Deciphering the Link: Correlating REM Sleep Patterns with Depressive Symptoms via Consumer Wearable Technology.

This study investigates the correlation between REM sleep patterns, as measured by the Apple Watch, and depressive symptoms in an undiagnosed population. Employing the Apple Watch for data collection, REM sleep duration and frequency were monitored over a specified period. Concurrently, participants' depressive symptoms were evaluated using standardized questionnaires. The analysis, primarily using Spearman's correlation, revealed noteworthy findings. A significant correlation was observed between an increased REM sleep proportion and higher depressive symptom scores, with a correlation coefficient of 0.702, suggesting a robust relationship. These results highlight the potential of using wearable technology, such as the Apple Watch, in early detection and intervention for depressive symptoms, suggesting that alterations in REM sleep could serve as preliminary indicators of depressive tendencies. This approach offers a non-invasive and accessible means to monitor and potentially preempt the progression of depressive disorders. This study's implications extend to the broader context of mental health, emphasizing the importance of sleep assessment in routine health evaluations, particularly for individuals exhibiting early signs of depressive symptoms.

Inflammatory Status Assessment by Machine Learning Techniques to Predict Outcomes in Patients with Symptomatic Aortic Stenosis Treated by Transcatheter Aortic Valve Replacement.

(1) Background: Although transcatheter aortic valve replacement (TAVR) significantly improves long-term outcomes of symptomatic severe aortic stenosis (AS) patients, long-term mortality rates are still high. The aim of our study was to identify potential inflammatory biomarkers with predictive capacity for post-TAVR adverse events from a wide panel of routine biomarkers by employing ML techniques. (2) Methods: All patients diagnosed with symptomatic severe AS and treated by TAVR since January 2016 in a tertiary center were included in the present study. Three separate analyses were performed: (a) using only inflammatory biomarkers, (b) using inflammatory biomarkers, age, creatinine, and left ventricular ejection fraction (LVEF), and (c) using all collected parameters. (3) Results: A total of 338 patients were included in the study, of which 56 (16.5%) patients died during follow-up. Inflammatory biomarkers assessed using ML techniques have predictive value for adverse events post-TAVR with an AUC-ROC of 0.743 and an AUC-PR of 0.329; most important variables were CRP, WBC count and Neu/Lym ratio. When adding age, creatinine and LVEF to inflammatory panel, the ML performance increased to an AUC-ROC of 0.860 and an AUC-PR of 0.574; even though LVEF was the most important predictor, inflammatory parameters retained their value. When using the entire dataset (inflammatory parameters and complete patient characteristics), the ML performance was the highest with an AUC-ROC of 0.916 and an AUC-PR of 0.676; in this setting, the CRP and Neu/Lym ratio were also among the most important predictors of events. (4) Conclusions: ML models identified the CRP, Neu/Lym ratio, WBC count and fibrinogen as important variables for adverse events post-TAVR.

Evolutionary Image Registration: A Review.

Image registration is one of the most important image processing tools enabling recognition, classification, detection and other analysis tasks. Registration methods are used to solve a large variety of real-world problems, including remote sensing, computer vision, geophysics, medical image analysis, surveillance, and so on. In the last few years, nature-inspired algorithms and metaheuristics have been successfully used to address the image registration problem, becoming a solid alternative for direct optimization methods. The aim of this paper is to investigate and summarize a series of state-of-the-art works reporting evolutionary-based registration methods. The papers were selected using the PRISMA 2020 method. The reported algorithms are reviewed and compared in terms of evolutionary components, fitness function, image similarity measures and algorithm accuracy indexes used in the alignment process.

Emergency surgical decompression and long-term survival of glioblastoma presenting in coma in old age: case report and review of prognostic factors.

We present a case demonstrating that older age does not exclude long-term survival with glioblastoma. This is a malignant neoplasm with a median life expectancy of 14 months in patients treated with radical intent. Survival is dependent on several independent and interacting prognostic factors of which advancing age is a negative factor. We present a septuagenarian with a 3.5-year survival following aggressive management. The potential to improve glioblastoma survival in an elderly population by examination of additional prognostic factors and identifying biomarkers warrants further research.

