bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single fluorescent protein-based Ca2+sensors with increased dynamic range
Authors: Souslova Ekaterina A , Belousov Vsevolod V , Lock John G , Strömblad Staffan , Kasparov Sergey , Bolshakov Alexey P , Pinelis Vsevolod G , Labas Yulii A , Lukyanov Sergey , Mayr Lorenz M , Chudakov Dmitriy M 
Published: June 2007

Abstract

Background
Genetically encoded sensors developed on the basis of green fluorescent protein (GFP)-like proteins are becoming more and more popular instruments for monitoring cellular analytes and enzyme activities in living cells and transgenic organisms. In particular, a number of Ca2+ sensors have been developed, either based on FRET (Fluorescence Resonance Energy Transfer) changes between two GFP-mutants or on the change in fluorescence intensity of a single circularly permuted fluorescent protein (cpFP).

Results
Here we report significant progress on the development of the latter type of Ca2+ sensors. Derived from the knowledge of previously reported cpFP-based sensors, we generated a set of cpFP-based indicators with different spectral properties and fluorescent responses to changes in Ca2+ concentration. Two variants, named Case12 and Case16, were characterized by particular high brightness and superior dynamic range, up to 12-fold and 16.5-fold increase in green fluorescence between Ca2+-free and Ca2+-saturated forms. We demonstrated the high potential of these sensors on various examples, including monitoring of Ca2+ response to a prolonged glutamate treatment in cortical neurons.

Conclusion
We believe that expanded dynamic range, high brightness and relatively high pH-stability should make Case12 and Case16 popular research tools both in scientific studies and high throughput screening assays.
The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders
Authors: Papamichalis Panagiotis A , Zachou Kalliopi , Koukoulis George K , Veloni Aikaterini , Karacosta Efthimia G , Kypri Lampros , Mamaloudis Ioannis , Gabeta Stella , Rigopoulou Eirini I , Lohse Ansgar W , Dalekos George N 
Published: June 2007

Abstract

Background
We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases.

Methods
We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group.

Results
The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass.

Conclusion
The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients.
Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis
Authors: Zhang Huili , Zhi Liang , Moochhala Shabbir M , Moore Philip Keith , Bhatia Madhav 
Published: June 2007

AbstractHydrogen sulfide (H2S) is recognized increasingly as a proinflammatory mediator in various inflammatory conditions. Here, we have investigated the role of H2S in regulating expression of some endothelial adhesion molecules and recruitment of leukocytes to inflamed sites in sepsis. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with saline (i.p.), DL-propargylglycine (PAG; 50 mg/kg, i.p.), an inhibitor of H2S formation or NaHS (10 mg/kg, i.p.), an H2S donor. PAG was administered 1 h before or after the induction of sepsis, and NaHS was given at the same time of CLP. Using intravital microcopy, we found that in sepsis, prophylactic and therapeutic administration of PAG reduced leukocyte rolling and adherence significantly in mesenteric venules coupled with decreased mRNA and protein levels of adhesion molecules (ICAM-1, P-selectin, and E-selectin) in lung and liver. In contrast, injection of NaHS up-regulated leukocyte rolling and attachment significantly, as well as tissue levels of adhesion molecules in sepsis. Conversely, normal mice were given NaHS (10 mg/kg, i.p.) to induce lung inflammation, with or without NF-κB inhibitor BAY 11-7082 pretreatment. NaHS treatment enhanced the level of adhesion molecules and neutrophil infiltration in lung. These alterations were reversed by pretreatment with BAY 11-7082. Moreover, expression of CXCR2 in neutrophils obtained from H2S-treated mice was up-regulated significantly, leading to an obvious elevation in MIP-2-directed migration of neutrophils. Therefore, H2S acts as an important endogenous regulator of leukocyte activation and trafficking during an inflammatory response.
Heroin-assisted treatment for opioid dependence
Authors: Haasen Christian , Verthein Uwe , Degkwitz Peter , Berger Juergen , Krausz Michael , Naber Dieter 
Published: June 2007

BackgroundHeroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance.AimsTo study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment.MethodIn an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis.ResultsRetention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use.ConclusionsHeroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.
Long-term outcomes after discharge from medium secure care: a cause for concern
Authors: Davies Steffan , Clarke Martin , Hollin Clive , Duggan Conor 
Published: June 2007

