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Overview of BioCreAtIvE task 1B: normalized gene lists.

BACKGROUND: Our goal in BioCreAtIve has been to assess the state of the art in text mining, with emphasis on applications that reflect real biological applications, e.g., the curation process for model organism databases. This paper summarizes the BioCreAtIvE task 1B, the "Normalized Gene List" task, which was inspired by the gene list supplied for each curated paper in a model organism database. The task was to produce the correct list of unique gene identifiers for the genes and gene products mentioned in sets of abstracts from three model organisms (Yeast, Fly, and Mouse). RESULTS: Eight groups fielded systems for three data sets (Yeast, Fly, and Mouse). For Yeast, the top scoring system (out of 15) achieved 0.92 F-measure (harmonic mean of precision and recall); for Mouse and Fly, the task was more difficult, due to larger numbers of genes, more ambiguity in the gene naming conventions (particularly for Fly), and complex gene names (for Mouse). For Fly, the top F-measure was 0.82 out of 11 systems and for Mouse, it was 0.79 out of 16 systems. CONCLUSION: This assessment demonstrates that multiple groups were able to perform a real biological task across a range of organisms. The performance was dependent on the organism, and specifically on the naming conventions associated with each organism. These results hold out promise that the technology can provide partial automation of the curation process in the near future.

Animals↗

Variability of human blood pressure with reference mostly to the non-chronobiologic literature.

The voluminous literature on the variability encountered in 24-h recordings of human blood pressure in health is here presented by reference to selected clinical articles. Most references are cited by number for the sake of brevity, with a few cited by author when this appears to be of particular interest. Reports of work on laboratory animals are included when the findings are directly pertinent as background to studies on human beings. Results from semiautomatic and automatic direct and indirect measurements are briefly reviewed and aligned with results from work in which blood pressure was self-measured or measured conventionally by staff. The considerable and not generally recognized range of human blood pressure variability is thus extracted from the literature. An apparently limited extent of variation is shown to result mostly from the averaging of data from individuals constituting the groups investigated. Once variation is overwhelmingly documented and recognized as a fact, the different ways in which variations are presented and utilized by different author-investigators gain in importance. In a number of studies, methods of time series analysis are used. Thus, major attention can be paid to the extent to which predictable changes, so-called rhythms, characterize the data. Circadian rhythms are found to be quite prominent. By the assessment of these rhythms and about-yearly (circannual) ones, one quantifies health and individualized risk as well as disease. Otherwise 'unmanageable' variability, reviewed herein, can be resolved by relatively simple inferential statistical procedures as a set of new endpoints. A formidable foe thus becomes a powerful friend: the rhythm characteristics can be used in cardiovascular physiology and epidemiology, and preventive and curative medicine. Long-term blood pressure monitoring is no longer a mere research tool and a curiosity for the practitioner of medicine. Results from such monitoring should immediately be used in the clinic, in the school and at home. Automatic blood pressure monitoring, cost-effectively used in combination with self-measurement, as needed, may become a routine procedure if data collection can be wedded to appropriate analyses yielding new endpoints as sensitive gauges of health.

Adolescent↗

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

OBJECTIVE: The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA: A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results. METHODS: Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS: Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group (log-rank, p = 0.737). No reduction of locoregional recurrence rates was apparent in the groups. CONCLUSIONS: Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated. However, the benefit in this study was small; routine use of adjuvant chemoradiotherapy is not warranted as standard treatment in cancer of the head of the pancreas or periampullary region.

Adenocarcinoma↗

The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies.

AIMS: The debate on the funding and availability of cytotoxic drugs raises questions about the contribution of curative or adjuvant cytotoxic chemotherapy to survival in adult cancer patients. MATERIALS AND METHODS: We undertook a literature search for randomised clinical trials reporting a 5-year survival benefit attributable solely to cytotoxic chemotherapy in adult malignancies. The total number of newly diagnosed cancer patients for 22 major adult malignancies was determined from cancer registry data in Australia and from the Surveillance Epidemiology and End Results data in the USA for 1998. For each malignancy, the absolute number to benefit was the product of (a) the total number of persons with that malignancy; (b) the proportion or subgroup(s) of that malignancy showing a benefit; and (c) the percentage increase in 5-year survival due solely to cytotoxic chemotherapy. The overall contribution was the sum total of the absolute numbers showing a 5-year survival benefit expressed as a percentage of the total number for the 22 malignancies. RESULTS: The overall contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults was estimated to be 2.3% in Australia and 2.1% in the USA. CONCLUSION: As the 5-year relative survival rate for cancer in Australia is now over 60%, it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival. To justify the continued funding and availability of drugs used in cytotoxic chemotherapy, a rigorous evaluation of the cost-effectiveness and impact on quality of life is urgently required.

