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PubMed2026

RP3Net: a deep learning model for predicting recombinant protein production in Escherichia coli.

MOTIVATION: Recombinant protein expression can be a limiting step in the production of protein reagents for drug discovery and other biotechnology applications. We introduce RP3Net (Recombinant Protein Production Prediction Network), an AI model of small-scale heterologous soluble protein expression in Escherichia coli. RP3Net utilizes the most recent protein and genomic foundational models. A curated dataset of internal experimental results from AstraZeneca and publicly available data from the Structural Genomics Consortium was used for training, validation and testing of RP3Net. RESULTS: RP3Net achieves an increase in area under the receiver operator curve (AUROC) of 0.15, compared to a baseline model. When experimentally validated on an independent, prospective, manually selected set of 97 constructs, RP3Net outperformed currently available models, with an AUROC of 0.83, delivering accurate predictions in 77% of the cases, and correctly identifying successfully expressing constructs in 92% of cases. AVAILABILITY AND IMPLEMENTATION: The model, along with installation and running instructions, is available under an MIT licence at https://github.com/RP3Net/RP3Net, DOI 10.5281/zenodo.17243498.

Escherichia coli↗

PubMed2005

A procedure for assessing GO annotation consistency.

MOTIVATION: The Gene Ontology (GO) is widely used to annotate molecular attributes of genes and gene products. Multiple groups undertaking functional annotations of genomes contribute their annotation sets to the GO database resource and these data are subsequently used in comparative functional analysis research. Although GO curators adhere to the same protocols and standards while assigning GO annotations, the specific procedure followed by each annotation group can vary. Since differences in application of annotation standards would dilute the effectiveness of comparative analysis, methods for assessing annotation consistency are essential. The development of methodologies that are broadly applicable for the assessment of GO annotation consistency is an important issue for the comparative genomics community. RESULTS: We have developed a methodology for assessing the consistency of GO annotations provided by different annotation groups. The method is completely general and can be applied to compare any two sets of GO annotations. This is the first attempt to assess cross-species GO annotation consistency. Our method compares annotation sets utilizing the hierarchical structure of the GO to compare GO annotations between orthologous gene pairs. The method produces a report on the annotation consistency and inconsistency for each orthologous pair. We present results obtained by comparing GO annotations for mouse and human gene sets. AVAILABILITY: The complete current MGI_GOA GO annotation consistency report is available online at http://www.spatial.maine.edu/~mdolan/

Animals↗

PubMedDate not supplied

Campylobacter pylori: its link to gastritis and peptic ulcer disease.

Bismuth salts have been used to treat acid peptic disease for 150 years. Recently, the discovery of Campylobacter pylori and the observation that this bacterium is inhibited by bismuth salts have regenerated interest in the antibacterial properties of bismuth. Bismuth and heavy metals inhibit growth of all Campylobacter species and many enteric anaerobes. Bismuth alone cures C. pylori infection in only 30% of patients, but in combination with other broad-spectrum antibiotics, it can achieve a cure rate of 80%-90% in 2-4 weeks. Data from several studies indicate that eradication of C. pylori is curative for most patients with duodenal ulcer. Epidemiologic studies in the United States suggest that the incidence of new C. pylori infections is declining, so antibacterial therapy for symptomatic cases may be adequate therapy. In developing countries, however, curative therapy may not be possible in the presence of environmental sources of reinfection. In these areas intermittent suppressive therapy with bismuth salts may be useful.

Bismuth↗

PubMed1998

Survival and recurrence after liver transplantation versus liver resection for hepatocellular carcinoma: a retrospective analysis.

