bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looming cognitive style and quality of life in a cancer cohort
Authors: Levin Tomer T. , Riskind John , Li Yuelin 
Published: September 2010

AbstractObjective:Looming cognitive styles (LCS) bias the velocity of potential threats and have been implicated in anxiety and depression vulnerability. This study aims to explore their contribution to impaired quality of life (QOL), beyond that of depression and anxiety, in a cancer cohort.Method:In a cross-sectional design, an ambulatory chronic lymphocytic leukemia (CLL) cohort completed a psychological battery that included the Beck Depression and Anxiety Inventories, the SF-36 Health Survey, the Functional Assessment of Chronic Illness Therapy (FACT), the Looming Cognitive Style Questionnaire (LCSQ), and the Looming Cancer measure.Results:The Looming Cancer measure correlated significtly with overall QOL (FACT-G, p = 0.005). This effect was largely due to the contribution of emotional QOL (Mental Component Score: SF-36, p = 0.001; FACT-emotional, p = 0.001) and functional QOL (FACT-functional, p = 0.001). Looming, unlike anxiety and depression, did not correlate with a worse physical QOL (Physical Component Score: SF-36, FACT-physical). Looming did not impact on social QOL. Hierarchical regression analysis showed that looming predicted 5.4% of the varience on the FACT-emotional, 5.1% on the Mental Component Score (SF-36), and 9.3% on the mental health subscale (SF-36), above and beyond the varience predicted by a constellation of psychosocial factors (including age, marital status, education, income) and the combined effect of depression and anxietySignificance of results:LCS predicts worse emotional and functional QOL, above and beyond the contribution of anxiety, depression, and other psycho-social variables. This suggests that it makes a unique contribution to a worse QOL. Nevertheless, the looming construct still remains primarily a research tool in psycho-oncology at this time.
Does chemotherapy reduce stress?
Authors: Gil Francisco , Costa G. , Pérez F.J. 
Published: September 2010

AbstractObjective:The purpose of this study was to assess the psychological care needs of cancer patients throughout the healthcare process: after diagnosis, after medical treatment (surgery, chemotherapy, radiotherapy) and during follow-up.Method:A total of 703 ambulatory cancer patients were assessed in this study. The inclusion period was from April 1, 2005 to April 30, 2007. The first psychological scales used were the 14-item Hospital Anxiety and Depression Scales (HADS), which has two sub-scales for anxiety (7 items) and for depression (7 items). All patients with a score ≥14 were assessed through the Structured Clinical Interview for Psychiatric Disorder (SCID-I) of the DSM-IV. All data were compared with sociodemographic and medical characteristics.Results:Of the 703 cancer patients in the study, 349 were men and 354 women, with a mean age of 53 years. The median time between the cancer diagnosis and our clinical interview was 6 months (range, 12 days to 190 months). Overall, the screening tools indicated that one in four patients needed psychological care. The most common psychiatric diagnosis was adjustment disorder (129 cases), whereas 10 patients were diagnosed with major depression. Using a HADS cut-off score of >7 for anxiety and depression, 28% and 17% of patients, respectively, were classified as “possible clinical cases.” Risk factors for distress included age <65 years, asthenia, constipation, and a low performance status. However, chemotherapy treatment was found to be a protector against distress in cancer patients.Significance of Results:Chemotherapy treatment is interpreted by the patients as a protector against cancer, thereby reducing distress levels.
Journey of struggle: Kalothanasia and the hospice way of dying
Authors: Floriani Ciroaugusto , Schramm Fermin Roland 
Published: September 2010

AbstractThe purpose of this article is to characterize the notion of a “good death” both historically and conceptually, grounding the philosophy of the modern hospice movement. This concept encompasses elements originating in ancient societies, such as peasant societies, where death was prepared for and shared socially, with ethical and aesthetic elements originating from Ancient Greece. These Greek elements emerged from a “journey of struggle” and can be recognized in the current day as a journey to cope with illness. From this conceptualization emerged a category of “good death” (kalothanasia), adding to the expertise of advocates of the modern hospice movement, who seek to revive a process of dying that is socially ritualized. However, this is challenging in the setting of a medical practice that is constantly incorporating new technology, in accordance with its present bio-techno-scientific paradigm, and in a medical scenario that identifies itself with the continued and persistent use of new technologies.
Diagnosis and treatment of akathisia in a cancer patient who cannot stand up or sit down, because of poor performance status: Factors that make the diagnosis of akathisia difficult, and diagnosis clues
Authors: Onishi Hideki , Wada Makoto , Wada Tomomi , Wada Mei , Ishida Mayumi , Kawanishi Chiaki , Mizuno Keiko , Ito Hiroshi , Narabayashi Masaru , Sasaki Yasutsuna 
Published: September 2010

