bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole proteome identification of plant candidate G-protein coupled receptors in Arabidopsis, rice, and poplar: computational prediction and in-vivo protein coupling
Authors: Gookin Timothy E , Kim Junhyong , Assmann Sarah M 
Published: July 2008

Abstract
Background
The classic paradigm of heterotrimeric G-protein signaling describes a heptahelical, membrane-spanning G-protein coupled receptor that physically interacts with an intracellular Gα subunit of the G-protein heterotrimer to transduce signals. G-protein coupled receptors comprise the largest protein superfamily in metazoa and are physiologically important as they sense highly diverse stimuli and play key roles in human disease. The heterotrimeric G-protein signaling mechanism is conserved across metazoa, and also readily identifiable in plants, but the low sequence conservation of G-protein coupled receptors hampers the identification of novel ones. Using diverse computational methods, we performed whole-proteome analyses of the three dominant model plant species, the herbaceous dicot Arabidopsis thaliana (mouse-eared cress), the monocot Oryza sativa (rice), and the woody dicot Populus trichocarpa (poplar), to identify plant protein sequences most likely to be GPCRs.

Results
Our stringent bioinformatic pipeline allowed the high confidence identification of candidate G-protein coupled receptors within the Arabidopsis, Oryza, and Populus proteomes. We extended these computational results through actual wet-bench experiments where we tested over half of our highest ranking Arabidopsis candidate G-protein coupled receptors for the ability to physically couple with GPA1, the sole Gα in Arabidopsis. We found that seven out of eight tested candidate G-protein coupled receptors do in fact interact with GPA1. We show through G-protein coupled receptor classification and molecular evolutionary analyses that both individual G-protein coupled receptor candidates and candidate G-protein coupled receptor families are conserved across plant species and that, in some cases, this conservation extends to metazoans.

Conclusion
Our computational and wet-bench results provide the first step toward understanding the diversity, conservation, and functional roles of plant candidate G-protein coupled receptors.
Characterization and TCR variable region gene use of mouse resident nasal γδ T lymphocytes
Authors: Kim Chang-Hoon , Witherden Deborah A , Havran Wendy L 
Published: July 2008

AbstractTissue-resident γδ T lymphocytes, such as dendritic epidermal T cells, intestinal intraepithelial lymphocytes (IEL), and resident pulmonary lymphocytes, are known to support local tissue homeostasis and host defense. Inhaled antigens, toxins, and microorganisms first interact with the immune system through contact with the nasal mucosa. Herein, we characterized two populations of resident nasal lymphocytes (RNL) that are present in the nasal mucosa: nasal IEL (nIEL) and nasal lamina propria lymphocytes (nLPL). γδ TCR+ and αβ TCR+ nIEL and nLPL were detected by immunofluorescent staining. Mononuclear cells (5–15%) were CD3+ RNL by FACS analysis. Among the CD3+ RNL, 20–30% were GL3+ γδ T cells, which were double-negative for CD4 and CD8 and predominantly expressed a Vγ4/Vδ1 TCR. These results demonstrate that RNL might be crucial for the host defense and tissue homeostasis in the nasal mucosa.
Questionnaires for 360-degree assessment of consultant psychiatrists: Development and psychometric properties
Authors: Lelliott Paul , Williams Richard , Mears Alex , Andiappan Manoharan , Owen Helen , Reading Paul , Coyle Nick , Hunter Stephen 
Published: July 2008

BackgroundExpert clinical judgement combines technical proficiency with humanistic qualities.AimsTo test the psychometric properties of questionnaires to assess the humanistic qualities of working with colleagues and relating to patients using multisource feedback.MethodAnalysis of self-ratings by 347 consultant psychiatrists and ratings by 4422 colleagues and 6657 patients.ResultsMean effectiveness as rated by self, colleagues and patients, was 4.6, 5.0 and 5.2 respectively (where 1=very low and 6=excellent). The instruments are internally consistent (Cronbach's alpha > 0.95). Principal components analysis of the colleague questionnaire yielded seven factors that explain 70.2% of the variance and accord with the domain structure. Colleague and patient ratings correlate with one another (r=0.39, P<0.001) but not with the self-rating. Ratings from 13 colleagues and 25 patients are required to achieve a generalisability coefficient (Eρ2) of 0.75.ConclusionsReliable 360-degree assessment of humane judgement is feasible for psychiatrists who work in large multiprofessional teams and who have large case-loads.
Effect of anxiety and depression on blood pressure: 11-year longitudinal population study
Authors: Hildrum Bjørn , Mykletun Arnstein , Holmen Jostein , Dahl Alv A. 
Published: July 2008

