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PubMed2026

Exploring shared biomarkers and their mechanisms in thyroid cancer and systemic lupus erythematosus via bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE), an autoimmune disorder, is linked to a heightened risk of multiple malignancies, including thyroid cancer. Thyroid cancer is the most prevalent malignancy of the endocrine system, and its autoimmune-related pathological features render it an optimal subject for investigating the mechanisms of their comorbidity. The molecular mechanisms underlying this comorbidity are still ambiguous. The accurate diagnosis and treatment of thyroid cancer urgently necessitate innovative molecular targets that extend beyond conventional pathological characteristics. This study seeks to employ integrated bioinformatics approaches to elucidate potential shared molecular mechanisms and immunological features between thyroid cancer and systemic lupus erythematosus (SLE), aiming to enhance understanding of their comorbidity and identify novel intervention targets. METHODS: This study initially acquired gene expression data for TC and SLE from the GEO database and subsequently screened and identified differentially expressed genes (DEGs) shared by both diseases. Subsequently, we conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome functional enrichment analyses on these 46 shared differentially expressed genes (DEGs) and further assessed the activation status of pertinent pathways using Gene Set Enrichment Analysis (GSEA). Subsequently, we employed CIBERSORTx to examine immune infiltration patterns and developed protein-protein interaction networks utilising the STRING database. We identified hub genes utilising the MCODE and cytoHubba plugins and visualised the findings with Cytoscape software. We additionally assessed the diagnostic efficacy of these core hub genes in an independent dataset utilising ROC curves and investigated their prognostic relevance in thyroid cancer through Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. Ultimately, we employed the Network Analyst platform to forecast transcription factor-gene and miRNA-gene regulatory networks and identified potential targeted therapeutic compounds utilising the DSigDB database. RESULTS: This study identified 46 differentially expressed genes (DEGs) commonly linked to thyroid cancer and systemic lupus erythematosus (SLE), which were significantly enriched in signalling pathways associated with immune-inflammatory activation, type I interferon responses, and complement pathway activation. Moreover, GSEA findings validated that immune-inflammatory and autoimmune-related pathways are markedly activated in both conditions. Twelve hub genes were discerned through protein-protein interaction networks. Analysis of immune infiltration indicated that thyroid cancer and systemic lupus erythematosus exhibit a shared characteristic of innate immune dysregulation, marked by the infiltration of myeloid cells (neutrophils, M0/M2 macrophages). Receiver operating characteristic (ROC) curve analysis identified six significant core hub genes with substantial diagnostic value: C1QB, LCN2, C1QC, LTF, VSIG4, and C3AR1. Univariate survival analysis indicated that elevated expression of C1QC and C3AR1 significantly enhances overall survival in thyroid cancer patients; however, multivariate COX regression analysis revealed that their independent prognostic significance necessitates further validation. This study predicted the interaction networks of transcription factors and miRNAs regulating key genes, with LCN2 demonstrating the highest connectivity to miRNAs, and identified candidate therapeutic compounds linked to it. CONCLUSION: This study employed bioinformatics analysis to identify critical shared hub genes and molecular pathways connecting thyroid cancer and systemic lupus erythematosus, offering novel insights into their shared pathogenesis and the advancement of targeted biomarkers and therapeutic strategies.

Bioinformatics analysis↗

PubMedDate not supplied

Internet-based support for bioscience research: a collaborative genome center for human chromosome 12.

This paper describes an approach that provides Internet-based support for a genome center to map human chromosome 12, as a collaboration between laboratories at the Albert Einstein College of Medicine in Bronx, New York, and the Yale University School of Medicine in New Haven, Connecticut. Informatics is well established as an important enabling technology within the genome mapping community. The goal of this paper is to use the chromosome 12 project as a case study to introduce a medical informatics audience to certain issues involved in genome informatics and in the Internet-based support of collaborative bioscience research. Central to the approach described is a shared database (DB/12) with Macintosh clients in the participating laboratories running the 4th Dimension database program as a user-friendly front end, and a Sun SPARCstation-2 server running Sybase. The central component of the database stores information about yeast artificial chromosomes (YACs), each containing a segment of human DNA from chromosome 12 to which genome markers have been mapped, such that an overlapping set of YACs (called a "contig") can be identified, along with an ordering of the markers. The approach also includes 1) a map assembly tool developed to help biologists interpret their data, proposing a ranked set of candidate maps, 2) the integration of DB/12 with external databases and tools, and 3) the dissemination of the results. This paper discusses several of the lessons learned that apply to many other areas of bioscience, and the potential role for the field of medical informatics in helping to provide such support.