AbstractObjective:Akathisia is a common adverse effect of antipsychotics and, less commonly, antidepressants. Akathisia can cause great discomfort and is often described by the patient as a most distressing sensation; however, the condition is often underdiagnosed or misdiagnosed. In oncological settings, neuroleptics and antidepressants that induce akathisia are also administered. However, reports of akathisia in oncology settings are few and a case of akathisia in a bedridden patient has not been reported as far as we know.Case report:A 72-year-old man with esophageal cancer who could not sit down or stand up was administered 5 mg/day haloperidol to relieve agitation as a symptom of major depressive disorder. Three days after the administration of haloperidol, the agitation had become worse. Careful observation revealed that the patient sometimes showed slight rubbing movement of the lower extremities and slight twisting movements of the body, which were not observed before the administration of haloperidol. The patient moved his body and lower extremities to relieve restlessness, which had developed after the administration of haloperidol. Although symptoms were atypical, akathisia was suspected and discontinuation of haloperidol resolved the symptoms.Results and significance of results:In patients with poor performance status, clues leading to the correct diagnosis of akathisia might be absent, which would not be the case in patients who were able to walk, stand up, or sit down. Careful observations of patients before and after the administration of drugs that may cause akathisia may be required to ensure correct diagnosis.
The English Profile Programme – the first three years
Authors: Saville Nick , Hawkey Roger 
Published: September 2010

AbstractThe English Profile Programme is a major inter-disciplinary, research-based collaborative project to develop detailed reference level descriptions (RLDs) of the English of L2 language learners, linked to the general principles and approaches of the Council of Europe. The Common European Framework of Reference (CEFR) provides language proficiency bands against which the profile is categorised. Large samples of writing and speech are required for the Programme, with the Cambridge Learner Corpus providing data for the initial phase.
Comparison of racecadotril and loperamide in adults with acute diarrhoea
Authors: Vetel J.M. , Berard H. , Fretault N. , Lecomte J.M. 
Published: September 2010

MethodsA multicentre, randomized, double‐blind, double‐placebo, parallel‐group study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg three times daily) and loperamide (2 mg after each diarrhoeic stool) in 157 adults with acute diarrhoea. Patients were treated for 7 days or until recovery, if this took place earlier.ResultsBoth groups of patients passed similar numbers (mean ± S.E.M.) of stools before recovery (3.5 ± 0.5 for racecadotril vs. 2.9 ± 0.4 for loperamide), and the duration of diarrhoea (mean ± S.E.M.) was similar in both groups (14.9 ± 2.0 h for racecadotril and 13.7 ± 2.2 h for loperamide). Both treatments reduced the incidence of associated symptoms and signs during the study, and both were similarly well tolerated. However, more patients on loperamide reported rebound constipation during treatment (18.7% vs. 9.8% with racecadotril).ConclusionsThe enkephalinase inhibitor, racecadotril, and the intestinal transit inhibitor, loperamide, were similarly and rapidly effective in resolving the symptoms and associated signs of diarrhoea.
Comparison of racecadotril and loperamide in children with acute diarrhoea
Authors: Turck D. , Berard H. , Fretault N. , Lecomte J.M. 
Published: September 2010

MethodsA multicentre, parallel‐group, double‐blind, double‐placebo study was carried out to compare the efficacy, tolerability, and safety of racecadotril and loperamide in children aged 2 to 10 years who were suffering from acute diarrhoea. Patients received racecadotril (1.5 mg/kg) or loperamide (0.03 mg/kg) three times daily plus matching placebo until recovery. Fifty‐two children received racecadotril and 50 loperamide.ResultsPatients on racecadotril passed a mean (± S.E.M.) of 2.7 ± 0.4 stools before recovery compared with 2.1 ± 0.4 stools for loperamide. The duration of diarrhoea was similar with both treatments. The incidence of adverse events was lower with racecadotril than with loperamide (11.5% vs. 22%), and significantly more patients on loperamide suffered from constipation (58% vs. 36.5%;P = 0.03). Moreover, significantly more children receiving loperamide required concomitant medication during the study (38%v19.2%;P = 0.047). Measurement of abdominal circumference at the final consultation, 6 days after entry to the study, revealed no significant differences between treatments.ConclusionsRacecadotril and loperamide were equally effective in treating acute diarrhoea in these children, and racecadotril had a superior tolerability and safety profile.
Review article: effects of the 5‐HT3 receptor antagonist alosetron on neuromuscular transmission in canine and human intestinal muscle
Authors: Audolfsson G. , Bayguinov O. , Yamamoto T. , Somogyi G.T. , Schraut W.H. , Sanders K.M. , Bauer A.J. 
Published: September 2010

