Sensitivity and specificity of machine learning and deep learning algorithms in the diagnosis of thoracolumbar injuries resulting in vertebral fractures: A systematic review and meta-analysis.

Introduction: Clinicians encounter challenges in promptly diagnosing thoracolumbar injuries (TLIs) and fractures (VFs), motivating the exploration of Artificial Intelligence (AI) and Machine Learning (ML) and Deep Learning (DL) technologies to enhance diagnostic capabilities. Despite varying evidence, the noteworthy transformative potential of AI in healthcare, leveraging insights from daily healthcare data, persists. Research question: This review investigates the utilization of ML and DL in TLIs causing VFs. Materials and methods: Employing Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, a systematic review was conducted in PubMed and Scopus databases, identifying 793 studies. Seventeen were included in the systematic review, and 11 in the meta-analysis. Variables considered encompassed publication years, geographical location, study design, total participants (14,524), gender distribution, ML or DL methods, specific pathology, diagnostic modality, test analysis variables, validation details, and key study conclusions. Meta-analysis assessed specificity, sensitivity, and conducted hierarchical summary receiver operating characteristic curve (HSROC) analysis. Results: Predominantly conducted in China (29.41%), the studies involved 14,524 participants. In the analysis, 11.76% (N = 2) focused on ML, while 88.24% (N = 15) were dedicated to deep DL. Meta-analysis revealed a sensitivity of 0.91 (95% CI = 0.86-0.95), consistent specificity of 0.90 (95% CI = 0.86-0.93), with a false positive rate of 0.097 (95% CI = 0.068-0.137). Conclusion: The study underscores consistent specificity and sensitivity estimates, affirming the diagnostic test's robustness. However, the broader context of ML applications in TLIs emphasizes the critical need for standardization in methodologies to enhance clinical utility.

Augmented Reality Integration in Skull Base Neurosurgery: A Systematic Review.

Background and Objectives: To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery. Materials and Methods: Utilizing PRISMA methodology, PubMed and Scopus databases were explored to extract data related to AR integration in SB surgery. Results: The majority of 19 included studies (42.1%) were conducted in the United States, with a focus on the last five years (77.8%). Categorization included phantom skull models (31.2%, n = 6), human cadavers (15.8%, n = 3), or human patients (52.6%, n = 10). Microscopic surgery was the predominant modality in 10 studies (52.6%). Of the 19 studies, surgical modality was specified in 18, with microscopic surgery being predominant (52.6%). Most studies used only CT as the data source (n = 9; 47.4%), and optical tracking was the prevalent tracking modality (n = 9; 47.3%). The Target Registration Error (TRE) spanned from 0.55 to 10.62 mm. Conclusion: Despite variations in Target Registration Error (TRE) values, the studies highlighted successful outcomes and minimal complications. Challenges, such as device practicality and data security, were acknowledged, but the application of low-cost AR devices suggests broader feasibility.

Morphometric and Ki-67 proliferative index-related characteristics of meningiomas and their correlation with demographic, clinical, histopathological, and postoperative features.

Aim To investigate the correlations between tumour characteristics, symptoms, intraoperative findings, and outcomes in patient with meningioma. Methods A retrospective study was conducted on 86 surgically treated patients at Department of Neurosurgery of Cantonal Hospital Zenica from 2010 to 2020. Patients with intracranial meningiomas underwent neurological evaluation and MRI scans to analyse tumour characteristics, including volume (TV), peritumoral brain oedema (PTBE) and oedema index (EI). Surgical treatment was performed, followed by postoperative MRI and outcome assessment. Intraoperatively, the tumour's relationship with cortex, pial membrane, skull bones, and sinuses was evaluated, and the extent of tumour resection was graded. Meningioma samples underwent histopathological analysis to assess the grade and regularity of borders, and Ki-67 labelling index was determined using immunohistochemistry. Results Significant correlations were found between PTBE and Ki67 expression (p<0.001), PTBE and vomiting/nausea (p=0.002), cognitive impairment (p=0.047), venous compression (p=0.001), cortical, pial and dural invasion (p<0.05), and the postoperative presence of oedema (p=0.002). Venous compression, cortical, pial, dural and bone invasion positively correlated with Ki-67 expression (p<0.001). Grade and tumour border positively correlated with Ki-67 expression (p<0.001). Oedema persistence postoperatively showed a positive correlation with Ki-67 expression (p<0.001). Conclusion The study revealed significant correlations between Ki-67 expression and PTBE, with notable associations with clinical symptoms, tumour characteristics, and postoperative oedema presence.

