bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating GENeral practitioners dialogue with patients on their Agenda (MultiCare AGENDA) study protocol for a cluster randomized controlled trial
Authors: Altiner Attila , Schäfer Ingmar , Mellert Christine , Löffler Christin , Mortsiefer Achim , Ernst Annette , Stolzenbach Carl-Otto , Wiese Birgitt , Scherer Martin , van den Bussche Hendrik , Kaduszkiewicz Hanna 
Published: December 2012

Abstract

Background
This study investigates the efficacy of a complex multifaceted intervention aiming at increasing the quality of care of GPs for patients with multimorbidity. In its core, the intervention aims at enhancing the doctor-patient-dialogue and identifying the patient’s agenda and needs. Also, a medication check is embedded. Our primary hypothesis is that a more patient-centred communication will reduce the number of active pharmaceuticals taken without impairing the patients’ quality of life. Secondary hypotheses include a better knowledge of GPs about their patients’ medication, a higher patient satisfaction and a more effective and/or efficient health care utilization.

Methods/design
Multi-center, parallel group, cluster randomized controlled clinical trial in GP surgeries. Inclusion criteria: Patients aged 65–84 years with at least 3 chronic conditions. Intervention: GPs allocated to this group will receive a multifaceted educational intervention on performing a narrative doctor-patient dialogue reflecting treatment targets and priorities of the patient and on performing a narrative patient-centred medication review. During the one year intervention GPs will have a total of three conversations à 30 minutes with the enrolled patients. Control: Care as usual. Follow-up per patient: 14 months after baseline interview. Primary efficacy endpoints: Differences in medication intake and health related quality of life between baseline and follow-up in the intervention compared to the control group. Randomization: Computer-generated by an independent institute. It will be performed successively when patient recruitment in the respective surgery is finished. Blinding: Participants (GPs and patients) will not be blinded to their assignment but will be unaware of the study hypotheses or outcome measures.

Discussion
There is growing evidence that the phenomenon of polypharmacy and low quality of drug use is substantially due to mis-communication (or non-communication) in the doctor patient interaction. We assume that the number of pharmaceutical agents taken can be reduced by a communicational intervention and that this will not impair the patients’ health-related quality of life. Improving communication is a core issue of future interventions, especially for patients with multimorbidity.

Trial registration
Current Controlled Trials ISRCTN46272088.
Actinomycetoma in SE Asia: the first case from Laos and a review of the literature
Authors: Rattanavong Sayaphet , Vongthongchit Sivay , Bounphamala Khamhou , Vongphakdy Phouvong , Gubler Jacques , Mayxay Mayfong , Phetsouvanh Rattanaphone , Elliott Ivo , Logan Julie , Hill Robert , Newton Paul N , Dance David 
Published: December 2012

Abstract

Background
Mycetoma is a chronic, localized, slowly progressing infection of the cutaneous and subcutaneous tissues caused either by fungi (eumycetoma or implantation mycosis) or by aerobic actinomycetes (actinomycetoma). It is acquired by traumatic implantation, most commonly in the tropics and subtropics, especially in rural agricultural communities. Although well recognized elsewhere in Asia, it has not been reported from the Lao People’s Democratic Republic (Laos).

Case presentation
A 30 year-old female elementary school teacher and rice farmer from northeast Laos was admitted to Mahosot Hospital, Vientiane, with a massive growth on her left foot, without a history of trauma. The swelling had progressed slowly but painlessly over 5 years and multiple draining sinuses had developed. Ten days before admission the foot had increased considerably in size and became very painful, with multiple sinuses and discharge, preventing her from walking. Gram stain and bacterial culture of tissue biopsies revealed a branching filamentous Gram-positive bacterium that was subsequently identified as Actinomadura madurae by 16S rRNA gene amplification and sequencing. She was treated with long-term co-trimoxazole and multiple 3-week cycles of amikacin with a good therapeutic response.

Conclusion
We report the first patient with actinomycetoma from Laos. The disease should be considered in the differential diagnosis of chronic skin and bone infections in patients from rural SE Asia.
Brain computer tomography in critically ill patients - a prospective cohort study
Authors: Purmer Ilse M , van Iperen Erik P , Beenen Ludo F M , Kuiper Michael J , Binnekade Jan M , Vandertop Peter W , Schultz Marcus J , Horn Janneke 
Published: December 2012

Abstract

Background
Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients.

