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[Colliculus atlantis--a rarely observed anatomic structure--in a transoral roentgen image of the thoracic spine].

PURPOSE: To study the time and mode of the development of the colliculus atlantis, the rate of its occurrence, the causes for its absence, and the radiological-clinical importance in the analysis of open-mouth-view radiographs. MATERIAL AND METHODS: Retrospective analysis of standardized radiographs of the cervical spine in more than 20,000 adults and 100 children. Study of 234 human skeletons of different ages and of 38 isolated adult atlases. Cadaveric dissection of 42 adults (age 48-87). Axial radiographs of isolated atlases and analysis of the bony structures of the colliculus atlantis. RESULTS: The colliculus atlantis develops between age 10 and 13 years. It is always present after age 13 years. For the development of the colliculus atlantis a normal function of the craniocervical joints is necessary. In congenital dysmorphias of the craniocervical region with dysfunction of the craniocervical joints and in fractures of the dens axis before age 10 years with instable healing the colliculus atlantis is absent. CONCLUSIONS: The colliculus atlantis is developed at age 13 years apart from some rare exceptions as mentioned. Changes of the site and the structure of the colliculus atlantis allow an early diagnosis of certain traumatically and inflammatory diseases of this region. Furthermore, it serves as an additional parameter in functional analysis of the craniocervical joints.

Adolescent↗

Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats.

In cats the global (gCBF) as well as the regional cerebral blood flow (rCBF) and blood pressure were measured before, during, and after noxious inward and outward rotations of normal and inflamed elbow joints. The animals were anesthetized with halothane and immobilized by gallamine triethiodide. The gCBF as well as the rCBF were measured using positron emission tomography (PET) with a camera specifically designed for use in small animals. Slow intravenous bolus injections of 15O-labeled water were followed by 3-min acquisition of regional radioactivity starting at the time of injection. In all experiments the gCBF as well as the blood pressure were increased by noxious inward-outward rotations of the normal and of the inflamed joint, whereas the blood pressure and the rCBF remained unchanged during bolus injections under control conditions (without any joint movement). Movements of the inflamed joint evoked significantly greater increases in blood pressure and gCBF than corresponding ones of the normal joint. These increases in gCBF were paralleled by increases in rCBF along the complete anterior to posterior axis of the brain. Again, the increases in rCBF were larger, more extensive and more uniform following the stimulation of the inflamed joint relative to the results obtained with stimulation of the normal joint. No significant laterality was seen, but when an atlas-based region of interest (ROI) analysis was carried out and when the individual variations in rCBF were removed with two-way ANOVA, significant differences were disclosed in rCBF between the stimulated condition and the resting condition in a large number of brain regions. In particular, noxious rotation of the normal (right) elbow joint induced a significant increase in rCBF over the cerebral cortex and in the right thalamus and hippocampus. The same stimulation of the (left) inflamed joint induced a significant increase in rCBF throughout the brain; the biggest increase being over the right posterior cortex. It is concluded that under the conditions of the present experiments the generally accepted autoregulation of the cerebral blood flow is not fully functioning, and various factors that may be responsible for this failure (which obscures rCBF differences) are discussed. The more pronounced increases in rCBF when moving inflamed joints instead of normal ones is thought to be a direct consequence of the peripheral sensitization of the articular nociceptors and the consequent central hyperexcitability induced in the articular nociceptive pathways.

Anesthesia↗

Three-dimensional finite element analysis of weakened roots restored with different cements in combination with titanium alloy posts.