Antineoplastic Combined Chemotherapy Protocols↗

Hepatic resection for bilobar hepatocellular carcinoma: is it justified?

HYPOTHESIS: Patients with bilobar stage IVa hepatocellular carcinoma (HCC) are generally considered unsuitable for hepatic resection. Recent data suggest that palliative hepatic resection in selected patients with advanced HCC may result in a favorable survival outcome. The aim of the present study was to evaluate the operative outcome and survival benefits of hepatic resection for patients with bilobar HCC. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: The study comprised 78 patients who were diagnosed as having unilobar HCC and considered initially suitable candidates for curative hepatic resection on preoperative investigations from 1989 to 2000. Bilobar disease with discrete tumor nodules in the contralateral lobe was diagnosed in these patients on laparoscopy (44 patients) or laparotomy (34 patients) with the help of intraoperative ultrasonography. Fifteen patients (19%) underwent palliative hepatic resection (group A), and hepatic resection was not performed in the remaining 63 patients (81%) (group B). MAIN OUTCOME MEASURES: The clinicopathologic data and operative and survival outcomes of both groups of patients were compared. RESULTS: The clinicopathologic parameters were comparable in both groups of patients. In group A, 12 patients (80%) underwent major hepatic resection, and the mean +/- SEM size of the resected tumors was 8.3 +/- 0.9 cm. The operative morbidity and mortality were 20% and 0%, respectively. Treatment for tumors in the contralateral lobe included wedge excision (5 patients), alcohol injection (5 patients), cryotherapy (2 patients), and transarterial oily chemoembolization (3 patients). In group B, treatment for HCC included transarterial oily chemoembolization (42 patients), systemic chemotherapy (3 patients), transarterial oily chemoembolization and systemic chemotherapy (5 patients), cryotherapy (2 patients), tamoxifen (3 patients), and no treatment (8 patients). The median survival of patients in group A was 19.5 months, with 4 patients surviving for more than 3 years. The survival in group A was significantly better than in group B (median = 7.1 months; P =.008). On multivariate analysis, hepatic resection and preoperative serum alpha-fetoprotein level were the 2 independent factors that significantly affected patient survival. CONCLUSIONS: Hepatic resection for HCC in patients with stage IVa bilobar disease results in a better survival outcome than nonresectional therapies. It should be considered in selected patients with low operative risks and satisfactory liver function.

Adolescent↗

Evaluation of intensive adjuvant chemotherapy in gastric cancer using life expectancy compared with log-rank test as a measure of survival benefit.

BACKGROUND: The goal of radical cancer surgery with or without adjuvant therapy is to cure disease rather than to delay death. There is concern that the survival benefit of curative treatment may not be properly appreciated by the log-rank test (LRT), which is more sensitive to treatment that delays death than to treatment that achieves cure. To confirm this concern and to evaluate the survival benefit of adjuvant chemotherapy, the data from a previous randomized controlled trial are analyzed using both traditional and new methods. METHODS: In this trial, 1410 gastric cancer patients with serosal or subserosal invasion had been classified by nodal and serosal status into four strata and randomized to receive high-dose or low-dose adjuvant regimens (mitomycin and tegafur-uracil) after gastrectomy. The two treatment groups were compared using the LRT as well as the life expectancy (LE) derived from the Boag model and the competing risk model. RESULTS: The LRT showed no significant difference between the two groups, whereas the LE increased significantly with high-dose chemotherapy (1.4-year gain; 95% CI = 0.1-2.8). A greater gain of 4.4 years occurred exclusively in the serosa-negative node-positive stratum, associated with a 21% increase in cure rate. The gain in LE was particularly greater in younger patients. CONCLUSIONS: Parametric LE analysis offers more relevant information about curative treatment than LRT. It suggests that high-dose chemotherapy may achieve cure in a subset of patients, eradicating residual malignancies left behind after gastrectomy and providing greater survival benefit than expected from LRT.

Adult↗

[Associated trauma with urinary tract injuries].