Chromosome Mapping↗

PubMed2001

An open, component-based information infrastructure to support integrated regional healthcare networks.

A fundamental requirement for achieving continuity of care is the seamless sharing of multi-clinical information. Several different technological approaches can be followed to enable the sharing of health record segments. In all cases interoperability between systems is a prerequisite and this requires presently a major technological challenge. Inter-operability can be achieved either through messages or through a more advanced approach based on a federation of autonomous systems. Message based integration is centered mainly on the exchange of HL7 and DICOM messages for achieving the functional integration of clinical information systems (CIS) at institutional or regional level. The federated approach is principally used for facilitating the virtual view of the Integrated Electronic Health Record (I-EHR), without having to replicate unnecessary information. Within the context of HYGEIAnet, which is the regional health telematics network of Crete, both approaches have been utilized for providing end users with seamless access to clinical information. Both are based on an open architecture, which provides the framework for the reuse of standardized common components and public interfaces. This work presents the experiences related to the implementation of "messaging" and "federating" in HYGEIAnet, which are used complementary to each other. A comparison of the two parallel approaches, together with their strengths and weaknesses is described, and evaluation is given from the technological as well as the end users' perspective. Emphasis is given on the technological challenges in developing open, component-based information infra-structure to support integrated service delivery.

Computer Communication Networks↗

PubMed2006

Injury prevention in child and adolescent sport: whose responsibility is it?

OBJECTIVE: Sport and recreational injuries are a leading cause of morbidity in youth. There is a significant body of literature on risk factors for sport-related injuries and a growing body of research supporting the effectiveness of sport-specific prevention strategies in youth. Given the predictability and preventability of injuries in youth sport, the purpose of this article is to develop a model that considers societal responsibility for injury prevention in youth sport, and to discuss the evidence that supports this model. DATA SOURCES/SYNTHESIS: Previously published papers have provided a basis for expert opinion to discuss an approach to examining the shared societal responsibility for implementing countermeasures to reduce the risk of injury to youth during sports. RESULTS: Based on a historical perspective, broad conceptual framework, and specific evidence for prevention strategies in youth sport, the authors have developed and supported a theoretical model that defines a responsibility hierarchy in preventing injuries in youth sport. An argument has been made for a hierarchy of responsibility, with the lowest level of responsibility assigned to the child, and the highest level to those organizations or groups with the potential to effect the most change. The justification for this approach has been discussed in the context of the desirability of passive prevention strategies, the limited evidence for the effectiveness of strategies relying solely on behavior change in children and parents, and the level of perceptual and cognitive development in children that inadequately prepares them to take primary responsibility for their own safety in sport. CONCLUSIONS: The development of effective programs to reduce the burden of sport injury among youth necessitates a scientific approach, the identification of key risk factors for injury, a thorough examination of how factors interact to affect risk, and the identification of potential barriers to the effectiveness of injury-prevention programs.

Athletic Injuries↗

PubMed2002

Pilot study of a utilities-based treatment decision intervention for prostate cancer patients.

