tbuckley/cabot-search huggingface dataset:
Outbreak of Influenza in the Army
Authors: D. G. Milne, J. D. Cruickshank
Journal: BMJ (1949)

~~~SUBACUTE PANCREATITIS MDCAJ6RAL571in diagnosis would largely be obviated if serum-amylase investigations were more often employed in elucidating obscure cases of upper abdominal pain.Subacute pancreatitis is not a rare condition, and its diagnosis depends largely on being aware of the existence of this clinical syndrome.SummarySubacute pancreatitis is a clinical entity readily differentiated from acute haemorrhagic pancreatitis and other abdominal emergencies.Patients suffering from this condition present as an acute abdominal emergency but settle down on conservative treatment.The condition is very apt to recur.Of the 19 cases presented 13 were recurrent attacks.It is suggested that estimation of the serum-amylase level should be more widely employed to differentiate this condition from other acute abdominal lesions.I would like to thank Professor F.
Inpatient hospital care or hospital-at-home for COPD exacerbations: A discrete choice experiment
Authors: Lucas Goossens, Cecile Utens, Frank Smeenk, Bas Donkers, Onno van Schayck, Maureen Rutten-van Mölken
Journal: European Respiratory Journal (2012)

Objective  Quantifying patient preferences for different aspects of hospital-at-home in the Netherlands for patients with a COPD exacerbation.  Methods  In a discrete-choice experiment, respondents were asked to make multiple choices between hospital treatment as usual (7 days) and two combinations of hospital admission (3 days) followed by treatment at home. The latter was described by attributes: training of homecare nurses (general/pulmonary), number of different nurses involved, number of daily visits, co-payments, readmission risk, contact in case of worsening disease (GP/hospital), and informal caregiver burden. Hospital treatment was constant. Respondents were COPD patients in an RCT investigating the cost-effectiveness of early assisted discharge, and their informal caregivers. The data for each group were analyzed in latent-class conditional logit regression.  Results  202 questionnaires were returned. 25% of patients and caregivers opted for hospital treatment regardless of the description of the hospital-at-home program, 46% never chose the hospital. The best models contained four latent classes, defined by different preferences for the hospital and for the caregiver burden. Preferences for other attributes were shared by all classes. Except for the number of visits, all attributes had a significant effect on choices in the expected direction.  Conclusion  Considerable proportions of patients and caregivers have a preference for either admission or hospital-at-home, irrespective of the characteristics of the hospital-at-home program. Financial burden and informal caregiver burden weighed most on the choice between hospital-at-home options. The number of daily visits did not play a role.
CC-122 Degrades the Lymphoid Transcription Factor Aiolos (IKZF3) By Modulating Cereblon and Shows Clinical Activity in a Phase Ib Study of Subjects with Relapsed or Refractory Non-Hodgkin’s Lymphoma and Multiple Myeloma
Authors: Vincent Ribrag, Silvia Damien, Mecide Gharibo, Mercede Gironella, Armando Santoro, Drew W Rasco, William Edenfield, Xin Wei, Angela James, Patrick Hagner, Anita K. Gandhi, Rajesh Chopra, Jorge F. DiMartino, Michael Pourdehnad, Anne-Marie Stoppa
Journal: Blood (2014)
Long-term results of concurrent and adjuvant chemotherapy for advanced nasopharyngeal carcinoma
Authors: D. L. Kwong, J. S. Sham, G. K. Au, D. T. Choy
Journal: Journal of Clinical Oncology (2008)