BACKGROUND: It is very difficult and relatively unpredictable to preserve and restore severely weakened pulpless roots. To provide much needed benefit basis for clinical practice, this study was carried out to analyze the stress distribution in weakened roots restored with different cements in combination with titanium alloy posts. Finite element analysis (FEA) was employed in the study. METHODS: A pseudo three-dimensional model of a maxillary central incisor with flared root canal, theoretically restored with titanium alloy posts in combination with different cements, was established. The analysis was performed by use of ANSYS software. The tooth was assumed to be isotropic, homogenous and elastic. A load of 100 N at an angle of 45 degrees to the longitudinal axis was applied at the palatal surface of the crown. The distributions of stresses in weakened roots filled with cements of different elastic modulus were analyzed by the three-dimensional FEA model. RESULTS: Several stress trends were observed when the stress cloud atlas obtained in the study was analyzed. With the increase of the elastic modulus of cements from 1.8 GPa to 22.4 GPa, the stress values in dentin decreased from 39.58 MPa to 31.43 MPa and from 24.51 MPa to 20.76 MPa (respectively, for maximum principle stress values and Von Mises stress values). When Panavia F and zinc phosphate cement were used, the stress peak values in dentin were very small with no significant difference observed, and the Von Mises stress values were 20.87 MPa and 20.76 MPa respectively. On the other hand, maximum principle stress value and Von Mises stress value in cement layer increased with the increase of the elastic modulus of cements. CONCLUSIONS: The result of this study demonstrated that elastic modulus was indeed one of the important parameters to evaluate property of the cements. Our three-dimensional FEA model study also found that the cement with elastic modulus similar to that of dentin could reinforce weakened root and reduce the stress in dentin. Thus, it may be a better choice for the restoration of weakened roots in clinical practice.

Adult↗

Stromal Hedgehog Signaling Drives Segment-Specific Malignant Transformation of Gastrointestinal Stem Cells by Producing Bone Morphogenetic Protein Antagonists.

BACKGROUND & AIMS: Hedgehog signaling plays a complex role in epithelial-stromal interactions, but its effects on gastrointestinal stem cells mediated by heterogeneous stromal cell populations remain incompletely defined. Here, we investigate how stromal Hedgehog signaling regulates gastric stem cells and tumorigenesis in a segment-specific manner. METHODS: We genetically activated Hedgehog signaling in distinct stromal cell lineages using Col1a2-, Pdgfra-, Gli1-, Acta2-, and Prrx1-CreERT mouse lines, combined with lineage tracing, RNA sequencing, chromatin immunoprecipitation-quantitative polymerase chain reaction, and pharmacologic interventions. Human gastric cancer data from The Cancer Genome Atlas were also analyzed. RESULTS: We show that genetic activation of Hedgehog signaling in stromal cells marked by Col1a2, Pdgfra, or Gli1, but not by Acta2, induces tumorigenesis in the stomach and gastroesophageal junction, but not in the small or large intestine. Hedgehog signaling increases the expression of multiple bone morphogenetic protein antagonists in gastric but not colonic stromal cells, via Gli1-mediated transcription. These bone morphogenetic protein antagonists, in turn, activate Wnt/β-catenin signaling in gastric stem cells, driving their proliferation and initiating gastric cancer expressing CD44 and Sox9, but not Lgr5. Activating bone morphogenetic protein or inhibiting Wnt signaling blocks tumor initiation. Analysis of patient data from The Cancer Genome Atlas reveals elevated Hedgehog signaling in gastric cancers, which correlates with suppressed bone morphogenetic protein signaling. CONCLUSIONS: These findings uncover a gastrointestinal segment-specific oncogenic role for Hedgehog signaling in Col1a2+Acta2- stromal cells, mediated through the bone morphogenetic protein-Wnt-β-catenin axis.

BMP Antagonists↗

Atlanto-occipital fusion for dislocation in children with neurologic preservation. A case report.

STUDY DESIGN: A retrospective clinical review of patients with atlanto-occipital dislocations. OBJECTIVES: To determine if fusion of the occiput to C1 can be accomplished without extension to the axis. SUMMARY OF BACKGROUND DATA: Patients with atlanto-occipital dislocations who have preservation of spinal cord function are quite rare. The standard approach to stabilization has been fusion of the occiput to the axis (C2). This may compromise rotation unnecessarily, however. The authors investigated the success of attempting to fuse only the occiput to C1 in children. METHODS: Two children with atlanto-occipital dislocation who had normal neurologic function underwent fusion from the occiput to the atlas after reduction. RESULTS: Both cases showed successful fusion with no unwanted extension to lower levels. Full head rotation was preserved. CONCLUSIONS: This technique restores stability without restricting rotation.