OBJECTIVE: This study compares the results of liver transplantation (LTx) and liver resection (LR) for hepatocellular carcinoma (HCC) to test the widespread hypothesis that LTx is the preferable approach for small HCCs. SUMMARY BACKGROUND DATA: With respect to scarcity of donor organs and poor results, LTxs for large HCCs are obsolete. Small HCC transplantations have been reported to result in an excellent survival rate. However, the data of comparative studies are controversial. METHODS: Patients who were treated curatively by LTx (n = 50) or LR (n = 52) for HCC were included in this retrospective study. Survival and freedom from recurrence were analyzed. Patients were stratified according to prognostic factors (pT classification, tumor size, number of tumor nodules, vascular infiltration, and cirrhosis). RESULTS: Overall, after LTx and LR the 3-year survival rate and recurrence rate were not significantly different. In the Cox analysis, tumor size (p = 0.02) and vascular infiltration (p = 0.04) were independent variables after LTx, whereas after LR, none of the tested prognostic parameters was significant. With regards to recurrence, tumor size was the only independent factor, after both LTx and LR (p = 0.02, respectively). Directly comparing the two therapeutic approaches, a 3-year survival rate in pT 1/2, oligocentric (1-5 nodules), and oligocentric and small tumors proved to be superior after LTx. The recurrence rate after LTx was superior to LR in pT 1/2 and oligocentric tumors. Remarkably, for small (< or = 5 cm) tumors, LTx and LR resulted in a similar 3-year survival rate and freedom from recurrence. CONCLUSIONS: According to our analysis, the oncological advantage of LTx compared with LR is questionable. This applies especially for small tumors. Superior results of LTx in early stage HCC and particularly in oligocentric tumors may be attributed to incorrect preoperative diagnosis. Nevertheless, LTx is a reasonable treatment for patients with early stage tumors if a LR is impossible because of tumor localization or poor functional hepatic capacity.

Adult↗

PubMed2000

Indicators for treatment strategies of colorectal liver metastases.

OBJECTIVE: To analyze the survival predictors of patients undergoing hepatectomy for colorectal liver metastasis to determine useful indicators for therapy selection. SUMMARY BACKGROUND DATA: Although recurrence develops in more than two thirds of patients undergoing hepatectomy for colorectal liver metastasis, preoperative characteristics that might predict such recurrence have yet to be clearly identified. METHODS: Clinicopathologic data of 85 consecutive patients with colorectal cancer who underwent a curative resection of primary lesions and metastatic liver diseases at one institute were analyzed using the multivariate method with respect to both the metastatic state and the primary lesion. RESULTS: Multivariate analysis indicated that the aggressiveness of the primary tumor, early liver metastasis, and a large number of liver metastases were the characteristics that could be detected before hepatectomy and that independently indicated a worse survival. A three-ranked classification based on these coefficients (H-staging) was significantly related to both the recurrence rate within 6 months (7% in H-stage A, 30% in B, and 44% in C) and the 5-year survival rates (55%, 14%, and 0% respectively). An additional scoring system (H'-staging) based on the aggressiveness of the primary tumor and the level of carcinoembryonic antigen 1 to 3 months after hepatectomy was found to be related to the mode of subsequent recurrence and surgical resectability of the recurrent foci. CONCLUSIONS: H-staging can provide useful prognostic information for the treatment of liver metastasis. H-staging could also help in predicting the possible mode of recurrence after hepatectomy and in determining the most suitable mode of additional therapy. Further multiinstitutional studies based on a large collective database will confirm the utility of these two staging systems.

Adult↗

PubMedDate not supplied

MGI 114: augmentation of antitumor activity when combined with topotecan.

PURPOSE: 6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the mushroom toxin illudin S that has been shown to be a potent cytotoxic agent with an improved therapeutic index compared with its parent compound. The studies were conducted to evaluate the antitumor activity of MGI 114 as a single agent and in combination with topotecan against pediatric solid tumor cell lines and xenograft models. MATERIALS AND METHODS: In vitro studies were designed to determine the cytotoxic potential of MGI 114 using the MTT assay and 13 pediatric tumor cell lines. In addition, combination in vitro studies were performed with MGI 114 and topotecan to generate isoeffect plots. Single agent and combination in vivo studies were also performed using MGI 114 against rhabdomyosarcoma and neuroblastoma xenograft models. RESULTS: After a 1-hour exposure to MGI 114, the mean IC50 (+/-standard error of mean) for medulloblastoma, neuroblastoma, Ewing sarcoma/primitive neuroectodermal tumor, and rhabdomyosarcoma cell lines were 1.58+/-0.51, 1.60+/-0.82, 1.18+/-0.08, and 3.99+/-1.69 microg/mL, respectively. When tumor cells were exposed concurrently to MGI 114 and topotecan, evidence of synergy was observed in 10 of 12 (83%) cell lines. Single agent and combination in vivo studies with MGI 114 showed that this agent had substantial, and at times curative, antitumor activity against rhabdomyosarcoma and neuroblastoma xenograft tumors. CONCLUSIONS: These data suggest that MGI 114 has significant efficacy as a single agent in preclinical studies against pediatric tumors. In addition, based on previous reports and the results presented here, combining MGI 114 with topotecan appears to be an attractive approach to the treatment of pediatric malignancies. After completion of the pediatric phase I studies of MGI 114, consideration should be given to phase II single agent and phase I combination studies with a topoisomerase I inhibitor such as topotecan or irinotecan.