The authors analyze the peculiarities in the diagnostic and curative behavior in cases of associated traumatic injuries with participation of the urinary system in adults and children. A trauma is defined as associated when one kind of traumatic agent affects more then one organ or system. The authors do not discuss the combined trauma where we observed different damaging agents as for example mechanical trauma plus radiation or burn. The experience of the treatment of 64 children and 109 adults suffering from associated traumatic injuries for the period 1981-1997 has been summarized. In cases of associated traumatic injuries the kidneys are the most common participants on the part of the urinary system (70.3% of the children and 51.4% of the adults). On the second place we witness bladder damages in adults and urethra damages in children. The data concerning the combination between urological trauma and other organs traumas are available in details--the most common are: bone fractures, lesions of intraabdominal organs, skull and brain traumas, etc. The three basic problems caused by such kind of trauma are also discussed--organizational, diagnostic and curative. At the end the authors present the most typical characteristics of associated traumatic injuries in children compared to those in adults.

Accidents, Home↗

Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.

BACKGROUND: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. METHODS: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. RESULTS: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time. CONCLUSIONS: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Adenocarcinoma↗

Resistance to drug by different isolates Trypanosoma evansi in China.

In order to understand drug resistance in Chinese Trypanosoma evansi isolates, the in vitro growth inhibition test was carried out to detect the sensitivities to suramin and antrycide of 12 T. evansi isolates. For suramin, 50% inhibitory concentrations (IC(50)) ranged from 0.041 to 0.752 microg/ml; for antrycide, the IC(50) values ranged from 0.00151 to 0.06694 microg/ml. In vivo experiments in mice with selected isolates showed that the isolate most resistant to suramin was not cured at a dosage of 10 mg/kg, while the isolate that was most resistant to antrycide showed only 50% cure rate at a dose rate of 5 mg/kg. The data presented here indicate that T. evansi isolates from China had differences in drug resistance, with some isolates exhibiting low sensitivity to suramin or antrycide, while a few isolates showed complete drug resistance to curative dosages of suramin or antrycide. No drug cross-resistance was observed between suramin and antrycide.

Animals↗

RNA splicing evidence enables robust classification of BRCA1 exon 18 variants: Results from the ENIGMA consortium.

The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) research consortium conducted a comprehensive study to characterize spliceogenic variants in BRCA1 exon 18. The absence of systematic RNA-based assessment for these variants has led to inconsistent interpretation, limiting accurate classification and management of individuals and their families. The splicing profile of 166 variants was assessed using minigene assays; 32 were additionally analyzed in blood-derived RNA from 51 individuals and 18 in mouse embryonic stem cell (mESC)-based assays to evaluate homology-directed repair (HDR) capacity. mRNA assessment by RT-PCR in blood samples and minigene assays showed a significant positive correlation, with splicing analysis in mESCs displaying highly concordant results. The mESC-based HDR assay showed that the in-frame exon 18 skipping (&#x394;18) transcript encodes a non-functional protein lacking rescue activity. Linear regression analysis using mESC splicing and functional data indicated that &#x2265;59% of full-length (FL) levels and <34% of &#x394;18 were associated with benign HDR activity. These thresholds differ from those recommended by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) specifications for applying BP7_strong(RNA): >30% functional transcripts or <70% non-functional transcripts. Incorporation of RNA splicing evidence into variant interpretation increased pathogenic (28.6%-31.7%) and benign (3.7%-24.4%) classifications while reducing likely pathogenic (19.5%-17.7%), uncertain (18.9%-8.5%), and likely benign (29.3%-17.7%) categories. Experimental mRNA profiling impacted the interpretation of 34% of variants and resolved uncertainty in approximately 10% of cases. Exon 18 skipping was less tolerated, indicating that the degree of splice perturbation required to impair BRCA1 function may depend on the nature of the resulting non-functional transcript.

Humans↗

Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

Administration, Oral↗

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4&#x202f;>&#x202f;0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗

Estimating the association of antimicrobial resistance genes with minimum inhibitory concentration in Escherichia coli: an observational study.