Atlanto-Occipital Joint↗

Radiographic study of the upper cervical spine in the 22q11.2 deletion syndrome.

BACKGROUND: The chromosome abnormality, deletion of 22q11.2, is one of the most common genetic syndromes. The 22q11.2 deletion syndrome encompasses a wide spectrum of abnormalities including cardiac, palate, and immunological anomalies. The purposes of the current study were (1) to define and determine the frequency of variations of the occiput and cervical spine on plain radiographs in patients with the 22q11.2 deletion syndrome and (2) to postulate the potential clinical importance of these variations. METHODS: Seventy-nine consecutive patients with the 22q11.2 deletion underwent clinical and radiographic evaluation of the occiput and cervical spine. Radiographic studies included lateral plain radiographs of the cervical spine in neutral, flexion, and extension; anteroposterior radiographs; and open-mouth odontoid radiographs. RESULTS: At least one developmental variation of the occiput or cervical spine was observed in every patient. The occipital variations were platybasia in fifty-two (91%) of the fifty-seven patients for whom data were available and basilar impression in two (3%) of the seventy-nine patients. The atlas variations were dysmorphic shape in fifty-nine (75%) of the seventy-nine patients, open posterior arch in forty-seven (59%) of the seventy-nine patients, and occipitalization in two (3%) of the seventy-one patients with adequate radiographs. The axis variations were dysmorphic dens in forty-six (58%) and upswept lamina and posterior elements or "C2 swoosh" in forty-seven (59%) of the seventy-nine patients. Of the seventy-one patients with adequate radiographs, twenty-four (34%) had fusion of C2-C3, fifteen (21%) had fusion of the posterior elements only, and nine (13%) had a complete block fusion. Increased segmental motion was observed in forty (56%) of the seventy-one patients. Thirteen (33%) of the forty patients had increased segmental motion at more than one level. Thirty-one patients (44%) had increased occipitoatlantal motion, seven (10%) had increased atlantoaxial motion, and four had increased C2-C3 motion. Eleven (15%) of the seventy-one patients had increased C3-C4 mobility, always adjacent to a fusion of C2-C3. CONCLUSIONS: Variations of the upper cervical spine, including increased segmental motion, are common in the 22q11.2 deletion syndrome. It is premature to predict the clinical implications of these radiographic findings, but advanced imaging and further observation may be needed to clarify their clinical course.

Adolescent↗

Traumatic lesions of the occipitoatlantoaxial complex.

Injuries of the occipitoatlantoaxial complex are relatively rare but form a group of ligamentous and bony lesions that may unnecessarily confuse the clinician. Since fractures of the dens and traumatic spondylolisthesis of the axis have been well described in a number of large series, this article concentrates on the lesions less frequently seen and described. The ligamentous injuries are occipitoatlantal dislocation, rupture of the transverse ligament, and atlantoaxial rotatory fixation. The bony injuries are fractures of the occipital condyles, atlas, and the lateral masses of C2. The incidence, diagnostic criteria, and treatment modalities depend on the nature of localization of the traumatic lesions.

Atlanto-Axial Joint↗

Providing visualisation support for the analysis of anatomy ontology data.

