generate a model of human tumor-induced TIL hypofunction to study mechanisms and to test anti-human therapeutics.We transduced human T cells with a published, optimized T-cell receptor (TCR) that is directed to a peptide within the cancer testis antigen, NY-ESO-1. After demonstrating antigen-specific in vitro activity, these cells were used to target a human lung cancer line that expressed NY-ESO-1 in the appropriate HLA context growing in immunodeficient mice. The ability of anti-PD1 antibody to augment efficacy was tested.Injection of transgenic T cells had some antitumor activity, but did not eliminate the tumors. The injected T cells became profoundly hypofunctional accompanied by upregulation of PD1, Tim3, and Lag3 with coexpression of multiple inhibitory receptors in a high percentage of cells. This model allowed us to test reagents targeted specifically to human T cells. We found that injections of an anti-PD1 antibody in combination with T cells led to decreased TIL hypofunction and augmented the efficacy of the adoptively transferred T cells.This model offers a platform for preclinical testing of adjuvant immunotherapeutics targeted to human T cells prior to transition to the bedside. Because the model employs engineering of human T cells with a TCR clone instead of a CAR, it allows for study of the biology of tumor-reactive TILs that signal through an endogenous TCR. The lessons learned from TCR-engineered TILs can thus be applied to tumor-reactive TILs.
Çeşitli Tedavi Yöntemlerinin 352 Vitiligo LezyonundaRepigmentasyon Patterni, Hız Ve Stabilitesi ÜzerindekiEtkilerinin İncelendiği Klinik Bir Çalışma
Authors: Davinder Parsad, Roma Pandhi, Sunil Dogra
Journal: Journal of the American Academy of Dermatology (2004)
Role of oxidants during lung development and bronchial hyper-reactivity after in utero nicotine exposure
Authors: Filippo Zanetti, Yves Donati, Stephanie Carnesecchi, Constance Barazzone
Journal: European Respiratory Journal (2013)

Maternal smoke during pregnancy is associated with several adverse fetal outcomes that strongly increase the susceptibility to develop secondary diseases in late infancy. Nicotine, the principal active component in cigarette smoke, can freely cross the placenta and accumulate in the developing fetus and in maternal milk, affecting lung development and reducing pulmonary functions. In vitro, nicotine can directly increase reactive oxygen species (ROS) production in different cell types, suggesting their possible involvement in nicotine-induced oxidative stress. In this study we aim to characterize the NADPH oxidase (NOX) contribution to nicotine-mediated oxidative stress. We therefore cultured MLE-12, a lung epithelial cell line, with saline or-with 1μM or 100μM nicotine for 48 hours. Nicotine increased ROS production as well as apoptosis, as assessed by dihydroethidium staining, TUNEL staining and cleaved caspase-3 levels. ROS production was blocked in a stably transfected MLE-12 with NOX1 shRNA. We also exposed pregnant wild-type mice to oral saccharin (2%, control) or nicotine (200 ng/ml in 2% saccharin) during the gestation and for 16 days after birth. Pups were euthanized at day 2, 8 and 16 (postnatal, PND); we observed a significant increase in the expression of NOX1, NOX2 and NOX4 mRNA in lungs of PND2 pups.  These preliminary results suggest that nicotine can induce oxidative stress, counteracted by genetic ablation of NOX1, and caspase-mediated apoptosis in a murine lung epithelial cell line and a possible involvement of NOXs enzymes in nicotine-induced lung development alterations in utero.
The assessment and treatment of performance anxiety in musicians
Authors: D B Clark, W S Agras
Journal: American Journal of Psychiatry (1991)

