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At least 577 records · Page 32Linked to original sources
PubMed2026

Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.

BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to the central nervous system (CNS). While thyroid-stimulating hormone receptor (TSHR) is the primary driver of pathological remodeling in the thyroid and orbital tissues, emerging evidence suggests it is also expressed in the brain and may participate in neuroimmune signaling. However, the molecular mechanisms linking peripheral TSHR-driven autoimmunity to these extended systemic features remain unclear. Thus, GD and GO provide a unique window to investigate how peripheral autoantibodies influence CNS involvement as part of its broader pathological spectrum. METHODS: Genome-wide association studies (GWAS) and post-GWAS analyses were integrated with bulk RNA sequencing, single-cell and spatial transcriptomics, and brain imaging phenotypes to comprehensively characterize peripheral and central alterations in GD and GO. Mendelian randomization was applied to test causal relationships between genetic variants and brain signatures. Structural biology analyses were further conducted including protein-protein docking, small-molecule docking, and normal mode dynamics to identify prospective modulators of TSHR. Immunofluorescence staining was performed in a GO mouse model to validate the colocalization of potential interacted proteins in the specific brain region. RESULTS: Brain imaging-derived phenotypes (IDPs) alterations in GO and GO were systematically analyzed to identify neuroanatomical and functional alterations. TSHR was further identified as a shared genetic driver across peripheral and central compartments. TSHR was expressed in spiny projection neurons, microglia, and peripheral T cells, with cell-cell communication analyses highlighting TSHR-mediated interactions among neurons, endothelial cells, and microglia. Immunofluorescence staining in a GO mouse model confirmed the colocalization of TSHR with FN1 and GNAS in the basal ganglia, providing tissue-level validation of the computationally predicted ligand-receptor interactions. Immune profiling further showed immune alterations in GD and GO. Structural modeling supported plausible physical interfaces between TSHR and interacting proteins, and small-molecule screening identified three repurposable compounds - venetoclax, irinotecan, and dutasteride - with predicted favorable docking scores and stable binding poses in our simulations. CONCLUSIONS: These findings demonstrate that TSHR acts as a molecular hub mediating peripheral-central neuroimmune crosstalk in GD and GO. The results support a broader "disease-molecule axis" framework that links genetic susceptibility with multi-level immune and neural mechanisms. This work provides mechanistic insights relevant to the development of TSHR-targeted therapies, with implications for both peripheral immune modulation and central regulation. However, the limited sample size, lack of longitudinal follow-up, and absence of in vivo validation warrant cautious interpretation and further investigation.

Receptors, Thyrotropin↗
PubMed2003

Clinical team functioning and IT innovation: a study of the diffusion of a point-of-care online evidence system.

OBJECTIVES: To investigate the association between clinical team functioning and diffusion (awareness, use, and impact) of a 24-hour online evidence retrieval system. To examine the relationships between clinical team characteristics and the adoption of the online evidence system. DESIGN: 18 clinical teams, consisting of 180 clinicians from three Australian hospitals, were identified and studied. Teams were categorized as small ( 15). MEASUREMENTS: Clinical team functioning was assessed using the Team Climate Inventory (TCI). Awareness, use, and impact of an online evidence retrieval system were measured using a self-administered questionnaire. The relationships between TCI scores and awareness, use, and impact were examined using t-tests and one-way ANOVAs. Chi square analyses were used to examine differences between small and large teams. RESULTS were interpreted within a diffusion of innovations framework. RESULTS: Clinical team functioning was not related to awareness or use of the online evidence retrieval system. However, clinical team functioning was significantly associated with the impact of online evidence in terms of reported experience of improved patient care following system use. Clinicians in small teams ( 15) teams. CONCLUSIONS: Team functioning had the greatest impact on the fourth stage of innovation diffusion, the effective use of online evidence for clinical care. This supports Rogers' diffusion of innovation theory, to the effect that different types of communication about an innovation are important at different stages in the diffusion process. Members of small teams were more aware of the system than members of large teams. Team functioning is amenable to improvement through interventions. The findings suggest that the role of team climate in the diffusion of information systems is a promising area for future research.

Analysis of Variance↗
PubMed2005

[Development and testing of a sexually transmitted diseases prevention program in at-risk prostitutes].