Methods
In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An “expected abnormality” was any finding that had been predicted by the physician requesting the brain CT. A brain CT was “diagnostically positive”, if the abnormality found was new or if an already known abnormality was increased. It was “diagnostically negative” if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as “treatment as planned”, “treatment changed, not as planned”, “treatment unchanged”.

Results
Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), p 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned.

Conclusions
The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.
Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme’s active site closure
Authors: Park Jaeok , Lin Yih-Shyan , De Schutter Joris W , Tsantrizos Youla S , Berghuis Albert M 
Published: December 2012

Abstract

Background
Human farnesyl pyrophosphate synthase (FPPS) controls intracellular levels of farnesyl pyrophosphate, which is essential for various biological processes. Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme’s C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP). This conformational change, which occurs through a yet unclear mechanism, seals off the enzyme’s active site from the solvent environment and is essential for catalysis. The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation.

Results
We have determined crystal structures of human FPPS in ternary complex with YS0470 and the secondary ligands inorganic phosphate (Pi), inorganic pyrophosphate (PPi), and IPP. Binding of PPi or IPP to the enzyme-inhibitor complex, but not that of Pi, resulted in full ordering of the C-terminal tail, which is most notably characterized by the anchoring of the R351 side chain to the main frame of the enzyme. Isothermal titration calorimetry experiments demonstrated that PPi binds more tightly to the enzyme-inhibitor complex than IPP, and differential scanning fluorometry experiments confirmed that Pi binding does not induce the tail ordering. Structure analysis identified a cascade of conformational changes required for the C-terminal tail rigidification involving Y349, F238, and Q242. The residues K57 and N59 upon PPi/IPP binding undergo subtler conformational changes, which may initiate this cascade.

Conclusions
In human FPPS, Y349 functions as a safety switch that prevents any futile C-terminal closure and is locked in the “off” position in the absence of bound IPP. Q242 plays the role of a gatekeeper and directly controls the anchoring of R351 side chain. The interactions between the residues K57 and N59 and those upstream and downstream of Y349 are likely responsible for the switch activation. The findings of this study can be exploited for structure-guided optimization of existing inhibitors as well as development of new pharmacophores.
Pulmonary benign metastasizing leiomyoma: a case report and review of the literature
Authors: Fu Yili , Li Hui , Tian Bo , Hu Bin 
Published: December 2012

Abstract
Pulmonary benign metastasizing leiomyoma characterized by the growth of uterine leiomyoma in the lung is a very rare disease. We herein report the case of a 46-year-old asymptomatic woman who underwent a total abdominal hysterectomy for her multiple uterine leiomyomas 5 years ago, with the presence of multiple shadows in her chest roentgenogram during the regular check-up. Chest computerized tomography (CT) showed multiple solitary nodules in both lungs. Video-assisted thoracoscopic surgery with a wedge resection of the lesion was performed. Histopathologically, the pulmonary nodule was composed of benign smooth muscle cells and demonstrated low mitotic activity and absence of necrosis. Immunohistochemical staining for smooth muscle actin (SMA) and Desmin were extremely positive. CD10, CD117 and S-100 were negative in the tumor cells. Positive immunoreactivity for estrogen receptor (ER) and progesterone receptor (PR) were detected. The pathological diagnosis was pulmonary benign metastasizing leiomyoma.
Chemical constituents of ambient particulate air pollution and biomarkers of inflammation, coagulation and homocysteine in healthy adults: A prospective panel study
Authors: Wu Shaowei , Deng Furong , Wei Hongying , Huang Jing , Wang Hongyi , Shima Masayuki , Wang Xin , Qin Yu , Zheng Chanjuan , Hao Yu , Guo Xinbiao 
Published: December 2012

Abstract

Background
Ambient air pollution has been associated with activation of systemic inflammation and hypercoagulability and increased plasma homocysteine, but the chemical constituents behind the association are not well understood. We examined the relations of various chemical constituents of fine particles (PM2.5) and biomarkers of inflammation, coagulation and homocysteine in the context of traffic-related air pollution.

Methods
A panel of 40 healthy college students underwent biweekly blood collection for 12 times before and after their relocation from a suburban campus to an urban campus with changing air pollution contents in Beijing. Blood samples were measured for circulatory biomarkers of high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), von Willebrand factor (vWF), soluble platelet selectin (sP-selectin), and total homocysteine (tHcy). Various air pollutants were measured in a central air-monitoring station in each campus and 32 PM2.5 chemical constituents were determined in the laboratory. We used three different mixed-effects models (single-constituent model, constituent-PM2.5 joint model and constituent residual model) controlling for potential confounders to estimate the effects of PM2.5 chemical constituents on circulatory biomarkers.