Performance anxiety in musicians may be severe enough to require intervention but has been the subject of relatively little clinical research. The authors' objectives were to describe the results of a comprehensive clinical and laboratory assessment and to perform a double-blind, placebo-controlled study comparing buspirone, cognitive-behavior therapy, and the combination of these treatments for performance anxiety.Ninety-four subjects were recruited by mass media announcements and were seen in a university-based outpatient psychiatric clinic. Assessments were 1) questionnaires for all 94 subjects, 2) diagnostic interview of 50 subjects, and 3) laboratory performance of 34 subjects. Treatment conditions were 1) 6 weeks of buspirone, 2) 6 weeks of placebo, 3) a five-session, group cognitive-behavior therapy program with buspirone, or 4) the cognitive-behavior therapy program with placebo. Treatment outcome measures included subjective anxiety ratings and heart rate measures during a laboratory performance, a questionnaire measure of performance confidence, and a blind rating of musical performance quality.All subjects fulfilled criteria for DSM-III-R social phobia. Of the 15 full-time professional musicians, ten had tried propranolol and three had stopped performing. Most of the subjects had substantial anxiety and heart rate increases during laboratory speech and musical performances. Cognitive-behavior therapy resulted in statistically significant reductions in subjective anxiety, improved quality of musical performance, and improved performance confidence. Buspirone was not an effective treatment.Cognitive-behavior therapy is a viable treatment approach for performance anxiety in musicians.
Cutaneous Nerve Fibre Depletion in Vibration White Finger
Authors: P C Goldsmith, F Abadia Molina, C B Bunker, G Terenghi, T A Leslie, Clare J Fowler, J M Polak, Pauline M Dowd
Journal: Journal of the Royal Society of Medicine (1994)

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the ‘white attacks’. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger. There was a significant reduction in both the number of CGRP and protein gene product 9.5 (PGP) immunoreactive nerve fibres in the digital cutaneous biopsies from the patients with vibration white finger when compared to the biopsies from the heavy manual workers and the healthy workers exposed to vibration. The pattern of the loss of CGRP immunoreactive nerve fibres was similar to that described previously in Raynaud's phenomenon and may account for the episodic vasospasm seen in both conditions. PGP is a constitutive protein of all nerves therefore the reduced PGP immunostaining indicates generalized structural neuronal damage which could account for the persistent pain and paraesthesiae characteristic of vibration white finger. The nerve conduction studies revealed sensory nerve action potentials within the low range of normal in five patients with vibration white finger and mild median nerve compression in the remaining patient implying that the neuronal damage in the patients with vibration white finger is confined mainly to the small unmyelinated nerve fibres. The immunohistochemical findings may provide the basis for a diagnostic test for vibration white finger.
Children’s radiology services lack specialist input, audit finds:
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Children in the United Kingdom are being failed by radiology services that are missing targets set out by the Department of Health five years ago, an audit has found.1

It warned that a large proportion of radiographers and radiologists who take and interpret children’s radiographs and scans lack specialist training and experience and are not keeping up to date with developments in the field.

The Royal College of Radiologists received responses from 87 of 198 eligible hospitals from all four countries of the United Kingdom for its audit, which began in 2012. It assessed how these hospitals were performing against a 2010 …
Abstract 3056: Sirt1 Limits Endothelial Notch Signaling During Blood Vessel Growth Through NICD Deacetylation
Authors: Michael Potente, Virginia Guarani, Gianluca Deflorian, Raul Mostoslavsky, Ralf Brandes, Marina Mione, Holger Gerhardt, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2009)

Expansion of the blood vascular network through sprouting angiogenesis requires the specification of endothelial cells into leading (sprouting) tip and following (non-sprouting) stalk cells. This s...
BK Nephritis and Venous Thrombosis in Renal Transplant Recipient Detected by 111In Leukocyte Imaging
Authors: Darko Pucar, Kandace Klein, James Corley, Hadyn T. Williams
Journal: Clinical Nuclear Medicine (2015)