Differences between Active and Semi-Active Students Regarding the Parameters of Body Composition Using Bioimpedance and Magnetic Bioresonance Technologies.

The aim of the study was to identify differences in obesity-related parameters between active sports students and semi-active or sedentary students, differentiated by sex, in order to optimize health. The study sample included 286 students, of which the male experimental sample consisted of 86 active sports students, age X ± SD 21.25 ± 0.32 years; height X ± SD 181.08 ± 3.52 cm; control group consisting of 89 semi-active students aged X ± SD 21.07 ± 0.1.13 years; height X ± SD 182.11 ± 1.32. The female experimental sample includes 57 active sports students, age X ± SD 21.02 ± 0.92 years; height X ± SD 167.48 ± 1.34 cm; the control group includes 54 semi-active students aged X ± SD 21.57 ± 0.1.98 years; height X ± SD 168.42 ± 1.76. The study used a thalliometer, Tanita Health Ware software and Quantum Resonance Magnetic Analyzer equipment to investigate height (cm), Body Mass Index (BMI), muscle mass (kg, %), as well as the obesity analysis report, and componential analysis of body and nourishment. The differences registered between the samples of active and semi-active sports subjects were predominantly statistically significant for p < 0.05. The differences registered between the samples of active and semi-active sports subjects were predominantly statistically significant for p < 0.05. The most important parameters regarding obesity and body composition that registered significant differences between the two male groups were in favor of the group of active athletes: triglyceride content of abnormal coefficient 0.844 (CI95% 0.590-1.099), abnormal lipid metabolism coefficient 0.798 (CI95% 1.091-0.504), obesity degree of body (ODB %) 10.290 (CI95% 6.610-13.970), BMI 2.326 (CI95% 1.527-3.126), body fat (kg) 2.042 (CI95% 0.918-3.166), muscle volume (kg) 2.565 (CI95% 1.100-4.031), Lean body weight (kg) 2.841 (CI95% 5.265-0.418). In the case of female samples, the group of active sportswomen registered the biggest differences compared to the group of students who were significantly active in the parameters: abnormal lipid metabolism coefficient 1.063 (CI95% 1.380-0.746), triglyceride content of abnormal coefficient 0.807 (CI95% 0.437-1.178), obesity degree of body (ODB%) 8.082 (CI95% 2.983-13.181), BMI 2.285 (CI95% 1.247-3.324), body fat (kg) 2.586 (CI95% 0.905-4.267), muscle volume (kg) 2.570 (CI95% 0.154-4.985), lean body weight (kg) 4.118 (CI95% 1.160-7.077). The results of the study directly facilitate the understanding of the complexity of the impact of obesity on multiple parameters of body composition and health.

A Geospatial Semantic Enrichment and Query Service for Geotagged Photographs.

With the increasing abundance of technologies and smart devices, equipped with a multitude of sensors for sensing the environment around them, information creation and consumption has now become effortless. This, in particular, is the case for photographs with vast amounts being created and shared every day. For example, at the time of this writing, Instagram users upload 70 million photographs a day. Nevertheless, it still remains a challenge to discover the "right" information for the appropriate purpose. This paper describes an approach to create semantic geospatial metadata for photographs, which can facilitate photograph search and discovery. To achieve this we have developed and implemented a semantic geospatial data model by which a photograph can be enrich with geospatial metadata extracted from several geospatial data sources based on the raw low-level geo-metadata from a smartphone photograph. We present the details of our method and implementation for searching and querying the semantic geospatial metadata repository to enable a user or third party system to find the information they are looking for.

Intraparenchymal meningioma mimicking cavernous malformation: a case report and review of the literature.