The New Era of Spinal Surgery: Exploring the Use of Exoscopes as a Viable Alternative to Operative Microscopes-A Systematic Review and Meta-Analysis.

BACKGROUND: The growing interest in exoscopic (EX) technology has prompted a comprehensive evaluation of its clinical, functional, and financial outcomes in neurosurgery. This systematic review and meta-analysis aimed to explore the utilization of EX in spine surgery and assess their safety, efficacy, and impact on surgical outcomes. METHODS: A thorough literature review was conducted using PubMed, Scopus, and Embase databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study focused on articles concerning the application of EXs in spinal surgical procedures. The inclusion criteria encompassed various study designs presenting clinical data and intraoperative experiences related to EX utilization in spine surgery. RESULTS: The meta-analysis included studies examining various aspects of EX utilization, such as intraoperative complications, video/image quality, surgical field visualization, ease of manipulation, ergonomic characteristics, educational utility, surgical duration, and team involvement. Findings indicated that EXs offered superior video quality and favorable ergonomic features. Comparable outcomes were observed in surgical duration, intraoperative blood loss, time to discharge, and postoperative pain levels between EX and conventional microscope approaches. CONCLUSIONS: This study provides valuable insights into the utilization of EXs in spine surgery, demonstrating their potential advantages and comparable outcomes with conventional microscopes.

Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Accessible Spinal Surgery: Transformation Through the Implementation of Exoscopes As Substitutes for Conventional Microsurgery in Low- and Middle-Income Settings.

Advancements in neurosurgical visualization have been made possible by the introduction of the operating microscope (OM) and the emergence of exoscopic technology (EX). Both OMs and EXs provide enhanced magnification and illumination, but they come with their own set of advantages and disadvantages. OMs provide high-quality magnification and illumination and have been used successfully in a variety of surgical procedures. They can be customized to fit the specific needs of the surgeon and are a well-established technology. However, they can be bulky, expensive, and cause discomfort during extended procedures. EXs provide high-definition magnification and illumination, improved depth perception and ergonomics, and can be cost-effective. They can be customized to fit the specific needs of the surgeon and can be made using locally available materials, reducing the need for expensive imports. However, they may require adjustment and have a learning curve for surgeons who are used to operating with OMs. Additionally, they may have limited availability in some healthcare settings. The choice between OMs and EXs will depend on the specific needs of the surgeon and the healthcare setting. The integration of 3D EX systems has revolutionized neurosurgery, offering improved depth perception and ergonomics. EX's cost-effectiveness addresses accessibility concerns, making it an attractive alternative, particularly for low and middle-income healthcare settings. The exoscope seems to be a safe alternative compared to an operative microscope for the most common brain and spinal procedures. The exoscope may help expand access to neurosurgical care and training worldwide. In conclusion, both technologies have their own set of advantages and disadvantages, and the choice between them will depend on the specific needs of the surgeon and the healthcare setting.

Breaking Barriers in Cranioplasty: 3D Printing in Low and Middle-Income Settings-Insights from Zenica, Bosnia and Herzegovina.

Background and Objectives: Cranial defects pose significant challenges in low and middle-income countries (LIMCs), necessitating innovative and cost-effective craniofacial reconstruction strategies. The purpose of this study was to present the Bosnia and Herzegovina model, showcasing the potential of a multidisciplinary team and 3D-based technologies, particularly PMMA implants, to address cranial defects in a resource-limited setting. Materials and Methods: An observational, non-experimental prospective investigation involved three cases of cranioplasty at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between 2019 and 2023. The technical process included 3D imaging and modeling with MIMICS software (version 10.01), 3D printing of the prototype, mold construction and intraoperative modification for precise implant fitting. Results: The Bosnia and Herzegovina model demonstrated successful outcomes in cranioplasty, with PMMA implants proving cost-effective and efficient in addressing cranial defects. Intraoperative modification contributed to reduced costs and potential complications, while the multidisciplinary approach and 3D-based technologies facilitated accurate reconstruction. Conclusions: The Bosnia and Herzegovina model showcases a cost-effective and efficient approach for craniofacial reconstruction in LIMICs. Collaborative efforts, 3D-based technologies, and PMMA implants contribute to successful outcomes. Further research is needed to validate sustained benefits and enhance craniofacial reconstruction strategies in resource-constrained settings.

A correlation of demographic characteristics, preoperative conservative therapy and timing with postoperative outcome in herniated disc-associated cauda equina syndrome: Do they really matter?