BACKGROUND: Surveillance and prediction of antibiotic resistance in Escherichia coli relies on curated databases of genes and mutations. We aimed to quantify the effect of acquiring specific genetic elements on minimum inhibitory concentrations (MICs) for particular antibiotic-species combinations, addressing the current scarcity of such data in existing databases. METHODS: For this observational study, we evaluated a collection of E coli isolates with linked whole-genome sequencing and MIC data, originating from human urinary or bloodstream infections obtained from the Oxford University Hospitals National Health Service Foundation Trust in Oxfordshire, UK. We used multivariable interval regression models to estimate the change in MIC (with 95% CIs) for specific antibiotics associated with the acquisition of antibiotic resistance genes and associated mutations in the National Center for Biotechnology Information AMRFinder database, with and without an adjustment for population structure. We then tested the ability of these models to predict MIC and binary resistance or susceptibility using leave-one-out cross-validation. FINDINGS: We evaluated 2875 E coli isolates obtained during 2013-2018 and 2020. Although most ARGs and resistance mutations (89 [80%] of 111) were associated with an increased MIC, a much smaller number (27 [24%] of 111) was found to be putatively independently resistance-conferring (ie, associated with an MIC above the European Committee on Antimicrobial Susceptibility Testing breakpoint) when acquired in isolation. We found evidence of differential effects of acquired ARGs and resistance mutations between different generations of cephalosporin antibiotics and showed that sub-breakpoint variation in MIC can be linked to genetic mechanisms of resistance. 20&#x2009;697 (83&#xb7;3%; range 52&#xb7;9-97&#xb7;7 across all antibiotics) of 24&#x2009;858 MICs were correctly exactly predicted and 23&#x2009;677 (95&#xb7;2%; 87&#xb7;3-97&#xb7;7) of 24&#x2009;858 MICs were predicted to within one doubling dilution. INTERPRETATION: Quantitative estimates of the independent effect of the acquisition of ARGs on MIC add to the interpretability and utility of existing databases. Compared with approaches using machine learning models, the use of these estimates yields similar or better performance in the prediction of antibiotic resistance phenotype with more readily interpretable results. The methods outlined here could be readily applied to other antibiotic-pathogen combinations. FUNDING: The National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC).

Escherichia coli↗

A review of carcinoma of the stomach at a tertiary care referral hospital.

BACKGROUND: Carcinoma of the stomach continues to cause a significant mortality in the United States. We reviewed the characteristics, treatment modalities, and survival of a group of patients with this cancer at a tertiary care referral hospital. MATERIALS AND METHODS: A retrospective computer based review of all patients with a diagnosis of carcinoma of the stomach in the Ohio State University (OSU) tumor registry was made. One hundred ninety-two analytical cases were found and the data was entered into a computerized database and analyzed. RESULTS: The overall median survival in this series of patients is 10 months with a median survival of 16 months (n.s.) in patients who underwent curative surgery (50% of the patients). There was an increased number of cardia lesion (37%) predominately in male patients (P < 0.05). A significantly greater number of female patients presented with linitis plastica and male patients with adenocarcinoma, although there was no difference in the operability, types of operations, and survival between the genders. Patients with signet ring cell cancer were significantly younger than the other two histological types reviewed but this did not alter outcome. CONCLUSION: Carcinoma of the stomach, despite newer image modalities, continues to present at advanced stages at time of diagnosis with an overall dismal prognosis. The increased incidence of cardia lesions noted require innovative therapies if any progress is to be made.

Adenocarcinoma↗

EUS-guided FNA of lung masses adjacent to or abutting the esophagus after unrevealing CT-guided biopsy or bronchoscopy.

BACKGROUND: The accuracy, the safety, and the cost-effectiveness of EUS-guided FNA for screening patients with lung cancer for mediastinal metastasis are well established, but the utility of EUS-guided FNA in evaluating lung mass per se has not been investigated. This study retrospectively evaluated experience with EUS-guided FNA of lung mass lesions after unsuccessful attempts by CT-guided or bronchoscopic tissue sampling to establish a tissue diagnosis. METHODS: A database was searched for all patients who had EUS-guided FNA of lung mass lesions over a 3-year period. The diagnostic yield and safety of EUS-guided FNA were evaluated. OBSERVATIONS: Eighteen patients (11 men, 7 women) underwent EUS-guided FNA of lung mass lesions adjacent to or abutting the esophagus. The indication for EUS-guided FNA was evaluation of the mediastinum of patients with lung mass of unclear etiology. EUS-guided FNA yielded tissue for diagnosis in 100% of patients: 15 non-small-cell lung cancer, one small-cell lung cancer, two metastatic lung disease. Ten patients had unresectable disease; in 8, the mass was confined to the lung parenchyma. The mean number of needle passes required to establish a diagnosis was two (range 1-6). No complication was encountered (mean follow-up 141 days; range 72-396 days). Five patients underwent curative surgery, and 13 had palliative chemoradiation. CONCLUSIONS: In this study, EUS-guided FNA of lung mass was safe, and it established a diagnosis in all patients with accessible lesions. Given these preliminary data, a prospective evaluation of this new indication for EUS-guided FNA is justified.

Adult↗

Lung cancer following previous extrapulmonary malignancy.

