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PubMed2026

AI-Driven Multi-Omics Integration of Synthetic Colon Adenocarcinoma for Cluster-Guided PROTAC Candidate Design Targeting KRASG12D.

Colorectal cancer is a leading cause of cancer death, yet its molecular heterogeneity remains poorly translated into individualized treatment. We present a reproducible artificial intelligence (AI) framework that integrates multi-omics benchmarking, sample-level drug prioritization, E3 ubiquitin ligase selection, and shape-anchored Proteolysis Targeting Chimera (PROTAC) design for KRASG12D in colon adenocarcinoma (COAD). A controlled synthetic benchmark comprising 425 tumor and 41 simulated normal profiles, parameterized to match The Cancer Genome Atlas (TCGA) distributions, was used for pipeline verification. Among sixteen methods, the Balanced Latent Integration with Stability Selection (BLISS) model achieved the highest silhouette width (0.86) and competitive agreement (Adjusted Rand Index, ARI, 0.90). The pipeline was validated on real data: a TCGA COAD cohort (186 tumors) with independent Consensus Molecular Subtype (CMS) labels and a CPTAC cohort (104 tumors). Integration modestly recovered CMS (ARI 0.28), and stage, not molecular cluster, drove survival (log-rank p = 0.005 versus 0.81). Sample-level prioritization differed from cluster-level ranking in 82.6% of profiles, below chance (p < 0.0001), without indicating efficacy. Candidate NOVEL00489 showed a good MM-GBSA estimate, matching the reference ASP3082. Compounds are computational candidates requiring experimental validation. This establishes a transparent benchmark for in silico degrader generation in precision oncology.

Humans↗
PubMed2003

Spatial normalization of diffusion tensor MRI using multiple channels.

Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the detection of brain abnormalities in diseases characterized by compromised neural connectivity. To quantify diffusion tensor abnormalities based on voxel-based statistical analysis, spatial normalization is required to minimize the anatomical variability between studied brain structures. In this article, we used a multiple input channel registration algorithm based on a demons algorithm and evaluated the spatial normalization of diffusion tensor image in terms of the input information used for registration. Registration was performed on 16 DT-MRI data sets using different combinations of the channels, including a channel of T2-weighted intensity, a channel of the fractional anisotropy, a channel of the difference of the first and second eigenvalues, two channels of the fractional anisotropy and the trace of tensor, three channels of the eigenvalues of the tensor, and the six channel tensor components. To evaluate the registration of tensor data, we defined two similarity measures, i.e., the endpoint divergence and the mean square error, which we applied to the fiber bundles of target images and registered images at the same seed points in white matter segmentation. We also evaluated the tensor registration by examining the voxel-by-voxel alignment of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear warping using six independent tensor components as input channels showed the best performance in effectively normalizing the tract morphology and tensor orientation. We also present a nonlinear method for creating a group diffusion tensor atlas using the average tensor field and the average deformation field, which we believe is a better approach than a strict linear one for representing both tensor distribution and morphological distribution of the population.

Adult↗
PubMed2006

Epilepsy Care in the World: results of an ILAE/IBE/WHO Global Campaign Against Epilepsy survey.

PURPOSE: Information about existing resources available within the countries to tackle the huge medical, social, and economic burden caused by epilepsy is lacking. To fill this information gap, a survey of country resources available for epilepsy care was conducted within the framework of the ILAE/IBE/WHO Global Campaign Against Epilepsy. METHODS: The study represents a major collaborative effort involving the World Health Organization (WHO), the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). RESULTS: Data were collected from 160 countries representing 97.5% of the world population. The information included availability, role, and involvement of professional and patient associations for epilepsy, epilepsy treatment and services including antiepileptic drugs, human resources involved in epilepsy care, teaching in epileptology, disability benefits, and problems encountered by people with epilepsy and health professionals involved in epilepsy care. The data confirm that epilepsy care is grossly inadequate compared with the needs in most countries. In addition, large inequities exist across regions and income groups of countries, with low-income countries having extremely meager resources. Complete results of this survey can be found in the Atlas: Epilepsy Care in the World. CONCLUSIONS: The data reinforce the need for urgent, substantial, and systematic action to enhance resources for epilepsy care, especially in low-income countries.

