tbuckley/cabot-search huggingface dataset:
Internal consistency reliability and predictive validity of a modified N. Huang clinical scoring system in adult cystic fibrosis patients
Authors: E Matouk, RH Ghezzo, J Gruber, R Hidvegi, K Gray-Donald
Journal: European Respiratory Journal (1997)

We described a modified N. Huang scoring system and its application as a measure of disease status and progression in a population of adult cystic fibrosis patients. We evaluated the scoring for internal consistency reliability and predictive validity. We applied the scoring system to 109 adult cystic fibrosis patients followed at the Montreal Chest Institute. Complete data were available on 36 deceased patients. The total score represented the sum of the clinical, radiological and pulmonary function subscores, minus the complications subscore. It ranged between 0 (worst health) and 100 points (best health). The total score showed a high degree of internal consistency and reliability with an estimated Cronbach coefficient alpha of 0.934. Both total score and forced expiratory volume in one second (FEV1) percentage predicted were significant predictors of survival at 36 and 24 months. However, there was a progressive decrease in the discriminating power of FEV1 percentage pred for predicting survival at 24, 18, 12 and 6 months. The total score showed a progressive and consistent pattern clearly predicting the outcome. A total score &lt; 41, &lt; 38, &lt; 35 and &lt; 30 points was associated with a poor prognosis for survival at 24, 18, 12, and 6 months, respectively. The clinical and complications subscores were the most discriminating components of the total score. The total score of the modified N. Huang scoring system offered a better discriminating scale, as compared to forced expiratory volume in one second % predicted, in the prognostic evaluation of end-stage cystic fibrosis patients. It could be of value in decisions for lung transplantation in these patients.
The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study
Authors: John Henderson, Kate Northstone, Simon P. Lee, Haihui Liao, Yiwei Zhao, Marcus Pembrey, Somnath Mukhopadhyay, George Davey Smith, Colin N.A. Palmer, W. H. Irwin McLean, Alan D. Irvine
Journal: Journal of Allergy and Clinical Immunology (2008)
Tridimensional photographic reconstruction in a study of the pathogenesis of honeycomb lung
Authors: J. C. Pimentel
Journal: Thorax (1967)

Tridimensional photographic reconstruction of the lesions found in honeycomb lung in 10 different types of pulmonary disease was made. The pathological picture was characteristic and well defined by tridimensional microscopy and quite independent of the accompanying disease. The lesions responsible for its appearance involved the whole lobular bronchiolar system but were most marked in the terminal and respiratory bronchioli. The changes were fundamentally diffuse, saccular, and cystic bronchiolectasis. Other bronchiolar lesions were found such as changes in direction and mode of division, amputations, and anastomoses between bronchioles and cysts belonging to anatomically independent airways. There was some evidence that the bullous aspects of honeycomb lung were due to multiple valvular arrangements which let the air in but do not let it out. Honeycomb lung was, in the majority of cases, a complication of interstitial pulmonary fibrosis. Honeycombing was usually due to marked changes in the lobular bronchioles caused by the obliteration or rigidity of alveolar ducts and the corresponding alveoli and even by localization of the interstitial fibrosis in the bronchiolar wall.
Understanding dyspnoea by its language
Authors: G. Scano
Journal: European Respiratory Journal (2005)

Dyspnoea is a general term used to characterise a range of qualitatively distinct descriptors that vary in intensity. Based on the hypothesis that various qualities of respiratory discomfort result from different pathophysiological abnormalities, language could help to define one or more of the abnormalities responsible for breathing discomfort. The use of descriptors of dyspnoea may contribute to the understanding of the mechanisms of dyspnoea, and assist in identifying or predicting a specific diagnosis. Symptoms that can be reliably discriminated imply different pathophysiological mechanisms, whereas symptoms that cannot be reliably discriminated imply similar pathophysiological mechanisms. Since dyspnoea is a fundamental part of patient9s clinical history, physicians should become more fluent in the language of dyspnoea.
Two Consecutive Phase II Window Trials of Irinotecan Alone or in Combination With Vincristine for the Treatment of Metastatic Rhabdomyosarcoma: The Children's Oncology Group
Authors: Alberto S. Pappo, Elizabeth Lyden, Phillip Breitfeld, Sarah S. Donaldson, Eugene Wiener, David Parham, Kristine R. Crews, Peter Houghton, William H. Meyer
Journal: Journal of Clinical Oncology (2007)