INTRODUCTION: A primary intraparenchymal meningioma located in the subcortical region of the brain without a dural attachment is extremely rare. To the best of our knowledge, this is the first report showing that meningioma can mimic cavernous malformations. CASE PRESENTATION: We present the case of a 42-year-old German man who presented to our institution with seizure. Both computed tomography and magnetic resonance imaging scans showed characters of an intra-axial subcortical lesion with a 'popcorn' appearance and hemosiderin deposits in the right parietal lobe. The initial diagnosis was cavernous malformation. Intraoperatively, the lesion presented as a subcortical mass that had no connection to the dura or the ventricle. The histological diagnosis showed a WHO Grade 1 'raddled' psammomatous meningioma with extensive metaplastic ossification. A literature review of 29 cases of intraparenchymal meningiomas regarding their clinical presentations, location and management was performed. CONCLUSIONS: Meningiomas can be found in any region of the brain with and without dural attachment. Intraparenchymal meningiomas can have multiple entities mimicking their presentation. Caution must be used regarding the preoperative differential diagnosis.

Recurrent paraganglioma of Meckel's cave: Case report and a review of anatomic origin of paragangliomas.

BACKGROUND: Paragangliomas are rare, usually benign tumors of neural crest origin. They account for only 0.6% of all head and neck tumors. In the craniocervical area, they are more common in the carotid body and tympanico-jugular regions. To the authors' knowledge, a case of paraganglioma in Meckel's cave has not yet been reported in the medical literature. The pathogenesis and natural history of paragangliomas are still not well understood. We present a case of recurrent paraganglioma in Meckel's cave. CASE DESCRIPTION: A 53-year-old woman was diagnosed with trigeminal neuralgia, dysesthesia and hypoesthesia on the left side of the face, hearing disturbance and a history of chronic, persistent temporal headaches. Magnetic resonance imaging (MRI) showed a lesion located in Meckel's cave on the left side, extending to the posterior cranial fossa and compressing the left cerebral peduncle. The lesion was first thought to be a recurrence of an atypical meningioma, as the pathologist described it in the tissue specimen resected 3 years earlier, and a decision for re-operation was made. A lateral suboccipital approach to the lesion was used under neuronavigational guidance. The tumor was removed, and histological examination proved the lesion to be a paraganglioma. Five months later, the follow-up MRI showed local regrowth, which required subsequent surgical intervention. CONCLUSIONS: A paraganglioma in Meckel's cave is an uncommon tumor in this location. Although ectopic paragangliomas have been described in the literature, a paraganglioma atypically located in Meckel's cave makes a topographic correlation difficult, mainly because paraganglionic cells are usually not found in Meckel's cave. Another peculiarity of the case is the local recurrence of the tumor in a relatively short time despite an attempted, almost gross total resection.

Primary meningeal hemangiosarcoma in a grower pig.

A juvenile female pig found dead was submitted for necropsy. A focal meningeal red mass measuring 3.5 cm in diameter was located over the left olfactory bulb. Histologically, the mass was composed of polygonal-to-spindle-shaped cells forming vascular clefts with focal invasion of the neuropil of the olfactory bulb. Immunohistochemistry revealed strong expression of vimentin, and a variable labeling of factor VIII-related antigen, smooth muscle actin, and neurotrophin receptor p75. The final diagnosis was a primary meningeal hemangiosarcoma.

Desmoplastic ganglioglioma of the spinal cord in a western European hedgehog (Erinaceus europaeus).

Gangliogliomas are composed of neoplastic glial and neuronal cells and are extremely rare tumors of the central nervous system of domestic animals. The present report describes the clinical presentation and the pathomorphological and immunophenotypical characteristics of a desmoplastic ganglioglioma in the spinal cord of a 3-year-old male western European hedgehog (Erinaceus europaeus). Clinically, the hedgehog exhibited a skin wound and therapy-resistant paresis of the left hind limb. Necropsy showed dilatation of the urinary bladder. Histologic examination of the thoracic spinal cord revealed a focally extensive infiltrative mass, which consisted of multiple nodules of smaller bipolar or oligopolar glial cells and variably sized polygonal, ganglionic, neuron-like cells embedded in variable amounts of microcystic neuropilic matrix. An area of spindle-shaped cells arranged in interwoven fascicles and surrounded by a prominent network of reticulin fibers was interpreted as desmoplastic leptomeningeal stroma. Immunohistochemistry revealed a moderate number of glial fibrillary acidic protein and S-100-positive cells and processes. In addition, the ganglionic neuron-like cells expressed neurofilament, microtubule-associated protein-2, and neuron-specific enolase. In summary, this spinal cord tumor was composed of astroglial and neuronal cellular elements, justifying the diagnosis of a desmoplastic ganglioglioma.