BACKGROUND: Improvements in technology have been accompanied by the generation of large amounts of complex data. This same technology must be harnessed effectively if the knowledge stored within the data is to be retrieved. Storing data in ontologies aids its management; ontologies serve as controlled vocabularies that promote data exchange and re-use, improving analysis. The Edinburgh Mouse Atlas Project stores the developmental stages of the mouse embryo in anatomy ontologies. This project is looking at the use of visual data overviews for intuitive analysis of the ontology data. RESULTS: A prototype has been developed that visualises the ontologies using directed acyclic graphs in two dimensions, with the ability to study detail in regions of interest in isolation or within the context of the overview. This is followed by the development of a technique that layers individual anatomy ontologies in three-dimensional space, so that relationships across multiple data sets may be mapped using physical links drawn along the third axis. CONCLUSION: Usability evaluations of the applications confirmed advantages in visual analysis of complex data. This project will look next at data input from multiple sources, and continue to develop the techniques presented to provide intuitive identification of relationships that span multiple ontologies.

Anatomy↗

A contribution by the ascending pharyngeal artery to the arterial supply of the odontoid process of the axis vertebra.

The origin of transverse arterial branches that contribute to the arterial supply of the odontoid process (dens axis) is not clear. Dissections were performed on 20 injected fetal and adult human cranio-cervical junctions to demonstrate the origin of the arteries that contribute feeding branches to the arteries supplying the neck of the odontoid process. At its termination near the anterior arch of the atlas, the ascending pharyngeal artery gave off transverse branches that anastomosed with the anterior ascending arteries to the odontoid process. It also gave off a branch that traversed the hypoglossal canal and anastomosed with the posterior ascending artery. A small branch linked the posterior ascending artery to the first transverse branch. This investigation complements previous work on the arterial supply to the odontoid process.

Adult↗

The role of the supramammillary commissure in MR localization of the subthalamic nucleus.

PURPOSE: We have discovered a method for localization of the subthalamic nucleus (STN) utilizing the supramammillary commissure (SMC) as reference point. It is our purpose to present our experience and compare our methods with others. MATERIALS AND METHODS: Sixteen patients targeted for bilateral DBS for 32 total STN targets were studied by 1 mm MP-RAGE images with coronal T2W images. A modified red nucleus and mustache method was applied. The predicted target points were then confirmed with electronic calipers measuring the differences in methods. RESULTS: Modified red nucleus method using Surgiplan, and EBAL and BAGM electronic brain map atlas matched the target loci of 12 mm, -3 mm, -4 mm on an X-, Y-, and Z-coordinate system with zero at the mid-commissural point. From the coronal view Y is fixed at -3 mm. The mustache method was in error with values of X-axis at 14.25 (+/- 1.41 SD) (p = 0.69), and of Z-axis at -5.0 (+/- 1.60 SD) (p = 0.55). Three-fourths had moderate to marked ventricular enlargement of the III, but only 3 had enlargement of the frontal horns. CONCLUSION: The mustache method erred in the X-axis because the thalamocaudate groove was located lateral to the target point of the STN, and in the Z-axis because of varying thicknesses of the SMC. The top of the SMC is directly lateral from the STN target by 12 mm from the anterior and posterior commissures line. The SMC being a recognizable structure with constant relation to the STN should be the target structure.

Brain Mapping↗

[Harms technique of C1-C2 fixation with polyaxial screws and rods].