BackgroundThe long-term effect of anxiety and depression on blood pressure is unclear.AimsTo examine the prospective association of anxiety and depression with change in blood pressure in a general population.MethodData on 36530 men and women aged 20–78 years participating in the Nord-Tr⊘ndelag Health Study (HUNT) in Norway in 1984–86 were re-examined 11 years later.ResultsA high symptom level of anxiety and depression at baseline predicted low systolic blood pressure (< 10th percentile) at follow-up (OR=1.30, 95% CI 1.08–1.57) when those with low systolic blood pressure at baseline were excluded. Change in symptom level of anxiety and depression between baseline and follow-up was inversely associated with change in systolic blood pressure. For diastolic blood pressure, the findings were weaker or non-significant.ConclusionsSymptoms of anxiety and depression predicted lower blood pressure 11 years later.
Maintenance pharmacotherapy for recurrent major depressive disorder: 5-year follow-up study
Authors: Holma Irina A. K. , Holma K. Mikael , Melartin Tarja K. , Isometsä Erkki T. 
Published: July 2008

SummaryPractice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment. The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period.
Homicide due to mental disorder in England and Wales over 50 years
Authors: Large Matthew , Smith Glen , Swinson Nicola , Shaw Jenny , Nielssen Olav 
Published: July 2008

BackgroundIt has been stated that rates of homicide due to mental disorder are constant over time.AimsTo examine whether there were changes in the rates of homicide due to mental disorder over time, and whether changes in these rates were associated with changes in the rates of other homicides in England and Wales.MethodExamination of four sets of official homicide statistics from England and Wales from 1946 to 2004.ResultsThe rate of total homicide and the rate of homicide due to mental disorder rose steadily until the mid-1970s. From then there was a reversal in the rate of homicides attributed to mental disorder, which declined to historically low levels, while other homicides continued to rise.ConclusionsThe reasons for the rise and fall in homicides attributed to mental disorder are not clear. The earlier increase in such homicides may have been due to the same sociological factors that caused the increase in other homicides over that time. The subsequent decline may have been due to improvements in psychiatric treatments and service organisation. Another possibility is that there has been an informal change to the legal tests for the finding of homicide due to mental disorder.
Community treatment orders are not a good thing
Authors: Lawton-Smith Simon , Dawson John , Burns Tom 
Published: July 2008

SummaryDoes politicians' enthusiasm for community treatment orders lie primarily in the area of public protection? If so, can such orders reduce homicide rates? Is there adequate evidence of their value, given their adverse effects on individual liberty? This well-researched and provocative debate will enlighten readers on these and many more of the complicated questions surrounding this issue.
Ethnicity and quality of antipsychotic prescribing among in-patients in south London
Authors: Connolly Anne , Taylor David 
Published: July 2008

SummaryEthnicity may influence treatment decisions in mental disorders. We undertook a survey of the prescribing of antipsychotics for in-patients in three south London mental health trusts. A total of 255 patients (152 White, 103 Black) were included. Median dose of antipsychotic (% of licensed dose) was 58.3% for White and 50.0% for Black patients (adjusted effect size=0.14, 95% CI −0.34 to 0.63). High-dose antipsychotics were prescribed to 15.1% of White and 11.7% of Black patients (adjusted odds ratio (OR)=0.5, 95% CI 0.19–1.33), and antipsychotic polypharmacy was recorded for 25.7% and 31.1% respectively (adjusted OR=3.05, 95% CI 1.44–6.46). Prescribing quality was similar for Black and White patients.
Neuropsychiatry in the UK: national survey of existing service provision
Authors: Agrawal Niruj , Fleminger Simon , Ring Howard , Deb Shoumitro 
Published: July 2008

Aims and MethodTo elucidate and describe current neuropsychiatry service provision in the UK. A questionnaire was developed and posted to members of the Royal College of Psychiatrists who had expressed an interest in neuropsychiatry. the responses were tabulated and analysed using descriptive statistics and SPSS version 11.0 for Windows. the neuropsychiatry services provided, sources of referrals, setting of the services and funding streams are described.ResultsOut of 251 respondents, 70 reported providing a neuropsychiatry service, 21 having been principally appointed as neuropsychiatrists.Clinical ImplicationsNeuropsychiatry services in the UK are currently based in a few regional centres, representing a patchy and inadequate service provision.
Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity
Authors: Azad Nilofer S. , Posadas Edwin M. , Kwitkowski Virginia E. , Steinberg Seth M. , Jain Lokesh , Annunziata Christina M. , Minasian Lori , Sarosy Gisele , Kotz Herbert L. , Premkumar Ahalya , Cao Liang , McNally Deborah , Chow Catherine , Chen Helen X. , Wright John J. , Figg William D. , Kohn Elise C. 
Published: July 2008