Three months after deceased donor kidney transplant, a patient who presented with proteinuric renal dysfunction and fever of undetermined origin was found to have BK viruria by quantitative polymerase chain reaction analysis. An ¹¹¹In leukocyte scan showed increased renal transplant uptake consistent with nephritis and linear uptake in the knee. Venous duplex ultrasound revealed acute occlusive thrombosis in the superficial right lesser saphenous vein in the area of increased radiolabeled leukocyte uptake. This ¹¹¹In leukocyte scan performed for fever of undetermined origin demonstrated findings of BK nephritis in a renal transplant patient and associated acute venous thrombosis related to leukocyte colonization.
High-flow Transtracheal Insufflation Treats Obstructive Sleep Apnea
Authors: HARTMUT SCHNEIDER, DANIEL J. O'HEARN, KAREN LEBLANC, PHILIP L. SMITH, CHRISTOPHER P. O'DONNELL, DAVID W. EISELE, J. H. PETER, ALAN R. SCHWARTZ
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To determine the effect of transtracheal insufflation (TTI) on obstructive sleep apnea (OSA), we examined breathing patterns in five tracheostomized patients with OSA at varying TTI flow rates when breathing with a closed tracheostomy. The breathing patterns and polysomnographic responses to air insufflation were studied as TTI was increased from 0 to 15 L/min for brief periods of non–rapid eye movement (NREM) sleep (Experiment 1). The frequency of sleep-disordered breathing episodes remained high at 0 and 5 L/min (87.0 ± 33.7 and 79.4 ± 24.4 episodes per hour NREM) and decreased significantly to 41.3 ± 31.5 and 43.4 ± 31.4 episodes/h NREM sleep at rates of 10 and 15 L/min, respectively (p = 0.003). At high levels of TTI (10 and 15 L/min), obstructive apneas and hypopneas decreased but periodic laryngeal obstructions were induced during stage 1 NREM sleep. To prevent laryngeal obstructions, a servo-control system was used to briefly interrupt TTI during these events. When this system was implemented for more prolonged periods of sleep (Experiment 2, total sleep time 176.6 ± 12.5 min), high-flow TTI (hf-TTI, 15 L/min) led to an overall reduction in the combined frequency of obstructive apneas and laryngeal obstructions from 63.8 ± 21.8 to 10.7 ± 9.1 (p < 0.03) and was associated with a marked reduction in arousal frequency from 60.0 ± 26.0 to 8.3 ± 5.4/h in NREM sleep, and from 67.5 ± 3.5 to 0 ± 0/h in rapid eye movement (REM) sleep. Our findings demonstrate that hf-TTI stabilized breathing patterns in apneic patients, and was safe and efficacious for prolonged periods of sleep.
Authors’ reply to Waldron and Doherty
Authors: Alexander Kumar, Gail Beckett, Martin Wiselka
Journal: BMJ (2015)

We welcome Waldron and Doherty’s reply and are reassured by local efforts.1 2 We agree that for UK and Northern Ireland alone, the threat is low. However, our letter was aimed at an international readership, and Middle East respiratory syndrome coronavirus (MERS-CoV) infected travellers pose different threats to each receiving country because awareness and diagnosis are not uniform worldwide.

The case …
Second Year of Bezmialem Vakif University pediatric pulmonology bronchoscopy unit: Anesthesia and laryngeal mask airway experiences
Authors: Erkan Cakir, Ahmet Hakan Gedik, Tarik Umutoglu, Ufuk Topuz, Erdogan Ozturk
Journal: European Respiratory Journal (2013)