Aim To examine a correlation of demographic characteristics of patients, preoperative modality of conservative therapy and timing on the postoperative outcome of patients six months after the operation. Methods A retrospective, non-randomized, clinical study involved 48 patients of different age and gender with a verified diagnosis of cauda equina syndrome (CES). The inclusion criteria were patients with CES caused by discus hernia. Observed research variables were age, gender, affected vertebral level, conservative modalities of perioperative therapy (nonsteroidal anti-inflammatory drugs - NSAIDs and physiotherapy), duration of symptoms, and outcome parameters (motor and sensory function, sphincter function of the urinary bladder and bowel). Results A statistically significant negative correlation was found between age and postoperative outcome (p<0.05). The affected vertebral level was positively correlated with the motor and sensory outcome (p<0.05). A positive correlation between the use of NSAIDs and the outcome was found (R=0.570; p<0.001), as well as a negative correlation with perioperative physiotherapy (R=-0.201; p= 0.001). Postponement of surgery was negatively correlated with outcome variables (p<0.001). Conclusion The results of the study bring new conclusions that were not previously observed. Possible new characteristics associated with the outcome of cauda equina syndrome were determined.

A Rare Case of Third Ventricular Glioblastoma.

Glioblastoma, also known as glioblastoma multiforme, is an aggressive type of cancer that is made up of abnormal astrocytic cells, but also contain a mixture of different cell types (including blood vessels) and areas of necrosis. It is often seen in the brain and spinal cord, but glioblastomas are rarely found in the third ventricle. In this case, it was diagnosed in a 22-year-old male patient and we intended to draw attention to its atypical localization and surgical access to this third ventricle glioblastoma.

Incidence of Gliomas in Municipalities of Zenica - Doboj Canton in Bosnia and Herzegovina - A 10-Year Study.

OBJECTIVE: To determine the incidence of gliomas in Zenica - Doboj Canton. Moreover, to analyse its potential connection to sociodemographic characteristics and its distribution throughout municipalities of Zenica - Doboj Canton in the period of 2009-2019. METHOD: This retrospective, descriptive - analytical, 10 - year study included 146 patients from Zenica -Doboj Canton. Data were obtained and reviewed from patient's medical records. Patients' sociodemographic characteristics and pathohistological diagnosis were included in the study. Age, gender, and the place of birth were analysed and correlated with types and grades of glial tumors according to the World Health Organisation's latest classification. RESULTS: The study consisted of 146 patients including 84 (58%) males and 62 (42%) females. The most common pathohistological diagnosis was glioblastoma multiforme, a grade IV glioma in both females (26%) and males (35%), in total 91 (62%) patients, and the rarest was oligoastrocytoma, in 2 (1%) cases. The municipality of Kakanj had the highest incidence of glioma with 29 out of total of 146 cases (0.077%) and the highest incidence in females (0.069%) with 13 cases. The municipality of Vares had the highest incidence of glioma (0.114%) with 5 out of 84 male cases, while in the cities of Breza and Olovo any cases with glioma were not detected The results showed statistically significant differences in incidences of gliomas according to the region of residence. CONCLUSION: The analysis of data indicated that there are significant connections between the occurrence of gliomas and sociodemographic characteristics of patients from Zenica - Doboj Canton.

CORRELATION OF PERITUMORAL BRAIN EDEMA WITH MORPHOLOGICAL CHARACTERISTICS AND KI67 PROLIFERATIVE INDEX IN RESECTED INTRACRANIAL MENINGIOMAS.

The aim of the study was to analyze correlation between morphological characteristics of intracranial meningiomas and Ki67 labeling index (Ki67 LI), and their influence on peritumoral brain edema (PTBE). There were 41 consecutive patients with intracranial meningiomas surgically treated at the Department of Neurosurgery, Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina, during the period from January 2010 to December 2015. We reviewed clinical data including patient age, gender, magnetic resonance imaging (MRI) characteristics of the tumor and peritumoral edema, tumor margins, intraoperative characteristics, histopathologic grade and Ki67 LI. In all cases, follow up MRI was obtained at about three months after resection and PTBE was analyzed. Our research showed the tumor volume, tumor margins, and intraoperative signs of arachnoidal and pial invasion to be associated with PTBE in intracranial meningiomas. Ki67 LI expression correlated with PTBE. This study showed the resolution of PTBE to depend on invasive behavior of meningioma and KI67 LI. PTBE, pial/cortical and arachnoidal invasion significantly influence the extent of surgical resection.