Animals↗

PubMed2004

Integrative genomics: in silico coupling of rat physiology and complex traits with mouse and human data.

Integration of the large variety of genome maps from several organisms provides the mechanism by which physiological knowledge obtained in model systems such as the rat can be projected onto the human genome to further the research on human disease. The release of the rat genome sequence provides new information for studies using the rat model and is a key reference against which existing and new rat physiological results can be aligned. Previously, we described comparative maps of the rat, mouse, and human based on EST sequence comparisons combined with radiation hybrid maps. Here, we use new data and introduce the Integrated Genomics Environment, an extensive database of curated and integrated maps, markers, and physiological results. These results are integrated by using VCMapview, a java-based map integration and visualization tool. This unique environment allows researchers to relate results from cytogenetic, genetic, and radiation hybrid studies to the genome sequence and compare regions of interest between human, mouse, and rat. Integrating rat physiology with mouse genetics and clinical results from human by using the respective genomes provides a novel route to capitalize on comparative genomics and the strengths of model organism biology.

Animals↗

PubMed1991

Assessment of primary care nursing in relation to adolescent health behaviour by means of trigger films.

The patterns of adolescents' behaviour place them at a risk from developing health and social pathology. In order to assess whether primary care nursing meets adolescents' health needs, the reported performance of 306 registered nurses working in different primary health care settings was studied. The research tool developed especially for the study was a video-taped trigger film. Demographic, education and work-related variables were studied by means of a questionnaire. The behaviour patterns studied were smoking, sexual activity, alcohol and drug consumption, and eating habits. The clinical issues were hypertension, obesity and anorexia nervosa. Reported performance was low--35% of the total possible score--with the lowest scores in the areas of preventive care, data gathering and recording, and somewhat higher in the areas of curative care and follow-up. The video-taped trigger films were considered to have face validity; they were found to be reliable, with an ability to assess the nurses' reported performance and to differentiate between the nurses in the three different work settings. This is the first study of its kind in Israel. The results show that primary health nursing of adolescents is insufficient, and that teenagers should get higher priority as a target population from the nursing profession in order to achieve WHO's aims of 'health for all by the year 2000'.

Adult↗

PubMed2026

Markers of microvascular instability predict severity and survival in idiopathic pulmonary fibrosis.

INTRODUCTION: Most research on idiopathic pulmonary fibrosis (IPF) has focused on the interplay among fibroblasts, the immune system and epithelial cells. There is growing evidence that microvascular dysfunction also plays a role in disease progression, but large human translational studies are lacking. In this research, we aim to identify a proteomic signature of microvascular instability and assess the impact of current therapeutics on the microvasculature. METHODS: Olink proteomic data from patients with IPF were obtained from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=914) and an independent validation cohort (n=366). Among the PFF-PR, 640 patients also have whole-blood RNA sequencing data available. A subset of 79 microvascular-associated proteins was curated, and their associations with disease severity and transplant-free survival were examined. An adaptive least absolute shrinkage and selection operator was used to generate a novel microvascular risk score. RESULTS: Higher plasma levels of five microvascular-associated proteins (SDC1, MMP10, THBS2, HGF and SERPINA5) were associated with lung function and survival in both cohorts. Whole-blood RNA sequencing of patients with microvascular risk revealed enrichment of immune-mediated processes. Patients with higher microvascular risk who were subsequently put on nintedanib in the following year had significantly better 3-year transplant-free survival compared with patients who did not receive antifibrotic intervention (HR 0.56, 95% CI 0.35 to 0.89, p=0.0142). DISCUSSION: Integrative multi-omics analyses suggest that perturbations to microvascular remodelling contribute to disease severity and progression in IPF. This analysis offers a framework for a precision medicine approach for IPF.

