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Collecting and harvesting biological data: the GPCRDB and NucleaRDB information systems.

The amount of genomic and proteomic data that is entered each day into databases and the experimental literature is outstripping the ability of experimental scientists to keep pace. While generic databases derived from automated curation efforts are useful, most biological scientists tend to focus on a class or family of molecules and their biological impact. Consequently, there is a need for molecular class-specific or other specialized databases. Such databases collect and organize data around a single topic or class of molecules. If curated well, such systems are extremely useful as they allow experimental scientists to obtain a large portion of the available data most relevant to their needs from a single source. We are involved in the development of two such databases with substantial pharmacological relevance. These are the GPCRDB and NucleaRDB information systems, which collect and disseminate data related to G protein-coupled receptors and intra-nuclear hormone receptors, respectively. The GPCRDB was a pilot project aimed at building a generic molecular class-specific database capable of dealing with highly heterogeneous data. A first version of the GPCRDB project has been completed and it is routinely used by thousands of scientists. The NucleaRDB was started recently as an application of the concept for the generalization of this technology. The GPCRDB is available via the WWW at http://www.gpcr.org/7tm/ and the NucleaRDB at http://www.receptors.org/NR/.

Binding, Competitive↗

Microbiology Galaxy Lab: The first community-driven gateway for reproducible and FAIR analysis of microbial data.

The explosion of microbial omics data has outpaced the ability of many researchers to analyze it, with complex tools and limited computational resources creating barriers to discovery. To address this gap, we present the Microbiology Galaxy Lab: a free, globally accessible, community-supported platform that combines state-of-the-art analytical power with user-friendly accessibility. Supported by the Galaxy and global microbiology communities, this platform integrates over 315 tool suites and 115 curated workflows, enabling comprehensive metabarcoding, (meta)genomic, (meta)transcriptomic, and (meta)proteomic data analysis within a FAIR-aligned environment. It also supports research in the health and infectious disease sectors, as well as in environmental microbiology. The platform's utility is exemplified through various use cases, including antimicrobial resistance tracking, biomarker prediction, microbiome classification, and functional annotation of key microbes. Built on reproducibility and community engagement, it supports creation, sharing, and updating of best-practice workflows. Over 35 tutorials and learning paths empower scientists, fostering an ecosystem that keeps resources at the forefront of microbial science. The Microbiology Galaxy Lab enables collective analysis, democratising research, thereby accelerating discovery across the global microbiology community (microbiology.usegalaxy.org, .eu, .org.au, .fr).

Journal Article↗

Development of an integrated genome informatics, data management and workflow infrastructure: a toolbox for the study of complex disease genetics.

The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D), chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC) and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.

Animals↗

Benefits of colonoscopic surveillance after curative resection of colorectal cancer.

OBJECTIVE: The authors determined the usefulness of routine colonoscopy after colorectal cancer surgery. SUMMARY BACKGROUND DATA: Some studies suggest benefit to colonoscopy in the routine follow-up of patients with colorectal cancer who are resected for cure, whereas other studies show no benefit. METHODS: Chart review was conducted for 290 patients who underwent curative resection for colorectal cancer between 1967 and 1991 at a colorectal surgeon's practice. Colonoscopy was performed every 6 months during the first year, then every 1 to 2 years, or when intercurrent symptoms appeared. RESULTS: Overall, 31 patients (10.7%) developed recurrent disease, which increased as a function of stage (C2 > B2 > A), with a median time to diagnosis of 20 months. Of these 31 recurrences, 14 (45.2%) were solely local (of whom 12 were asymptomatic); 17 (54.8%) involved distant disease. Nine locally recurrent patients were able to undergo curative resection. Of 19 symptomatic patients, only 3 (15.8%) were amenable to curative resection. Six patients (2.1%) developed a metachronous second primary colorectal cancer, of whom four (66.7%) were asymptomatic, and five (83.3%) were able to undergo curative resection. Overall, because of surveillance colonoscopies, 13 asymptomatic patients (4.5%) had curative resection for localized recurrent disease or a metachronous second primary cancer. CONCLUSIONS: Colonoscopy is a useful modality in the early detection of recurrent and metachronous disease after colorectal cancer, increasing the potential for curative resection and improved survival.

Aged↗

Preventive and curative role of a 43kD protein from the leaves of the herb Cajanus indicus L on thioacetamide-induced hepatotoxicity in vivo.