Morphometric study of the anatomic relationship between large retroperitoneal blood vessels and intervertebral discs of the distal segment of the lumbar spine: a clinical significance.

Aim To analyse potential clinical implications of the distance between large retroperitoneal vessels and lower segment of the lumbar spine in the supine and prone position. Methods Prospective, non-randomised study included 40 patients of different age and gender. For all patients magnetic resonance imaging of the lumbar spine was performed in supine and prone position. The level of aortal bifurcation, common iliac vein confluence, the distance from the anterior and posterior aspect of the annulus to the posterior wall of the large retroperitoneal vessels were analysed. Results The study included 40 patients, 22 (55%) males and 18 (45%) females. The level of aortal bifurcation was higher in prone compared to supine position (χ2 = 29.88571; p<0.05). In supine and prone positions, the common iliac veins confluence was most commonly at the level of the lower third of the L4 vertebra (p>0.05). There was a statistically significant difference between the distance from the left common iliac artery to the anterior contour of L4/L5 intervertebral disc (p<0.05). Conclusion Knowledge of the anatomic relationship between iliac vessels and structures of the lower segment of the lumbar spine is very important in the prevention of a potentially severe complication, such as artificial common iliac vessels rupture. Our study showed that the risk of lesions of the common left iliac artery was lesser in the prone position.

Spontaneous brain and arachnoid herniation into the dural venous sinuses: a rare anatomic variation or clinical entity?

Aim To investigate the presence, type and distribution of spontaneous brain and arachnoid herniation into the dural venous sinuses as well as a clinical significance of these herniations. Methods This retrospective - prospective, non-randomised anatomical and clinical study included 990 patients who were referred to Magnetic Resonance Imaging at the Department of Radiology of the Cantonal Hospital in Zenica in the period from January to December 2016. The T1 and T2 sequences in axial, sagittal, and coronary section were used for brain or arachnoid herniation analysis. In all patients with intra-sinusal herniation health records were analysed and symptoms and reasons to refer for MRI examination were evaluated . Results In 26 (2.6%) patients (19 females; 73.08%) the arachnoid or brain herniation was found. Average age of patients was 40.269±16.496 years. Arachnoid herniation was presented in 15 (57.69%) and brain herniation in 11 (42.31%) patients. Statistical significance in relation to type of herniation was not found (p=11.070). Statistical significance between the symptoms and localisation of herniation (except for nausea and vomiting and posterior fossa herniations) (p=0.05) as well us between symptoms and type of herniation was not found (p>0.05). Conclusion The results suggest that there is a possibility of interconnection between arachnoid or/and brain herniations and some clinical symptoms such as nausea and vomiting.

Management of acute spontaneous thoracic spinal epidural hematoma causing paraplegia.

Aim To emphasize the importance of early recognition, diagnostic processing and emergent surgical treatment of spontaneous spinal epidural hematoma (SSEH). Methods A 39-year-old female presented with sudden onset of severe pain between the shoulder blades followed by paraparesis and alerted sensibility in the lower extremities. An hour later she developed paraplegia with sensory deficits below ThIV level, absence of patellar reflex, ankle jerk reflex and sphincter dysfunction. Results Magnetic resonance imaging (MRI) demonstrated acute extensive epidural mass of thoracic spinal segments (ThI-ThIII). The patient underwent emergent decompressive laminectomy ThI-ThIII with epidural hematoma evacuation within 24 hours of symptoms onset. After the surgical treatment, because of suspicion on spinal arteriovenous malformation, complete diagnostic evaluation with spinal angiography was done and no form of vascular malformation was found. Idiopathic SSEH was diagnosed. Two months later the patient reached complete neurological improvement. Conclusion The SSEH is a rare condition that should be kept in mind in patients presenting with neurological deficit and a sudden onset of back pain like it was in our case. For early diagnosis, immediate MRI is essential. Prompt surgical decompression such as laminectomy is an absolute surgical indication widely accepted for patients with progressive neurological deficit. The SSEH should be considered as one of the important differential diagnoses in patients who have developed acute myelopathy.

Anatomic variations of posterior paranasal sinuses and optic nerve.

