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At least 217 records · Page 12Linked to original sources

PubMed2002

Bioinformatics of cellular signalling.

The completion of the human genome sequencing provides a unique opportunity to understand the complex functioning of cells in terms of myriad biochemical pathways. Of special significance are pathways involved in cellular signalling. Understanding how signal transduction occurs in cells is of paramount importance to medicine and pharmacology. The major steps involved in deciphering signalling pathways are: (a) identifying the molecules involved in signalling; (b) figuring out who talks to whom, i.e. deciphering molecular interactions in a context specific manner; (c) obtaining the spatiotemporal location of the signalling events; (d) reconstructing signalling modules and networks evoked in specific response to input; (e) correlating the signalling response to different cellular inputs; and (f) deciphering cross-talk between signalling modules in response to single and multiple inputs. High-throughput experimental investigations offer the promise of providing data pertaining to the above steps. A major challenge, then, is the organization of this data into knowledge in the form of hypothesis, models and context-specific understanding. The Alliance for Cellular Signaling (AfCS) is a multi-institution, multidisciplinary project and its primary objective is to utilize a multitude of high throughput approaches to obtain context-specific knowledge of cellular response to input. It is anticipated that the AfCS experimental data in combination with curated gene and protein annotations, available from public repositories, will serve as a basis for reconstruction of signalling networks. It will then be possible to model the networks mathematically to obtain quantitative measures of cellular response. In this paper we describe some of the bioinformatics strategies employed in the AfCS.

Animals↗

PubMed2001

Experience as a factor influencing the indications for laparoscopic colorectal surgery and the results.

BACKGROUND: The influence of experience on the results of treatment with laparoscopic surgery is indisputable. The establishment of indications and contraindications is relative, and varies depending on the experience of the surgeon. Learning curves have been described for a number of laparoscopic interventions, in particular laparoscopic cholecystectomy. The current prospective multicenter study investigates, among other things, the interrelation between experience and the results of treatment using laparoscopic colorectal surgery. The study makes no pronouncements on the long-term results achieved in patients with colorectal carcinoma who underwent an operation with curative intent, although relevant data were indeed collected. RESULTS: Between August 1, 1995 and February 1, 1999, a total of 1,658 patients were recruited to the prospective multicenter study initiated by the Laparoscopic Colorectal Surgery Study Group. To investigate the influence of surgical experience, two groups were formed. Group A comprised all the institutions and surgeons with experience of more than 100 laparoscopic colorectal operations. Group B contained institutions and surgeons with experience of fewer than 100 such interventions. The results of this study clearly show that in Group A, significantly more procedures involving the rectum were performed (26.7% vs 9.5%), and significantly more carcinomas were surgically managed (37.3% vs 17.3%). Despite this significantly higher level of technically difficult procedures in the patient population of group A, which was comparable in terms of age, gender, height, and weight with the patient in group B, the postoperative mortality and morbidity was, with the exception of urinary tract infections, identical between the two groups. Conversion to open surgery was significantly less frequent in group A (4.3% vs 6.9%), and, finally, the duration of the procedures performed by the more experienced surgeons of group A was appreciably shorter than in institutions with a smaller frequency of such operations. CONCLUSIONS: Laparoscopic colorectal surgery is very demanding, and can be performed with low morbidity and mortality rates only by a surgeon with above-average experience with this type of surgery and a large caseload of laparoscopic colorectal procedures. The learning curve for such procedures is appreciably longer than for other laparoscopic operations. With increasing experience, technically more demanding operations, including radical oncologic rectal laparoscopic procedures, can be performed with appreciably reduced operating times and conversion rates, but with no increase in morbidity or mortality.

Adult↗

PubMed2002

Oral complications in Chinese cancer patients undergoing chemotherapy.

