tbuckley/cabot-search huggingface dataset:
The diagnosis of food allergy: a systematic review and meta‐analysis
Authors: K. Soares‐Weiser, Y. Takwoingi, S. S. Panesar, A. Muraro, T. Werfel, K. Hoffmann‐Sommergruber, G. Roberts, S. Halken, L. Poulsen, R. van Ree, B. J. Vlieg‐Boerstra, A. Sheikh
Journal: Allergy (2013)

Abstract Background We investigated the accuracy of tests used to diagnose food allergy. Methods Skin prick tests (SPT), specific‐IgE ( sIgE ), component‐resolved diagnosis and the atopy patch test (APT) were compared with the reference standard of double‐blind placebo‐controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS‐2 to assess risk of bias. Where possible, meta‐analysis was undertaken. Results Twenty‐four (2831 participants) studies were included. For cows’ milk allergy, the pooled sensitivities were 53% (95% CI 33–72), 88% (95 % CI 76–94), and 87% (95% CI 75–94), and specificities were 88% (95% CI 76–95), 68% (95% CI 56–77), and 48% (95% CI 36–59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80–97) and 93% (95% CI 82–98), and specificities were 58% (95% CI 49–67) and 49% (40–58%) for skin prick tests and specific–IgE. For wheat, pooled sensitivities were 73% (95% CI 56–85) and 83% (95% CI 69–92), and specificities were 73% (95% CI 48–89) and 43% (95% CI 20–69%) for SPT and sIgE . For soy, pooled sensitivities were 55% (95% CI 33–75) and 83% (95% CI 64–93), and specificities were 68% (95% CI 52–80) and 38% (95% CI 24–54) for SPT and sIgE . For peanut, pooled sensitivities were 95% (95% CI 88–98) and 96% (95% CI 92–98), and specificities were 61% (95% CI 47–74), and 59% (95% CI 45–72) for SPT and sIgE . Conclusions The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE‐mediated food allergy.
HISTIOCYTOSIS IN BABY WITH DELAYED CORD SEPARATION
Authors: MichaelJ. Gannon, Marc Blayney, Eamon Cosgrove, Freda Gorman, JohnF.A. Murphy, J.K.C. Chan, C.S. Ng, Shinsaku Imashuku, Shigeyoshi Hibi, Noriko Esumi, Shinjiro Todo
Journal: The Lancet (1987)
FcγRIIIa Expression Is Not Increased on Natural Killer Cells Expressing the FcγRIIIa-158V Allotype
Authors: Nicolas Congy-Jolivet, Armelle Bolzec, David Ternant, Marc Ohresser, Herve Watier, Gilles Thibault
Journal: Cancer Research (2008)

Abstract The presence of a valine (V) versus a phenylanaline (F) at position 158 of FcγRIIIa/CD16a improves the affinity for IgG and is associated with higher therapeutic response to rituximab. Increased CD16 expression on natural killer (NK) cells from donors with the VV or VF versus FF genotype has recently been reported. We indeed observed higher binding of the anti-CD16 monoclonal antibody (mAb) 3G8 on NK cells from V carriers (VV = VF &amp;gt; FF). However, the binding of two other anti-CD16 mAbs, LNK16 and DJ130c, decreased with the number of V allele (VV &amp;lt; VF &amp;lt; FF). CD16 transcript levels were independent on the genotype. Rituximab binding to NK cells from V carriers was higher than its binding to FF NK cells at low concentrations (10 and 100 μg/mL). However, the difference was nearly completely abolished at saturating concentrations (≥1,000 μg/mL). Finally, nearly 100% of CD16-expressing NK cells displayed a complete down-modulation of the receptor after optimal engagement by plate-bound 3G8, whatever the genotype. By contrast, the percentages of NK cells down-modulating CD16 after competitive engagement of the receptor by plate-bound rituximab increased with the number of V allele (FF, 18.2 ± 8.6%; VF, 32.0 ± 4.9%; and VV, 42.4 ± 9.9%). These results are in discrepancy with the expected increased competition that would result from an increased expression of CD16 on VV and VF NK cells. We conclude that increased binding and functional and clinical responses associated with the high-affinity FcγRIIIa-158V are unrelated to an increased expression of this allotype. [Cancer Res 2008;68(4):976–80]
The Neurofibromatosis Type 1 Tumor Suppressor Controls Cell Growth by Regulating Signal Transducer and Activator of Transcription-3 Activity <i>In vitro</i> and <i>In vivo</i>
Authors: Sutapa Banerjee, Jonathan N. Byrd, Scott M. Gianino, Scott E. Harpstrite, Fausto J. Rodriguez, Robert G. Tuskan, Karlyne M. Reilly, David R. Piwnica-Worms, David H. Gutmann
Journal: Cancer Research (2010)

Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome in which affected individuals develop benign and malignant nerve tumors. The NF1 gene product neurofibromin negatively regulates Ras and mammalian target of rapamycin (mTOR) signaling, prompting clinical trials to evaluate the ability of Ras and mTOR pathway inhibitors to arrest NF1-associated tumor growth. To discover other downstream targets of neurofibromin, we performed an unbiased cell-based high-throughput chemical library screen using NF1-deficient malignant peripheral nerve sheath tumor (MPNST) cells. We identified the natural product, cucurbitacin-I (JSI-124), which inhibited NF1-deficient cell growth by inducing apoptosis. We further showed that signal transducer and activator of transcription-3 (STAT3), the target of cucurbitacin-I inhibition, was hyperactivated in NF1-deficient primary astrocytes and neural stem cells, mouse glioma cells, and human MPNST cells through Ser(727) phosphorylation, leading to increased cyclin D1 expression. STAT3 was regulated in NF1-deficient cells of murine and human origin in a TORC1- and Rac1-dependent manner. Finally, cucurbitacin-I inhibited the growth of NF1-deficient MPNST cells in vivo. In summary, we used a chemical genetics approach to reveal STAT3 as a novel neurofibromin/mTOR pathway signaling molecule, define its action and regulation, and establish STAT3 as a tractable target for future NF1-associated cancer therapy studies.
Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial
Authors: R.A. Pauwels, M.R. Sears, M. Campbell, C. Villasante, S. Huang, A. Lindh, W. Petermann, M. Aubier, G. Schwabe, T. Bengtsson
Journal: European Respiratory Journal (2003)

The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations.
Family studies in Crohn's disease: new horizons in understanding disease pathogenesis, risk and prevention: Figure 1
Authors: Charlotte R Hedin, Andrew J Stagg, Kevin Whelan, James O Lindsay
Journal: Gut (2011)

Crohn9s disease (CD) is an incurable intestinal disorder in which the loss of immune tolerance to the commensal gut microbiota leads to chronic inflammation. The reason this occurs in specific individuals is unclear; however, a genetic predisposition is fundamental and relatives of patients with CD are at significant risk of developing the disease. Knowledge relating to the genetic loci that predispose to CD is accumulating, which raises the possibility of disease prediction and prevention in susceptible populations. However, the genetic basis of CD is complex and genotyping alone is likely to be insufficient to predict disease risk accurately. Specific physiological abnormalities associated with CD, such as increased intestinal permeability and raised faecal calprotectin, are also abnormal in some relatives of patients with CD. The combination of genotypic factors and biomarkers of risk makes the development of models of disease prediction a realistic possibility. Furthermore, enhanced understanding of the genotype and phenotype of the at-risk state in relatives of patients with CD allows the earliest stages in the pathogenesis of CD to be investigated and may allow intervention to prevent disease onset. This article reviews current knowledge of the at-risk phenotype in relatives of patients with CD and focuses on the implications for the design of future studies.
The Attitudes of Cancer Patients and Their Families Toward the Disclosure of Terminal Illness
Authors: Young Ho Yun, Chang Geol Lee, Si-young Kim, Sang-wook Lee, Dae Seog Heo, Jun Suk Kim, Keun Seok Lee, Young Seon Hong, Jung Suk Lee, Chang Hoon You
Journal: Journal of Clinical Oncology (2004)

To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient.We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea.380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P <.001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41).Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.
Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells.
Authors: W L Nelson, J C Makielski
Journal: Circulation Research (1991)

Heptanol blocks sodium current (INa) in nerve, but its effects on cardiac INa have not been well characterized. Block of INa by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described by a single-site binding curve with half block at 1.3 mM (20 degrees C) and showed no "use dependence." With 1.5 mM heptanol, block increased slightly by 0.7%/degrees C from 10 degrees C to 27 degrees C. With 3.0 mM heptanol, steady-state availability shifted by 9.4 +/- 1.3 mV (n = 6) in the hyperpolarizing direction, and steady-state activation shifted by 8.3 +/- 2.2 mV (n = 5) in the depolarizing direction, thus closing off the INa "window current." Heptanol also decreased the time to peak and accelerated the decay of INa. Similar results were found with octanol at lower concentrations. These alcohols have important effects on cardiac INa at concentrations used in studies for cellular uncoupling in heart.
Dopamine Synthesis Capacity Before Onset of Psychosis: A Prospective [<sup>18</sup>F]-DOPA PET Imaging Study
Authors: Oliver D. Howes, Subrata K. Bose, Federico Turkheimer, Isabel Valli, Alice Egerton, Lucia R. Valmaggia, Robin M. Murray, Philip McGuire
Journal: American Journal of Psychiatry (2011)