U373-MG cells express PepT2 and accumulate the fluorescently tagged dipeptide-derivative ß-Ala-Lys-N(ε)-AMCA.

Aim of this study was to examine the dipeptide transport of ß-Ala-Lys-N(ɛ)-AMCA in the human glioma cell line U373-MG and its potential regulation by diverse hormones and culture media. A mixed glial primary cell culture of the newborn rat served as reference cell system. ß-Ala-Lys-N(ɛ)-AMCA (ß-Ala-Lys-N(ɛ)-7-amino-4-methyl-coumarin-3-acetic acid) is a highly specific reporter substrate to investigate the dipeptide transport system PepT2. We were able to demonstrate that U373-MG cells express PepT2-mRNA and translocate ß-Ala-Lys-N(ɛ)-AMCA via PepT2 into the cytoplasm. Previous results demonstrated that ß-Ala-Lys-N(ɛ)-AMCA specifically accumulates in differentiated and dedifferentiated astrocytes but neither in differentiated nor dedifferentiated oligodendrocytes and in neurons. U373-MG cells were incubated with estradiol, testosterone, thyronine, dexamethasone, dibutyryl cyclic adenosine monophosphate and tetradecanoylphorbol acetate in order to detect potential substance-dependent changes in dipeptide uptake. There was no significant increase or decrease of ß-Ala-Lys-N(ɛ)-AMCA-uptake after stimulation. Northern blot analyses confirmed that PepT2-mRNA is expressed in U373-MG and glial cells but showed no regulation of PepT2-mRNA expression in both cell types. Future investigations might offer the opportunity of an anti-tumor therapy with cytotoxic agents linked to a dipeptide-derivative such as ß-Ala-Lys.

PepT2 transporter protein expression in human neoplastic glial cells and mediation of fluorescently tagged dipeptide derivative beta-Ala-Lys-Nepsilon-7-amino-4-methyl-coumarin-3-acetic acid accumulation.

OBJECT: The present study was aimed at analyzing the accumulation of the fluorescently tagged dipeptide derivative, beta-Ala-Lys-N(epsilon)-7-amino-4-methyl coumarin-3-acetic acid (AMCA), in primary cultures of human neoplastic glial cells. This molecule is a highly specific reporter used to investigate the dipeptide transport system hPepT2. METHODS: In this study the authors used immunocytochemical methods to determine the cell-specific accumulation of a small and fluorescently tagged reporter molecule named beta-Ala-Lys-N(epsilon)-AMCA to detect dipeptide transport capacity of neoplastic glial cells. Furthermore, specific mRNA levels were quantified using Northern blot analysis and the tissue distribution of hPepT2 mRNA transcripts was demonstrated with in-situ hybridization histochemical analysis. RESULTS: Recent fluorescent immunocytochemical analyses have revealed that beta-Ala-Lys-N(epsilon)-AMCA specifically accumulates within anaplastic cells of astrocytic lineage but not in anaplastic oligodendrocytes or neurons. Northern blot analysis demonstrated that human hPepT2 mRNA is specifically detected in primary cell cultures of human glioblastoma but not in oligodendroglioma. Moreover, in situ hybridization analyses revealed an astrocytic localization of hPepT2 transcripts in human glioblastoma and astrocytoma cells. The hPepT2 transcription levels were clearly dependent on the grade of glial cell differentiation: within low-grade gliomas (WHO Grade II), more hPepT2 mRNA was detected compared with tumors of a higher grade of dedifferentiation (WHO Grade IV). Analysis of expression levels of hPepT2 mRNA in human neoplastic glial cells xenografted into the brains of athymic rats (han rnu(+/+)) showed a markedly increased expression of hPepT2 after 2 weeks of growth in vivo compared with the primary counterparts grown in vitro. CONCLUSIONS: The authors concluded that expression of the hPepT2 transporter protein is a characteristic of glial cells of astrocytic lineage, and is dependent on the grade of astroglial cell differentiation and the extracellular matrix (here brain neuropil). The authors found that beta-Ala-Lys-N(epsilon)-AMCA is as an excellent reporter molecule for assessing neoplastic glial cell function and physiological characteristics.