Idiopathic pulmonary fibrosis↗

PubMed1986

Esophageal cancer staging by CT: long-term follow-up study.

To evaluate the utility of computed tomographic (CT) staging in patients with esophageal cancer, the length of patient survival was compared with pretherapy CT findings in 89 patients. Regardless of therapy, patients with evidence of mediastinal invasion, liver metastases, or abdominal adenopathy had a statistically shortened survival (P less than .05). Specific CT criteria that predicted a shortened survival included evidence of tracheal, aortic, or pericardial invasion. Patients with evidence of both mediastinal invasion and abdominal metastases had a mean survival of 180.4 days; those with no evidence, 479.6 days. The presence of enlarged upper abdominal lymph nodes indicated the worst prognosis (mean survival, 90 days). The patients with squamous cell tumors were classified by the CT staging system, and survival data were compared according to surgical procedure. Patients who underwent attempted curative surgery did not have a statistically significant difference in survival by analysis of survival curves but demonstrated a longer mean survival than those who underwent palliative or no surgery.

Adult↗

PubMed2005

PineappleDB: an online pineapple bioinformatics resource.

BACKGROUND: A world first pineapple EST sequencing program has been undertaken to investigate genes expressed during non-climacteric fruit ripening and the nematode-plant interaction during root infection. Very little is known of how non-climacteric fruit ripening is controlled or of the molecular basis of the nematode-plant interaction. PineappleDB was developed to provide the research community with access to a curated bioinformatics resource housing the fruit, root and nematode infected gall expressed sequences. DESCRIPTION: PineappleDB is an online, curated database providing integrated access to annotated expressed sequence tag (EST) data for cDNA clones isolated from pineapple fruit, root, and nematode infected root gall vascular cylinder tissues. The database currently houses over 5600 EST sequences, 3383 contig consensus sequences, and associated bioinformatic data including splice variants, Arabidopsis homologues, both MIPS based and Gene Ontology functional classifications, and clone distributions. The online resource can be searched by text or by BLAST sequence homology. The data outputs provide comprehensive sequence, bioinformatic and functional classification information. CONCLUSION: The online pineapple bioinformatic resource provides the research community with access to pineapple fruit and root/gall sequence and bioinformatic data in a user-friendly format. The search tools enable efficient data mining and present a wide spectrum of bioinformatic and functional classification information. PineappleDB will be of broad appeal to researchers investigating pineapple genetics, non-climacteric fruit ripening, root-knot nematode infection, crassulacean acid metabolism and alternative RNA splicing in plants.

Alternative Splicing↗

PubMed1996

Indigenous healers in the North West Province: a survey of their clinical activities in health care in the rural areas.

The purpose of this study was to explore the clinical conditions brought to indigenous healers by people in the rural areas in search of health care. The demographic variables and preventive, promotive, curative and follow-up activities of indigenous healers were investigated. Data were collected from a simple random sample of 35 indigenous healers. A questionnaire designed by Mogoba (1984) for investigation of training and functioning of traditional doctors in Southern Africa was modified and used to collect data. Findings showed that indigenous healers deal with the same health problems confronting formal health workers, especially in the paediatric field. Infertility, mental illness problems and sexually transmitted diseases ranked high in the adult conditions brought to the healers. There seem to be conditions that can be handled only by the indigenous healers due to their cultural nature. Findings also show that the services of indigenous healers are not confined to any specific group or social class within black population.

Adult↗

PubMed1999

[An analysis of transfusion in adult surgery].