Objective: While there is robust evidence of elevated dopamine synthesis capacity once a psychotic disorder has developed, little is known about whether it is altered prior to the first episode of frank illness. The authors addressed this issue by measuring dopamine synthesis capacity in individuals at ultra-high risk of psychosis and then following them to determine their clinical outcome. Method: This prospective study included 30 patients who met standard criteria for being at ultra-high risk of psychosis and 29 healthy volunteers. Participants were scanned using [18F]6-fluoro-l-dopa positron emission tomography. The ultra-high-risk patients were scanned at presentation and followed up for at least 3 years to determine their clinical outcome. Six patients had comorbid schizotypal personality disorder and were excluded from the analysis (data are provided for comparison). Of the remaining patients, nine developed a psychotic disorder (psychotic transition group) and 15 did not (nontransition group). Results: There was a significant effect of group on striatal dopamine synthesis capacity. The psychotic transition group had greater dopamine synthesis capacity in the striatum (effect size=1.18) and its associative subdivision (effect size=1.24) than did the healthy comparison subjects and showed a positive correlation between dopamine synthesis capacity and symptom severity. Dopamine synthesis capacity was also significantly greater in the psychotic transition group than in the nontransition group. Conclusions: These findings provide evidence that the onset of frank psychosis is preceded by presynaptic dopaminergic dysfunction. Further research is needed to determine the specificity of elevated dopamine synthesis capacity to particular psychotic disorders.
Respiratory muscles during ventilatory support
Authors: JW Fitting
Journal: European Respiratory Journal (1994)

Knowledge of the fate and behaviour of the respiratory muscles during ventilatory support is important for the guidance of clinical care. Full support facilitates muscle metabolic repletion, but exposes them to the risk of disuse atrophy. The effect of partial support varies according to the selected mode: assisted mechanical ventilation (AMV) and synchronized intermittent mechanical ventilation (SIMV) result in much less respiratory muscle rest than generally anticipated. On the other hand, inspiratory pressure support (IPS) is able to rest the respiratory muscles and to prevent fatiguing contractions. Opposite interventions have been proposed in case of difficult weaning: either to unload the respiratory muscles by using partial support, or to overload them according to a training programme. The optimal strategy is not known and may combine both approaches.
Blood Hyperosmolality and Pulmonary Vascular Resistance in the Cat
Authors: ANTON HAUGE, GUNNAR Bφ
Journal: Circulation Research (1971)

Blood osmolality rises during general muscle exercise. The purpose of this work was to investigate the effect of similar slow, graded rises of blood osmolality on pulmonary vascular resistance. Hyperosmolar solutions of sodium chloride, mannitol, urea, glucose, thiourea and ethylene glycol were infused into the left lower lobe pulmonary arterial branch in the cat. Lobe blood flow, pulmonary arterial, left atrial and systemic arterial pressures were recorded. With the exception of ethylene glycol, all the test solutions caused dose-dependent, reversible reductions in lobe vascular resistance (LVR). Maximal reduction in LVR was 30% of initial value. A rise of blood osmolality of 25 milliosmols/liter, comparable with levels found during exercise, caused a 10% reduction in LVR. Hyperosmolar solutions of ethylene glycol, which has the highest rate of cell wall penetration of the test substances, caused no change in LVR. Bolus injections of 1M solutions of sodium chloride caused rapid transient rises in LVR. It appears that the resistance vessels of the lungs react to graded rises of blood osmolality in a way qualitatively similar to that seen in the resistance vessels of skeletal muscle.
Evaluation of the Anti-HER2 C6.5 Diabody as a PET Radiotracer to Monitor HER2 status and Predict Response to Trastuzumab Treatment
Authors: Smitha Reddy, Calvin C. Shaller, Mohan Doss, Irina Shchaveleva, James D. Marks, Jian Q. Yu, Matthew K. Robinson
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The rapid tumor targeting and pharmacokinetic properties of engineered antibodies make them potentially suitable for use in imaging strategies to predict and monitor response to targeted therapies. This study aims to evaluate C6.5 diabody (C6.5db), a noncovalent anti-HER2 single-chain Fv dimer, as a radiotracer for predicting response to HER2-targeted therapies such as trastuzumab. Experimental Design: Immunodeficient mice bearing established HER2-positive tumor xenografts were injected with radioiodinated C6.5db and imaged by PET/CT. Radiotracer biodistribution was quantified by biopsied tumor and normal tissues. Potential competition between trastuzumab and C6.5db was examined in vitro by flow cytometry and coimmunoprecipitations. Results: Biodistribution analysis of mice bearing xenografts with varying HER2 density revealed that the tumor uptake of 125I-C6.5db correlates with HER2 tumor density. In vitro competition experiments suggest that the C6.5db targets an epitope on HER2 that is distinct from that bound by trastuzumab. Treatment of mice affected with SK-OV-3 tumor with trastuzumab for 3 days caused a 42% (P = 0.002) decrease in tumor uptake of 125I-C6.5db. This is consistent with a dramatic decrease in the tumor PET signal of 124I-C6.5db after trastuzumab treatment. Furthermore, mice affected with BT-474 tumor showed an approximately 60% decrease (P = 0.0026) in C6.5db uptake after 6 days of trastuzumab treatment. Immunohistochemistry of excised xenograft sections and in vitro flow cytometry revealed that the decreased C6.5db uptake on trastuzumab treatment is not associated with HER2 downregulation. Conclusions: These studies suggest that 124I-C6.5db–based imaging can be used to evaluate HER2 levels as a predictor of response to HER2-directed therapies. Clin Cancer Res; 17(6); 1509–20. ©2010 AACR.
Improved Glycemic Control With the Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib
Authors: Steffen Böhm, Dagmar Hess, Silke Gillessen, Michael Brändle
Journal: Diabetes Care (2010)