Results
We found consistent positive associations between the following biomarkers and PM2.5 chemical constituents across different models: TNF-α with secondary organic carbon, chloride, zinc, molybdenum and stannum; fibrinogen with magnesium, iron, titanium, cobalt and cadmium; PAI-1 with titanium, cobalt and manganese; t-PA with cadmium and selenium; vWF with aluminum. We also found consistent inverse associations of vWF with nitrate, chloride and sodium, and sP-selectin with manganese. Two positive associations of zinc with TNF-α and of cobalt with fibrinogen, and two inverse associations of nitrate with vWF, and of manganese with sP-selectin, were independent of the other constituents in two-constituent models using constituent residual data. We only found weak air pollution effects on hs-CRP and tHcy.

Conclusions
Our results provide clues for the potential roles that PM2.5 chemical constituents may play in the biological mechanisms through which air pollution may influence the cardiovascular system.
Identification of new cell size control genes in S. cerevisiae
Authors: Dungrawala Huzefa , Hua Hui , Wright Jill , Abraham Lesley , Kasemsri Thivakorn , McDowell Anthony , Stilwell Jessica , Schneider Brandt L 
Published: December 2012

Abstract
Cell size homeostasis is a conserved attribute in many eukaryotic species involving a tight regulation between the processes of growth and proliferation. In budding yeast S. cerevisiae, growth to a “critical cell size” must be achieved before a cell can progress past START and commit to cell division. Numerous studies have shown that progression past START is actively regulated by cell size control genes, many of which have implications in cell cycle control and cancer. Two initial screens identified genes that strongly modulate cell size in yeast. Since a second generation yeast gene knockout collection has been generated, we screened an additional 779 yeast knockouts containing 435 new ORFs (~7% of the yeast genome) to supplement previous cell size screens. Upon completion, 10 new strong size mutants were identified: nine in log-phase cells and one in saturation-phase cells, and 97% of the yeast genome has now been screened for cell size mutations. The majority of the logarithmic phase size mutants have functions associated with translation further implicating the central role of growth control in the cell division process. Genetic analyses suggest ECM9 is directly associated with the START transition. Further, the small (whi) mutants mrpl49Δ and cbs1Δ are dependent on CLN3 for cell size effects. In depth analyses of new size mutants may facilitate a better understanding of the processes that govern cell size homeostasis.
Amyloidosis cutis dyschromica
Authors: Qiao Jianjun , Fang Hong , Yao Hongtian 
Published: December 2012

Abstract

Background
Amyloidosis cutis dyschromica is a rarely documented variant of cutaneous amyloidosis. To date, only 26 cases have been reported.

Objective
The purpose of this study was to improve the clinical and histopathological data for this variant of amyloidosis and to highlight the immunohistochemical features of the disease. The published cases were also reviewed.

Methods
We performed a retrospective review of patients with amyloidosis cutis dyschromica in a single centre. The clinical, histopathological and immunohistochemical features were documented and analysed.

Observations
We described 10 cases of amyloidosis cutis dyschromica. Six of them were female. Five patients were from the same family, and the other 5 were sporadic. The distinguishing features of the clinical presentation included generalised mottled hyper- and hypopigmented macules, which were asymptomatic or mild pruritic. The typical onset of the lesions occurred in childhood (n = 7) and occasionally after puberty (n = 3). No evidence of systemic amyloidosis deposition was observed in these cases of amyloidosis cutis dyschromica. Amyloid deposits were observed in the papillary dermis and were positive for the Congo red stain. An immunohistochemical study showed that the amyloid expresses cytokeratins CK34βE12 and CK5/6.