6056 Background: Preliminary results of a factorial trial investigating concurrent chemoradiation (CRT) and adjuvant chemotherapy (AC) for nasopharygngeal carcinoma (NPC) was reported in 2004 (JCO 22 (13): 2643–2653). This is a report on the long-term follow-up results of the study. Methods: Ho's stage T3 or N2 /N3 or > 4cm neck node, M0 disease were eligible. Patients were first randomized to receive CRT or RT alone and then further randomized to receive AC or no AC after completion of CRT/RT. Patients randomized to CRT received UFT (uracil and tegafur in 4:1 molar ratio) 200mg, 3 times a day, during radiotherapy. AC consisted of alternating PF (cisplatin 100mg/m2 D1 and 5FU 1g/m2 D1–3) and VBM (vincristine 2mg, bleomycin 30mg and methotrexate 150mg/m2, all on D1) for 6 cycles. The 4 treatment arms were: A. RT, B. CRT, C. RT + AC, D. CRT + AC. Patients in arms A and C were compared with those in arms B and D (i.e. RT vs. CRT) for efficacy of CRT. Patients in arms A and B were compared with those in arms C and D (i.e. no AC vs. AC) for efficacy of AC. Loco- regional control (LRC), distant metastases free survival (DMFS), failure-free survival (FFS) and disease-specific survival (DSS) were estimated with Kaplan-Meier methods and compared with log-rank test. Results: From May 1995 to October 2001, 222 patients were recruited. 3 patients were excluded from analysis. Median follow up time was 7 years. There were 55, 53, 54, 57 patients in arm A, B, C, D respectively. The 7-year LRC of the 4 arms were 64.2%, 74.8%, 78.7%, 78.8% respectively; DMFS were 71.7%, 85.8%, 65.5%, 80.4%; FFS were 51.7%, 69%, 53.2%, 64.4%; DSS were 71.7%, 75.4%, 66.1%, 81.5%. CRT significantly improved the DMFS and FFS compared with RT (p=0.014 and 0.016 respectively). There was a trend of improvement in DSS with CRT also (p=0.057). The use of AC failed to improve survival. Multivariate analysis showed CRT, T stage and N stage were significant for both FFS and DSS. Conclusions: CRT significantly improved DMFS and FFS in advanced NPC. The benefit of CRT was confirmed on long-term follow-up. No significant financial relationships to disclose.
Role of countercurrent multiplication in renal ammonium handling
Authors: R K Packer, S S Desai, K Hornbuckle, M A Knepper
Journal: Journal of the American Society of Nephrology (1991)

Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diuresis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state.
Quality of life and distress in oncologic patients: Follow-up study of a mental health program.
Authors: D. Gercovich, E. L. Morgenfeld, F. Torrente, P. Lopez, H. Hirsch, P. Margiolakis, E. Gil Deza, B. Rolnik, E. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2010)

e19594 Background: Even though the study of psychological aspects associated to oncological diseases has seen an important development in the past few years, there is little objective evidence of the usefulness of psychiatric and psychological treatments in the decrease of distress and improvement of quality of life. The aim of this study is to evaluate the results of psychological treatments, structured in a naturalistic context, using psychometric instruments that enable the quantification of the response to treatment and its quality. Methods: The psychological treatment process of 185 patients from the mental health service of an oncological institution was studied. A total of 66.5% of the treatments were carried out in a combined treatment context, while in the remaining 33.5% of the cases, the patients only received psychotherapy. A comparison of the Hospital Anxiety and Depression Scale (HADS) and the Cancer Quality of Life Questionnaire (QLQ-30) results was then done between the admission interview and the third, fifth and tenth sessions. Results: The comparison of scores in the HADS and QLQ-30 between the admission interview and the third session showed statistically significant differences in all the HADS subscales and in numerous QLQ-30 subscales. A similar effect was found when comparing the admission interview with the fifth and tenth session. However, when the session scores were compared between them, a plateau could be found from the 5th session and onwards. Conclusions: The significative differences found in both instruments indicate a decrease in distress and an increase in the patients' quality of life during therapy. No significant financial relationships to disclose.