Purpose To estimate the antitumor activity and toxicity of irinotecan alone and in combination with vincristine when administered as window therapy and in combination with standard chemotherapy in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma. Patients and Methods Nineteen patients younger than age 21 years with newly diagnosed metastatic rhabdomyosarcoma or undifferentiated sarcoma received window therapy with two cycles of irinotecan (20 mg/m 2 daily for 5 days, repeated for 2 weeks) and 50 patients received window therapy with vincristine 1.5 mg/m 2 (weeks 0, 1, 3, and 4) and two cycles of irinotecan (20 mg/m 2 daily for 5 days, repeated for 2 weeks). Patients who achieved a partial response (PR) or complete response (CR) received these agents alternating with vincristine (V; 1.5/mg/m 2 ), dactinomycin (A; 1.5 mg/m 2 ), and cyclophosphamide (C; 2.2 g/m 2 ) during weeks 6 through 41. Nonresponders were treated with VAC alone. Radiotherapy was administered to sites of disease at weeks 15 to 21. Results The window response rate (PR/CR) for patients who received irinotecan was 42% (95% CI, 38% to 80%) but the high progressive disease (PD) rate of 32% (95% CI, 11% to 52%) prompted closure of the trial. The window CR/PR rate for patients who received vincristine and irinotecan was 70% (95% CI, 57% to 83%), and the PD rate was only 8%. GI toxicities (abdominal pain, diarrhea, dehydration) were the most common adverse effects associated with the administration of irinotecan. Conclusion The combination of vincristine and irinotecan is highly active in metastatic rhabdomyosarcoma. The different mechanism of action and nonoverlapping toxicity profile with VAC makes this combination an attractive candidate for further testing in intermediate risk patients with rhabdomyosarcoma.
4-Hydroxytamoxifen Inhibits Proliferation of Multiple Myeloma Cells <i>In vitro</i> through Down-Regulation of c-Myc, Up-Regulation of p27Kip1, and Modulation of Bcl-2 Family Members
Authors: Juliette Gauduchon, Fabrice Gouilleux, Sébastien Maillard, Véronique Marsaud, Jack-Michel Renoir, Brigitte Sola
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Multiple myeloma is an incurable B-cell malignancy requiring new therapeutic strategies. Our approach was to analyze the in vitro effects of a selective estrogen receptor modulator, 4-hydroxytamoxifen (4-OHT), on six multiple myeloma cell lines. Experimental Design: Cultured multiple myeloma cells were treated with various 4-OHT concentrations and the cellular response was studied: cell proliferation, cell viability, induction of apoptosis, caspase activities, and expression of signaling proteins. Results: We found that pharmacologic concentrations of 4-OHT inhibit cell proliferation (4 of 6 cell lines). This inhibition is achieved by two independent events: a block at the G1 phase of the cell cycle and the induction of apoptotic death. The cellular response to 4-OHT depends on the presence of functional estrogen receptors. 4-OHT treatment activates an intrinsic mitochondrial caspase-9-dependent pathway but not the Fas/FasL death pathway. Signaling pathways known to be involved in the survival and/or proliferation of multiple myeloma cells are not affected by 4-OHT treatment. 4-OHT-induced G1 arrest is accompanied by the up-regulation of the cell cycle inhibitor p27Kip1 and the down-regulation of c-Myc. Among the Bcl-2 family members tested, the proapoptotic BimS protein is induced whereas the antiapoptotic protein Mcl-1 is decreased. Conclusions: Although the effects of 4-OHT are observed at micromolar concentrations, cellular mechanisms responsible for G1 arrest, as well as apoptosis induction, are similar to those observed in breast cancer cells. Our data support the concept that 4-OHT may represent an alternative approach to inhibit proliferation and induce apoptosis of multiple myeloma cells.
Erk2 but not Erk1 regulates crosstalk between Met and EGFR in squamous cell carcinoma cell lines
Authors: Simone Gusenbauer, Emanuele Zanucco, Pjotr Knyazev, Axel Ullrich
Journal: Molecular Cancer (2015)