Cross-Cultural Comparison↗
PubMed2005

Patellofemoral osteoarthritis coexistent with tibiofemoral osteoarthritis in a meniscectomy population.

OBJECTIVES: To evaluate the frequency of patellofemoral osteoarthritis and its relevance to symptoms and function in a meniscectomy population. METHODS: 317 patients with no cruciate ligament injury were evaluated (mean (SD) age, 54 (11) years). They had undergone meniscal resection 15 to 22 years earlier (follow up rate 70%). Standing tibiofemoral and skyline patellofemoral radiographs were graded according to the OARSI atlas. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to quantify symptoms and function. Controls were 68 unoperated subjects identified from national population records. RESULTS: Patellofemoral osteoarthritis (isolated or coexisting with tibiofemoral osteoarthritis) was present in 66 of 317 index knees (21%) and 21 of 263 unoperated contralateral knees (8%, p<0.001). In 57/66 (86%) of these index knees, tibiofemoral osteoarthritis was present (mixed osteoarthritis). In a model adjusted for age, sex, and body mass index, the odds ratio for patellofemoral osteoarthritis (alone or in combination with tibiofemoral osteoarthritis) was 2.6 (95% confidence interval, 1.1 to 6.6) after medial meniscectomy and 5.3 (1.9 to 15.0) after lateral meniscectomy, using controls as the reference. Individuals with a mixed knee osteoarthritis pattern had more symptoms, lower function in sports and recreation, and worse knee related quality of life than subjects with isolated tibiofemoral osteoarthritis. CONCLUSIONS: Mixed patellofemoral and tibiofemoral osteoarthritis is common in a meniscectomy population. Patellofemoral osteoarthritis is a contributing cause of knee symptoms and reduced knee related quality of life and is relevant to the management of knee complaints of this group of patients.

Adult↗
PubMed2005

Incorporating statistical measures of anatomical variability in atlas-to-subject registration for conformal brain radiotherapy.

Deforming a digital atlas towards a patient image allows the simultaneous segmentation of several structures. Such an intersubject registration is difficult as the deformations to recover are highly inhomogeneous. A priori information about the local amount of deformation to expect is precious, since it allows to optimally balance the quality of the matching versus the regularity of the deformation. However, intersubject variability makes it hard to heuristically estimate the degree of deformation. Indeed, the sizes and shapes of various structures differ greatly and their relative positions vary in a rather complex manner. In this article, we perform a statistical study of the deformations yielded by the registration of an image database with an anatomical atlas, and we propose methods to re-inject this information into the registration. We show that this provides more accurate segmentations of brain structures.

Algorithms↗
PubMed2003

Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery.

We present a method of constructing a database of intraoperatively observed human subcortical electrophysiology. In this approach, patient electrophysiological data are standardized using a multiparameter coding system, annotated to their respective magnetic resonance images (MRIs), and nonlinearly registered to a high-resolution MRI reference brain. Once registered, we are able to demonstrate clustering of like interpatient physiologic responses within the thalamus, globus pallidus, subthalamic nucleus, and adjacent structures. These data may in turn be registered to a three-dimensional patient MRI within our image-guided visualization program enabling prior to surgery the delineation of surgical targets, anatomy with high probability of containing specific cell types, and functional borders. The functional data were obtained from 88 patients (106 procedures) via microelectrode recording and electrical stimulation performed during stereotactic neurosurgery at the London Health Sciences Centre. Advantages of this method include the use of nonlinear registration to accommodate for interpatient anatomical variability and the avoidance of digitized versions of printed atlases of anatomy as a common database coordinate system. The resulting database is expandable, easily searched using a graphical user interface, and provides a visual representation of functional organization within the deep brain.

Brain↗
PubMedDate not supplied

Some upper cervical spine norms.