Ret Translocation in Adenocarcinoma of the Lung
Authors: S. Michels, A. Schultheis, M. Scheffler, T. Rosner, S. Merkelbach-Bruse, L.C. Heukamp, W. Engel-Riedel, M. Serke, S. Krüger, J. Benedikter, U. Gerigk, W. Schulte, A. Draube, Y. Ko, R. Büttner, J. Wolf
Journal: Annals of Oncology (2014)
Abstract 4: Lymphatic Vessels Mediate the Mobilization of Cardiac Progenitor Cells after Myocardial Infarction
Authors: Polina Goichberg, Maria Cimini, Antonio Cannata, Sergio Signore, Kanako Waight, Marcello Rota, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2014)

The delivery of adult cardiac progenitor cells (CPCs) or their activation in situ constitute an evolving approach for the treatment of heart failure. CPCs are endowed with regenerative capacity, producing differentiating myocytes and vascular structures in the course of homeostasis and upon injury. The regenerative function of CPCs is contingent to their ability to migrate to and engraft within the wounded area. Yet, the mechanisms governing CPC trafficking in the diseased myocardium are largely unknown. The lymphatic system is vital for tissue repair, and the role of the lymphatic vasculature in the trafficking of hematopoietic and cancer cells is well documented. We examined whether cardiac lymphatic vessels mediate the translocation of CPCs in the infarcted myocardium. By imaging of the heart from transgenic c-kit-GFP reporter mice, we found that as early as 4 hours after myocardial infarction (MI), uncommitted lineage-negative progenitors accumulated in the vicinity of the lymphatic vessels located in the region bordering the necrotic area. Histologically, extensive lymphangiogenesis was documented in the mouse heart in the acute (8-48 hours) and chronic (15-35 days) phases of infarct healing and scar formation. CPCs were detected traversing the wall of lymphatic vessels at different stages after MI, indicative of the functional role of the lymphatic circulation in the recruitment of primitive cells to the site of injury. Furthermore, isolated human CPCs exhibited chemotaxis and specific binding to the human lymphatic endothelial cells (LECs) in steady-state conditions and, increasingly, after exposure to an inflammatory cytokine, TNFα. CPCs performed trans-endothelial migration in vitro, and actively intravasated into the lumen of microvessels formed by LECs in three-dimensional matrices. Finally, our data suggest that sphingosine-1-phosphate (S1P)-stimulated signaling governs the interactions of CPCs with LECs. These findings on the direct role of lymphatic vasculature in CPC trafficking may contribute to the development of novel therapeutic modalities to increase mobilization of endogenous or transplanted CPCs, promoting myocardial repair in patients with ischemic heart diseases.
A child chronic cough-specific quality of life measure: development and validation
Authors: Peter A Newcombe, Jeanie K Sheffield, Helen L Petsky, Julie M Marchant, Carol Willis, Anne B Chang
Journal: Thorax (2016)

Quality of life (QoL) measures are an important patient-relevant outcome measure for clinical studies. Cough is the most common symptom that results in new medical consultations. Although adult and parent-proxy cough-specific QoL instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QoL measure for children with chronic cough exists. We report on the statistical properties of a chronic cough-specific QoL (CC-QoL) questionnaire for children.130 children (median age 10 years, IQR 8-12 years; 65 girls) participated. A preliminary 37-item version was developed from conversations with children with chronic cough (>4 weeks). Children also completed generic QoL questionnaires (Pediatric QoL Inventory 4.0 (PedsQL4.0), Spence Children's Anxiety Scale (SCAS)) and cough diary scores.The clinical impact method of item reduction resulted in 16 items that had excellent internal consistency (Cronbach's α=0.94) among these items and also within each domain. Evidence for construct and criterion validity was established with significant correlations between CC-QoL subscales with cough scores, PedsQL and SCAS scores. CC-QoL scores were sensitive to change following an intervention and significant differences were noted between those children coughing and those who had ceased coughing. Minimum important difference (MID) for overall and domain CC-QoL ranged from 0.37-1.36 (distribution-based approach) to 1.11-1.58 (anchor-based approach).Chronic cough significantly impacts the QoL of children. The CC-QoL is a reliable, valid and sensitive to change outcome measure that assesses QoL from the child's perspective. Pending data from a confirmatory cohort, a MID for the CC-QoL of 1.1 is recommended when evaluating health status change.
Phase I Study of Ym155, Selective Survivin Suppressant Plus Erlotinib in Patients with Egfr-Mutant Advanced Nsclc
Authors: Toshio Shimizu, Isamu Okamoto, Kunio Okamoto, Kazuto Nishio, Kazuko Sakai, Hidemi Aida, Chiaki Hashii, Koji Aoyama, Maiko Morishita, Kazuhiko Nakagawa
Journal: Annals of Oncology (2014)
Specificity of basolateral organic anion exchanger in proximal tubule for cellular and extracellular solutes.
