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At least 19 recordsLinked to original sources
PubMed2026

Screening of molecular biomarkers ASPN and LBH and construction of a prediction nomogram for the progression of esophagogastric junction adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) is an aggressive malignancy of the digestive system with poor prognosis. Early diagnosis and accurate prediction of tumor progression remain major clinical challenges. This study aimed to identify and validate molecular biomarkers and construct a precise diagnostic model, providing a scientific basis for individualized treatment. METHODS: Differentially expressed genes (DEGs) associated with EGJA were identified using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed for further screening. The protein expression levels of ASPN and LBH were validated by immunohistochemistry in both tumor and adjacent non-tumor tissues. A nomogram was constructed by integrating clinical and pathological features, and its performance and clinical utility were assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: Immunohistochemistry demonstrated that the protein expression of ASPN was significantly upregulated in tumor tissues, with expression levels increasing with tumor stage. Conversely, LBH was downregulated in tumor tissues and decreased with advancing stages. The predictive model achieved an area under the curve (AUC) value of 0.977, indicating excellent diagnostic and prognostic performance. DCA confirmed the clinical net benefit of the model. CONCLUSIONS: ASPN and LBH are critical molecular biomarkers for EGJA. The nomogram combining these two markers enables accurate distinction between early and advanced-stage tumors, offering significant support for early diagnosis of EGJA.

ASPN↗
PubMedDate not supplied

Spontaneous abortion in primary care. A report from ASPN.

The Ambulatory Sentinel Practice Network (ASPN) conducted an observational study of usual primary care of spontaneous abortion (SAB). Forty-nine practices in 18 states and four Canadian provinces reported and audited 171 SABs. Contrary to recommendations in some texts, 40 percent were managed completely in the office and/or at home, and only 51 percent had a dilation and curettage (D&C). SABs occurring later in pregnancy were more likely to be managed in the emergency room/hospital, receive consultation, and have a D&C. Patients managed with D&C had a greater frequency of excessive blood loss at diagnosis, but otherwise they did not differ in terms of complications at diagnosis or follow-up from those who did not. Adverse psychological consequences were subjectively observed by ASPN clinicians in 24 percent of women, exceeding any other category of complications. Management of all SABs in a hospital with D&C, instead of the management observed in this study, could add $145,000,000 per year to health care expenditures in the United States.

Abortion, Spontaneous↗
PubMedDate not supplied

An exploratory report of chest pain in primary care. A report from ASPN.

Chest pain is important to patients and clinicians because it can signal a threat to life as well as present diagnostic and therapeutic challenges. Because prior clinical research has not provided clear guidance to primary care clinicians, the Ambulatory Sentinel Practice Network was interested in investigating chest pain as it presents and is managed in primary care. A contemporary exploratory study was required to characterize chest pain from a clinical perspective, to test the feasibility of investigating chest pain in a network of primary care practices, and to generate promising areas for investigation. This article provides a detailed distribution of demographic, diagnostic, and therapeutic variables associated with a convenience sample of 832 patients with chest pain. Most of the patients in this study were seen only by primary care clinicians in office settings. There were promising areas identified for further investigation, including an unexpected frequency of costochondritis in black women, clinician uncertainty in the management of patients with chest pain thought to be of gastrointestinal origin, constant vigilance for infrequent myocardial infarctions, perceived discordance between clinician and patient concerning the patient's chest pain, and the methodological requirement of improved delineation of episodes of chest pain.

Adolescent↗
PubMed1988

Patients with new headache in primary care: a report from ASPN.

From a consecutive series of 3,847 headache patients, 1,331 patients who made first visits for new headache to 120 primary care physicians were studied for usual care over a 14-month period. Either tension or vascular headache was the initial diagnosis in 23.8 percent and 12.8 percent of patients, respectively. Nearly one half (47.8 percent) were classified as having headaches other than tension or vascular. A total of 15.3 percent of headaches were undiagnosed or were regarded as a mixture of traditional diagnostic designations. At first visit, most patients (76.6 percent) were managed without diagnostic tests. Drugs were prescribed for 73.6 percent, and advice was given for 58.6 percent. Only 2.0 percent of patients had computerized tomographic scanning ordered at first visit, although at least 46 percent met National Institutes of Health criteria, a finding with potential economic consequences of at least $2 billion. These findings suggest the need for reevaluation of diagnostic categories for headache, reevaluation of strategies for headache management, and further investigations of headache in primary care patients.