This pilot study evaluates a shared decision-making approach to individual decision making in localized prostate cancer care. The approach is based on a decision analytic model that incorporates patient utilities, ie, patient preferences among possible health states that might occur with prostate cancer treatments. Data on comorbidities, histologic grade of the biopsy, and age were obtained for 13 patients with newly diagnosed localized prostate cancer who received care in a Veterans Administration medical center. Using a standard gamble technique, interviewers obtained patient utilities for 5 distinct health states related to prostate cancer treatment. Utilities and patient clinical and pathologic characteristics were incorporated into the decision analytic model, and the derived quality-adjusted life expectancies were shared with the treating urologist before the first patient-physician discussion about treatment options. The results of the pilot study raised 2 major concerns. First, 4 patients had utility scores of 1.0 for all of the possible health states, and 7 patients had inconsistent utilities in which they rated both impotence and incontinence as a better health state than having just one of these problems. Second, the model recommended radiation therapy to individuals with a broad range of clinical characteristics, pathologic findings, and utility scores. Many of the patients who were recommended radiation therapy by the model received discordant recommendations from the treating urologist. Future refinements of both the utility assessment exercise and decision analytic model may be needed before the feasibility of the model in the clinical setting can be determined.

Aged↗

PubMed1996

Feminist bioethics: toward developing a "feminist" answer to the surrogate motherhood question.

Although a wide variety of feminist approaches to bioethics presently share a common feminist methodology (sometimes referred to as "raising the woman question"), they do not all share the same feminist politics, ontology, epistemology, and ethics. As a result of their philosophical differences, feminist bioethicists do not always agree on which biomedical principles, practices, and policies are best suited to serving women's interests. In other words, some feminist bioethicists insist that so-called "assisted reproduction" enhances women's procreative liberty, while others claim that it does nothing of the sort. Although such disagreement among feminist bioethicists reassures the general public that the feminist "program" for bioethics is not ideologically monolithic, it also confuses the public, especially women. In order to overcome this confusion, feminist bioethicists should work toward developing the kind of shared theoretical base that will foster frequent consensus on the biomedical principles, practices, and policies most likely to serve the interests of most women in the U.S. today.

Bioethical Issues↗

PubMed2002

An open, component-based information infrastructure for integrated health information networks.

A fundamental requirement for achieving continuity of care is the seamless sharing of multimedia clinical information. Different technological approaches can be adopted for enabling the communication and sharing of health record segments. In the context of the emerging global information society, the creation of and access to the integrated electronic health record (I-EHR) of a citizen has been assigned high priority in many countries. This requirement is complementary to an overall requirement for the creation of a health information infrastructure (HII) to support the provision of a variety of health telematics and e-health services. In developing a regional or national HII, the components or building blocks that make up the overall information system ought to be defined and an appropriate component architecture specified. This paper discusses current international priorities and trends in developing the HII. It presents technological challenges and alternative approaches towards the creation of an I-EHR, being the aggregation of health data created during all interactions of an individual with the healthcare system. It also presents results from an ongoing Research and Development (R&D) effort towards the implementation of the HII in HYGEIAnet, the regional health information network of Crete, Greece, using a component-based software engineering approach. Critical design decisions and related trade-offs, involved in the process of component specification and development, are also discussed and the current state of development of an I-EHR service is presented. Finally, Human Computer Interaction (HCI) and security issues, which are important for the deployment and use of any I-EHR service, are considered.

Abstracting and Indexing↗

PubMed2002

Use of measures of disproportionality in pharmacovigilance: three Dutch examples.

Spontaneous reporting systems for suspected adverse drug reactions (ADRs) remain a cornerstone of pharmacovigilance. In The Netherlands 'the Netherlands Pharmacovigilance Foundation Lareb' maintains such a system. A primary aim in pharmacovigilance is the timely detection of either new ADRs or a change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case by case analysis or qualitative signal detection) is becoming time consuming given the increasingly large number of data, as well as less effective, especially in more complex associations such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic that they express to what extent the number of observed cases differs from the number of expected cases. In this paper three Dutch examples are described in which a measure of disproportionality is used in quantitative signal detection in pharmacovigilance: (i) the association between antidepressant drugs and the occurrence of non-puerpural lactation as an example of an association between a single drug and a single event; (ii) the onset or worsening of congestive heart failure associated with the combined use of nonsteroidal anti-inflammatory drugs and diuretics as an example of an association between two drugs and a single event (drug-drug interaction); and the (iii) (co)-occurrence of fever, urticaria and arthralgia and the use of terbinafine as an example of an association between a single drug and multiple events (syndrome). We conclude that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance. More research is necessary into the performance of these approaches, especially its predictive value, its robustness as well as into further extensions of the methodology.