PURPOSE OF THE STUDY: The Harms technique of stabilizing C1-C2 by fixation with polyaxial screws and rods is a further option for atlantoaxial fixation from the dorsal approach. Harms and Melcher published this method in 2001, but the operation had first been performed by Harms in August 1997. The aim of this study is to evaluate the first results and try to assign the Harms C1-C2 fixation an appropriate standing in the in broad range of options for stabilization of the atlantoaxial complex. MATERIAL: Between December 2002 and January 2004 we carried out the Harms fixation of C1-C2 on 22 patients admitted to the Department of Spine Surgery, Motol University Hospital, 2nd Medical Faculty in Prague. Out of these, 18 patients were included in this study, 10 men and 8 women between 23 and 84 years of age (average, 55.4 years) followed-up longer than 6 months. In 14 patients we used the Harms technique as a permanent fixation of C1-C2 in order to achieve atlantoaxial arthrodesis and, in four patients, we applied it only for a period of 4 to 6 months without the use of bone grafts or their substitutions. We employed the permanent fixation to treat the following conditions: fracture of the atlas in three patients, type IIA comminuted fracture of the dens base in three patients, fracture of C2 categorized as "other" in two patients, atlantoaxial vertical instability in one patient with rheumatoid arthritis, malunion of the fractured dens in one patient, and complicated trauma to C1-C2 in four patients. The temporary fixation was used for type III displaced fractures of the dens in two and fixed atlantoaxial rotatory dislocations also in two cases. Only one patient showed signs of Frankel C neurological deficit on admission, the rest were without neurological findings. METHODS: All screws were inserted under an image intensifier always in lateral projection. First we retracted the greater occipital nerve in a caudal direction towards C2 with a fine raspatory and, using an awl, marked the entry point in the C1 lateral mass; a pilot hole, reaching through the anterior cortical bone, was made with a 2.5 mm drill. It followed a straight or slightly convergent trajectory in an anterior-posterior direction and parallel to the plane of the C1 posterior arch in the sagittal direction. Individual anatomical variations in the atlantoaxial complex of every patient were respected. The hole was tapped through the entire vertebral body, with the exception of osteoporous bone in which only the posterior cortical bone was treated with a screw tap. At this stage profuse bleeding usually arose from dissection around the epidural venous plexus along the C1-C2 joint. This was effectively controlled by a quick insertion of a screw and compression of the venous plexus with the screw head. To control bleeding by bipolar electrocautery is difficult and is always associated with a risk of nerve injury. Screws 3.5 mm thick, with polyaxial heads, were inserted bicortically into the lateral mass of C1. Subsequently, the intervertebral C2-C3 joint was localized and its medial border in the spinal canal was palpated. The entry point for placement of a C2 pedicle screw was marked with an awl at the point of intersection at a distance of 2 mm from the medial border and 5 mm from the caudal border of the C2 articular process. Under an X-ray intensifier in lateral projection, a hole was drilled approximately parallel to the screws inserted in C1, i. e., at an angle of 20 to 30 degrees cranially, up to and through the anterior cortical bone. In the transversal plane, the screws were situated in a convergent direction at an angle of 20 to 25 degrees. After all screws had been inserted, we reduced the antlantoaxial complex in the correct anatomical position by manipulating the patient's head or by directly adjusting the screws. Connecting 3.0-mm rods were then applied and fastened by cap nuts or inner nuts according to the instrumentation used. RESULTS: Operative time ranged from 35 to 155 min, with an average of 81 min. Intra-operative blood loss ranged from 50 to 1500 ml, with an average of 560 ml. The X-ray intensifier was used for a period of 0.4 to 2.6 min, with an average of 0.9 min. A total of 36 screws were inserted in the atlas; their length ranged from 16 to 34 mm (average, 30.6 mm). All screws were positioned correctly in the C1 lateral mass; two screws did not reach up to the anterior cortical bone and one protruded over it, but without causing clinical problems. Thirty-six screws were inserted in the axis. Their length ranged from 28 to 36 mm (average, 31.7) mm). Twenty-seven screws were correctly applied through the isthmus into the C2 anterior cortical bone, three were too short to reach it and five were placed too close to the vertebral artery canal. Of these, two protruded into the artery canal, but without clinical consequences. One screw inserted too medially passed into the spinal canal, but this also was without clinical response. Of the 36 screws inserted in C2, three (8.3 %) were malpositioned. Bony fusion at C1-C2 was the goal of this operation in 14 patients. At 6 weeks post-operatively, it was achieved in two patients, at 12 weeks in 12 patients and at 6 months in all 14 patients. The C1-C2 segment was stable at 12 weeks in all 18 treated patients. Four patients reported restriction of motion in rotation by 10 to 25 % after removal of the instrumentation. DISCUSSION: Operative time, longer at the beginning than with the Magerl technique, gradually shortened to between 45 and 60 min. Similar trends were seen when intra-operative blood loss and X-ray exposure were evaluated. Using the Harms and Melcher procedure we saved the greater suboccipital nerve. In contrast to these authors, however, we did not resect the atlantoaxial joint. Solid fusion was achieved in all our patients. Of the total of 72 screws inserted, only three (4.2 %) were assessed as malpositioned; however, when related to the 36 screws inserted in C2, this was 8.3 %, which indicates that insertion of screws in C2 was more difficult. We did not observe any clinical consequences in any of these cases. CONCLUSIONS: The Harms fixation of C1-C2 is a very effective technique for stabilizing the atlantoaxial complex. It enables us to provide temporary fixation without damage to atlantoaxial joints and to reduce the vertebrae after the screws and rods had been inserted, which is unique. These advantages compensate for a higher cost of the implant.