PURPOSE: The purpose of the study was to test the effectiveness of an 8 session intervention program to prevent sexually transmitted diseases (STDs) among at-risk prostitutes. METHOD: An experimental research design was employed. Subjects were 59 prostitutes (29 in the control group and 30 in the experimental group) who agreed to participate in this study. An STD Prevention Framework derived from Cox's Interaction Model of Client Health Behavior guided the overall intervention and the components. The intervention had 8 sessions with STD-prevention strategies and was led by Public Health Nurses. Analysis included change scores, chi(2)-test, and t-test. RESULT: The results revealed significant increase in feelings and skills of condom use, peer belief on condom use, condom use practice, and satisfaction with service at public health centers (PHC) on STDs knowledge and skills in the experimental group. However, newly contracted STDs were not significant statistically between groups. CONCLUSION: The 8 session STDs prevention program showed a effect on emotions, skills and behaviors of condom use even with the limitation of methodological rigors because of subject-specific conditions. In the future, a capacity-building model based on collaborating networks among community-based organizations will be needed to develop in effective STDs prevention.

Adult↗
PubMed2004

Characterizing alterations in executive functioning across distinct subtypes of cortical and subcortical dementia.

Differential patterns of executive function deficits (EFD) exist in cortical and subcortical dementia; however, little work exists attempting to integrate these findings into a conceptual framework. The current study aimed to characterize EFD in cortical and subcortical dementia. Patients with Alzheimer's disease (AD; n = 65), subcortical ischemic vascular dementia (IVD; n = 64), or Parkinson's disease with dementia (dPD; n = 21) completed a variety of measures purported to require executive systems. We extracted variables of interest from measures shown in a growing body of literature to be associated with EFD in dementia. These measures included the Boston Revision of the WMS Mental Control subtest, letter fluency, WAIS-R Similarities subtest, CVLT, the Graphical Sequence Test-Dementia version, and Clock Drawing. When submitted to a PCA with varimax rotation, these variables produced a four-component solution (62% of the variance). Component 1 appeared to reflect adequacy of working memory, Component 2 irrelevant or context nonspecific interference, Component 3 reflected response preparation and Component 4 relevant or context-specific interference. Post hoc analyses of z-transformed composite scores revealed that AD differentially affected context-specific interference, IVD and dPD disrupted working memory and response preparation while IVD differentially affected context non-specific interference. EFD in dementia can be divided into specific components that are differentially impaired by cortical and subcortical dementias. Implications for an overall conceptual framework of EFD in dementia are discussed.

Aged↗
PubMed1995

Genetic mapping of adrenergic receptor genes in humans.

We have genetically mapped the genes encoding four human adrenergic receptors (ARs) of subtypes alpha 1C, alpha 2A, alpha 2B, and beta 1, which are prototypic G protein coupled receptors that mediate the physiological effects of neurotransmitters, hormones, and drugs. We placed these genes onto the Cooperative Human Linkage Center (CHLC) and Genethon framework maps, within confidence intervals with greater than 1000:1 odds. With multipoint analysis the alpha 1C gene (locus ADRA1C) mapped to the interval between NEFL and D8S283; alpha 2-C4, the gene encoding the alpha 2C AR (locus ADRA2C), mapped to the interval between D4S126 and D4S62; and the alpha 2-C10 (alpha 2A AR)/beta 1 haplotype (loci ADRA2A/ADRB1) mapped to the interval between D10S259 and D10S187. A fifth AR gene, beta 2, yielded significant LOD scores with markers on the long arm of chromosome 5; however, this locus (ADRB2) could not be mapped to any specific interval with odds of greater than 1000:1. The two AR genes that are completely linked, alpha 2-C10 and beta 1, were oriented on their shared 225-kb genomic fragment relative to the direction of transcription, with beta 1 being 5' to alpha 2-C10. The positioning of these genes on high-density framework maps allows them to be tested as candidates in a spectrum of diseases that might involve AR dysfunction.

Base Sequence↗
PubMed2002

A framework for evidence-adaptive quality assessment that unifies guideline-based and performance-indicator approaches.