Calcifying pseudoneoplasm of the inferior colliculus: an unusual location for a rare tumor: case report.

OBJECTIVE: Quadrigeminal plate lesions are rare and usually present with a silent clinical course. Tumors, vascular lesions, inflammatory and infectious processes have been described in this region. Calcifying pseudoneoplasms, also reported as fibro-osseous lesions, cerebral calculi, and brain stones, are unusual lesions in the central nervous system. They can be revealed by cranial radiography, computed tomography, and magnetic resonance imaging as calcified masses and should be differentiated from neoplastic, inflammatory, and vascular lesions. To the best of our knowledge, the occurrence of a calcifying pseudoneoplasm located at the quadrigeminal plate has not yet been reported. CLINICAL PRESENTATION: A 67-year-old woman with a 6-month history of several daily attacks of dizziness presented to our service. Magnetic resonance imaging studies revealed a tumor in the right inferior colliculus. This lesion was isointense on T1-weighted imaging, hypointense on T2-weighted imaging, and homogeneously enhanced with contrast. INTERVENTION: The lesion at the quadrigeminal plate was completely removed, and the patient was successfully treated without any new neurological deficit. At the time of follow-up, all preoperative symptoms had resolved. CONCLUSION: We report the first case of a calcifying pseudoneoplasm of the inferior colliculus. Complete surgical removal of this type of tumor is feasible. We propose surgical treatment in this location when this tumor becomes symptomatic.

Bilateral osteomas arising from the internal auditory canal: case report.

OBJECTIVE: Osteomas arising from the internal auditory canal and developing in the cerebellopontine angle have rarely been reported. We present the first case of bilateral osteomas in this region and describe our management strategy. CLINICAL PRESENTATION: A 30-year-old woman presented with strong vertigo, tinnitus, and hypacusis on the left side. Brain magnetic resonance imaging and computed tomographic scans displayed bilateral cerebellopontine angle osteomas arising from the internal auditory canal. The larger tumor on the left side was found to be compressing the vestibulocochlear nerve. INTERVENTION: Surgery was performed on the symptomatic side via the retrosigmoid approach, and the tumor was removed completely. The vertigo resolved completely after surgery, and the patient had no further tinnitus attacks. An audiogram showed slightly improved hearing with a mean of 20 dB in the main speech area. CONCLUSION: Osteomas should be considered in patients with bilateral cerebellopontine angle tumors. Surgical removal might provide resolution of symptoms.

Bilateral malignant melanoma metastases to the internal auditory canal/cerebellopontine angle: surgical management and preservation of function.

Although intracranial metastases of malignant melanomas are common, localization at the cerebellopontine angle (CPA) or in the internal auditory canal (IAC) is rare, and bilateral presentation especially so. We present the case of a 46-year-old Caucasian woman with bilateral IAC/CPA lesions and a prior history of malignant melanoma on the right leg. During preoperative investigations, the presence of the bilateral IAC/CPA lesions along with several radiologically identified lesions along the neural axis led to the suspicion that she had neurofibromatosis Type 2 despite her history of malignant melanoma and the lack of characteristic skin lesions and family history. Histopathological analysis of the resected lesion confirmed the intraoperative diagnosis of bilateral CPA malignant melanoma metastases. Surgical removal of the tumors via the retrosigmoid approach with preservation of normal bilateral facial nerve function and unilateral serviceable hearing, combined with control of the systemic disease, provided this patient with a near-normal quality of life for at least 42 months after the initial diagnosis of melanoma.