Adult↗

[Biomechanics of AF new 3-d pedical screw system and treatment of 31 patients with unstable thoracolumbar fracture].

For anatomic reduction of the spinal frectures, the 3 dimensional multiple correction forces were needed. Several pedical screw systems were designed for reducion and fixation of the spinal fractures as the AO universal joint system and the RF angle screw system. Because of the contradiction of the universal joint and the fixed angle, a new generation of RF was designed and named AF (atlas fixator) system. This is a new concept of 3-D reduction, without complex structure as universal joint, but has truly 3-D adjustment that allowed to reduce the intra-canal compromise. It also provided rigid fixation to maintain the reduction. Comparison with CD, AO, Steffee, and RF, the AF was truly 3-D reduction in XTZ axis. It provided strong symmetric transmitter orthotic force to correct the deformity. 31 patients with unstable thoracolumbar fractures were treated with the new AF system. 17 had partial (15) or complete (2) neurologic deficits. The AF system provided accurate angle to restore the normal thoracic-lumbar lordosis and to maintain it. All patients had a anatomic reduction by AF system. The spinal canal area increased over 33% by CT scan (P < 0.01). All cases were followed up over 8 months. No one deteriorated neurologically after AF fixation.

Adult↗

The quantitative anatomy of the vertebral artery groove of the atlas and its relation to the posterior atlantoaxial approach.

STUDY DESIGN: An evaluation of the vertebral artery groove of the atlas vertebra using dry bony vertebrae. OBJECTIVES: To measure the dimension of the vertebral artery groove of the atlas and to define its relation to the posterior midline. SUMMARY OF BACKGROUND DATA: Anatomic descriptions of the vertebral artery groove of the atlas exist, but very little quantitative data focused on this groove have been reported. METHODS: Fifty dry atlas vertebrae were obtained for this study. Anatomic evaluation focused on the vertebral artery groove and its relation to the midline. A total of eight linear and two angular measurements were made bilaterally. The mean, range, and standard deviation were calculated for all of the specimens and for male and female specimens separately. RESULTS: Differences in dimensions of male and female specimens were found to be statistically significant in one linear and two angular parameters. The average depths of the medial and lateral entrances, lengths of the axis, and thicknesses of the vertebral artery groove for male and female specimens were 9 mm, 6 mm, 14 mm, and 4 mm, respectively. The average angle of the vertebral artery groove axis for both genders was 64 degrees lateral to the sagittal plane. The distances from the midline to the medial-most edge of the vertebral artery groove on the inner and outer cortexes for male and female specimens averaged 10 mm, with a minimum of 8 mm, and 18 mm, with a minimum of 12 mm, respectively. CONCLUSIONS: The results of this study suggest that dissection on the posterior aspect of the posterior ring should remain within 12 mm lateral to the midline, and dissection on the superior aspect of the posterior ring should remain within 8 mm of the midline.

Adult↗

Asymmetry in the human skeleton. A study on prehistoric Polynesians and Thais.