An approximately 43kD protein has been isolated and purified from the herb Cajanus indicus L and believed to be the most active principle for its hepatoprotective action. In this study, experiments have been performed to evaluate the effectiveness of that protein for the preventive and curative action against thioacetamide-induced toxicity in vivo using a murine model. Mice were treated with the protein intraperitoneally at a dose of 2mg/kg body weight for 2 and 6 days before and separately 1-5 days after thioacetamide administration to evaluate its preventive and curative role, respectively. Thioacetamide was administered once at a dose of 150mg/kg body weight and after 48h of its application, the animals were sacrificed. Levels of various markers related to physiological and pathological conditions of the liver, e.g., glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), etc. were determined in the murine sera under different experimental conditions. In addition, antioxidant enzymes glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) as well as thiobarbituric acid reactive substances (TBARS), were measured from the liver homogenates. The antioxidant property of the protein was compared with the potent antioxidant, vitamin E (used as a positive control). The active principle effectively reduced the elevated GPT and ALP levels in serum and lipid peroxidation in the liver tissue. The reduced levels of SOD, CAT and GST by thioacetamide were again brought back to almost normal levels upon pre- and post-treatment with the protein. Histopathological changes in the liver of TAA control and protein-treated groups also prove that the protein possesses hepatoprotective activity. The protein acts dose-dependently and maximum hepatoprotectivity was obtained when administered at a dose of 2mg/kg body weight. Data suggest that the active principle plays an important preventive and curative role against thioacetamide-induced hepatotoxicity.

Journal Article↗

[Curative treatment of prostatic cancer in Norway in 1998 and 2001].

BACKGROUND: The two major therapeutic options for early diagnosed prostate cancer are radical prostatectomy or radiation therapy. The National Program for Prostate Cancer in Norway conducted this study in order to document the use of treatment with curative intention in five geographical regions in Norway. MATERIAL AND METHODS: The study is based on data from the Cancer Registry of Norway on patients diagnosed with prostate cancer in 1998 and 2001. The departments of oncology have provided relevant information about radiation therapy. Treatment with curative intention is defined as radical prostatectomy or radiation therapy with > or = 64 Gy. RESULTS: About one third of all patients under the age of 75 years with recently diagnosed prostate cancer were treated with curative intention in 1998 and 2001 (1998: 28%, 2001: 33%); the total number increased from 440 in 1998 to 556 in 2001. There were marked variations between the geographical regions in the use of treatment with curative intention and in the use of radical prostatectomy versus radiation therapy. INTERPRETATION: The fact that no more than one third of the patients were treated with curative intention is probably due to uncertainty about the therapeutic benefit in relation to side effects. The regional variations probably reflect different opinions on the true effect of early diagnosis and treatment.

Adenocarcinoma↗

Radiographically occult lung cancer treated with fibreoptic bronchoscopic electrocautery: a pilot study of a simple and inexpensive technique.

The curative potential of bronchoscopic intervention, e.g. photodynamic therapy (PDT) and brachytherapy, for resectable radiographically occult lung cancer has been reported previously. Bronchoscopic electrocautery is currently feasible using an insulated flexible bronchoscope to coagulate and vaporize tumour tissue. Since the lesions are usually small, noninvasive bronchoscopic electrocautery may be able to eradicate radiographically occult lung cancer completely. In a prospective study, 13 patients with 15 radiographically occult lung cancer lesions were treated with bronchoscopic electrocautery. The duration of follow-up was > or = 16 months. The median age of the patients was 69 yrs (range 48-79 yrs). Fibreoptic bronchoscopy under local anaesthesia was used to coagulate the occult lung cancer. Approximately 30 W of energy was applied until visible necrosis of the tumour area became apparent. There were no immediate complications. In 10 patients with 12 lesions, a complete response (CR) was obtained (CR rate 80%; 95% confidence interval (95% CI) 52-96%). Median duration of follow-up was 21 months (range 16-43 months). Bronchoscopic electrocautery did not obtain a CR in the remaining three patients, but PDT also failed to achieve CR. Two patients underwent radical resection, and the tumours were histologically confirmed to be more invasive. One patient received external radiotherapy. Three patients with a CR died during follow-up, two as a result of myocardial infarction and apoplexy, and one because of metastasis from his previously resected T3N1 primary large cell cancer. Current data show bronchoscopic electrocautery to be equally effective and potentially as curative as photodynamic therapy for treating patients with radiographically occult lung cancer. Obvious advantages are that it is an inexpensive and simple procedure, which does not cause photosensitivity.

Aged↗

GermOnline, a cross-species community knowledgebase on germ cell differentiation.

GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics.

Animals↗

AutoDep: a web-based system for deposition and validation of macromolecular structural -information.

This paper describes the design and full implementation of a new concept in data deposition and validation: AutoDep (copyright Brookhaven Science Associates LLC). AutoDep changes the traditional procedure for data acceptance and validation of the primary databases into an interactive depositor-driven operation which almost eliminates the delay between the acceptance of the data and its public release. The system takes full advantage of the knowledge and expertise of the experimenters, rather than relying on the database curators for the complete and accurate description of the structural experiment and its results. AutoDep, developed by the Protein Data Bank at Brookhaven National Laboratory (BNL) as a flexible and portable system, has already been adopted by other primary databases and implemented on different platforms/operating systems. AutoDep was introduced at BNL in 1996 [see Manning (1996), Protein Data Bank Quart. Newslett. 77, 2 (ftp://ftp.rcsb. org/pub/pdb/doc/newsletters/bnl/newsletter96jul/newslttr+ ++.txt); Manning (1996), Protein Data Bank Quart. Newslett. 78, 2 (ftp://ftp. rcsb.org/pub/pdb/doc/newsletters/bnl/newsletter96oct/+ ++newslttr.txt)].

Computer Security↗

Incidence of initial local therapy among men with lower-risk prostate cancer in the United States.

BACKGROUND: The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment. METHODS: Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided. RESULTS: We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P<.05). Assuming that initial expectant management is appropriate for all lower-risk cancers, 2564 men (10%) in this population-based sample were overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy. CONCLUSIONS: These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.

Aged↗

IRESite: the database of experimentally verified IRES structures (www.iresite.org).

IRESite is an exhaustive, manually annotated non-redundant relational database focused on the IRES elements (Internal Ribosome Entry Site) and containing information not available in the primary public databases. IRES elements were originally found in eukaryotic viruses hijacking initiation of translation of their host. Later on, they were also discovered in 5'-untranslated regions of some eukaryotic mRNA molecules. Currently, IRESite presents up to 92 biologically relevant aspects of every experiment, e.g. the nature of an IRES element, its functionality/defectivity, origin, size, sequence, structure, its relative position with respect to surrounding protein coding regions, positive/negative controls used in the experiment, the reporter genes used to monitor IRES activity, the measured reporter protein yields/activities, and references to original publications as well as cross-references to other databases, and also comments from submitters and our curators. Furthermore, the site presents the known similarities to rRNA sequences as well as RNA-protein interactions. Special care is given to the annotation of promoter-like regions. The annotated data in IRESite are bound to mostly complete, full-length mRNA, and whenever possible, accompanied by original plasmid vector sequences. New data can be submitted through the publicly available web-based interface at http://www.iresite.org and are curated by a team of lab-experienced biologists.

5' Untranslated Regions↗

Preoperative predictors of survival after resection of small hepatocellular carcinomas.

OBJECTIVE: To determine preoperative predictors of survival that can guide the choice of treatment for patients with small hepatocellular cancers (HCCs). SUMMARY BACKGROUND DATA: The treatment of patients with small (</=5 cm in diameter) HCCs is controversial. METHODS: A cohort of 249 patients (69 women, 180 men; median age 62 years) who underwent resection with curative intent for small HCC was identified from a multiinstitutional database. For each patient, the clinical data and pathology slides were reviewed. Six clinical factors (age, gender, preoperative alpha-fetoprotein level, hepatitis serology, number of tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade) that can be determined before surgery were correlated with survival. Log-rank tests and Cox proportional hazards modeling were used to determine factors influencing survival. RESULTS: The median overall survival for the entire cohort was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and 19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score, Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant predictors of survival after resection. A prognostic scoring system based on these covariates was derived and applied to the entire cohort. Patients lacking all three risk factors were assigned a score of 1, patients with one risk factor were assigned a score of 2, and patients with two or three risk factors were assigned a score of 3. Pairwise log-rank tests indicated significant differences in survival between scores 1 and 2, scores 2 and 3, and scores 1 and 3. This scoring system retained its prognostic significance when a subset of 98 patients with positive hepatitis C serology was analyzed separately. CONCLUSIONS: Patients with small HCCs who will derive the least benefit from resection can be identified before surgery using a score based on tumor grade and the severity of underlying liver disease. In these patients, transplantation and/or ablation should be considered as possible alternative therapies.

Carcinoma, Hepatocellular↗

Effective control of hypertension: a project of the Hungarian Society of Hypertension, baseline data.