Headache↗
PubMed2025

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin.

Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor β (TGF-β)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.

Animals↗
PubMed1991

AIDS in primary care: a report from the Ambulatory Sentinel Practice Network.

BACKGROUND: Despite the importance of the epidemic of acquired immune deficiency syndrome (AIDS), little is known about the incidence and prevalence of AIDS in the patient population of primary care physicians. This study was designed as an initial step in evaluating the impact of this disease on primary care practices. METHODS: We conducted a survey to characterize the AIDS cases in the Ambulatory Sentinel Practice Network (ASPN). ASPN is a practice-based primary care research network. In 1987 it was composed of 65 practices and 193 clinicians serving approximately 270,000 patients in the United States and Canada. Clinicians representing each practice were asked to report the number of AIDS patients that their practice cared for between January 1982 and December 1987. They were further asked to characterize relevant data for these patients. RESULTS: Thirty-nine prevalent cases of AIDS were reported in ASPN from January 1982 through December 1987. Seventy-nine percent of the patients were male, 15 to 44 years of age; three patients (7.6%) were female; and all cases had at least one risk factor for AIDS. An expected number of cases for the 194,973 patients of 47 practices was calculated using age-sex register data and nationally based rates from 1986. The projected number, 13, corresponded with the number of AIDS cases, 11 and 15, reported from ASPN practices in 1986 and 1987, respectively. CONCLUSIONS: This survey suggests that AIDS is at least as prevalent in the primary care practices in ASPN as predicted using national estimates, and may, in fact, be more prevalent. Primary care clinicians need to be prepared to assume a major role in addressing the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1991

An analysis of reasons for discontinuing participation in a practice-based research network.

Now that primary care practice-based research networks are known to be feasible, it is important to learn more about the reasons practices participate and withdraw. The Ambulatory Sentinel Practice Network (ASPN) experience presents a special opportunity to study 32 practices that withdrew from the Network since it began in 1982. One hundred percent of these practices responded to a structured telephone survey. The desire to be part of a group doing research (47%) and response to recruitment by an esteemed colleague (28%) were the most important reasons for joining the Network. Changes within the practice (50%), the additional burdens associated with ASPN (22%), and lack of support among practice colleagues and staff (13%) were the most important reasons for withdrawing. Six suggestions were made that could have helped these practices continue in ASPN. Thirteen percent of practices that withdrew rejoined the Network at a later date. Eight years after initiating investigations, 70% of the practices that were ever part of ASPN remained fully involved.

Primary Health Care↗
PubMedDate not supplied

The development and management of a primary care research network, 1978-87.

The Ambulatory Sentinel Practice Network (ASPN) was created to increase the knowledge of primary care. Building on the experiences of other national and regional primary care research networks, ASPN has evolved as a North American network including practices in 25 U.S. states and four Canadian provinces in 1987. This paper summarizes ASPN's growth and development since 1978, the involvement of the ASPN practices, and the mechanisms used in developing and managing studies.

Ambulatory Care Information Systems↗
PubMed2026

Graph neural network-based risk stratification of prostate cancer using gene expression and SHAP interpretability.