Atlantal, long bone, and craniofacial measurements of prehistoric Polynesian and Thai skeletons were analysed to ascertain the extent and direction of bilateral asymmetry. The atlantal articular mass was constantly and significantly higher on the right side than on the left. In Thais, the midlongitudinal axis of the atlanto-occipital facet on the right side had a steeper inclination than that on the left. In both groups the dental occlusion was less mesial on the right side and the mandible was shorter, significantly so in the Thais. The long bones were more asymmetric in the Polynesians than in the Thais. Height asymmetry of atlas lateral tuberculum correlated inversely with mandibular ramal width asymmetry. Atlanto-occipital facet length asymmetry correlated with asymmetry of the gonial angle and facet angulation asymmetry correlated inversely with radial length asymmetry. Our results suggest a pervading asymmetry of skeletal structures which we ascribe as local adaptations to functional demands rather than as due to a uniform asymmetric growth pattern.

Animals↗

Hypoxia-Induced ADAM23 Drives Neuron-Tumor Crosstalk and Therapeutic Resistance in Hepatocellular Carcinoma.

Hypoxia and nutrient deprivation are fundamental drivers of tumor aggressiveness and therapeutic resistance in hepatocellular carcinoma (HCC). While the involvement of neural components in the tumor microenvironment (TME) is increasingly recognized, the molecular transducers linking metabolic stress to neuron-tumor crosstalk remain elusive. Here, we identify ADAM23 (A disintegrin and metalloproteinase 23) as a hypoxia-responsive mediator that mediates communication between HCC cells and neuronal cells. ADAM23 expression was markedly upregulated in HCC cells under both chemical (CoCl2) and physical hypoxia (1% O2), a process further amplified by glucose deprivation and directly modulated by HIF-1&#x3b1;. Functional assays revealed that ADAM23 overexpression promotes epithelial-mesenchymal transition (EMT) and enhances cell viability under metabolic stress. Notably, sorafenib-resistant HCC cells (Huh7SR) exhibited high levels of ADAM23 secretion, which triggered proliferative and metabolic activation in neuronal SH-SY5Y cells. In 3D co-culture spheroid models, Huh7SR cells mixed with SH-SY5Y cells displayed significantly larger spheroid volumes and enhanced neuronal fluorescence compared with parental controls, suggesting that ADAM23-mediated interactions facilitate a supportive neural niche. Analysis of The Cancer Genome Atlas (TCGA) datasets and patient microarrays confirmed that ADAM23 is significantly overexpressed in HCC and positively correlates with HIF-1&#x3b1; expression. Moreover, elevated expression of ADAM23 was significantly correlated with poor overall survival. Collectively, our findings underscore ADAM23 as a critical metabolic-neural linker that promotes HCC progression and drug resistance. These findings suggest that the ADAM23-mediated neuron-tumor axis may represent a potential therapeutic target in aggressive HCC.

ADAM23↗

CCNA2 orchestrates the PI3K/AKT signaling axis to propel prostate cancer metastasis.