Lateral cervical spine films from 175 normal examinations of adults performed in the emergency room of North Carolina Baptist Hospital were analyzed to establish some norms and relationships in the upper cervical spine. The predens angle was found to be between 0 degree-13 degrees (mean 5.57 degrees) in neutral position and 0-18 degrees (mean 9.27 degrees) in flexion in most persons. Ninety-two percent of persons have angles greater than 3 degrees in flexion. A V-shaped predens space is not indicative of injury to the cruciate ligament. Virtually every person has posterior slanting or tilting of the dens and the range of values is up to 35 degrees (mean 17.43 degrees). Ninety-eight percent of persons have an angle greater than 6 degrees. A tilted dens does not indicate acute or remote trauma. No relationship was identified between the predens angle and the dens tilt angle. The posterior arch of the atlas can be found at any position between the occiput and spinous process of C2 in all positions of the head and neck. Hence, fanning or widening of the C1-C2 interspinous distance is not a reliable index of ligamentous injury in the upper cervical spine.

Adolescent↗
PubMed1981

Prevertebral hematoma in cervical spine injury: incidence and etiologic significance.

In a consecutive series of 30 hospitalized cervical injury patients, 18 proved to have widening of the prevertebral soft tissue space due to hematoma. The upper limit of normal width in 50 noninjury patients was used as a reference. Hematoma almost exclusively manifested at C1-C4 and proved to be closely related to fractures of anterior elements of the spine. Relatively small hematomas were encountered in odontoid fractures and compression fractures of vertebral bodies; relatively large hematoma in disruptive hyperextension injury. Large hematomas are explained by extensive anterior ligamentous damage with rupture of larger blood vessels. As a rule, most hematomas disappeared within 2 weeks after the injury.

Adolescent↗
PubMed2000

Congenital arthrogryposis associated with atlantoaxial subluxation and dysraphic abnormalities. Case report.

The authors report the case of a 27-year-old woman with an arthrogryposis multiplex congenita (AMC) associated with atlantoaxial subluxation. To the authors' knowledge, this is the first report of its kind. The authors review the literature with reference to dysraphic abnormalities associated with atlantoaxial subluxation and with AMC. The patient presented with severe tetraparesis following a minor traffic accident. She underwent a procedure in which transoral decompression and dorsal stabilization were performed and, postoperatively, made a good clinical outcome. The authors stress the need for diagnostic neuroimaging of the craniocervical junction in patients with AMC.

Accidents, Traffic↗
PubMed1996

Fatal transdental posterior rotary subluxation of the cervical spine. A case report.

STUDY DESIGN: The cervical spine of an 86-year-old man known to have a fracture of the odontoid process was removed at autopsy and dissected. OBJECTIVES: To establish the cause of death, which was not apparent. SUMMARY OF BACKGROUND DATA: Ruptures of the vertebral arteries in patients with fractures of the odontoid process are rare. Only a few reports are published in the literature. Those that address postmortem findings in patients with fractures of the odontoid process do not make any reference to associated capsular and ligamentous injuries and the resultant instabilities. METHODS: Because of legal constraints, the cervical spine was removed en bloc 1 week after the patient's death and carefully dissected. RESULTS: In addition to the known bony injury, rupture of the left vertebral artery, epidural hematoma, disruption of the posterior atlantoaxial ligaments, hemorrhage into the anterior ligamentous structures, rupture of the capsule of the right atlantoaxial joint, and stretching of the capsule of the left joint were found to be present. Displacement of the spinal cord by an epidural hematoma secondary to rupture of the left vertebral artery was recorded as the apparent cause of death. The rupture had obviously been caused by the abnormal rotation of the atlas on the axis in a clockwise direction. CONCLUSIONS: Both the fatal outcome and the pathologic examination showed that established management concepts, particularly screw fixation of a fractured odontoid process, should be reconsidered in light of the potential occurrence of transdental posterior rotary subluxation. Because the incidence of capsular, ligamentous, and vascular injuries associated with fractures of the odontoid process is still poorly understood, more autopsies would be needed. The case also raises the question of whether, in an elderly patient like ours, a fracture of the odontoid process should prompt immediate surgical stabilization.

Aged↗
PubMed2003

Case studies from morning report: librarians' role in helping residents find evidence-based clinical information.