PURPOSE: To analyze the transfusion rate of adult transfused patients undergoing standard curative surgery made in operating room (not ambulatory). PATIENTS AND METHODS: Data from discharge reports of patients having surgery during 1996, codified according to the International Diseases Classification (ICE-9-MC). Age, sex, diagnosis, procedures (including transfusions), were analysed along with the surgical procedures and if the patient was subsequently admitted. RESULTS: 11,673 adult patients had surgery, of whom 890 underwent transfusion (7.6%). The transfusion rate was greater in males, in patients over 60 years old, in patients with several surgical procedures simultaneously, in patients who were subsequently admitted, and in patients with surgery procedures of pancreas, spleen, dorsolumbar column, liver, pharynx, hip and stomach. CONCLUSIONS: Given the variability in the blood transfusion practices among the hospitals, to know the transfusion rates of each clinic and surgical situation would permit a better planning of: the surgical blood transfusions, the autologous blood transfusion program, the criteria on crossmatching tests, as well as to increase the information to the patient in the surgical Informed Consent.

Adult↗

PubMed2001

Splenic abscess: report of six cases and review of the literature.

Splenic abscesses are rare but appear to be increasing in frequency. Recent advances in radiologic techniques have affected the diagnosis and management. The purpose of this study was to evaluate these effects. The medical records of one institution were retrospectively reviewed and six cases of splenic abscesses seen between 1989 and 1999 were identified. All patients had predisposing conditions with metastatic hematogenous infection in three and one each with trauma, immunodeficiency, and a contiguous site of infection. Fever was present in all patients with chills and vomiting in five and three patients, respectively. Left upper quadrant tenderness appeared in four patients and leukocytosis was found in every patient except one with the acquired immunodeficiency syndrome. Chest roentgenograms were abnormal in five patients with a left pleural effusion most common. Ultrasound revealed the defect in both patients it was utilized in and computed tomography was diagnostic in all cases. The causative organisms were anaerobes in two cases and Candida albicans, Streptococcus viridans, Escherichia coli, and Citrobacter freundii each present in one case. Radiology guided percutaneous drainage was attempted in four patients but was only successful in one. Splenectomy with antibiotics was curative in the remainder with a 100 per cent survival. These data suggest that percutaneous drainage may be appropriate for certain patients initially, but the high failure rate demonstrates that splenectomy remains the standard treatment.

Abdominal Abscess↗

PubMed2001

Chromogranin A assay and (131)I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma.

UNLABELLED: We assessed the performance of a new serum chromogranin A (CgA) assay in combination with the results of (131)I-metaiodobenzylguanidine (MIBG) scintigraphy for diagnosis and follow-up in 89 patients with clinical findings suggestive of pheochromocytoma. METHODS: The study population consisted of 41 patients with proven pheochromocytoma and 48 patients with refuted pheochromocytoma. Eighty-seven scintigraphy examinations were performed, 52 in patients with proven pheochromocytoma (39 before surgery and 13 after surgery) and 35 in patients with refuted pheochromocytoma. RESULTS: The sensitivity of the CgA level was 90.2%, and the specificity was 99.0% and 92.3% in the control and refuted pheochromocytoma groups, respectively. A significant relationship was seen between serum levels of CgA and tumor mass (r = 0.70; P < 10(-5)). The postoperative CgA level was an early and accurate predictor of curative surgery or relapse. The concordance between CgA levels and scintigraphic data was 90.8%. CONCLUSION: Serum CgA level is an effective marker of pheochromocytoma. Increased levels strongly correlate with tumor mass; therefore, small tumors may go undetected. The concordance between CgA level and the results of (131)I-MIBG scintigraphy is high. A CgA level in the reference range is highly predictive of normal scintigraphy findings.

3-Iodobenzylguanidine↗

PubMed2002

[Infiltration of dendritic cells and lymphocytes in hepatocellular carcinoma tissue].