Authors: L P Sullivan, J J Grantham
Journal: Journal of the American Society of Nephrology (1992)

We used an epifluorimetric technique to study the mechanism of organic anion transport across the basolateral surface of isolated S2 segments of rabbit proximal tubules. Fluorescein influx and efflux rates across the basolateral surface of lumen-collapsed tubules were determined from serial measurements of cellular fluorescein content after its addition to or removal from the bathing medium. We examined the effect on fluorescein transport of monocarboxylic and dicarboxylic metabolic intermediates added to the bathing medium or preloaded into the cells. The presence of the monocarboxylates (octanoate, valerate, butyrate, propionate, and acetate) in the bathing medium inhibited fluorescein influx. The eight-carbon-chain fatty acid, octanoate, was nearly as potent an inhibitor as probenecid and was more potent than p-aminohippurate (PAH) (IC50 = 10, 6, and 141 microM, respectively); the shorter chain fatty acids were much less effective (IC50 greater than or equal to 1,000 microM). The dicarboxylates (succinate, adipate, and alpha-ketoglutarate) moderately inhibited fluorescein influx (IC50 = 505, 245, and 257 microM, respectively). To determine the effect of intracellular organic anions on fluorescein influx, tubules were preincubated with organic anions to load the cells; the compounds were then removed from the bath, and fluorescein influx was measured. Preincubation with monocarboxylates, octanoate, butyrate, acetate, and PAH had no effect. In contrast, the dicarboxylates alpha-ketoglutarate, glutarate, and adipate stimulated fluorescein influx by 58, 53, and 43%, respectively, but succinate had no effect. Fluorescein efflux was accelerated by medium octanoate, PAH, alpha-ketoglutarate, and succinate but not by acetate. Probenecid alone had no effect on fluorescein efflux, but it blocked the stimulation caused by medium PAH.(ABSTRACT TRUNCATED AT 250 WORDS)
Incidence and outcomes of hospitalized for COPD exacerbations with and without pneumonia, 2006-2012: A nationwide cohort study
Authors: Mette Søgaard, Morten Madsen, Anders Løkke, Ole Hilberg, Allan G. Jensen, Jens Dollerup, Reimar W. Thomsen
Journal: European Respiratory Journal (2014)

Background:  Pneumonia may be a major contributor to hospitalizations for COPD exacerbations. We examined the incidence and outcomes of hospitalizations for exacerbations with and without pneumonia in Denmark, 2006-2012.   Methods:  Using nationwide databases we retrieved complete individual-level data on first-time and successive exacerbations among patients ≥40 years. We estimated exacerbation rates with and without pneumonia per 100,000 persons. We used logistic regression to estimate odds ratios (ORs) of 30-day mortality for with exacerbations with and without pneumonia, adjusted for age, sex, comorbidity, and use of medication as proxy for COPD severity.   Results:  We identified 156,743 hospitalizations for COPD exacerbation, including 63,591 (41%) first-time exacerbations. Pneumonia was frequent in first exacerbations (46%) but declined in successive exacerbations to 27% in the seventh and following exacerbations. Exacerbations with pneumonia increased by 49%, from 1.23 per 1000 population in 2006 to 1.83 in 2012 while exacerbations without pneumonia increased by 21%, from 1.55 to 1.88. 30-day mortality was 13.1% in patients with first exacerbation with pneumonia and 9.1% in those without pneumonia (aOR 1.25, 95% CI 1.19-1.32). Presence of pneumonia also predicted increased mortality at second exacerbation (aOR 1.22, 95% CI 1.13-1.32), and up to the seventh and following exacerbations (aOR 1.30, 95% CI 1.13-1.50).   Conclusions:  More than 40% of hospitalized exacerbations in Denmark are associated with pneumonia. Presence of pneumonia predicts increased mortality, both in first and successive exacerbations, and after adjustment for prognostic factors.