Adverse Drug Reaction Reporting Systems↗

PubMed1994

Computation of identity-by-descent proportions shared by two siblings.

I provide a novel approach to computing the mean and variance of the proportion of genetic material shared identical by descent (IBD) by sibling pairs in a specified chromosomal region, conditional on observed marker data. I first show that each chromosome in an offspring can be represented by a two-state Markov chain, with the time parameter being the map distance along the chromosome. On this basis, I show that IBD proportion can be written as a stochastic integral and that the computation of its mean and variance can be reduced to evaluation of an integral of some elementary functions. In addition, I show how Goldgar's model can be extended to include dominance effects. Several examples are provided to illustrate the calculation.

Analysis of Variance↗

PubMedDate not supplied

[Bronchial asthma and allergic rhinitis: a new therapeutic challenge. Disfunction co-morbidities--shared therapies?].

More and more it is spoken about this morbid association between asthma and allergic rhinitis; this two diseases are interconnected but were often distinctly approached over time. Anyway, they share interesting pathogenic and therapeutic features. The current article reviews epidemiologic data, pathogenic mechanisms, common actions as well as common elements coming from experimental medicine, everything pleading for a new concept, "one airway" or "Combined Allergic Rhinitis and Asthma Syndrome". From here we can also draw conclusions marking new therapeutic directions where anti- leukotrienes often prove to be useful.

Acetates↗

PubMed2004

'Add women & stir'--the biomedical approach to cardiac research!

In conditions shared by women and men, the biomedical model of disease assumes that illness-symptoms and outcomes are biologically and socially 'neutral'. Consequently, up until a decade ago, white middle-aged men were the model subjects in most funded cardiac trials, with the assumption that whatever the findings, the results would also hold true for women. This 'add women and stir' approach has resulted in imbalances in cardiac care and an image of coronary artery disease, which portrays a middle-aged male as its victim. Moreover, cardiac health care has been designed with the male anatomy and male experience of illness in mind, and health promotional measures have been targeted towards men. Women have received these health promotional messages to protect the hearts of men, and have been less likely to modify their own lifestyles in a cardio-protective manner. However, the biological and social differences that exist between women and men, must surely invalidate such biased biomedical assertions, and signify a need to delve beyond the realm of biomedical reductionism for greater insights and understanding. This review examines how scientific reductionism has failed to explore the impact of coronary artery disease on the lives of women and how the gendered image of this disease has privileged the normative frame.

Attitude to Health↗

PubMed1995

Shared risk factors for falls, incontinence, and functional dependence. Unifying the approach to geriatric syndromes.

OBJECTIVE: To determine whether a set of factors representing impairments in multiple areas could be identified that predisposes to falling, incontinence, and functional dependence. DESIGN: Population-based cohort with a 1-year follow-up. SETTING: General community. PARTICIPANTS: A total of 927 New Haven, Conn, residents, aged 72 years and older who completed the baseline and 1-year interviews. MAIN OUTCOME MEASURES: At least one episode of urinary incontinence per week, at least two falls during the follow-up year, and dependence on human help for one or more basic activities of daily living. RESULTS: At 1 year, urinary incontinence was reported by 16%, at least two falls by 10%, and functional dependence by 20% of participants. The four independent predisposing factors for the outcomes of incontinence, falling, and functional dependence included slow timed chair stands (lower extremity impairment), decreased arm strength (upper extremity impairment), decreased vision and hearing (sensory impairment), and either a high anxiety or depression score (affective impairment). There was a significant increase in each of incontinence, falling, and functional dependence as the number of these predisposing factors increased. For example, the proportion of participants experiencing functional dependence doubled (7% to 14% to 28% to 60%) (chi 2 = 119.8; P < .001) as the number of predisposing factors increased from zero to one to two at least three. CONCLUSIONS: Our findings suggest that predisposition to geriatric syndromes and functional dependence may result when impairments in multiple domains compromise compensatory ability. It may be possible to restore compensatory ability and prevent or delay the onset of several geriatric syndromes and, perhaps, functional dependence by modifying a shared set of predisposing factors. Perhaps it is time to take a more unified approach to the geriatric syndromes and functional dependence.