Accurate risk stratification is essential for guiding treatment decisions and preventing over treatment of prostate cancer, which remains one of the most prevalent cancers among adult men. While the Gleason score, obtained from prostate biopsies, is routinely used to assess tumor aggressiveness, the biopsy procedure carries risks such as pain, infection, and, in some cases, serious complications such as sepsis. In this study, we proposed an artificial intelligence-based framework that integrates mRNA expression profiles with functional interaction networks to classify prostate cancer patients into low-, medium-, and high-risk groups defined by Gleason scores. The pipeline comprised five steps: (1) data collection from The Cancer Genome Atlas (TCGA), (2) preprocessing of gene expression data, (3) two-stage feature selection to identify informative biomarkers, (4) risk classification using a dual-branch graph neural network (GNN) that combines gene-gene interaction graphs with sample-level expression features, and (5) model interpretation using SHAP to quantify feature contributions. Differentially expressed genes were identified in the High (ASPN, GMNN, PEBP4, C2, KNCK17), Medium (C2, IGSF1, ASPN, CDKN3, AMH), and Low (TNMD, VWA5B2, ST6GALNAC5, CYP3A5, PHGR1) risk groups, underscoring the molecular heterogeneity of disease progression. On an independent held-out test set, the model achieved AUCs of 0.86, 0.88, and 0.95 for the low-, medium-, and high-risk groups, respectively, with an overall accuracy of 80%. These results suggest that combining GNN-based modeling with explainable AI can capture both global and local molecular patterns relevant to tumor aggressiveness. However, as the model was developed and evaluated solely on the TCGA cohort, the findings should be regarded as exploratory, and external validation will be required to establish generalizability. Within these limitations, the proposed framework highlights the potential of molecular profiling and graph-based deep learning to support more precise, potentially less invasive, risk assessment and individualized treatment planning in prostate cancer.

Prostatic Neoplasms↗
PubMed1992

Patients presenting to family physicians after a fall: a report from the Ambulatory Sentinel Practice Network.

BACKGROUND: Patients who fall present a diagnostic challenge to family physicians. The diagnostic workup of these patients must be thorough enough to detect and treat important causes of the fall yet not subject patients to unnecessary tests. Previous studies have provided only limited guidance for primary care physicians because in general they occurred in settings other than primary care and focused on a single age group. METHODS: The Ambulatory Sentinel Practice Network (ASPN) conducted a 6-month study of primary care patients of all ages presenting after a fall, or with medical problems resulting from a fall. ASPN clinicians collected information about the history, physical examination findings, and follow-up of these patients. Causes of falls were grouped into three categories: external reasons for falling, internal reasons related to gait, and internal reasons unrelated to gait. RESULTS: Participating clinicians identified 431 patients who had falls out of the 256,680 seen for any reason during the study period. The patients ranged in age from 1 to 94 years. The rate of falls for patients increased rapidly after age 65 years. Most falls occurred for reasons external to the patient, but internal reasons, both nonlocomotor and locomotor, increased after age 65 years. No nonlocomotor causes for a fall were found in patients younger than 65 years of age. Also, the rate of hospitalization of patients seen for falls was greater in the geriatric age group. CONCLUSIONS: The results highlight the need for further research about falls, particularly those occurring in pediatric and young adult patients. Furthermore, correcting environmental hazards and modifying gait problems in the elderly by increasing lower extremity and truncal strength could decrease the risk of falling.

Accidental Falls↗
PubMedDate not supplied

Pelvic inflammatory disease in primary care.

The Ambulatory Sentinel Practice Network (ASPN) conducted an observational study of pelvic inflammatory disease (PID) in the primary care setting. During 14 months from 1982 to 1983, 38 practices in 16 states and two Canadian provinces reported 384 first visits for patients with PID. PID, as diagnosed by the clinicians in ASPN, was less severe than other published clinical descriptions of PID. Fewer patients had fever, palpable adnexal masses, and extensive tenderness than reported in other series. Although 43% of patients met published recommendations for hospitalization, the clinicians hospitalized only 9% on the initial visit, similar to the hospitalization rate by office gynecologists in a national study. Whether this management represented optimal care in the primary care setting is unknown. If office based physicians in the United States admitted to the hospital all PID patients who met current recommendations for hospitalization, the added annual cost could exceed $1.2 billion. Given both the serious clinical consequences of PID and the enormous financial implications of different clinical strategies, there is a compelling need to investigate the diagnosis and management of PID in primary care.

Adult↗
PubMed1990

Role of mass spectrometry in mapping strain variation and post-translational modifications of viral proteins.