In this study the oral status and mucositis-related symptoms in 94 Chinese cancer patients undergoing chemotherapy for with curative intent were examined. Data were collected by a research nurse at three stages over a period of 16 days: at the start, on day 8, and on day 16 of chemotherapy. The majority of subjects experienced a mild to moderate degree of mucositis with the highest score reported on day 8. Patients with head and neck cancer had consistently higher scores for mucositis and symptoms in most phases. Oral mucositis and symptoms were significantly and positively correlated with consumption of spicy and/or hot (temperature) food, and frequency of use of mouthwashes. Significantly higher scores were found in patients who: ate hot (temperature) food, had low tolerance for hot food and spicy foods, and were taking Chinese medicinal herbs. Careful monitoring of patient diet preferences, cancer site, and use of Chinese medicine is recommended for comprehensive oral assessment. The alleviation of oral mucositis and the associated symptoms through promotion of an appropriate food/fluid intake and more frequent use of mouthwashes should be emphasized in oral care.

Adolescent↗

PubMed2002

Acute toxicity of conventional radiation therapy for high-risk prostate cancer in EORTC trial 22863.

OBJECTIVES: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients. METHODS: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal. Univariate and multivariate analyses were performed using the World Health Organisation (WHO) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups. RESULTS: Overall, our data show that age, previous surgery and irradiation dose are important predictive factors for acute toxicity, but not the use of combined hormone therapy. Fifteen percent of patients suffered of moderate to severe acute toxicity (WHO G3-G4). Life threatening toxicity was observed in six cases (1.5%). CONCLUSIONS: The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature. Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation. These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques.

Adult↗

PubMed2026

ProteoParc: A Reference Protein Database Builder for Ancient and Nonmodel Organisms.

Over the past few years, the increasing interest in analyzing the proteome of extinct and nonmodel organisms has generated a new field of research expanding the scope of proteomics. The lack of curated databases and/or molecular data from these organisms forces researchers to manually search in different public repositories for related protein sequences, either for MS/MS peptide identification or ZooMS marker annotation. This can lead to format incongruences and hinder reproducibility between studies. To address this issue, we introduce ProteoParc, a user-friendly software that builds reference databases by systematically downloading and processing protein sequences from the most widely used public repositories. The pipeline's output is a nonredundant protein database, formatted in a way to be interpreted by typical peptide identification software. Moreover, the user can adjust the database dimension and composition by applying different criteria to include only a certain number of genes or species. Thus, ProteoParc is an easy and fast, custom-made bioinformatic tool useful for future paleoproteomics analysis in ancient samples related to understudied organisms.

Databases, Protein↗

PubMed2005

Urbanization, malaria transmission and disease burden in Africa.

Many attempts have been made to quantify Africa's malaria burden but none has addressed how urbanization will affect disease transmission and outcome, and therefore mortality and morbidity estimates. In 2003, 39% of Africa's 850 million people lived in urban settings; by 2030, 54% of Africans are expected to do so. We present the results of a series of entomological, parasitological and behavioural meta-analyses of studies that have investigated the effect of urbanization on malaria in Africa. We describe the effect of urbanization on both the impact of malaria transmission and the concomitant improvements in access to preventative and curative measures. Using these data, we have recalculated estimates of populations at risk of malaria and the resulting mortality. We find there were 1,068,505 malaria deaths in Africa in 2000 - a modest 6.7% reduction over previous iterations. The public-health implications of these findings and revised estimates are discussed.