The aim of the project is to assess the quality and improve the preventive and curative practices at the primary care level in Hungary. A total of 50 general practitionaires were selected on a voluntary basis in Budapest, Hungary, and from them, 30 were randomized to the intervention (I) group and 20 to the reference (R) group. The members in the I group have been trained for the official hypertension guideline and their everyday work is monitored. Those in the R group have only been monitored to measure the efficacy of the training. In all, 10% from the known hypertensive persons (N=10,799) and 5% of the remaining (nonhypertensive) patients (N=60,341) were selected randomly from the GP's computer files and invited for screening investigation performed by trained medical students. They measured the blood pressure of patients, assessed the cardiovascular risk status and the quality of education of patients by standardized questionnaires. In total, 4083 patients were invited, but only 39.2% attended the screening visit. The prevalence of undetected hypertension was 34.6%. This prevalence was significantly higher in the older (>60 years: 46.8%) than in the younger (<50 years: 20.8%, P<0.0001) age group and it was higher in men (41.5%) than in women (30.1%, P<0.001). The proportion of H patients on drug treatment was 85.3% and the frequency of patients under effective blood pressure control (eg<140/90 mmHg) was 27.8%. Counselling to patients for a healthier lifestyle (exercise, smoking, alcohol consumption, diet) was very rare. In conclusion, our data represent the primary care of Budapest and may not be relevant to the whole country. As a consequence of this study, education of primary care physicians and patients is a must for further improvement of hypertension care.

Adult↗

Association between transfusion with plasma and the recurrence of colorectal carcinoma.

Data was collected from patients with colonic or rectal tumours undergoing potentially curative surgery. Univariate analysis showed an association between perioperative transfusion with plasma and the earlier recurrence of tumour. Allowing for possible confounding factors the relative risk of recurrence for patients receiving plasma was 2.44 (95 per cent confidence interval = 1.10-5.46, P = 0.041) and for patients receiving whole blood or plasma, it was 2.39 (95 per cent confidence interval = 1.19-4.83, P = 0.021). The risk of recurrence for those receiving a transfusion of plasma was, therefore, more than twice that of those not given it. We were unable to demonstrate an independent harmful effect of transfusion with packed cells. These data suggest that the plasma protein, rather than the cellular component of whole blood, mediates the accelerated tumour recurrence.

Blood Proteins↗

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province.

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70-79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Adult↗

ASAP, a systematic annotation package for community analysis of genomes.

ASAP (a systematic annotation package for community analysis of genomes) is a relational database and web interface developed to store, update and distribute genome sequence data and functional characterization (https://asap.ahabs.wisc.edu/annotation/php/ASAP1.htm). ASAP facilitates ongoing community annotation of genomes and tracking of information as genome projects move from preliminary data collection through post-sequencing functional analysis. The ASAP database includes multiple genome sequences at various stages of analysis, corresponding experimental data and access to collections of related genome resources. ASAP supports three levels of users: public viewers, annotators and curators. Public viewers can currently browse updated annotation information for Escherichia coli K-12 strain MG1655, genome-wide transcript profiles from more than 50 microarray experiments and an extensive collection of mutant strains and associated phenotypic data. Annotators worldwide are currently using ASAP to participate in a community annotation project for the Erwinia chrysanthemi strain 3937 genome. Curation of the E. chrysanthemi genome annotation as well as those of additional published enterobacterial genomes is underway and will be publicly accessible in the near future.

Databases, Genetic↗

[Diagnosis of chronic backache in health resort patients].

Conservative treatment of backache requires an accurate diagnosis because sometimes such patients are suffering from a serious but unrecognised disease of the abdomen or low back region. Diagnoses like cervical syndrome, lumbar syndrome or even cervicodorso-lumbar syndrome are not sufficiently conclusive to start conservative treatment, since they convey nothing in respect of cause, prognosis or aim of treatment. Patients undergoing a course of inpatient curative treatment of, say, four weeks in a hospital, need special therapy programmes that are meaningfully based on precise data on their disorder. It is important to set great store by the physical examination (which is often performed cursorily before the patients are referred to curative inpatients treatment), including a neurological examination and in some cases also EMG, special radiographs, myelography, CT, magnetic resonance imaging and the like to gather more information on the real cause of the low back pain. This will also help the physician in arriving at a fair estimation of the patient's performance rating. A useful classification of patients into two groups would be as follows: a) without neurological symptoms, and b) with signs of a nerve-root compression or even spinal cord symptoms.

Back Pain↗

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Adenoma↗