Squamous cell carcinoma (SCC) is the most common type of tongue and larynx cancer and a common type of lung cancer. In this study, we attempted to specifically evaluate the signaling pathway underlying HGF/Met induced EGFR ligand release in SSCs. The Met proto-oncogene encodes for a tyrosine kinase receptor which is often hyperactivated in human cancers. Met activation correlates with poor patient outcome. Several studies revealed a role of Met in receptor-crosstalk inducing either activation of other receptors, or inducing their resistance to targeted cancer treatments. In an epithelial tumor cell line screen we recently showed that the Met ligand HGF blocks the EGFR tyrosine kinase and at the same time activates transcriptional upregulation and accumulation in the supernatant of the EGFR ligand amphiregulin (Oncogene 32:3846-56, 2013). In the present work we describe the pathway responsible for the amphiregulin induction.Amphiregulin is transcriptionally upregulated and is released into the supernatant. We show that Erk2 but not Erk1 mediates amphiregulin upregulation upon treatment with monocyte derived HGF. A siRNA knockdown of Erk2 completely abolishes amphiregulin release in squamous cell carcinomas.These results identify Erk2 as the key downstream signal transducer between Met activation and EGFR ligand upregulation in squamous cell carcinoma cell lines derived from tongue, larynx and lung.
Reduced swelling-activated Cl− current densities in hypertrophied ventricular myocytes of rabbits with heart failure
Authors: Marcel M. G. J. van Borren, Arie O. Verkerk, Sakari K. Vanharanta, Antonius Baartscheer, Ruben Coronel, Jan H. Ravesloot
Journal: Cardiovascular Research (2002)

Objective: Hypertrophied myocytes of failing hearts have prolonged action potential durations. It is unknown how the swelling-activated Cl− current (ICl,swell) affects the abnormal AP configuration. Methods: We studied ICl,swell in ventricular myocytes isolated from failing and age-matched normal rabbit hearts. We applied whole-cell patch-clamp methodology and activated ICl,swell by lowering tonicity of the superfusate. Results: Neither with ruptured-patch nor with amphotericin B perforated-patch, whole-cell clamp we found ICl,swell active under isotonic conditions in either the normal or the hypertrophied failing heart (HFH) myocytes. ICl,swell caused AP shortening and resting membrane potential (Vm) depolarization in an osmotic gradient-dependent fashion. However, in the HFH myocytes swelling-induced AP changes were significantly smaller, even though the cells underwent the same relative change in planar cell surface area. Voltage-clamp experiments revealed that in HFH myocytes ICl,swell current density was ∼50% reduced. Conclusion: Reduced ICl,swell densities in HFH myocytes cause limited AP shortening and Vm depolarization upon swelling of the cells.
Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease.
Authors: N J Bell, R H Hunt
Journal: Gut (1992)

Gastro-oesophageal reflux disease is a common condition with a complex pathophysiology. Despite the spectrum of abnormalities, gastric acid has a central role in mucosal damage, and the mainstay of medical treatment is suppression of gastric acid secretion. The results of antisecretory treatment as assessed by endoscopic healing are reviewed. H2 receptor antagonists give more rapid symptom relief than placebo and can produce endoscopic improvement in 31-88% of cases depending on the severity of oesophagitis. Complete healing, however, is seen only in 27-45% of patients and these have mainly grades I-II disease. Improved healing rates can be obtained by increasing the degree of acid suppression or the length of treatment. The addition of a prokinetic agent may be beneficial. Omeprazole heals 67-92% of patients overall and although most successful in the lower grades of oesophagitis, can also heal 48-62% of patients with grade IV disease. The degree and rate of healing seem to be related to the reduction in oesophageal acid exposure and thus may correlate with the degree and duration of acid suppression over 24 hours obtained by the various treatments. The underlying pathophysiology is unchanged, however, and long term treatment may be needed to maintain remission.
Screening for neuroblastoma.
Authors: M H Duncan
Journal: BMJ (1993)