Adolescent↗

PubMed2026

Integrating Next-Generation Sequencing into von Willebrand Disease Diagnostics: Insights from the PCM-EVW-ES Multicenter Project.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by quantitative or qualitative defects in von Willebrand factor (VWF). Diagnosis is challenging and requires integrating bleeding history, VWF antigen and activity measurements, FVIII assays, and specialized phenotyping. Genetic testing is increasingly recognized as a key component. Here, we review current concepts in VWD diagnostics and highlight the Spanish Clinical and Molecular Profile of von Willebrand Disease (PCM-EVW-ES) project as a model for genomics-enabled precision medicine. PCM-EVW-ES is a multicenter initiative involving 48 hospitals, centralized phenotypic testing, and next-generation sequencing of the VWF coding region, enabling definitive classification in 730 individuals with VWD to date. Harmonized recruitment criteria and standardized workflows improve subtype assignment, uncover complex genotypes, refine genotype-phenotype correlations, and facilitate the identification of asymptomatic carriers. The PCM-EVW-ES variant spectrum highlights recurrent disease-causing variants in Spain and underscores the value of coordinated national registries for variant curation. Building on these data, we propose a diagnostic algorithm in which bleeding assessment and first-line VWF/FVIII assays, combined with, early VWF molecular testing increases diagnostic accuracy and guides targeted second-line investigations to confirm and refine VWD subtype classification. We also outline persisting challenges, including the interpretation of variants of uncertain significance and patients without identifiable pathogenic VWF variants, and future directions integrating third-generation sequencing, expanded gene panels, functional studies, and artificial-intelligence-driven multiomic approaches. Together, these advances illustrate how robust multicenter studies can bridge the gap between complex diagnostics and clinical practice in VWD.

Humans↗

PubMed1994

The structure of Yalom's Curative Factors Scale.

Factor analysis was used to evaluate the short form of Yalom's Curative Factors Scale with data from 372 participants in the 1986 American Group Psychotherapy Association Institute Groups. With the data randomly assigned to three subgroups, results showed 10 scale items loading on three factors across all three subgroups. When the data was organized into two self-selected subgroups corresponding to the two Institute group categories, factor analyses showed the first factor to be consistent with the previous analyses, but other factors showed differences interpreted to be characteristic of the two groups' modalities. The study suggests a framework for understanding the concept of therapeutic factors and how they work together.

Adult↗

PubMed2002

ASPD (Artificially Selected Proteins/Peptides Database): a database of proteins and peptides evolved in vitro.

ASPD is a new curated database that incorporates data on full-length proteins, protein domains and peptides that were obtained through in vitro directed evolution processes (mainly by means of phage display). At present, the ASPD database contains data on 195 selection experiments, which were described in 112 original papers. For each experiment, the following information is given: (i) description of the target for binding, (ii) description of the protein or peptide which serves as the template for library construction and description of the native protein which binds the target, (iii) links to the major proteomic databases (SWISS-PROT, PDB, PROSITE and ENZYME), (iv) keywords referring to the biological significance of the experiment, (v) aligned sequences of proteins or peptides retrieved through in vitro evolution and relevant native or constructed sequences, (vi) the number of rounds of selection/amplification and (vii) the number of occurrences of clones with each sequence. The literature data include a full reference, a link to the MEDLINE database and the name of the corresponding author with his email address. ASPD has a user-friendly interface which allows for simple queries using the names of proteins and ligands, as well as keywords describing the biological role of the interaction studied, and also for queries based on authors' names. It is also possible to access the database by means of the SRS system, allowing complex queries. There is a BLAST search tool against the ASPD for looking directly for homologous sequences. Research tools of the ASPD allow the analysis of pairwise correlations in the sequences of proteins and peptides selected against one target. The URL for the ASPD database is http://www.sgi.sscc.ru/mgs/gnw/aspd/.

Animals↗

PubMed1995

Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.

OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra-abdominal metastases. Laparoscopic ultrasonography improves the accuracy of laparoscopic staging in patients with potentially resectable pancreatic and periampullary carcinomas.

Adenocarcinoma↗

PubMed2004

Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study.