Automated quality assessment of clinician actions and patient outcomes is a central problem in guideline- or standards-based medical care. In this paper we describe a unified model representation and algorithm for evidence-adaptive quality assessment scoring that can: (1) use both complex case-specific guidelines and single-step population-wide performance-indicators as quality measures; (2) score adherence consistently with quantitative population-based medical utilities of the quality measures where available; and (3) give worst-case and best-case scores for variations based on (a) uncertain knowledge of the best practice, (b) guideline customization to an individual patient or particular population, (c) physician practice style variation, or (d) imperfect reliability of the quality measure. Our solution uses fuzzy measure-theoretic scoring to handle the uncertain knowledge about best-practices and the ambiguity from practice variation. We show results of applying our method to retrospective data from a guideline project to improve the quality of hypertension care.

Algorithms↗
PubMed1993

Linkage localization of TGFB2 and the human homeobox gene HLX1 to chromosome 1q.

We have identified genetic variation within two human genes, transforming growth factor-beta 2 (TGFB2) and the homeobox gene HB24 (HLX1). Reported here are four human RFLPs and SSCPs for TGFB2 in humans and gorillas. In addition, we describe an RFLP and a SSCP for HLX1. We propose that HLX1 is the human homologue of the mouse homeobox gene Hlx based on extensive sequence homology between the genes and the close proximity of both genes to TGFB2 in their respective species. We also report the chromosomal localization of HLX1 to the long arm of human chromosome 1. Finally, utilizing the polymorphisms described for TGFB2 and HLX1, we have been able to localize these genes within a framework map of the distal long arm of chromosome 1 and to study the linkage relationship between these two genes. Pairwise linkage analysis shows that these two genes are linked, with a recombination fraction of 3.1% and a lod score of 14.49.

Amino Acid Sequence↗
PubMed1993

A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21.

The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids (approximately 90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays(8000). Likelihood ratios of at least 1000:1 support the 10-locus framework order: cen-D17S250-ERBB2-(THRA1, TOP2A)-D17S855-PPY-D17S190-MTBT1-GP3A++ +-BTR-D17S588-tel. The order obtained from RH mapping, when used in conjunction with other methods, will be useful in linkage analysis of breast cancer families and will facilitate the development of a physical map of this region.

Base Sequence↗
PubMed2002

Post-extubation stridor in intensive care unit patients. Risk factors evaluation and importance of the cuff-leak test.

OBJECTIVE: To evaluate the incidence and identify factors associated with the occurrence of post-extubation stridor and to evaluate the performance of the cuff-leak test in detecting this complication. DESIGN: Prospective, clinical investigation. SETTING: Intensive care unit of a university hospital. PATIENTS: Hundred twelve extubations were analyzed in 112 patients during a 14-month period. INTERVENTION: A cuff-leak test before each extubation. MEASUREMENTS AND RESULTS: The incidence of stridor was 12%. When we chose the thresholds of 130 ml and 12% to quantify the cuff-leak volume, the sensitivity and the specificity of the test were, respectively, 85% and 95%. The patients who developed stridor had a cuff leak significantly lower than the others, expressed in absolute values (372+/-170 vs 59+/-92 ml, p<0.001) or in relative values (56+/-20 vs 9+/-13%, p<0.001). Stridor was associated with an elevated Simplified Acute Physiology Score (SAPS II), a medical reason for admission, a traumatic or difficult intubation, a history of self-extubation, an over-inflated balloon cuff at admission to ICU and a prolonged period of intubation. These results provide a framework with which to identify patients at risk of developing a stridor after extubation. CONCLUSION: A low cuff-leak volume (<130 ml or 12%) around the endotracheal tube prior to extubation is useful in identifying patients at risk for post-extubation stridor.

Airway Obstruction↗
PubMed2026

Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.

abundance estimation↗
PubMed1996

Relationship of social roles and nutrition beliefs to fat avoidance practices: investigation of a US model among Danish women.