Purpose Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects. Patients and Methods Patients had advanced solid tumors, Eastern Cooperative Oncology Group performance status of 0 to 1, and good end-organ function. A phase I dose-escalation trial of sorafenib and bevacizumab was initiated at below-recommended single-agent doses because of possible overlapping toxicity: sorafenib 200 mg orally twice daily and bevacizumab intravenously at 5 mg/kg (dose level [DL] 1) or 10 mg/kg (DL2) every 2 weeks. Additional patients were enrolled at the maximum-tolerated dose (MTD). Results Thirty-nine patients were treated. DL1 was the MTD and administered in cohort 2 (N = 27). Dose-limiting toxicity in DL2 was grade 3 proteinuria and thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, transaminitis, and fatigue. Partial responses (PRs) were seen in six (43%) of 13 patients with ovarian cancer (response duration range, 4 to 22+ months) and one of three patients with renal cell cancer (response duration, 14 months). PR or disease stabilization ≥ 4 months (median, 6 months; range, 4 to 22+ months) was seen in 22 (59%) of 37 assessable patients. The majority (74%) required sorafenib dose reduction to 200 mg/d at a median of four cycles (range, one to 12 cycles). Conclusion Combination therapy with sorafenib and bevacizumab has promising clinical activity, especially in patients with ovarian cancer. The rapidity and frequency of sorafenib dose reductions indicates that sorafenib at 200 mg twice daily with bevacizumab 5 mg/kg every 2 weeks may not be tolerable long term, and alternate sorafenib dosing schedules should be explored.
Variations in Quality of Care for Men With Early-Stage Prostate Cancer
Authors: Spencer Benjamin A. , Miller David C. , Litwin Mark S. , Ritchey Jamie D. , Stewart Andrew K. , Dunn Rodney L. , Gay E. Greer , Sandler Howard M. , Wei John T. 
Published: July 2008

Purpose The commencement of quality-improvement initiatives such as Pay for Performance and the Physician Consortium for Performance Improvement has underscored calls to evaluate the quality of cancer care on a patient level for nationally representative samples. Methods We sampled early-stage prostate cancer cases diagnosed in 2000 through 2001 from the American College of Surgeons National Cancer Data Base and explicitly reviewed medical records from 2,775 men (weighted total = 55,160 cases) treated with radical prostatectomy or external-beam radiation therapy. We determined compliance with 29 quality-of-care disease-specific structure and process indicators developed by RAND, stratified by race, geographic region, and hospital type. Results Overall compliance exceeded 70% for structural and pretherapy disease assessment indicators but was lower for documentation of pretreatment functioning (46.4% to 78.4%), surgical pathology (37.1% to 86.3%), radiation technique (62.6% to 88.3%), and follow-up (55%). Geographic variations were observed as higher compliance in the South Atlantic division than the New England division for having at least one board-certified urologist (odds ratio [OR], 9.2; 95% CI, 1.9 to 45.0), at least one board-certified radiation oncologist (OR, 3.3; 95% CI, 1.2 to 9.0), use of Gleason grading (OR, 4.1; 95% CI, 1.2 to 13.8), and administering total radiation dose ≥ 70 Gy (OR, 3.1; 95% CI, 1.6 to 6.1). Teaching/research hospitals and Comprehensive Cancer Centers had higher compliance than Community Cancer Centers, whereas racial differences were not observed for any indicator. Conclusion The significant and unwarranted variations observed for these quality indicators by census division and hospital type illustrate the inconsistencies in prostate cancer care and represent potential targets for quality improvement. The lack of racial disparities suggests equity in care once a patient initiates treatment.
Amifostine Protects Against Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma
Authors: Fouladi Maryam , Chintagumpala Murali , Ashley David , Kellie Stewart , Gururangan Sridharan , Hassall Tim , Gronewold Lindsey , Stewart Clinton F. , Wallace Dana , Broniscer Alberto , Hale Gregory A. , Kasow Kimberly A. , Merchant Thomas E. , Morris Brannon , Krasin Matthew , Kun Larry E. , Boyett James M. , Gajjar Amar 
Published: July 2008