compassion and love."'The same also appears in the BMA's discussion paper on the withdrawing of tube feeding and is incorrectly stated as represent- ing the Roman Catholic view.To elicit an authentic Catholic teaching, how- ever, it is best to go to a proper Catholic source such as the Vatican Statement of 1980: "Euthanasia includes not only active mercy killing but also the omission of treatments when the purpose of the omission is to kill the patient"2 or that of 50 American bishops early this year: "The harsh reality is that some who propose withdrawal of nutrition and hydration from certain patients do directly intend to bring about the patient's death ... nutrition and hydration (whether orally administered or medically assisted) are sometimes withdrawn not because a patient is dying but precisely because the patient is not dying (or not dying quickly enough) and someone believes the patient is perceived as having an unacceptably low 'quality of life,' or is imposing burden on others."I Bishop Christopher Budd on behalf of the English and Welsh bishops, in the statement Euthanasia and Hard Cases, stated "A PVS patient is not dead in any normal or technical sense of the word.In spite of the expression 'permanent vegetative state' Tony Bland is still a live human being, he is not a vegetable, his soul has not left him.-Nor in fact is he dying.Accordingly he ought not to be killed by being starved to death any more than he should be killed by lethal injection.The quest for 'death with dignity' does not justify the deliberate taking of a human life, no matter how good the intention or how great the strain of waiting."4I hope the above clarifies the Roman Catholic position.The Linacre Centre established by the English and Welsh metropolitan bishops for the study of health care ethics in the Hospital of St John and St Elizabeth, London, is always available for consultation.
The Behavioral and Neural Mechanisms Underlying the Tracking of Expertise
Authors: Erie D. Boorman, John P. O’Doherty, Ralph Adolphs, Antonio Rangel
Journal: Neuron (2013)

Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms' expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent's prediction was concordant rather than discordant with the subject's own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network—medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus—represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning.
Developing a dynamic elastomeric fabric orthosis to aid return to sport after lumbopelvic injury
Authors: L Sawle, M Mathews, J Freeman, J Marsden
Journal: British Journal of Sports Medicine (2010)

Lumbopelvic pain (LPP) often results from trauma or overuse that can lead to conditions including adductor tears, sacroiliac joint dysfunction and osteitis pubis. Such injuries are often refractory to treatment and can limit the return to competitive sport. Previous research shows that selective compressive forces applied transversely to the pelvis can result in improved lumbopelvic stability and reduced pain, and, compression shorts may aid in preventing athletic lumbopelvic injury. This study applies transverse and diagonal compressive forces to the pelvis in athletes with LPP, and investigates the effects on pain and function. Participants with athletic LPP were screened using five clinical tests. They were included if at least two tests provoked pain. Transverse and diagonal circumferential forces were applied via a belt. Four belt arrays (anterior superior iliac spines (ASIS), right-left across the pelvis, left-right across the pelvis and in combination) and a "no-belt condition" were assessed with the order of presentation randomised. A force of 50 N was applied (determined using a load cell lying in series with the belt). The effect of the belt array on rest pain, pain associated with an active straight leg raise (ASLR) and a 1-m broad jump was assessed using a numerical rating scale. During resisted bilateral hip adduction the onset of pain was indicated using a hand held switch; the maximal force of adduction determined via a load cell. Data were analysed using paired t tests. Preliminary data on 12 participants (9 females, mean 37±10 years) indicate that different belt arrays can alleviate pain both at rest and during active tasks. Pain during ASLR (ipsilateral to the pain) improved with combined belts compared to an ASIS belt (p=0.025). Preliminary results suggest the direction and angle of force application relative to the laterality of pain is important in determining the degree and pattern of pain relief. A larger sample is needed to confirm this (required sample of 31 based on effect size of 0.51 and 80% power). Results will inform the design of a dynamic elastomeric fabric orthosis whose effect on athletic LPP and function will be assessed.
The changing risk of Plasmodium falciparum malaria infection in Africa: 2000–10: a spatial and temporal analysis of transmission intensity
Authors: Abdisalan M Noor, Damaris K Kinyoki, Clara W Mundia, Caroline W Kabaria, Jonesmus W Mutua, Victor A Alegana, Ibrahima Socé Fall, Robert W Snow
Journal: The Lancet (2014)