Enzymatically derived fragments of the nucleocapsid protein from one strain (V4) of the paramyxovirus, New castle disease virus (NDV), have been aligned with the sequence deduced for a related strain (D26) by gene sequence analysis. This process involved extensive use of fast atom bombardment (FAB) mass spectrometry of unfractionated tryptic digests and fragments separated from tryptic or AspN protease digests by high-performance liquid chromatography (HPLC). Amino acid analysis and stepwise Edman degradation sequence analysis were used to complement FAB mass spectral data or as alternatives where no ions were produced by FAB. The nature of biosynthetic processing and blockage (acetylation) at the N-terminus of the protein were confirmed using collision-induced dissociation. Data obtained by direct analysis of the V4 nucleocapsid protein facilitated mapping of sequence variations within the nucleocapsid protein of the antigenically distinct WA2116 strain of NDV. Most of the WA2116 protein was mapped by FAB mass spectrometric analysis of HPLC fractions, thus amino acid analysis or stepwise sequence analysis were only required where FAB mass spectral data were inconclusive or indicated amino acid variations. This approach to comparison of NDV nucleocapsid proteins is proposed as a general strategy for mapping strain variation and post-translational modifications of viral proteins.

Amino Acid Sequence↗
PubMed2026

Exploration and experimental verification of triaptosis-related prognostic genes and cells in gastric cancer.

BACKGROUND: Triaptosis is a recently characterized form of programmed cell death with unclear implications in cancer. This study aimed to investigate the prognostic significance and biological relevance of triaptosis in gastric cancer (GC). METHODS: Transcriptomic and clinical data from TCGA-STAD and GSE62254, and single-cell RNA sequencing data from GSE183904 were analyzed. Triaptosis-related gene (TRG) scores were calculated using single-sample gene set enrichment analysis. Differentially expressed genes identified in TRG-score and GC-versus-normal comparisons underwent functional enrichment, Cox regression, and least absolute shrinkage and selection operator regression to develop an externally validated signature. Immune profiles, pathway activity, somatic mutations, tumor mutational burden (TMB), predicted drug sensitivity, and clinical features were compared by risk group. Single-cell analyses assessed TRG activity, prognostic gene expression, cell-cell communication, and pseudotime. Reverse transcription-quantitative PCR and Western blotting assessed mRNA expression and protein levels, respectively. RESULTS: A TRG-based prognostic model comprising ASPN, GRB14, and VTN was developed and externally validated, effectively distinguishing patients into two distinct risk groups with notably different survival outcomes. mRNA expression of all three genes and their protein levels were significantly higher in SGC-7901 cells than in GES-1 cells. High-risk patients had higher stromal scores and distinct immune profiles; 15 immune cell types differed between groups. Single-cell analysis revealed fibroblasts and pericytes among high-TRG-active cell types. Prognostic genes were significantly overexpressed in fibroblasts, which also showed high TRG activity. Fibroblasts demonstrated enhanced communication with pericytes, whereas tumor-derived fibroblasts showed weaker communication with macrophages, indicating immune microenvironment remodeling. CONCLUSION: The three-gene prognostic signature predicted GC prognosis and was associated with distinct immune and genomic features, suggesting potential value for risk stratification and personalized treatment.

Humans↗
PubMed1990

Comparison of the positions and efficiency of cleavage activation of fusion protein precursors of virulent and avirulent strains of Newcastle disease virus: insights into the specificities of activating proteases.

The F1- and F2-polypeptide components of in ovo activated fusion proteins of one virulent (AV or Australia-Victoria) strain, one low-virulence (EG or Eaves-Grimes) strain, and two avirulent (V4 or Queensland and WA2116) strains of Newcastle disease virus (NDV) were isolated and subjected to structural analysis. This included complementary application of amino acid analysis, fast atom bombardment-mass spectrometry, and N-terminal sequence analysis to fragments isolated from AspN protease digests of the F2-polypeptides using HPLC. As a result, the complete sequences of the F2-polypeptides were determined, including documentation of glycosylation of asparagine 54. The sequence of the cleavage-activation site of the WA2116 F0-protein was found to be distinctly different from this site in any other NDV F0-protein. Cleavage activation at the C termini of the F2-polypeptide regions was found to have occurred to approximately equivalent extents at arginines 82 and 85 of the AV and EG strains, but was restricted largely to arginine 85 of the V4 strain and completely to arginine 85 of the WA2116 strain. In each case cleavage activation was apparently succeeded by trimming of the basic residues from the newly formed C termini. Immunochemical analysis with antipeptide antisera showed that the extent of cleavage was influenced by amino acids adjacent to these arginines. These data provide insight into the substrate specificities of the enzymes involved in cleavage activation of the fusion protein precursors.