OBJECTIVE: Our objective was to perform a prospective study of surgical treatment of hilar cholangiocarcinoma according to newly established guidelines for performing safe and curative resections. SUMMARY BACKGROUND DATA: The poor survival rate after resection of hilar cholangiocarcinoma is considered to be mainly the result of in-hospital death and positive ductal margins. METHODS: Between July 1999 and December 2002, 40 of 42 surgically explored patients with hilar cholangiocarcinoma underwent resection. They were managed with preoperative biliary decompression, portal embolization, cholangiographic evaluation, and a choice of surgical procedures and techniques. RESULTS: Hospital or 30-day mortality and morbidity rates were 0% and 48%, respectively. Hepatic failure was not encountered. Histopathologic examination revealed no positive ductal margins in all 40 patients, but 2 showed positive separation margins from the right hepatic artery. The overall 3-year survival rate and median survival time were 40% and 27 months. Survival of patients with Bismuth type III or IV tumors or of patients who underwent right hepatectomy was significantly better. Survival of patients who underwent concomitant vascular resection was similar to survival of those who did not. Univariate analysis indicated the type of hepatectomy, histopathologic grade, Bismuth classification, concomitant hepatic artery resection, and International Union Against Cancer stage as significant prognostic factors. CONCLUSIONS: No postoperative mortality and no positive ductal margins were achieved according to the above guidelines in a high-volume expert center. Long-term results, however, have not been significantly improved. A survival analysis of the patient series with homogeneous conditions derived from a short study period suggests the need for additional strategies including right hepatectomy for Bismuth type I or II tumors.

Adult↗

PubMed2026

CircExor enables interpretable prediction of circRNA localization into extracellular vesicles.

Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with k-mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.

Journal Article↗

PubMed1999

Hypermethylation of the p16 gene in sporadic T3N0M0 stage colorectal cancers: association with DNA replication error and shorter survival.

Hypermethylation in the promoter region of the p16 gene was suspected to be involved in the tumorigenesis of colorectal cancers, although its clinical and biological significance remains obscure. In this study, we collected 84 T3N0M0 stage primary colorectal cancers that were curatively resected. The clinicopathologic data were reviewed. p16 hypermethylation was determined by a methylation-specific polymerase chain reaction (PCR). p53 overexpression was detected by immunocytochemistry (ICC). The point mutations in the 12 and 13 codons of the K-ras gene were screened by restriction enzyme analysis. Loss of heterozygosity (LOH) of the DCC (Deleted in Colorectal cancer) gene was examined by PCR using primers of the DCC (18q21) microsatellite marker. The DNA replication error (RER) was examined using 7 microsatellite markers at distinct chromosomal loci. p16 hypermethylation, regarded as an indication of p16 inactivation, was evident in 24 (28.6%) of the tumors. No correlation was found between p16 hypermethylation and various clinicopathologic factors, includinig age, sex, tumor location, tumor size, growth pattern, tumor differentiation, mucin production, vascular and/or lymphatic invasion, lymphocyte infiltration of the tumor, and serum level of carcinoembryonic antigen. There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene. However, p16 hypermethylation was significantly associated with DNA RER (p = 0.01). Survival analysis revealed a significant survival disadvantage of p16-hypermethylated versus non-p16-hypermethylated tumors (p = 0.0001). These findings indicate that p16 hypermethylation plays a role in the carcinogenesis of a subset of colorectal cancers; and the presence of p16 hypermethylation predicts shorter survival in T3N0M0 stage colorectal cancers.

Aged↗

PubMed2007

The role of FDG-PET in the selection of patients with colorectal liver metastases.

BACKGROUND: Selection of patients for hepatic resection of colorectal liver metastases is still limited. After conventional work up by computed tomography (CT) scan, 60% of patients will develop recurrent disease in the early years after resection. The aim of the present study was to evaluate whether an additional fluorine-18-deoxyglucose positron emission tomography (FDG-PET) improves patient selection and therefore adds value to select patients for curative liver resection. METHODS: Data from 203 patients selected for surgical treatment of colorectal liver metastases between 1995 and 2003 were collected in a prospective database. Group A consisted of 100 consecutive patients selected for hepatic surgery by conventional diagnostic imaging (CT chest and abdomen) only. Group B consisted of 103 consecutive patients selected for hepatic surgery by conventional diagnostic methods plus an additional FDG-PET. RESULTS: The number of patients with futile surgery, in which further treatment was considered inappropriate at laparotomy, was 28.0% in group A and 19.4% in group B. The reason for unresectable disease differed between groups. In group A, 10/100 (10.0%) patients showed extrahepatic abdominal disease versus 2/103 patients (1.9%) in group B (P = .017). In all other cases, resection was not performed because liver disease proved too extensive at laparotomy. For patients ultimately undergoing surgical treatment of the metastases, survival was comparable between groups. Overall survival at 3 years was 57.1% in group A versus 60.1% in group B. Disease-free survival at 3 years was 23.0% in group A and 31.4% in group B. CONCLUSIONS: In patients with colorectal liver metastases, FDG-PET may reduce the number of negative laparotomies. However, the effect size on the selection of these patients seems not sufficient enough to affect the overall and disease-free survival after treatment.