Over a decade ago, the Roll Back Malaria Partnership was launched, and since then there has been unprecedented investment in malaria control. We examined the change in malaria transmission intensity during the period 2000-10 in Africa.We assembled a geocoded and community Plasmodium falciparum parasite rate standardised to the age group 2-10 years (PfPR2-10) database from across 49 endemic countries and territories in Africa from surveys undertaken since 1980. The data were used within a Bayesian space-time geostatistical framework to predict PfPR2-10 in 2000 and 2010 at a 1 × 1 km spatial resolution. Population distribution maps at the same spatial resolution were used to compute populations at risk by endemicity class and estimate population-adjusted PfPR2-10 (PAPfPR2-10) for each of the 44 countries for which predictions were possible for each year.Between 2000 and 2010, the population in hyperendemic (>50% to 75% PfPR2-10) or holoendemic (>75% PfPR2-10) areas decreased from 218·6 million (34·4%) of 635·7 million to 183·5 million (22·5%) of 815·7 million across 44 malaria-endemic countries. 280·1 million (34·3%) people lived in areas of mesoendemic transmission (>10% to 50% PfPR2-10) in 2010 compared with 178·6 million (28·1%) in 2000. Population in areas of unstable or very low transmission (<5% PfPR2-10) increased from 131·7 million people (20·7%) in 2000 to 219·0 million (26·8%) in 2010. An estimated 217·6 million people, or 26·7% of the 2010 population, lived in areas where transmission had reduced by at least one PfPR2-10 endemicity class. 40 countries showed a reduction in national mean PAPfPR2-10. Only ten countries contributed 87·1% of the population living in areas of hyperendemic or holoendemic transmission in 2010.Substantial reductions in malaria transmission have been achieved in endemic countries in Africa over the period 2000-10. However, 57% of the population in 2010 continued to live in areas where transmission remains moderate to intense and global support to sustain and accelerate the reduction of transmission must remain a priority.Wellcome Trust.
Block of C/EBPα function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations
Authors: Hanna S. Radomska, Daniela S. Bassères, Rui Zheng, Pu Zhang, Tajhal Dayaram, Yukiya Yamamoto, David W. Sternberg, Nathalie Lokker, Neill A. Giese, Stefan K. Bohlander, Susanne Schnittger, Marie-Hélène Delmotte, Roger J. Davis, Donald Small, Wolfgang Hiddemann, D. Gary Gilliland, Daniel G. Tenen
Journal: The Journal of Experimental Medicine (2006)

Mutations constitutively activating FLT3 kinase are detected in approximately 30% of acute myelogenous leukemia (AML) patients and affect downstream pathways such as extracellular signal-regulated kinase (ERK)1/2. We found that activation of FLT3 in human AML inhibits CCAAT/enhancer binding protein alpha (C/EBPalpha) function by ERK1/2-mediated phosphorylation, which may explain the differentiation block of leukemic blasts. In MV4;11 cells, pharmacological inhibition of either FLT3 or MEK1 leads to granulocytic differentiation. Differentiation of MV4;11 cells was also observed when C/EBPalpha mutated at serine 21 to alanine (S21A) was stably expressed. In contrast, there was no effect when serine 21 was mutated to aspartate (S21D), which mimics phosphorylation of C/EBPalpha. Thus, our results suggest that therapies targeting the MEK/ERK cascade or development of protein therapies based on transduction of constitutively active C/EBPalpha may prove effective in treatment of FLT3 mutant leukemias resistant to the FLT3 inhibitor therapies.
DISTRIBUTION OF BALLOT PAPERS
Authors: R.H. Cowdell, J.W. Keeling, J.O'D. Mcgee, P.R. Millard, N.A. Wright, L.G. Bobrow, M.M. Esiri, K.A. Fleming, G.B. Maclennan, J. Piris, R.I. Vanhegan, R.M. Williams
Journal: The Lancet (1978)