Accidental Falls↗

PubMed1999

Association tests using unaffected-sibling versus pseudo-sibling controls.

We used family-matched case-control data to screen the genome for markers associated with disease in the simulated data set. Two different types of controls were considered: (1) unaffected siblings and (2) 'pseudo siblings,' a comparison sample created using the parental alleles. The scans were conducted on the first replicate of each study population. Overall, the two methods identified 14 marker loci associated with disease at the 0.001 significance level. Marker D1G24 (locus D) was the only true disease locus found by both approaches. No associations were found at any of the markers flanking the unobserved disease susceptibility loci (A, B, or C). We subsequently pooled the 25 replicates from a single population. This large sample still did not yield any associations at the flanking markers. We tested for association at locus D using a pseudo-sib approach restricted to alleles shared identical by descent between affected sib pairs. The power was 44% (11/25 replicates) at a significance level of 0.001.

Alleles↗

PubMedDate not supplied

Transdisciplinary approach: an atypical strategy for improving outcomes in rehabilitative and long-term acute care settings.

In the rehabilitation and long-term acute care settings, an atypical strategy has emerged in the past few years whereby the central focus is on improving patient care through a team approach in which responsibilities are shared and the normal boundaries of the healthcare professions blurred. This article provides a conceptual analysis of this unique, transdisciplinary approach to care delivery. Differentiation between interdisciplinary, multidisciplinary, and transdisciplinary techniques is provided through case scenarios. Defining attributes, necessary antecedents, and the many possible positive outcomes from the transdisciplinary approach to practice is discussed. This concept analysis defines for the rehabilitation or long-term acute care nurse a method that can be used to redesign care delivery, to promote improved patient outcomes, and to achieve a cohesive team environment.

Arrhythmias, Cardiac↗

PubMed2003

KLF5/BTEB2, a Krüppel-like zinc-finger type transcription factor, mediates both smooth muscle cell activation and cardiac hypertrophy.

Cardiac and vascular biology need to be approached interactively because they share many common biological features as seen in activation of the local renin-angiotensin system, angiogenesis, and extracellular matrix production. We previously reported KLF5/BTEB2, a Krüppel-like zinc-finger type transcription factor, to activate various gene promoters that are activated in phenotypically modulated smooth muscle cells, such as a nonmuscle type myosin heavy chain gene SMemb, plasminogen activator inhibitor-1 (PAI-1), iNOS, PDGF-A, Egr-1 and VEGF receptors at least in vitro. KLF5/BTEB2 mRNA levels are downregulated with vascular development but upregulated in neointima that is produced in response to vascular injury. Mitogenic stimulation activates KLF5/BTEB2 gene expression through MEK1 and Egr-1. Chromatin immunoprecipitation assay showed KLF5/BTEB2 to be induced and to bind the promoter of the PDGF-A gene in response to angiotensin II stimulation. In order to define the role of KLF5/BTEB2 in cardiovascular remodeling, we targeted the KLF5/BTEB2 gene in mice. Homozygous mice resulted in early embryonic lethality whereas heterozygous mice were apparently normal. However, in response to external stress, arteries of heterozygotes exhibited diminished levels of smooth muscle and adventitial cell activation. Furthermore, cardiac fibrosis and hypertrophy induced by continuous angiotensin II infusion. We also found that RARa binds KLF5/BTEB2, and that Am80, a potent synthetic RAR agonist, inhibits angiotensin II-induced cardiac hypertrophy. These results indicate that KLF5/BTEB2 is an essential transcription factor that causes not only smooth muscle phenotypic modulation but also cardiac hypertrophy and fibrosis.

Angiotensin II↗

PubMed1993

Tolerizing mice to human leukocytes: a step toward the production of monoclonal antibodies specific for human dendritic cells.