Adult↗

PubMed2002

Online genomics facilities in the new millennium.

The review begins by providing a brief typology of biological databases on the Internet, illustrated by examples of the most influential resources of each kind. We then take an insider look at one typical on-line genomic resource -- the yeast genome database hosted at the Munich Information Center for Protein Sequences (MIPS) -- and explain how and why it has evolved from a basic sequence repository to a multidomain knowledge base. The role of community efforts in curating and annotating genome data is discussed. The crucial role of data integration and interoperability in developing next-generation genomic facilities is underscored.

Animals↗

PubMedDate not supplied

Hodgkin's disease: a retrospective analysis of 15 years experience at a large referral centre.

BACKGROUND: The prognosis of patients with Hodgkin's disease has improved significantly over the past two decades, primarily as a result of the development of curative combination chemotherapy. However, data on the presentation and results of treatment in Indian patients are scarce. We reviewed the clinical and pathological data and the treatment outcome of patients with Hodgkin's disease seen at our centre over the last 15 years. METHODS: The case records of 289 patients diagnosed to have Hodgkin's disease at our centre between 1977 and 1992 were reviewed. Their clinical characteristics, treatment outcome and prognostic factors for survival were analysed. RESULTS: The median age of the patients was 26 years with 30% being in the third decade. The male:female ratio was 4:1. The mixed cellularity histological subtype was the most common (68.5%), followed by nodular sclerosis (8.9%). 'B' symptoms were present in 73% of patients and 9.4% had bone marrow involvement. At the time of presentation, 70% of patients had advanced disease (stage III: 36%, stage IV: 34%). Complete response to treatment was obtained in 65.7% of patients while 17.3% had partial response. The predictors of decreased overall survival were age > 40 years, presence of 'B' symptoms, lymphocyte depletion histological subtype and stage IV disease. Disease-free survival was influenced by the presence of 'B' symptoms, bone marrow involvement and stage IV disease. CONCLUSION: Hodgkin's disease in Indian patients has a distinct clinico-pathological profile. Combination chemotherapy has high response rates even in patients with advanced disease at presentation.

Adolescent↗

PubMed2002

Surviving in a sea of data: a survey of plant genome data resources and issues in building data management systems.

Exponential growth of data, largely from whole-genome analyses, has changed the way biologists think about and handle data. Optimal use of these data requires effective methods to analyze and manage these data sets. Computers, software and the World Wide Web are now integral components of biological discovery. Understanding how information is obtained, processed and annotated in public databases allows researchers to effectively organize, analyze and export their own data into these databases. In this review we focus largely on two areas related to management of genomic data. We cite examples of resources available in the public domain and describe some of the software for data management systems currently available for plant research. In addition, we discuss a few concepts of data management from the perspective of an individual or group that wishes to provide data to the public databases, to use the information in the public databases more efficiently, or to develop a database to manage large data sets internally or for public access. These concepts include data descriptions, exchange format, curation, attribution, and database implementation.

Databases, Nucleic Acid↗

PubMedDate not supplied

[Effectiveness of individual units of aerosol therapy equipment].

Various methods of drug atomization and future prospects for their application in medical practice are considered. On the ground of a research into the influence produced by the administered doses and the density of the aerosol on the therapeutic activity the expediency of employing aerosol generators based upon pneumatic atomization by using the principle of ejecting an additional volume of air, as units yielding a substantial curative effect, is demonstrated. Data which bear proof to economic advantages of the units under review are given.

Adolescent↗