Introduction: Fiberoptic flexible bronchoscopy (FOB) has a widespread indication after a variety chronic respiratory disorders. Consequently the patient profile includes severe respiratory problems and even intubated patients. FOB procedure, anesthesia, and observational phases are tailor made for every individuals. Laryngeal mask airway (LMA) use at the pediatric FOB procedure in case of a necessity has many advantages. Aim: To present our experiences with anesthesia and LMA. Method: 615 cases between February 2011 and January 2013 evaluated. Findings: First 257 case were performed without the staff anesthesist support. Between December 2011 and January 2013, 358 case performed with the staff anesthesist support. At the Initial 16 cases with staff anesthesist; patients were sedated and upper airway structures examined via nasal FOB afterward sedation deepened and FOB performed via LMA. Since LMA instrumentation requires deep sedation, consequently at remaining 342 cases, FOB started and completed with nasal access under moderate sedation (n:262) and in case of a necessity procedure completed via LMA (n:80). LMA indications were; desaturation 9%, delayed procedure 6%, smaller size and weight of the patient for bronchoscopy 5%, viscous mucus secretions % 5, intubated patients 3%, tracheostomised patients 1%. Conclusion: We conclude that during pediatric FOB procedure presence and support of staff anesthesiologist; starting and completing nasal FOB and in case of a necessity the use of LMA seems to be most comfortable and advantageous way.
Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study
Authors: I.P. Korbila, A. Michalopoulos, P.I. Rafailidis, D. Nikita, G. Samonis, M.E. Falagas
Journal: Clinical Microbiology and Infection (2009)
Abstract 8603: Expression of Human Interleukine-37 Protects Mouse Heart Against Ischemic Injury Through Suppression of Monocyte Chemoattractant Protein-1-Mediated Mononuclear Cell Accumulation
Authors: Nasser G Yousif, Jilin Li, Fadhil Yousif, Lihua Ao, Chunhua Jin, David A Fullerton, Charles A Dinarello, Xianzhong Meng
Journal: Circulation (2011)

Myocardial inflammatory response to ischemia, involving up-regulated chemokine expression and leukocyte accumulation, contributes to the mechanism of myocardial injury and cardiac dysfunction. IL-37 is a new human cytokine and has an anti-inflammatory function. Currently, it is unknown whether IL-37 suppresses myocardial inflammatory response to ischemia. We tested the hypothesis that expression of human IL-37 in mouse protects the heart against ischemic injury and LV dysfunction through suppression of the myocardial inflammatory response. The purposes of this study were to determine: 1) the effect of expression of human IL-37 transgene on myocardial injury in mice after coronary artery ligation, 2) whether IL-37 suppresses myocardial chemokine expression and leukocyte accumulation following ischemia and 3) whether IL-37 modulates the inflammatory response of cardiac vascular endothelial cells (CVECs) to in vitro pro-inflammatory stimulation. Methods and results: IL-37 Tg and WT mice were subjected to left anterior descending coronary artery ligation. In addition, CVECs isolated from IL-37 Tg and WT mice were stimulated with TLR2 and TLR4 agonists. Expression of IL-37 markedly reduced infarct size and improved LV function. The protective effects of IL-37 were associated with reduced IKK phosphorylation, NF-κB intranuclear translocation, MCP-1 production and mononuclear cell accumulation in the ischemic myocardium. In WT mice, neutralization of MCP-1 or MCP-1 KO reduced mononuclear cell accumulation, infarct size and LV function deficit. Further, prior depletion of monocytes resulted in infarct size reduction and LV function improvement in WT mice. In vitro studies in mouse CVECs found that expression of IL-37 suppressed NF-κB activation and MCP-1 production induced by stimulation of TLR2 or TLR4. Conclusion: This study demonstrates that IL-37 protects the heart against ischemic injury and LV dysfunction through suppression of MCP-1 production and the resultant mononuclear cell accumulation. These findings suggest that this novel anti-inflammatory cytokine has a therapeutic potential for the regulation of myocardial inflammatory response to ischemia and for protection against ischemic myocardial injury.
Longitudinal development of lung function in extremely preterm infants
Authors: Maria Vollsaeter, Ola Røksund, Geir Egil Eide, Markestad Trond, Thomas Halvorsen
Journal: European Respiratory Journal (2011)