BackgroundThere are few long-term follow-up studies of patients discharged from medium secure units in the UK, even though these units were introduced over 20 years ago.AimsTo describe mortality, rates of reconviction at different time periods; violent behaviour (not leading to conviction), readmission and employment, after discharge from a medium secure unit.MethodOf 595 first admissions over a 20-year period, 550 discharged cases were followed-up. Multiple data sources were used.ResultsFifty-seven (10%) patients had died, of whom 18 (32%) died by suicide, and the risk of death was six times greater than in the general population. Almost half (49%) of those discharged were reconvicted and almost two-fifths (38%) of patients were readmitted to secure care.ConclusionsCommunity psychiatric services need to be aware that those discharged from medium secure care are a highly vulnerable group requiring careful follow-up if excess mortality high levels of psychiatric morbidity and further offending are to be prevented.
Young people who self-harm
Authors: Young Robert , van Beinum Michael , Sweeting Helen , West Patrick 
Published: June 2007

BackgroundSelf-harm among young people in the UK is possibly increasing but little is known about the reasons young people give for cessation and their link with gender or employment status.AimsTo investigate self-harm in young people, prevalence, methods used, motivations for starting and ceasing, service use, and how these are related to gender, parental social class and current labour market position.MethodPopulation-based survey of 1258 18-to 20-year-olds living in the Central Clydeside Conurbation, Scotland.ResultsBoth past and current rates of self-harm were highest among those outside the labour market. This group was most likely to want to kill themselves and did not cite specialist mental health services as helpful in ceasing self-harm. Those in full-time education more often self-harmed for a brief time, mainly to reduce anxiety.ConclusionsCurrent labour market position was a stronger predictor than parental social class or gender for self-harm, and was linked to level of severity, motivation for starting and ceasing, and service utilisation.
Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy in Advanced Non–Small-Cell Lung Cancer
Authors: Simon George , Sharma Anupama , Li Xueli , Hazelton Todd , Walsh Frank , Williams Charles , Chiappori Alberto , Haura Eric , Tanvetyanon Tawee , Antonia Scott , Cantor Alan , Bepler Gerold 
Published: June 2007

Purpose The treatment of patients with advanced non–small-cell lung cancer (NSCLC) is based on clinical trials experience. Molecular characteristics that impact metabolism and efficacy of chemotherapeutic agents are not used for decision making. Ribonucleotide reductase subunit 1 (RRM1) is crucial for nucleotide metabolism, and it is the dominant molecular determinant of gemcitabine efficacy. Excision repair cross-complementing group 1 gene (ERCC1), a component of the nucleotide excision repair complex, is important for platinum-induced DNA adduct repair. We hypothesized that selection of double-agent chemotherapy based on tumoral RRM1 and ERCC1 expression would be feasible and beneficial for patients with advanced NSCLC. Patients and Methods We conducted a prospective phase II clinical trial in patients with advanced NSCLC. Patients were required to have a dedicated tumor biopsy for determination of RRM1 and ERCC1 gene expression by real-time quantitative reverse transcriptase polymerase chain reaction. Double-agent chemotherapy consisting of carboplatin, gemcitabine, docetaxel, and vinorelbine was selected based on gene expression. Disease response and patient survival were monitored. Results Eighty-five patients were registered, 75 had the required biopsy without significant complications, 60 fulfilled all eligibility criteria, and gene expression analysis was not feasible in five patients. RRM1 expression ranged from 0 to 1,637, ERCC1 expression ranged from 1 to 8,103, and their expression was correlated (Spearman's rho = 0.46; P < .01). Disease response was 44%. Overall survival was 59% and progression-free survival was 14% at 12 months, with a median of 13.3 and 6.6 months, respectively. Conclusion Therapeutic decision making based on RRM1 and ERCC1 gene expression for patients with advanced NSCLC is feasible and promising for improvement in patient outcome.
Plasma Lysophosphatidylcholine Levels: Potential Biomarkers for Colorectal Cancer
Authors: Zhao Zhenwen , Xiao Yijin , Elson Paul , Tan Haiyan , Plummer Sarah J. , Berk Michael , Aung Phyu P. , Lavery Ian C. , Achkar Jean P. , Li Li , Casey Graham , Xu Yan 
Published: June 2007