OBJECTIVE: Having demonstrated a poor prognosis of operable lung cancer in patients with previous head and neck malignancies, we intended to evaluate prognosis of lung cancer in patients with a history of extrapulmonary and extracervical malignancies. METHODS: The population of this study included 55 patients; these were 40 males and 15 females, with a mean age 64.4+/-8.6 years. The previous malignancy was considered tobacco-induced in 15 patients (kidney, two; bladder, ten; esophagus, three), hormone-dependant in 18 (breast, six; female genital, eight; prostate, four), and miscellaneous in 22 (leukemia, four; skin, seven; colon, 11). Following complete resection, 25 patients were classified stage I, 13 were stage II, and 17 were stage IIIA. RESULTS: There were two early perioperative deaths (3.6%), and three during the second month owing to cardiovascular complications. At the conclusion of the study (July 1st, 1997), 32 further patients had died (58.2%): 25 had progression of lung cancer, one had progression of previous malignancy, and six were without evidence of disease. Five-year survival (Kaplan-Meier) was estimated 47+/-10.2% in stage I (median 44 months), 30.8+/-15.6% in stage II (median 26 months), and 16. 7+/-9.9% in stage IIIA (median 17 months). When excluding five early perioperative deaths, 5-year survival was 51.1+/-10.6% in stage I (median 93 months), 33.3+/-16.7% in stage II (median 36.5 months), and 19.0+/-11.2% in stage IIIA (median 20.5 months). Comparing the three groups defined according to location of previous malignancy, there was no significant difference neither in stage distribution (chi(2)=1.326; P=0.857), nor in 5-year survival estimates: 38.9+/-12. 9% (median 27 months) after tobacco-induced malignancies, 38.9+/-11. 5% (median 24 months) following hormone-dependant malignancies, and 28.4+/-10.2% (median 28 months) following miscellaneous cancers (chi(2)=0.059; P=0.9707). CONCLUSIONS: In opposition to data collected in patients with previous head and neck cancer, survival estimates according to stage were contained within the universally accepted range no high risk group has been identified. Resection of lung cancer with curative intent is a fair option in patients with previous extrapulmonary malignancy.

Adult↗

Locoregional recurrence of retroperitoneal soft tissue sarcoma: second chance of cure for selected patients.

BACKGROUND: Locoregional recurrence of a retroperitoneal soft tissue sarcoma (RSTS) may offer a second chance of curative surgical treatment. In a population-based study the proportion of patients developing isolated locoregional recurrences (LR) was determined and the outcome of these patients was analysed. METHOD: In a retrospective nationwide study, data were collected on 142 patients treated between 1 January 1989 and 1 January 1994 for primary RSTS. In patients who had been treated radically for their primary sarcoma (77/142, 54%), the pattern of recurrence was evaluated. Factors predictive of survival for patients with LR were studied. RESULTS: After a median follow-up of 86 (range 60-101) months, 32 patients (42%) had developed LR, and distant metastasis (DM) had been diagnosed in 17 patients (22%). Median disease-free interval between the initial operation and the establishment of LR or DM was 22 and 19 months, respectively. Five-year cumulative survival of patients with established LR was 37% in comparison with 11% for patients with DM (P=0.062). Factors predictive of favourable outcome in patients with LR were the absence of multifocal recurrence (n=13 P=0.01), lipomatous histomorphology (n=20 P=0.02), and a complete resection of recurrent sarcoma (n=17 P=0.04). CONCLUSION: After a median follow-up of 7 years following radical treatment of a primary RSTS, 42% of the patients had developed isolated locoregional recurrences. A complete resection of recurrent disease, lipomatous histomorphology and the absence of multifocal growth influenced prognosis favourably.

Adult↗

OLS4: a new Ontology Lookup Service for a growing interdisciplinary knowledge ecosystem.

SUMMARY: The Ontology Lookup Service (OLS) is an open source search engine for ontologies which is used extensively in the bioinformatics and chemistry communities to annotate biological and biomedical data with ontology terms. Recently, there has been a significant increase in the size and complexity of ontologies due to new scales of biological knowledge, such as spatial transcriptomics, new ontology development methodologies, and curation on an increased scale. Existing Web-based tools for ontology browsing such as BioPortal and OntoBee do not support the full range of definitions used by today's ontologies. In order to support the community going forward, we have developed OLS4, implementing the complete OWL2 specification, internationalization support for multiple languages, and a new user interface with UX enhancements such as links out to external databases. OLS4 has replaced OLS3 in production at EMBL-EBI and has a backward compatible API supporting users of OLS3 to transition. AVAILABILITY AND IMPLEMENTATION: The source code of OLS is available at https://github.com/EBISPOT/ols4 and DOI 10.5281/zenodo.14960290 with Apache 2.0 License. A freely available implementation is accessible at https://www.ebi.ac.uk/ols4.

Biological Ontologies↗