Introduction:  With the advent of modern neonatal intensive care, survival after extreme preterm (EP) birth increased considerably. Large cohorts of subjects born EP are now approaching adulthood; their lifelong pulmonary prospects being basically unknown.   Aims:  To construct spirometric growth curves to early adulthood for subjects born EP.   Methods:  Two area-based birth-cohorts of subjects born in 1982-85 and 1991-92 at gestational age ≤28 weeks or with birth weight ≤1000 grams (n=81) and individually matched control subjects born at term (n=74) were examined in 2001 and 2009. Paired multiple linear regression models were constructed to assess growth patterns.   Results:  Most measures of lung function were significantly reduced in subjects born EP over the full study period. Mean growth of FEV1 through puberty was 1.5 liters in both preterm and control subjects, and there was a small but not significant growth from age 18 to 25.   Conclusions:  Lung function deficits after EP birth persists to adult life. Growth in lung function was parallel in subjects born EP and at term, and no signs of age related decline was observed at age 25.
Fetal exposure to dietary carcinogens and risk of childhood cancer: what the NewGeneris project tells us: Table 1 
Authors: Jos Kleinjans, Maria Botsivali, Manolis Kogevinas, Domenico Franco Merlo
Journal: BMJ (2015)

Jos Kleinjans and colleagues summarise the evidence from a European study using biomarkers to assess how maternal diet affects the child

Cancer in childhood is rare. Globally, there are around 175 000 new cancer cases a year among children aged 0-14 years.1 However, in Europe, since the 1950s the incidence of cancer in this age group has increased by about 1% a year, with leukaemia, brain tumours, and lymphomas accounting for most cases.2 The increases in incidence of lymphoid leukaemia, in particular, are more apparent in European than in Asian or African children.3 The development of childhood cancer thus seems to be affected by both genetic and environmental factors. Given that the highest incidences of childhood leukaemia are reported in children younger than 6-7 years, that the latency period of leukaemia in children is relatively short,4 and that adverse genetic events in utero have been shown to give rise to leukaemia in childhood,5 we hypothesised that fetal exposure to environmental carcinogens may be an underlying cause. Diet is an important source of carcinogenic compounds because of the accumulation of environmental carcinogens within the food chain (dioxins, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs)), as well as of formation of carcinogens such as PAHs, heterocyclic amines, and acrylamide during baking, frying, and grilling of food.6 The New Generis (Newborns and Genotoxic Exposure Risks) project therefore set out to investigate whether intake of dietary carcinogens by the pregnant mother leads to exposures of the fetus and initiates adverse biological responses that can induce cancer in later childhood.

Investigation of this hypothesis in an epidemiological study would require a huge sample size because of the relatively low incidence of childhood cancer (about 140 cases per million children).2 3 Case-control studies have been informative but also have limitations. …
Comparative assessment of umeclidinium/vilanterol (UMEC/VI) combination therapy among symptomatic COPD patients
Authors: Eline Huisman, Sarah Cockle, Yogesh Punekar
Journal: European Respiratory Journal (2014)

UMEC/VI is a novel LAMA and LABA combination therapy in a single inhaler. This study assessed comparative efficacy of UMEC/VI(62.5/25µg) with QVA149(110/50µg) & indacaterol+tiotropium(150+18µg; IND+TIO).

A systematic review was used to identify RCTs of 12 weeks or longer duration in COPD patients receiving maintenance therapy. Studies comparing IND+TIO or QVA149 to tiotropium or placebo were selected. Outcomes of interest were change from baseline in FEV1, SGRQ total score, TDI focal score and rescue medication use (RMU). An indirect treatment comparison (ITC) was conducted using a frequentist approach.

The systematic review identified 2 studies for IND+TIO (INTRUST1 & INTRUST2) and 3 studies for QVA149 (SHINE, ENLIGHTEN & SPARK). UMEC/VI was not significantly different compared to QVA149 or IND+TIO on all assessed outcomes.

View this table:



Results excluding SPARK study for QVA149 were consistent.

Combination bronchodilators are broadly similar on clinical and patient reported endpoints.