OBJECTIVE: This study was designed to investigate the associations among women's social roles, their nutrition beliefs, and their dietary fat avoidance practices. Role theory and prior qualitative research among US women provided the theoretical framework. DESIGN/SUBJECTS: A random-sample mail survey (76% response) was used to gather information on the usual pattern of dietary fat use, nutrition beliefs, and social positions of Danish women aged 30 to 60 years. A fat avoidance score was calculated for each respondent on the basis of 12 fat consumption practices. Sequential multiple linear regression was used to develop an explanatory model for fat avoidance using responses from 594 women. RESULTS: Interactions between nutrition attitudes and beliefs and social roles suggested that the roles themselves did not influence fat avoidance practices, but the nutrition beliefs associated with particular roles did have an influence. Among employed women, fat avoidance was lower among those who perceived many barriers to healthful eating. Among women who were not employed, fat avoidance was lower among those who perceived little social support for healthful eating. The association of fat avoidance with caretaking responsibility varied by age group. Caretaking was positively associated with fat avoidance among women in their forties, but not in older or younger age groups. CONCLUSIONS: Nutrition messages should be tailored to fit women's unique social roles and the beliefs associated with them. Nutrition professionals in Denmark and the United States can adapt these findings to their own cultural context.

Adult↗
PubMed2001

Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy.

PURPOSE: To introduce the concept of pseudo beam's-eye-view (pBEV), to establish a framework for computer-assisted beam orientation selection in intensity-modulated radiation therapy (IMRT), and to evaluate the utility of the proposed technique. METHODS AND MATERIALS: To facilitate the selection of beam orientations for IMRT treatment planning, a scoring of beam direction was introduced. The score function was based on the maximum target dose deliverable by the beam without exceeding the tolerance doses of the critical structures. For the score function calculation, the beam portal at given gantry and couch angles was divided into a grid of beamlets. Each beamlet crossing the target was assigned the maximum intensity that could be used without exceeding the dose tolerances of the organs at risk (OARs) and normal tissue. Thereafter, a score was assigned to the beam according to the target dose delivered. The beams for the treatment were selected among those with the highest scores. In a sense, this technique is similar to the beam's-eye-view approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function, and beam modulation is taken into account. RESULTS: The pBEV technique was tested on two clinical cases: a paraspinal treatment and a nasopharyngeal cancer with both coplanar and noncoplanar beam configurations. The plans generated under the guidance of pBEV for the paraspinal treatment offered superior target dose uniformity and reduced OAR doses. For the nasopharyngeal cancer case, it was also found that the pBEV-selected coplanar and noncoplanar beams significantly improved the target coverage without compromising the sparing of the OARs. CONCLUSIONS: The pBEV technique developed in this work provides a comprehensive tool for beam orientation selection in IMRT. It is especially valuable for complicated cases, where the target is surrounded by several sensitive structures and where it is difficult to select a set of good beam orientations. The pBEV technique has considerable potential for simplifying the IMRT treatment planning process and for maximizing the technical capacity of IMRT.

Humans↗
PubMed2001

Predictors of pain catastrophizing in women with rheumatoid arthritis.

Catastrophizing has been conceptualized as an appraisal, a cognitive distortion, and a coping mechanism in the psychosocial literature. Regardless of its conceptualization, catastrophizing has been associated with negative psychological and physical outcomes in numerous studies, including our intervention study with 90 women with rheumatoid arthritis. Because of catastrophizing's robust relationship with negative outcomes, predictors of catastrophizing as a pain coping behavior were investigated in this sample, using data collected from two points in time before the intervention. Using Lazarus and Folkman's stress and coping theoretical framework to guide the analyses, variables with a proximal relationship to catastrophizing in the framework were examined for significant associations with pain catastrophizing using correlational analyses. Subsequent stepwise regression involving all variables from Time 1 with significant associations resulted in a model that explained 63% of the variance in Time 2 pain catastrophizing scores. The four predictors in this model were dispositional pessimism, passive pain coping, venting (as a pain coping behavior), and arthritis helplessness. Potential clinical implications related to these predictors are also discussed. Knowledge about predictors of catastrophizing may enhance efforts to address this maladaptive pattern through educational and therapeutic approaches.

Adaptation, Psychological↗
PubMed2000

Culturally sensitive assessment of narrative skills in children.

The clinical legacy of William Labov's narrative analysis framework is explored. In recent years, the importance of narration for children's developing literacy and discourse skills has been widely recognized. This article describes a three-step process for assessing children's narrative discourse: elicitation, coding, and scoring. The influences of cultural differences on narration are also presented, with implications and suggestions for culturally sensitive assessment.

Child↗
PubMed1997

Cognitive factors associated with facial pain.