Pazopanib is a novel antiangiogenic inhibitor of tyrosine kinases (TKIs) with high activity against vascular endothelial growth factor receptor (VEGFR1–3), platelet-derived growth factor receptor (PDGFRα+β), and c-Kit. Here we report on a patient with prostate cancer and type 2 diabetes whose glycemic control has been significantly improved with pazopanib during anticancer therapy and describe a potential mechanism of action.

The 73-year-old patient was diagnosed with prostate cancer in 1999 and underwent prostatectomy and radiotherapy, sequential hormonal therapies, and, in 2008, first line chemotherapy. Due to disease progression he was enrolled in a phase I trial with pazopanib (400 mg p.o. daily, day 1 to 21 every 3 weeks) in combination with epirubicine (75 mg/m2 i.v. q3w …
Dyspnoea, rhinorrhoea and pulmonary infiltrates in a healthy young woman
Authors: Mark G Jones, Kevin O Leslie, Neeta Singh, Stephen P Harden, Katherine M A O'Reilly
Journal: Thorax (2013)

Mark G Jones (MGJ) : A 33-year-old woman was referred for a respiratory opinion. Three months prior she had developed a ‘bad cold’. This had persisted with intermittent rhinorrhoea, non-productive cough, pleuritic chest pain and a weight loss of 6 kg. Her symptoms had transiently improved following courses of co-amoxiclav and clarithromycin from her primary care physician and local district general hospital. The patient was previously healthy with no medical history of note. She had smoked minimally and drank little alcohol. There were no occupational or environmental exposures of note. Her family kept two cats and she had travelled to Spain 4 months prior to symptom onset.

On examination she appeared unwell. Bilateral submandibular and cervical lymphadenopathies were detected. Bilateral crackles were auscultated in the chest. Cardiovascular, gastrointestinal and neurological examinations were normal. The chest radiograph showed lingular consolidation and patchy right basal ground-glass opacities. Initial laboratory investigations identified a neutrophilia (25.2 × 109/l) and a raised C reactive protein (CRP) (123 mg/l). Liver and renal function tests were within the normal range.

Katherine M A O'Reilly (KO'R): We have a previously healthy young woman who presents with pulmonary infiltrates, raised inflammatory markers, lymphadenopathy and weight loss. Although the initial presentation was suggestive of a community-acquired bacterial pneumonia (CAP), the response to broad-spectrum antibiotics is not as expected. So while CAP is unlikely, atypical infections including mycobacterial disease should be considered. The weight loss and lymphadenopathy are concerning and we should exclude an underlying malignancy such as lymphoma. In addition, HIV/AIDS, underlying inflammatory conditions such as vasculitis or cryptogenic organising pneumonia and recurrent aspiration should be considered.

MG J : Further questioning identified no history of gastro-oesophageal reflux disease, swallowing difficulties or risk factors for aspiration pneumonia. Serologies including mycoplasma, coxiella, bartonella, toxoplasma, borrelia and histoplasma were negative. Lactate dehydrogenase level …