Sequence variation at the major histocompatibility complex locus DQ beta in beluga whales (Delphinapterus leucas)
Authors: B W Murray, S Malik, B N White
Journal: Molecular Biology and Evolution (1995)

Genetic variation at the Major Histocompatibility Complex locus DQ beta was analyzed in 233 beluga whales (Delphinapterus leucas) from seven populations: St. Lawrence Estuary, eastern Beaufort Sea, eastern Chukchi Sea, western Hudson Bay, eastern Hudson Bay, southeastern Baffin Island, and High Arctic and in 12 narwhals (Monodon monoceros) sympatric with the High Arctic beluga population. Variation was assessed by amplification of the exon coding for the peptide binding region via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis. Five alleles were found across the beluga populations and one in the narwhal. Pairwise comparisons of these alleles showed a 5:1 ratio of nonsynonymous to synonymous substitutions per site leading to eight amino acid differences, five of which were nonconservative substitutions, centered around positions previously shown to be important for peptide binding. Although the amount of allelic variation is low when compared with terrestrial mammals, the nature of the substitutions in the peptide binding sites indicates an important role for the DQ beta locus in the cellular immune response of beluga whales. Comparisons of allele frequencies among populations show the High Arctic population to be different (P < or = .005) from the other beluga populations surveyed. In these other populations an allele, Dele-DQ beta*0101-2, was found in 98% of the animals, while in the High Arctic it was found in only 52% of the animals. Two other alleles were found at high frequencies in the High Arctic population, one being very similar to the single allele found in narwhal.
Use of total HER2 and HER2 homodimer levels to predict response to trastuzumab
Authors: K. Leitzel, A. Lipton, W. Koestler, E. Fuchs, S. M. Ali, J. Weidler, Y. Wu, J. Sperinde, W. Huang, M. Bates
Journal: Journal of Clinical Oncology (2008)

1002 Background: Current methods used to select HER2 positive patients with metastatic breast cancer for treatment with trastuzumab are semi-quantitative and yield response rates of less than fifty percent. Using a novel assay to quantitate total HER2 and HER2 homodimer levels, we examined the relationship between these measurements and clinical outcomes in a cohort of trastuzumab-treated metastatic breast cancer patients, previously assessed as IHC 3+ or FISH+ for HER2 overexpression or amplification. Methods: The VeraTag assay was used to measure total HER2 expression (H2T) and HER2 homodimers (H2D) in 106 formalin-fixed, paraffin-embedded primary tumor specimens. Using test for trend, multivariate Cox proportional hazards, and Kaplan-Meier analyses, the results were correlated with objective response, time-to-progression (TTP), and overall survival following trastuzumab-containing treatment. Results: Higher levels of H2T (p= 0.008) or H2D (p= 0.001) correlated with higher probability of objective response to trastuzumab therapy in a quartile analysis. Using the median value of the H2T distribution as a cutoff, higher H2T correlated with longer TTP (median TTP 11.6 mo vs. 5.4 mo, p=0.055), as did higher H2D (median TTP 11.6 mo. vs. 5.8 mo., p=0.055). Using incremental scanning to identify an optimal cutoff, higher H2T correlated with longer TTP (median TTP 11.3 mo. vs. 4.2 mo., p=0.003), as did higher H2D (median TTP 11.1 mo. vs. 4.2 mo., p=0.016). Using the optimal cutoff, higher H2T showed a non-significant trend toward longer overall survival (median survival 37.4 mo. vs. 28.7 mo., p=0.2). Cox multivariate models identified H2T above vs. below the optimal cutoff as a statistically significant correlate of both TTP (HR=0.41, p=0.0002) and overall survival (HR=0.45, p=0.009). Also in multivariate analyses, H2D above vs. below the optimal cutoff was a statistically significant correlate of both TTP (HR=0.64, p= 0.03) and overall survival (HR=0.6, p =0.02). Conclusions: In metastatic breast cancer patients previously selected by IHC or FISH, higher total HER2 and HER2 homodimer levels as measured by the VeraTag assay predict those patients more likely to respond to trastuzumab-containing therapy. Grant support: Supported by a grant from Susan G. Komen for the Cure Foundation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Monogram Biosciences Monogram Biosciences Monogram Bioscience Monogram Biosciences
Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits
Authors: Sebnem N. Tuncdemir, Brie Wamsley, Floor J. Stam, Fumitaka Osakada, Martyn Goulding, Edward M. Callaway, Bernardo Rudy, Gord Fishell
Journal: Neuron (2016)