Despite several attempts to isolate a mAb specific for human dendritic cells, none currently exists. Recent attempts have utilized an improved dendritic cell purification method to prepare immunogens and a rapid two-color flow cytometric screening procedure that allows large numbers of hybridoma supernatants to be examined in each fusion. Yet these improvements have also failed, yielding only hybridomas that bind "shared" antigens expressed by both dendritic cells and other leukocytes. Dendritic cells express many shared antigens, including CD45 [leukocyte common antigen], CD40, leukocyte [beta 2] integrins CD11a and CD11c, CD54 [ICAM-1], CD44 [Pgp-1], CD58 [LFA-3], and the B7/BB1 antigen. Therefore, we are attempting to bias the immune response toward rarer, dendritic cell-specific clones by tolerizing or immunosuppressing our animals to shared antigens. In one approach, adult mice held in barrier cages are injected with "nondendritic" cells and cyclophosphamide [CP], in order to ablate responding "nonspecific" B cell clones. Fifteen days after the last dose of CP, they are challenged with nondendritic cells. A week later they are bled, and serum antibody titers against nondendritic cells are determined by FACS, in order to demonstrate tolerance compared to controls injected with CP alone. In the second approach, neonatal mice are injected with human T lymphoblasts at birth, followed by boosting at 1 week. In adulthood, they are challenged sequentially with sheep erythrocytes [sRBC], then with T blasts, to demonstrate that they can respond to unrelated cells but not to tolerogenic cells. One week after each kind of challenge, mice are bled and serum antibody levels are determined for treated and sham-injected mice. When these two approaches were compared, CP led only to nonspecific immunosuppression, while neonatal injections produced selective, antigen-specific nonresponsiveness to the tolerizing T blasts.

Animals↗

PubMed2006

Parenting interventions for children with autism spectrum and disruptive behavior disorders: opportunities for cross-fertilization.

Empirical support exists for parent training/education (PT/PE) interventions for children with disruptive behavior disorders (DBD) and autism spectrum disorders (ASD). While the models share common roots, current approaches have largely developed independently and the research findings have been disseminated in two different literature traditions: mental health and developmental disabilities. Given that these populations often have overlapping clinical needs and are likely to receive services in similar settings, efforts to integrate the knowledge gained in the disparate literature may be beneficial. This article provides a systematic overview of the current (1995-2005) empirical research on PT/PE for children with DBD and ASD; attending to factors for cross-fertilization. Twenty-two ASD and 38 DBD studies were coded for review. Literature was compared in three main areas: (1) research methodology, (2) focus of PT/PE intervention, and (3) PT/PE procedures. There was no overlap in publication outlets between the studies for the two populations. Results indicate that there are opportunities for cross-fertilization in the areas of (1) research methodology, (2) intervention targets, and (3) format of parenting interventions. The practical implications of integrating these two highly related areas of research are identified and discussed.

Autistic Disorder↗

PubMed2006

Reproductive performance in infertile women with rectovaginal endometriosis: is surgery worthwhile?

OBJECTIVE: This study was undertaken to ascertain whether the incidence of pregnancy is increased and time-to-conception is reduced in infertile women with rectovaginal endometriosis undergoing conservative surgery compared with those on expectant management. STUDY DESIGN: A total of 105 infertile women under the age of 40 years with rectovaginal endometriosis and no other associated major infertility factor underwent first-line conservative surgery at laparotomy or expectant management according to a shared decision-making approach. RESULTS: Among the 44 women who had resection of rectovaginal endometriosis, 15 became pregnant, compared with 22 of the 61 women who choose expectant management (24-month cumulative probabilities, 44.9% and 46.8%, respectively; log-rank test, chi2(1) = 0.75; P = .38). One major and 9 minor postoperative complications occurred. Significant differences in pain-free survival time in favor of the surgery group were observed for dysmenorrhea, dyspareunia, and dyschezia. CONCLUSION: Conservative surgery for rectovaginal endometriosis in infertile women does not modify the reproductive prognosis although it does increase pain-free survival time.

Adult↗