In primary care specialties, Morning Report is a traditional vehicle for expanding medical residents' training in diagnosis and treatment. At one academic medical center, residents and faculty in the Department of Family and Community Medicine use case-based teaching, centered around planning and reviewing patient management, to review intriguing cases from patient encounters in the department's hospital service. Seeking to improve the level of evidence-based information exchanged at Morning Report, department leaders invited reference librarians from the health sciences library to attend weekly Morning Report. The librarians saw this as an opportunity not only to improve residents' information-seeking skills, but also to improve librarians' teaching skills and understanding of the needs of users in clinical settings. This paper describes the evolution of librarians' involvement in Morning Report, examples of the kinds of contributions librarians have made in this setting, and changes made in Morning Report sessions to facilitate this activity.

Academic Medical Centers↗
PubMed2026

Single-cell spatial transcriptomic atlas of the mouse adrenal gland reveals sexual dimorphism in steroidogenic enzyme and hormone receptor expression.

The adrenal cortex shows sexual dimorphism in structure and function. We analysed adrenal glands from 7-week-old male and female BALB/c mice using Visium HD with Cellpose 3 segmentation, comprising 236,077 cells across eleven populations, including four cortical zones. Using curated marker-gene-based zonal annotation, we focused on steroidogenic enzymes and hormone receptors, complementing our companion study based on the same primary dataset. The X-zone was nearly absent in males but prominent in females. Females showed higher Hsd3b1 expression across cortical zones and higher Cyp11b1 expression in outer cortical compartments. The strongest sex difference involved Srd5a2, with markedly higher expression in male zona fasciculata (inner: 77.1% vs. 28.9%), independently supported by RNAscope and immunohistochemistry. Mc2r and Mrap showed discordant spatial distributions, with limited co-expression, suggesting potential MC2R-independent MRAP roles. Agtr1a dominated angiotensin II receptor expression in zona glomerulosa without major sex differences, providing a zone-resolved reference for adrenal sexual dimorphism.

Adrenal cortex↗
PubMed2006

Towards multimodal atlases of the human brain.

Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided significant impetus for the human brain mapping initiatives, and have important applications in health and disease.

Anatomy, Artistic↗
PubMed2003

Comparison of gene expression profiles of lymphoma cell lines from transformed follicular lymphoma, Burkitt's lymphoma and de novo diffuse large B-cell lymphoma.

To determine the specific gene expression in B-cell lymphoma subtypes, we compared expression profiles of cell lines from transformed follicular lymphoma (tFL), Epstein-Barr virus-negative (EBV(-)) Burkitt's lymphoma (BL) and EBV(+)BL. Complementary DNAs were synthesized from these cell lines and hybridized with the Atlas Human 1.2 Array membrane. Hierarchical clustering analysis based upon the levels of 43 genes highlighted characteristic expression patterns of the 3 lymphoma subtypes. Genes expressed at higher levels in tFL than EBV(-)BL and EBV(+)BL included calcium/calmodulin-dependent protein kinase I (CAMK1) and mitogen-activated protein kinase 10 (MAPK10). EBV(-)BL was characterized by high-level expression of amyloid beta precursor protein (APP), heat shock 27 kD protein 1 (HSPB1) and mothers against decapentaplegic homolog 1 (MADH1). Gardner-Rasheed feline sarcoma viral oncogene homolog (FGR) was the most significant gene to delineate EBV(+)BL. A subtype prediction algorithm using 34 genes correctly classified 22 (92%) of 24 lymphomas into FL/tFL, EBV(-)BL or EBV(+)BL. By comparison with normal reference B-cell materials, the expression patterns of the selected genes were characteristic of lymphomas. We extended the clustering analysis to cell lines from de novo diffuse large B-cell lymphoma (DLBCL). The DLBCL cell lines were either separated from the former 3 lymphoma subtypes or segregated with EBV(+)BL, possibly reflecting variable genetic abnormalities. The associations of CAMK1 with tFL, APP and MADH1 with EBV(-)BL, FGR with EBV(+)BL, and BCL2 with tFL and DLBCL were confirmed by real-time quantitative reverse transcriptase-mediated polymerase chain reaction assays. This study has provided new molecular markers, expressions of which are closely associated with B-cell lymphoma subtypes.