Background: Currently, therapeutic treatments for irritable bowel syndrome fail to produce significant clinical results. We hypothesized that alosetron, a selective 5‐HT3 antagonist, may provide symptomatic relief in irritable bowel syndrome patients through a decrease in the amplitude of gastrointestinal contractions. Aim: To determine the in vitro effect of alosetron on neuromuscular transmission in the canine and human jejunal and colonic muscularis externa. Results: Alosetron diminished electrical field‐stimulated (EFS) contractions recorded from muscles of the canine and human small and large intestines. Mechanistically, the diminished EFS response could be explained by the ability of alosetron to decrease the fractional release of 14C‐choline radiolabelled acetylcholine evoked by EFS from human jejunal muscle. The inhibition of EFS contractions was not limited to atropine‐sensitive events, as non‐cholinergic excitatory EFS evoked contractions were also inhibited. Additionally, alosetron at high concentrations (> 30 μm) directly altered bethanechol stimulated contractions. Conclusion: Caution must be used in the interpretation of these data because significant alterations in EFS‐induced contractions were only observed with large pharmacological concentrations of alosetron, and the response was not selective for cholinergically‐mediated excitatory neuromuscular transmission.
Elicitation of structure-specific antibodies by epitope scaffolds
Authors: Ofek Gilad , Guenaga F. Javier , Schief William R. , Skinner Jeff , Baker David , Wyatt Richard , Kwong Peter D. 
Published: September 2010

Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant “2F5-epitope scaffolds” possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (
p
< 0.04), while antibody responses against the graft—as dissected residue-by-residue with alanine substitutions—resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.
Inhibition of the visual cycle by A2E through direct interaction with RPE65 and implications in Stargardt disease
Authors: Moiseyev Gennadiy , Nikolaeva Olga , Chen Ying , Farjo Krysten , Takahashi Yusuke , Ma Jian-xing 
Published: September 2010

Stargardt disease (STGD) is the major form of inherited juvenile macular degeneration. Pyridinium bis-retinoid A2E is a major component of lipofuscin which accumulates in retinal pigment epithelium (RPE) cells in STGD and contributes to the disease pathogenesis. However, the precise role of A2E in vision loss is unclear. Here we report that A2E efficiently inhibits RPE65 isomerohydrolase, a key enzyme in the visual cycle. Subretinal injection of A2E significantly inhibited retinoid isomerohydrolase activity in mice. Likewise, A2E also inhibited isomerohydrolase activity in cells coexpressing RPE65, lecithin retinol acyltransferase (LRAT), and cellular retinaldehyde-binding protein. In vitro isomerohydrolase activity assays confirmed that A2E inhibited enzymatic activity of recombinant RPE65 in a concentration-dependent manner, but did not inhibit LRAT activity. The inhibition type for isomerohydrolase was found to be reversible and competitive with
K

i

= 13.6 μM. To determine the direct interaction of A2E with RPE65 protein, fluorescence binding assays were performed. As shown by fluorimetric titration, binding of purified RPE65 with A2E enhanced the bis-retinoid fluorescence. Consistently, the fluorescence of RPE65 decreased upon incubation with A2E. Both of these experiments suggest a direct, specific binding of A2E to RPE65. The binding constant for A2E and purified RPE65 was calculated to be 250 nM. These results demonstrate that A2E inhibits the regeneration of 11-
cis
retinal, the chromophore of visual pigments, which represents a unique mechanism by which A2E may impair vision in STGD.
Pharmacological chaperone for the structured domain of human prion protein
Authors: Nicoll Andrew J. , Trevitt Clare R. , Tattum M. Howard , Risse Emmanuel , Quarterman Emma , Ibarra Amaurys Avila , Wright Connor , Jackson Graham S. , Sessions Richard B. , Farrow Mark , Waltho Jonathan P. , Clarke Anthony R. , Collinge John 
Published: September 2010