Purpose To determine the role of amifostine as a protectant against cisplatin-induced ototoxicity in patients with average-risk (AR) medulloblastoma treated with craniospinal radiotherapy and four cycles of cisplatin-based, dose-intense chemotherapy and stem-cell rescue. Patients and Methods The primary objective was to determine whether, in patients with AR medulloblastoma (n = 62), amifostine would decrease the need for hearing aids (defined as ≥ grade 3 ototoxicity in one ear) compared with a control group (n = 35), 1 year from initiating treatment. Ninety-seven patients received craniospinal irradiation (23.4 Gy) followed by 55.8 Gy to the primary tumor bed using three-dimensional conformal technique, and four cycles of high-dose cyclophosphamide (4,000 mg/m2/cycle), cisplatin (75 mg/m2/cycle), and vincristine (two 1.5 mg/m2 doses/cycle) and stem-cell rescue. When used, amifostine (600 mg/m2/dose) was administered as a bolus immediately before and 3 hours into the cisplatin infusion. Results The median age of the 97 patients was 8.7 years (range, 3.2 to 20.2 years). The study and control groups were similar in age and sex distribution. Amifostine was well-tolerated. One year after treatment initiation, 13 patients (37.1%) in the control group versus nine (14.5%; one-sided χ2 test P = .005) of the amifostine-treated patients had at least grade 3 ototoxicity, requiring hearing aid in at least one ear. Conclusion Amifostine administered before and during the cisplatin infusion can significantly reduce the risk of severe ototoxicity in patients with AR medulloblastoma receiving dose-intense chemotherapy.
Randomized Phase III Study Comparing Preoperative Radiotherapy With Chemoradiotherapy in Nonresectable Rectal Cancer
Authors: Brændengen Morten , Tveit Kjell M. , Berglund Åke , Birkemeyer Elke , Frykholm Gunilla , Påhlman Lars , Wiig Johan N. , Byström Per , Bujko Krzysztof , Glimelius Bengt 
Published: July 2008

Purpose Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. Patients and Methods The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). Results The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. Conclusion CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.
Is Hepatic Resection Justified After Chemotherapy in Patients With Colorectal Liver Metastases and Lymph Node Involvement?
Authors: Adam René , de Haas Robbert J. , Wicherts Dennis A. , Aloia Thomas A. , Delvart Valérie , Azoulay Daniel , Bismuth Henri , Castaing Denis 
Published: July 2008

Purpose For patients with colorectal liver metastases (CLM), regional lymph node (RLN) involvement is one of the worst prognostic factors. The objective of this study was to evaluate the ability of a multidisciplinary approach, including preoperative chemotherapy and hepatectomy, to improve patient outcomes. Patients and Methods Outcomes for a consecutively treated group of patients with CLM and simultaneous RLN involvement were compared with a cohort of patients without RLN involvement. Univariate and multivariate analysis of clinical variables was used to identify prognostic factors in this high-risk group. Results Of the 763 patients who underwent resection at our institution for CLM between 1992 and 2006, 47 patients (6%) were treated with hepatectomy and simultaneous lymphadenectomy. All patients had received preoperative chemotherapy. Five-year overall survival (OS) for patients with and without RLN involvement were 18% and 53%, respectively (P < .001). Five-year disease-free survival rates were 11% and 23%, respectively (P = .004). When diagnosed preoperatively, RLN involvement had an increased 5-year OS compared with intraoperative detection, although the difference was not significant (35% v 10%; P = .18). Location of metastatic RLN strongly influenced survival, with observed 5-year OS of 25% for pedicular, 0% for celiac, and 0% for para-aortic RLN (P = .001). At multivariate analysis, celiac RLN involvement and age ≥ 40 years were identified as independent poor prognostic factors. Conclusion Combined liver resection and pedicular lymphadenectomy is justified when RLN metastases respond to or are stabilized by preoperative chemotherapy, particularly in young patients. In contrast, this approach does not benefit patients with celiac and/or para-aortic RLN involvement, even when patients’ disease is responding to preoperative chemotherapy.
The anatomical tibial axis
Authors: Cobb J. P. , Dixon H. , Dandachli W. , Iranpour F. 
Published: July 2008

The rotational alignment of the tibia is an unresolved issue in knee replacement. A poor functional outcome may be due to malrotation of the tibial component. Our aim was to find a reliable method for positioning the tibial component in knee replacement. CT scans of 19 knees were reconstructed in three dimensions and orientated vertically. An axial plane was identified 20 mm below the tibial spines. The centre of each tibial condyle was calculated from ten points taken round the condylar cortex. The tibial tubercle centre was also generated as the centre of the circle which best fitted eight points on the outside of the tubercle in an axial plane at the level of its most prominent point. The derived points were identified by three observers with errors of 0.6 mm to 1 mm. The medial and lateral tibial centres were constant features (radius 24 mm (sd 3), and 22 mm (sd 3), respectively). An anatomical axis was created perpendicular to the line joining these two points. The tubercle centre was found to be 20 mm (sd 7) lateral to the centre of the medial tibial condyle. Compared with this axis, an axis perpendicular to the posterior condylar axis was internally rotated by 6° (sd 3). An axis based on the tibial tubercle and the tibial spines was also internally rotated by 5° (sd 10). Alignment of the knee when based on this anatomical axis was more reliable than either the posterior surfaces or any axis involving the tubercle which was the least reliable landmark in the region.