OBJECTIVE: To explore the clinical significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma (HCC) tissue. METHODS: Clinicopathological data were collected from 44 patients with HCC who had under/gone curative tumor resection in our hospital. Immunohistochemical staining was used to detect the infiltration of dendritic cells in the tumor tissue, and lymphocytes infiltration was assessed simultaneously. The correlation between the infiltration of dendritic cells and lymphocytes and postoperative tumor recurrence and survival rate was analyzed. RESULTS: Tumor recurrence was markedly late in patients with dendritic cells count >/= 20 and positive lymphocytes infiltration (group A, n = 17) as compared with those who did not meet both criteria simultaneously (group B, n = 27), with a median interval of 21.6 months for group A and 4.1 months for group B (U value = 105.5, P = 0.009). The 1-, 3-, 4-year survival rates were significantly greater in group A than in group B; they were 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (Log rank = 7.68, P < 0.01). CONCLUSION: The infiltration of dendritic cells and lymphocytes in HCC tissue, as an independent prognostic factor, was closely related to postoperative prognosis.

Adult↗

PubMed2003

Maximum gastric cancer diameter as a prognostic indicator: univariate and multivariate analysis.

It was suggested that there are no stronger prognostic factors in gastric cancer than nodal involvement or depth of wall invasion. The present paper evaluated the influence of maximum tumor diameter (MTD) value, measured on fixed resected specimens, on the extent of disease progression and the outcome in gastric cancer patients. Clinicopathological data were retrospectively retrieved from records of 122 patients who underwent curative gastrectomy. The patients' MTD values were grouped as follows: MTD1, up to 26 mm; MTD2, between 26 and 50 mm; and MTD3, over 50 mm. The three groups evidenced significant differences with regard to 5 year survival (MTD1: 54%, MTD2: 31%, MTD3: 20%; p = 0.00027), furthermore they were significantly different with respect to the type of gastrectomy (p = 0.021), depth wall invasion (p = 0.000), lymphatic microinvasion (p = 0.014), perineural microinvasion (p = 0.017), stromal reaction (p = 0.025), and stage (p = 0.035). ROC curve analysis individuated a best accurate MTD threshold value for nodal involvement of 32 mm (sensitivity = 56.6%; specificity = 60.9%; positive predictive value = 52.6%; negative predictive value = 64.6%). The logistic regression analysis suggested that the depth of wall invasion was the only independent variable associated with MTD value (p = 0.0005). Multivariate analysis showed that independent prognostic risk factors were sex (p < 0.0025), number of involved nodes (p < 0.001) and MTD (p < 0.001). In conclusion, the maximum tumor diameter value of gastric cancer may be a factor with greater prognostic implications than previously believed.

Aged↗

PubMed2005

[Clinical analysis of sixteen cases of lymphoepithelial carcinoma of salivary gland].

BACKGROUND & OBJECTIVE: Lymphoepithelial carcinoma of salivary gland is a rare and special kind of malignant tumor, and has seldom been reported. This study was to summarize the clinical features, treatment and curative effect of this disease according to our experiences. METHODS: Clinical data of 16 patients with pathologically confirmed primary lymphoepithelial carcinoma of salivary gland, treated in Cancer Center of Sun Yat-sen University from Jan. 1990 to Sep. 2004, were retrospectively analyzed, and survival analysis was performed with Kaplan-Meier method. RESULTS: The 16 patients with lymphoepithelial carcinoma of salivary gland accounted for 3.6% of all the patients diagnosed as malignant tumors of salivary gland simultaneously in our center. All patients had tumors occurred in unilateral gland, aged 15-57 years, with the female to male ratio of 1:1. All patients were from southern China. Except for 1 patient, the rest 15 had Epstein-Barr virus (EBV) serological tests. The positive rates of EBV-VCA-IgA, EBV-EA-IgA, and EBV-DNA enzyme were 93.3%, 66.7%, and 86.7%, respectively. All patients were treated with surgery, of which 9 received surgery only, 5 received surgery plus postoperative radiotherapy, 1 received surgery plus postoperative chemoradiotherapy, 1 received surgery plus chemotherapy. Four (25.0%) patients had postoperative pathology-proved ipsilateral cervical lymph node metastasis. The 1-, 3-, and 5-year survival rates of the 16 patients were 86.15%, 48.46%, and 24.23%. CONCLUSIONS: Although lymphoepithelial carcinoma of salivary gland is poorly differentiated, the prognosis of this disease is good. Complete resection plus postoperative radiotherapy is possibly accommodating.

Adolescent↗