B-Lymphocytes↗
PubMed1989

Technetium-99m RBC bleeding images in normal subjects: confusion with gastrointestinal bleeding sites.

The normal appearance of a gastrointestinal bleeding study using labeled red blood cells has been discussed frequently, but the actual appearance is not well known. In this atlas article, the authors report on unusual findings in non-bleeding subjects and have tabulated the visualization of various structures. Vascular structures other than the aorta and inferior vena cava were seen in 42 of 48 patients. One or both kidneys were seen in 10 (21%) of 48 patients. The urinary bladder was seen in 23 (48%) of 48 patients, although gastric activity caused by free pertechnetate was never observed.

Erythrocytes↗
PubMed1984

Current status of thoracic dorsal sympathectomy.

This article summarizes over 20 years of experience (1962 to 1982) with cervical sympathectomy (thoracic dorsal sympathectomy) in 46 patients undergoing 68 sympathectomies. All operations were performed through an anterior supraclavicular approach. Indications for surgery were intractable Raynaud's disease (26 patients), atherosclerotic obliterative arterial disease (five), causalgia (five), posttraumatic sympathetic dystrophy (seven), collagen vascular disorders (eight), hyperhidrosis (12), occupational-related digital thrombosis (four), and thrombosis secondary to intra-arterial injection (one). The incidence of complications and side effects, both temporary and permanent, including Horner's syndrome, is reviewed in detail. Particular reference is made to the various surgical techniques of managing the stellate ganglion; four patients had two-third to three-fourth resection of the stellate ganglion down to and including the T-3 thoracic ganglion, two had preservation of the stellate ganglion and resection of the T-2 through T-4 ganglia, seven had excision of the entire stellate ganglion down to and including the T-4 ganglion, seven had resection of the lower third of the stellate ganglion down to and including the T-4 ganglion, and 48 had removal of the lower half of the stellate ganglion down to and including the T-3 ganglion. The study reviews the literature germane to anatomic considerations and suggests revisions in current texts and atlases. By retrospective analysis of the records and a follow-up questionnaire, which provided an 86% follow-up (average 8.4 years), the paper points to the distinctive clinical characteristics of the different groups within the population undergoing the operation and provides guidelines for patient selection and conclusions on the place for this operation in the management of vascular diseases involving the upper extremity.

Adult↗
PubMed1991

A case of adult onset pure pallidal degeneration. II. Analysis of neurotransmitter markers, with special reference to the termination of pallidothalamic tract in human brain.

We analyzed neurotransmitter markers in a brain of a very rare case of pathologically confirmed adult-onset pure pallidal degeneration (PPD) as compared with 16 controls. Neurotransmitter concentrations are significantly altered in the globus pallidus (GP), subthalamic nucleus (ST) and the thalamic nuclei. Concentrations of gamma-aminobutyric acid (GABA) in the external segment (GPe) and internal segment (GPi) of GP and ST are decreased to 62, 45 and 55% of the control mean, respectively. Concentrations of glutamic acid are increased in GPi (144%) and ST (134%). Choline acetyltransferase (ChAT) activities are increased in GPe (232%), GPi (218%), ST (161%), and ventroanterior (VA, 210%) and ventrolateral nucleus (VL, 193%) of the thalamus. Noradrenaline (NA) concentrations in GPe and GPi are 56 and 43% of the control mean, respectively. Dopaminergic and serotonergic systems show no remarkable change. The grid microdissection analysis demonstrates a patchy GABA distribution in the thalamus of 3 controls, whereas a small GABA-rich area in the ventro-oral nucleus (VO) according to the atlas of Hopf disappears in adult onset PPD. These results strongly suggest that (1) GP GABAergic neurons are selectively degenerated and striatopallidal GABAergic nerve terminals are hypoactive; (2) ChAT activities in GP, ST, VA and VL are increased; (3) the subthalamopallidal glutamatergic system is not hypoactive; (4) activity of the noradrenergic system in GP is decreased; and that (5) VO in the thalamus specifically receives GABAergic nerve terminals from GP in human brain.

Adult↗
PubMed2002

Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei.

The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.

Adult↗