PurposePlasma levels of lysophospholipids were evaluated as potential biomarkers for colorectal cancer (CRC), where a highly reliable and minimally invasive blood test is lacking.Patients and MethodsPatients with CRC (n = 133) and control subjects (n = 125) were recruited through the Cleveland Clinic. Preoperative plasma samples were analyzed for lysophospholipid levels using liquid chromatography mass spectrometry in a blinded fashion. Participants were randomly divided in a 2:1 ratio into a “training set” (TS) and a “validation set” (VS). Logistic regression models were used in the TS to identify markers that best discriminated between CRC and controls. A cutoff point for the final discriminating model was developed using the receiver operating characteristic curve to achieve 95% specificity. All analyses were then independently validated in the VS.ResultsPlasma levels of several lysophosphatidylcholines (LPCs), including 18:1- and 18:2-LPC, were significantly decreased in CRC patients compared with controls (P < .001). A model based on total saturated LPC and the difference between the proportional amounts of 18:2-LPC and 18:1-LPC in the unsaturated LPC fraction was derived from the TS. This model achieved a sensitivity and specificity of 82% and 93%, respectively, in the VS. Overall, 118 (94%) of 125 control subjects and 113 (85%) of 133 CRC cases were correctly identified, including eight (89%) of nine CRC cases with stage T1 disease.ConclusionPercentage of 18:1-LPC or 18:2-LPC plasma levels compared with total saturated LPC levels, either individually or in combination, may represent potential biomarkers for CRC.
Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer
Authors: Mutch David G. , Orlando Mauro , Goss Tiana , Teneriello Michael G. , Gordon Alan N. , McMeekin Scott D. , Wang Yanping , Scribner Dennis R. , Marciniack Martin , Naumann R. Wendel , Secord Angeles Alvarez 
Published: June 2007

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.
Effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate byDrosophila melanogasterlarvae
Authors: Ruiz-Sanchez Esau , O'Donnell Michael J. 
Published: June 2007

SUMMARYThe effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate by D. melanogaster larvae were evaluated using salicylate-selective microelectrodes. Larvae chronically exposed to dietary salicylate showed 25% less salicylate in the haemolymph compared to the control group after feeding on a salicylate-enriched diet. By 1 h after transfer to a salicylate-free diet the levels of salicylate in the haemolymph of larvae raised on dietary salicylate were 46% lower than in the control group. Salicylate flux increased dramatically across Malpighian tubules but not across midgut or hindgut isolated from larvae chronically exposed to dietary salicylate, relative to the control group. Malpighian tubules isolated from experimental larvae showed a 4.7-fold increase in Kt and a nearly 5-fold increase in Jmax relative to the control. These changes in salicylate transport were accompanied by a 3.2-fold increase in fluid secretion rate. Moreover, the high rates of fluid secretion by the Malpighian tubules isolated from experimental larvae were stimulated 2.1-fold and 2.8-fold when tubules were challenged with 1 mmol l–1 cAMP and 10 μmol l–1 leucokinin I, respectively. Taken together, these results indicate that chronic exposure of D. melanogaster larvae to dietary salicylate alters elimination of such toxins from the haemolymph and increases the basal rate of fluid secretion and excretion of salicylate by the Malpighian tubules.
Thermoregulation in pronghorn antelope (Antilocapra americanaOrd) in the summer
Authors: Lust A. , Fuller A. , Maloney S. K. , Mitchell D. , Mitchell G. 
Published: June 2007