Expression of bcl-2 is associated with microvessel density in olfactory neuroblastoma.

Erythropoietin (Epo) expression is regulated via hypoxia-inducible factor (HIF)-1alpha-directed gene transcription. Activation of the erythropoietin receptor (EpoR) by Epo leads to elevated expression of the anti-apoptotic protein, bcl-2, which has recently been shown to promote angiogenesis in malignant tumors. Expression of HIF-1alpha, Epo, EpoR, and bcl-2 was studied by immunohistochemistry in a series of 20 olfactory neuroblastoma (ONB) samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens and survival analysis was performed to investigate the prognostic value of the examined factors. Immunohistochemical analysis revealed robust expression of HIF-1alpha, Epo, EpoR, and bcl-2 in ONB. Ninety percent of the samples showed HIF-1alpha immunoreactivity and in 60% of the cases, bcl-2 immunoreactivity was observed. A significant positive correlation between the expression levels of HIF-1alpha and bcl-2 and the microvessel density was found. Survival analysis did not reveal any prognostic significance for the tested factors. Expression of HIF-1alpha, Epo, Epo-R, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 may act as a stimulator of angiogenesis in ONB, and thus represents a novel target for anti-angiogenic treatment strategies in the therapy of ONB.

Solitary fibrous tumor of the foramen of Monro.

Solitary fibrous tumors have been described rarely in the central nervous system and only exceptionally within the ventricular system. This benign entity shows histoimmunochemically strong positivity for vimentin and calretinin. Little is known about the pathophysiological aspects. The authors report on a 75-year-old woman who presented with clinical signs of occlusive hydrocephalus including cognitive deficits, urine incontinence and gait disturbance. Imaging studies demonstrated a tumor at the foramen of Monro which was thought to be a colloid cyst and she underwent CSF shunting. After recurrent episodes of shunt dysfunction the tumor was removed via a transventricular approach guided by endoscopic ventriculoscopy. The histopathological examination revealed a solitary fibrous tumor. This is the first report on a solitary fibrous tumor located at the foramen of Monro in an elderly patient. Surgical removal has been considered to be the best therapeutic strategy in treating this rare entity with no need of postoperative adjuvant therapy. Further imaging and histological studies are needed to improve understanding of the pathophysiological aspects behind it.

Auditory midbrain implant: histomorphologic effects of long-term implantation and electric stimulation of a new deep brain stimulation array.

HYPOTHESIS: Chronic implantation and electric stimulation with a human prototype auditory midbrain implant (AMI) array within the inferior colliculus achieves minimal neuronal damage and does not cause any severe complications. BACKGROUND: An AMI array has been developed for patients with neural deafness and, based on animal studies, has shown to possess potential as an auditory prosthesis in humans. To investigate the safety of the AMI for clinical use, we characterized the histomorphologic effects of chronic implantation and stimulation within its target structure, the inferior colliculus. METHODS: Eight cats were chronically implanted for 3 months, and histologic sections were analyzed to assess long-term tissue effects. Four of the 8 cats were additionally stimulated for 60 days (4 h/d) starting 4 weeks after implantation to assess if clinically relevant stimuli further affected the tissue response. RESULTS: In general, both neurons and neuropil surrounding the implant track were apparently unaffected, whereas a fibrillary sheath (approximately 50 microm thick) developed around the array. There was a significant decrease in neuron density 50 to 100 microm away from the track with a significantly elevated number of glial cells out to approximately 250 to 350 microm. Chronic stimulation seemed to improve the tissue response and neuronal survival around the implant, although further studies are needed to confirm this finding. CONCLUSION: The histomorphologic effects and extent of neuronal damage observed for our AMI array are similar to those of other neural implants currently and safely used in humans. The minimal tissue damage surrounding the implanted array is encouraging with regard to the safety of the array for human use.

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer.

Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n=85) and primary breast cancers, with known involvement of the CNS (n=44) including paired primary and metastasized tumours (n=23), were investigated retrospectively for the expression of oestrogen- (ER) and progesterone- (PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.