Most well-accepted etiological models of facial pain (e.g., temporomandibular disorders and headache) implicate emotional distress as an important factor in the development and maintenance of pain. Data exists to support the notion that some facial pain sufferers are more emotionally distressed than no pain controls. However, many of these dependent measures of emotional distress are either lengthy assessment batteries, lack clear cut psychotherapeutic treatment implications, or focus exclusively on pain related sequela. As cognitive-behavioral interventions become more integrated into the treatment of chronic pain conditions, including various facial pain conditions, it becomes more imperative that the tools used to assess psychological functioning provide the clinician with specific cognitive/behavioral targets for change. The purpose of this study was to assess the degree to which symptomatic treatment seeking facial pain sufferers (N = 25), symptomatic non-treatment seeking facial pain sufferers (N = 48), and healthy pain-free controls (N = 70) differed on the Rational Beliefs Inventory (RBI). The RBI is a reliable, valid questionnaire assessing rational beliefs that are operationalized within a Rational Emotive Therapy (RET) framework. RET is a cognitive-behavioral treatment paradigm that focuses on how an individual's maladaptive cognitive errors or distortions exacerbate emotional distress. Group differences were assessed using a oneway Analysis of Covariance (ANCOVA) with the total RBI score serving as the dependent measure, and a Multivariate Analysis of Covariance (MANCOVA) using individual RBI belief subscales as dependent measures. These results indicated that groups differed significantly on the total score and several of the individual belief subscales. These findings indicated that facial pain sufferers generally hold maladaptive beliefs that may be of clinical significance for cognitive/behavioral treatment approaches.

Adult↗
PubMed1981

On the possibility of automated scoring of pollen mutants.

Both flow cytometry and automated image analysis techniques may be useful in relieving the drudgery, increasing the speed, and adding quantitation to the scoring of pollen mutants, but practical problems related to the detection of very rare events have to be overcome. The features of flow and image cytometry instrumentation that may be useful for pollen measurements are discussed and a qualitative framework is presented from which to view the rare event problem.

Cell Count↗
PubMed2026

Characterizing the Uncertainty, Misclassification and Inconsistency of Polygenic Prediction.

Polygenic risk scores (PRSs) hold promise for precision medicine, yet their clinical translation is hindered by substantial uncertainty in individual risk estimates and often limited agreement in risk stratification across multiple PRSs for the same disease. We develop a unified inferential framework to calibrate PRS point estimates and uncertainties for both quantitative traits and binary phenotypes, and to characterize how PRS accuracy, uncertainty, pairwise correlation jointly determine misclassification and classification inconsistency. We show, both theoretically and empirically, that individual- and population-level misclassification and inconsistency rates are highly predictable in independent datasets. We further evaluate PRS integration and uncertainty-aware probabilistic thresholding strategies that reduce misclassification and improve concordance in risk stratification. Together, these results demonstrate that instability in PRS-based classification is a predictable statistical consequence of uncertainty and establish a principled foundation for incorporating uncertainty into PRS-based risk interpretation, communication, and clinical decision-making.

Journal Article↗
PubMedDate not supplied

Marketing telehealth to align with strategy.

Telehealth is a twenty-first century solution to an old problem-how to deliver quality health services with shrinking resources. Telehealth enables healthcare providers to interact with and monitor patients remotely, thus adding value to service delivery models. On occasion, telehealth can substitute for live encounters, saving time and resources. Furthermore, as the geriatric population increases, telehealth will support independent living by supplementing the existing network of care. To be used most effectively, however, telehealth services must be carefully planned and executed. This study investigated management practices used to promote telehealth services, focusing on strategic goals for adopting telehealth. Interviews with senior managers from 19 home health agencies identified three strategic goals for adopting telehealth: (1) clinical excellence, (2) technological preeminence, and (3) cost containment. Organizational documents were analyzed to determine the extent to which the telehealth program was featured in marketing materials. Documents included the organization's brochure, newspaper ads and articles, and each home health agency's web site. Results showed that marketing practices vary widely but are correlated with motivations to adopt telehealth. The organizations with the highest marketing scores emphasize clinical excellence as a major reason for using telehealth, whereas those with the lowest marketing scores tend to focus on cost containment. Although this study focused on management practices in home health agencies, results are applicable to hospital and outpatient services as well as to other community-based programs. Using a strategic management framework, the authors offer recommendations to help organizations develop effective marketing approaches for telehealth programs.

Guidelines as Topic↗