Amino Acid Sequence↗
PubMed1973

Analysis of isoaccepting transfer ribonucleic acid species of Bacillus subtilis: chromatographic differences between transfer ribonucleic acids from spores and cells in exponential growth.

Differences between the transfer ribonucleic acid (tRNA) of spores and exponentially growing cells of Bacillus subtilis 168 were compared by co-chromatography on reversed-phase column RPC-5. This system gave excellent resolution of isoaccepting species in 1 to 2 hr using a 200-ml gradient. Two methods were used to extract spore tRNAs, a procedure using a Braun homogenizer and a pretreatment with dithiothreitol followed by lysis with lysozyme. Where changes were observed, column elution profiles of spore tRNAs were independent of the extraction method used. Three kinds of changes between the profiles of vegetative cell tRNA and spore tRNA were observed: (i) no change; phe-, val-, ala-, asp-, ileu-, pro-, met-, fmet-, and his-tRNAs, (ii) a change in the ratio of existing peaks; gly-, tyr-, leu-, ser-, thr-, aspn-, and arg-tRNAs, and (iii) the appearance or disappearance of unique peaks; lys-, glu-, and trp-tRNAs.

Acylation↗
PubMedDate not supplied

Immunohistochemical and ultrastructural classification of peripheral neuropathies with onion-bulbs.

By immunochemically and ultrastructurally identifying cellular components of onion-bulbs (Obs), this study attempts to delineate and classify types of hypertrophic neuropathies which are otherwise obscured by proliferation of the morphologically similar cells forming Obs. Fourteen cases with different forms of chronic localized or generalized hypertrophic neuropathy with Obs were retrospectively studied to include: one Dejerine-Sottas (D-S); two Charcot-Marie-Tooth (CMT); three chronic inflammatory demyelinating polyneuropathy (CIDP); one inflammatory localized hypertrophic mononeuritis (LHM); two perineuriomas (PNM); one traumatic amputation neuroma (TAN); one chronic diabetic neuropathy (CDN); two neurofibromas (NF); and one chronic arsenic polyneuropathy (AsPN). By immunostaining with 7 selected antibodies, we can distinguish at least 4 nosologically distinct types of neuropathy by identifying cellular components of given Obs: 1) primarily Schwann cells with no perineurial cells or macrophages in CMT or D-S, 2) predominantly Schwann cells, activated macrophages and a few fibroblasts in CIDP and LHM, 3) primarily perineurial and a few central Schwann cells with no macrophages in PNM and TAN, and 4) exclusively perineurial cells in the hamartomatous PNM associated with NF.

Adolescent↗
PubMed1991

Purification and primary structure of C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, from Streptomyces globisporus.

C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, was isolated by column chromatography on DEAE-cellulose, butyl-Toyopearl and Sephadex G-50 from a culture filtrate of Streptomyces globisporus. The amino acid sequence of purified C-1027-AG was determined with a protein sequencer on the basis of fragment peptides obtained by enzymatic hydrolysis with lysylendopeptidase, V8 protease, endopeptidase AspN and chymotrypsin, after performic acid oxidation. C-1027-AG is shown to consist of a single polypeptide chain cross-linked by two disulfide bonds, and to contain a total of 110 amino acid residues with alanine and glycine as its amino- and carboxyl-termini, respectively; its molecular weight was calculated to be 10,500 daltons. The primary structure of C-1027-AG is indicated to be identical to the protein moiety of C-1027, and is highly homologous to the sequences of antitumor proteins obtained from other Streptomyces species.

Amino Acid Sequence↗