BACKGROUND: Prostate cancer (PCa) remains one of the most common malignancies in men, posing a persistent global burden in terms of both public health and socioeconomic costs. Although early detection is essential for improving patient outcomes, existing clinical tools, including prostate-specific antigen (PSA) screening, digital rectal examination, and transrectal ultrasound-guided biopsy, are hampered by suboptimal specificity and positive predictive value, resulting in frequent overdiagnosis and overtreatment of indolent lesions while missing a subset of aggressive tumors at an early stage. In this context, the rapid advancement of high-throughput omics technologies, coupled with sophisticated machine learning (ML) algorithms, provides a powerful computational framework to dissect high-dimensional genomic data, uncover latent gene expression signatures, and identify candidate biomarkers with superior discriminative performance over conventional clinicopathological parameters. Therefore, in this study, we sought to screen for crucial ML-based biomarkers associated with PCa, with a particular focus on systematically assessing the diagnostic and prognostic value of CCNA2. Leveraging large-scale transcriptomic cohorts from public repositories, we employed an ensemble of ML approaches to prioritize candidate genes and subsequently evaluated the diagnostic performance of CCNA2 through receiver operating characteristic curve analysis, as well as its prognostic utility via Kaplan-Meier survival estimation and multivariate Cox proportional hazards modeling. Our findings are anticipated to elucidate the molecular landscape of PCa and offer a promising biomarker candidate for early detection and risk stratification. METHODS: This study integrated single-cell RNA sequencing, bulk transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, immunofluorescence, and multiple ML algorithms with in vitro functional assays to evaluate CCNA2 expression, clinical relevance, and biological behavior in PCa. RESULTS: CCNA2 was linked to metastasis and poor prognosis. High CCNA2 expression significantly correlated with adverse survival outcomes, and knockdown of CCNA2 suppressed proliferation, migration, and invasion in PCa cell lines. Mechanistically, CCNA2 modulated the PI3K/AKT signaling pathway. An ML-based diagnostic model incorporating CCNA2 demonstrated high predictive accuracy across multiple validation cohorts. CONCLUSIONS: CCNA2 serves as a promising prognostic biomarker and therapeutic target in prostate adenocarcinoma, driving tumor progression potentially via the PI3K/AKT axis.

CCNA2↗

Differential segmental growth of the vertebral column of the rat (Rattus norvegicus).

Despite the pervasive occurrence of segmental morphologies in the animal kingdom, the study of segmental growth is almost entirely lacking, but may have significant implications for understanding the development of these organisms. We investigate the segmental and regional growth of the entire vertebral column of the rat (Rattus norvegicus) by fitting a Gompertz curve to length and age data for each vertebra and each vertebral region. Regional lengths are calculated by summing constituent vertebral lengths and intervertebral space lengths for cervical, thoracic, lumbar, sacral, and caudal regions. Gompertz curves allow for the estimation of parameters representing neonatal and adult vertebral and regional lengths, as well as initial growth rate and the rate of exponential growth decay. Findings demonstrate differences between neonatal and adult rats in terms of relative vertebral lengths, and differential growth rates between sequential vertebrae and vertebral regions. Specifically, relative differences in the length of vertebrae indicate increasing differences caudad. Vertebral length in neonates increases from the atlas to the middle of the thoracic series and decreases in length caudad, while adult vertebral lengths tend to increase caudad. There is also a general trend of increasing vertebral and regional initial growth and rate of growth decay caudad. Anteroposterior patterns of growth are sexually dimorphic, with males having longer vertebrae than females at any given age. Differences are more pronounced (a) increasingly caudad along the body axis, and (b) in adulthood than in neonates. Elucidated patterns of growth are influenced by a combination of developmental, functional, and genetic factors.

Aging↗

Mathematical theory of stereotactic coordinate transformation: elimination of rotational targeting error by addition of a third reference point. Technical note.

All frame-based stereotactic procedures require localization of an anatomical target within the coordinate system of the stereotactic frame. If the target is defined by its coordinates given in a stereotactic atlas (indirect localization), the neurosurgeon faces the mathematical task of transforming atlas coordinates into frame coordinates. In the method usually used, the frame coordinates of two reference points (the anterior and posterior commissures) are obtained from computerized tomography or magnetic resonance images, and serve as the basis for the coordinate transformation. This two-point algorithm relies on the additional assumption that the frame sits on the patient's head without exhibiting roll, that is, rotation about the anteroposterior axis (y axis). Usually this assumption is nearly, but not exactly, correct. An amount of roll as small as 3 degrees can cause a targeting error on the order of 1 mm when a two-point algorithm is used. This potential source of error can be eliminated by using a new method of coordinate transformation, the derivation of which is mathematically reported in this article. The new method requires a third reference point located in the midsagittal plane, in addition to the two commissural reference points.

Algorithms↗