Conclusions
We described the largest series of amyloidosis cutis dyschromica to date and reviewed the published patients. This rare disease is featured by generalised mottled hyper- and hypopigmented lesions, and it is a rare variant of primary cutaneous amyloidosis without evidence of systemic amyloid deposition. Positive staining for the cytokeratins CK34βE12 and CK5/6 in amyloidosis cutis dyschromica suggests that the amyloid is derived from keratinocytes.
PCDq: human protein complex database with quality index which summarizes different levels of evidences of protein complexes predicted from H-Invitational protein-protein interactions integrative dataset
Authors: Kikugawa Shingo , Nishikata Kensaku , Murakami Katsuhiko , Sato Yoshiharu , Suzuki Mami , Altaf-Ul-Amin Md , Kanaya Shigehiko , Imanishi Tadashi 
Published: December 2012

Abstract

Background
Proteins interact with other proteins or biomolecules in complexes to perform cellular functions. Existing protein-protein interaction (PPI) databases and protein complex databases for human proteins are not organized to provide protein complex information or facilitate the discovery of novel subunits. Data integration of PPIs focused specifically on protein complexes, subunits, and their functions. Predicted candidate complexes or subunits are also important for experimental biologists.

Description
Based on integrated PPI data and literature, we have developed a human protein complex database with a complex quality index (PCDq), which includes both known and predicted complexes and subunits. We integrated six PPI data (BIND, DIP, MINT, HPRD, IntAct, and GNP_Y2H), and predicted human protein complexes by finding densely connected regions in the PPI networks. They were curated with the literature so that missing proteins were complemented and some complexes were merged, resulting in 1,264 complexes comprising 9,268 proteins with 32,198 PPIs. The evidence level of each subunit was assigned as a categorical variable. This indicated whether it was a known subunit, and a specific function was inferable from sequence or network analysis. To summarize the categories of all the subunits in a complex, we devised a complex quality index (CQI) and assigned it to each complex. We examined the proportion of consistency of Gene Ontology (GO) terms among protein subunits of a complex. Next, we compared the expression profiles of the corresponding genes and found that many proteins in larger complexes tend to be expressed cooperatively at the transcript level. The proportion of duplicated genes in a complex was evaluated. Finally, we identified 78 hypothetical proteins that were annotated as subunits of 82 complexes, which included known complexes. Of these hypothetical proteins, after our prediction had been made, four were reported to be actual subunits of the assigned protein complexes.

Conclusions
We constructed a new protein complex database PCDq including both predicted and curated human protein complexes. CQI is a useful source of experimentally confirmed information about protein complexes and subunits. The predicted protein complexes can provide functional clues about hypothetical proteins. PCDq is freely available at http://h-invitational.jp/hinv/pcdq/.
Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma
Authors: Mao Yuan , Zhang Da-Wei , Lin Hong , Xiong Lin , Liu Ying , Li Qing-Dong , Ma Jun , Cao Qing , Chen Ren-Jie , Zhu Jin , Feng Zhen-Qing 
Published: December 2012

Abstract

Background
Alpha B-crystallin (αB-crystallin) has been suggested to play an important role in the development of solid tumors. However, the association between αB-crystallin expression and clinicopathological characteristics of human laryngeal carcinoma is not well defined. This study aimed to examine the expression of αB-crystallin in human laryngeal squamous cell carcinoma (LSCC) and investigate the relationship between its expression and the prognosis of LSCC.

Methods
Real-time polymerase chain reaction (six LSCC samples, six tumor-adjacent normal samples) and immunohistochemistry by tissue microarrays (109 LSCC samples and 28 tumor-adjacent normal samples) were performed to characterize expression of the αB-crystallin gene in LSCC. Kaplan-Meier survival and Cox regression analyses were carried out to evaluate the prognosis of LSCC.

Results
Real-time polymerase chain reaction and immunohistochemistry analysis showed that the expression of αB-crystallin in LSCC was significantly higher than that in tumor-adjacent normal tissues. Moreover, the expression level of αB-crystallin protein in LSCC was significantly related to alcohol consumption (P = 0.022), tumor differentiation (P = 0.007), pTNM stage (P = 0.041) and 5 years’ survival (P =0.030). COX multi-factor analysis showed that αB-crystallin (P = 0.013), as well as pTNM stage (P =0.027) and lymphatic metastasis (P = 0.015) were independent prognosis factors for LSCC.

Conclusions
The data suggest that αB-crystallin expression is correlated with malignant phenotypes of LSCC and it may serve as a novel prognostic factor for LSCC.
Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial
Authors: Allegra Carmen J. , Yothers Greg , O'Connell Michael J. , Sharif Saima , Petrelli Nicholas J. , Lopa Samia H. , Wolmark Norman 
Published: December 2012

PurposeThe National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.Patients and MethodsPatients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.ResultsOf 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).ConclusionBevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.