In prion diseases, the misfolded protein aggregates are derived from cellular prion protein (PrPC). Numerous ligands have been reported to bind to human PrPC(huPrP), but none to the structured region with the affinity required for a pharmacological chaperone. Using equilibrium dialysis, we screened molecules previously suggested to interact with PrP to discriminate between those which did not interact with PrP, behaved as nonspecific polyionic aggregates or formed a genuine interaction. Those that bind could potentially act as pharmacological chaperones. Here we report that a cationic tetrapyrrole [Fe(III)-TMPyP], which displays potent antiprion activity, binds to the structured region of huPrP. Using a battery of biophysical techniques, we demonstrate that Fe(III)-TMPyP forms a 1∶1 complex via the structured C terminus of huPrP with aKdof 4.5 ± 2 μM, which is in the range of its IC50for curing prion-infected cells of 1.6 ± 0.4 μM and the concentration required to inhibit protein-misfolding cyclic amplification. Therefore, this molecule tests the hypothesis that stabilization of huPrPC, as a principle, could be used in the treatment of human prion disease. The identification of a binding site with a defined 3D structure opens up the possibility of designing small molecules that stabilize huPrP and prevent its conversion into the disease-associated form.
Accumulation of driver and passenger mutations during tumor progression
Authors: Bozic Ivana , Antal Tibor , Ohtsuki Hisashi , Carter Hannah , Kim Dewey , Chen Sining , Karchin Rachel , Kinzler Kenneth W. , Vogelstein Bert , Nowak Martin A. 
Published: September 2010

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development—providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small—0.004 ± 0.0004—and has major implications for experimental cancer research.
Quantifying Interhospital Patient Sharing as a Mechanism for Infectious Disease Spread
Authors: Huang Susan S. , Avery Taliser R. , Song Yeohan , Elkins Kristen R. , Nguyen Christopher C. , Nutter Sandra K. , Nafday Alaka A. , Condon Curtis J. , Chang Michael T. , Chrest David , Boos John , Bobashev Georgiy , Wheaton William , Frank Steven A. , Piatt Richard , Lipsitch Marc , Bush Robin M. , Eubank Stephen , Burke Donald S. , Lee Bruce Y. 
Published: September 2010

Background.Assessments of infectious disease spread in hospitals seldom account for interfacility patient sharing. This is particularly important for pathogens with prolonged incubation periods or carrier states.Methods.We quantified patient sharing among all 32 hospitals in Orange County (OC), California, using hospital discharge data. Same-day transfers between hospitals were considered “direct” transfers, and events in which patients were shared between hospitals after an intervening stay at home or elsewhere were considered “indirect” patient-sharing events. We assessed the frequency of readmissions to another OC hospital within various time points from discharge and examined interhospital sharing of patients with Clostridium difficile infection.Results.In 2005, OC hospitals had 319,918 admissions. Twenty-nine percent of patients were admitted at least twice, with a median interval between discharge and readmission of 53 days. Of the patients with 2 or more admissions, 75% were admitted to more than 1 hospital. Ninety-four percent of interhospital patient sharing occurred indirectly. When we used 10 shared patients as a measure of potential interhospital exposure, 6 (19%) of 32 hospitals “exposed” more than 50% of all OC hospitals within 6 months, and 17 (53%) exposed more than 50% within 12 months. Hospitals shared 1 or more patient with a median of 28 other hospitals. When we evaluated patients with C. difficile infection, 25% were readmitted within 12 weeks; 41% were readmitted to different hospitals, and less than 30% of these readmissions were direct transfers.Conclusions.In a large metropolitan county, interhospital patient sharing was a potential avenue for transmission of infectious agents. Indirect sharing with an intervening stay at home or elsewhere composed the bulk of potential exposures and occurred unbeknownst to hospitals.
Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials
Authors: Spiegel B. M. R. , Bolus R. , Agarwal N. , Sayuk G. , Harris L. A. , Lucak S. , Esrailian E. , Chey W. D. , Lembo A. , Karsan H. , Tillisch K. , Talley J. , Chang L. 
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1275–1291SummaryBackground  There is uncertainty about how to measure patient‐reported outcomes (PROs) in IBS. The Food and Drug Administration (FDA) emphasizes that PROs must be couched in a conceptual framework, yet existing IBS PROs were not based on such a framework.Aim  To perform qualitative analyses to inform a new conceptual framework for IBS symptoms.Methods  Following FDA guidance, we searched the literature for extant IBS questionnaires. We then performed interviews in IBS patients to learn about the illness experience in their own words. We cultivated vocabulary to inform a conceptual framework depicted with domains, sub‐domains, and item categories, per FDA guidance.Results  We identified 13 questionnaires with items encompassing 18 symptoms. We recruited 123 IBS patients for cognitive interviews. Major themes included: pain and discomfort are different – asking about discomfort is nonspecific and should be avoided in future PROs; bowel urgency is multifaceted – PROs should measure bowel immediacy, controllability, and predictability; and PROs should divide bloating into how it feels vs. how it looks. Symptom experience may be determined by 35‐item categories within five domains: (i) pain; (ii) gas/bloat; (iii) diarrhoea; (iv) constipation; and (v) extraintestinal symptoms.Conclusions  We applied FDA guidance to develop a framework that can serve as the foundation for developing a PRO for IBS clinical trials.