SUMMARY
We have used thermistor/data logger assemblies to measure temperatures in the brain, carotid artery, jugular vein and abdominal cavity, and subcutaneously, in five pronghorn antelope over a summer in Wyoming. Globe and air temperature varied by up to ∼50°C daily during the summer and maximum solar radiation was ∼900 W m–2. Brain temperature(38.9±0.3°C) was consistently ∼0.2–0.5°C higher than carotid blood temperature (38.6±0.3°C), which was the same as abdominal temperature (38.8±0.4°C). Jugular blood temperature(38.0±0.4°C) varied, probably because of changes in Respiratory Evaporative Heat Loss (REHL), and was lower than other temperatures. Subcutaneous temperature (38.3±0.6°C) varied, probably because of peripheral vasoactivity, but on average was similar to other temperatures. Carotid blood temperature had a circadian/nycthemeral rhythm weakly but significantly (r=0.634) linked to the time of sunrise, of amplitude 0.8±0.1°C. There were daily variations of up to 2.3°C in carotid body temperature in individual animals. An average range of carotid blood temperature of 3.1±0.4°C over the study period was recorded for the group, which was significantly wider than the average variation in brain temperature (2.3±0.6°C). Minimum carotid temperature(36.4±0.8°C) was significantly lower than minimum brain temperature(37.7±0.5°C), but maximum brain and carotid temperatures were similar. Brain temperature was kept relatively constant by a combination of warming at low carotid temperatures and cooling at high carotid temperatures and so varied less than carotid temperature. This regulation of brain temperature may be the origin of the amplitude of the average variation in carotid temperature found, and may confer a survival advantage.
Adaptive Idea Screening Using Consumers
Authors: Toubia Olivier , Florès Laurent 
Published: June 2007

Following a successful idea generation exercise, a company might easily be left with hundreds of ideas generated by experts, employees, or consumers. The next step is to screen these ideas and identify those with the highest potential. In this paper we propose a practical approach to involving consumers in idea screening.Although the number of ideas may potentially be very large, it would be unreasonable to ask each consumer to evaluate more than a few ideas. This raises the challenge of efficiently selecting the ideas to be evaluated by each consumer. We describe several idea-screening algorithms that perform this selection adaptively based on the evaluations made by previous consumers. We use simulations to compare and analyze the performance of the algorithms as well as to understand their behavior. The best-performing algorithm focuses on the ideas that are the most likely to have been misclassified (as “top” or “bottom” ideas) based on the previous evaluations, and avoids discarding ideas too fast by adding random perturbations to the misclassification probabilities. We demonstrate the convergent validity of this algorithm using a field experiment, which also confirms the convergence pattern predicted by simulations.
An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1–84) Is Overproduced in Parathyroid Carcinoma
Authors: Rubin Mishaela R , Silverberg Shonni J , D’Amour Pierre , Brossard Jean-Hugues , Rousseau Louise , Sliney James , Cantor Tom , Bilezikian John P 
Published: June 2007

AbstractBackground: A new parathyroid hormone (PTH) species, the N-terminal PTH form (N-PTH), is distinct from intact human PTH of 84 amino acid residues [hPTH(1–84)] and is recognized in a 3rd-generation assay of “whole” PTH (wPTH; the 1–2 epitope) but not in a 2nd-generation assay of “total” PTH (tPTH; the 12–18 epitope). N-PTH usually represents &lt;15% of wPTH but can be overproduced in severe primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism. We investigated whether N-PTH is also overproduced in parathyroid cancer and whether N-PTH concentration is influenced by calcimimetic therapy.Methods: We studied 8 patients with parathyroid carcinoma before and at week 16 of cinacalcet therapy, 6 patients with PHPT, and 6 control individuals. We fractionated sera with HPLC and analyzed fractions with the 2 assays to quantify hPTH(1–84), N-PTH, and non-(1–84) PTH fragments.Results: Half of parathyroid carcinoma patients had an increased wPTH:tPTH ratio [mean (SD), 1.35 (0.29)]; the others had a typical ratio [0.72 (0.12)]. HPLC fractionation of sera from 2 high-ratio patients confirmed N-PTH overproduction [65% (12%) of wPTH]. The N-PTH fraction was &lt;15% of wPTH in PHPT and healthy individuals. Calcimimetic therapy appreciably reduced calcium concentrations in parathyroid carcinoma patients but had little influence on PTH concentration, the wPTH:tPTH ratio, or the PTH HPLC profile.Conclusion: N-PTH is overproduced in some parathyroid cancer patients, but calcimimetic therapy does not influence its production. The clinical implications of this finding in parathyroid carcinoma await additional studies with an emphasis on N-PTH’s biological activity and with larger numbers of patients.