Aim To define direct anatomical relations of the sphenoidal (alae minores), ethmoidal sinuses and optic nerve, with an emphasis on determining the effect of age on pneumatisation and dehiscence. Methods This retrospective, descriptive study involved 60 consecutive patients: 30 patients younger than 30 and30 patients older than 60 years of age. All patients underwent computerized tomography(CT). The relationship of the optic nerve and the sphenoidal and ethmoidal sinuses was classified. The presence of dehiscence in the bone structures, forming the optic canal, was checked. Dehiscence was defined as absence of visible bone density located between the sinus and the optic nerve. Protrusion of the optic nerve into the sphenoidal sinus was defined as optic nerve surrounded by pneumatised space. Results The most common type of relation between the optic nerve and sphenoidal sinus was type I, where the optic nerve was immediately adjacent to the lateral or superior wall of the sphenoidal sinus, without impression on the sinus wall. Dehiscence was documented in 15 (25%) cases, it was more common in older patients (8, 27%) than in younger ones (7, 23%). The pneumatisation processes were more frequent in patients over 60 (5, 17%) than in those younger than 30 years (4, 13%). Conclusion Surgeons and ophthalmologists should be aware of high frequency of dehiscence of sphenoidal sinus walls when treating adult patients in our population, especially when evaluating risks and complications of surgical procedures or when diagnosing inflammatory or tumorous processes in the close vicinity of posterior paranasal sinuses.

Radiological evaluation of lumbosacral spine for post discectomy segmental instability.

Aim To establish presence of segmental instability in patients operated with standard discectomy comparing measurement of translation and rotation on postoperative functional radiographs of lumbosacral spine with reference values,and to explore difference between patients operated on one or two levels. Methods The study included 71 patients, who were operated due to herniated lumbar disc. They were divided into two groups operated on one level (group A) or two adjacent levels (group B). All patients had been imaged in a standing position with functional lateral radiography. Radiographic images were digitized and then computerized measurement of translation and rotation was made. Measurement data were compared between the groups and with reference values obtained in healthy adults. Results Standard lumbar discectomy leads to an increase in translation, however, it reached statistical significance only for L4/L5 level and a decrease of rotation, which showed statistical significance for all samples, relative to the reference values. There was no statistically significant difference in the values of translation and rotation between the groups for corresponding levels, except for the value of the rotation for L4/L5 level as adjacent, unoperated level. Comparison of translation and rotation between the operated and adjacent levels did not show a statistically significant difference. When it comes to comparing the measured and predicted translation, there was a statistically significant difference only at the L5/S1 as anunoperated level. Conclusion Standard discectomy does not lead to radiologically significant segmental instability, and two-level surgery has not caused more pronounced signs of instability comparing to onelevel surgery.

Impact of timing on surgical outcome in patients with cauda equina syndrome caused by lumbar disc herniation.

Aim To analyze the relationship between timing of surgery and outcome in patients with cauda equina syndrome caused by lumbar disc herniation. Methods A retrospective, non-randomized clinical study included 25 consecutive patients with cauda equina syndrome (CES) caused by lumbar disc herniation. All patients were operated within 24 hours after hospitalization at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between January 2000 and December 2010. All patients were evaluated before surgery on the basis of complete history, neurological examination and neuroimaging evaluations using CT (computed tomography)and MRI (magnetic resonance imaging). Results Statistically significant difference between preoperative and postoperative bladder (p=0.05) and bowel (p=0.05) function was found. A significant number of patients had bladder and bowel recovery after surgery, nine (36%) and 11 (44%), respectively. Significant recovery of muscle strength was noted with complete recovery(5/5) in 12 (48%) and partial recovery in 13 (52%) patients. Complete sensory recovery was noted in 16 (64%), incomplete in four (16%), and in five (20%) patients there were no changes. Most commonly, patients with complete sensory recovery were operated within 48 hours of symptom onset. In most patients early surgery was associated with better outcome. Conclusion This research showed that early decompression correlated with better outcome. Patients with cauda equina syndrome must be cleared for surgery in optimal conditions and, if it possible within optimal timing for recovery (within 48 hours).

[Dorsal extrusion of intervertebral disc as a cause of cauda equina syndrome].

We have presented a case of rare dorsally sequestrated lumbar disc herniation manifesting as cauda equina syndrome. The patient was admitted to the Neurological Department of Canton Hospital Zenica due to urinary retention and weakness in both lower extremities. Magnetic resonance imaging showed a compressing mass located in the dorsal extradural space at the L2-L3 level. An extruded intervertebral disc was found intraoperatively. The decompression was followed by good recovery.

Morphometric changes of the lumbar intervertebral space following discectomy on one or two levels.

AIM: To investigate a potential difference in postoperative morphological changes of two-level lumbar disc surgery as compared to one level surgery. METHODS: The standard lateral radiographs of lumbar spine obtained preoperatively and postoperatively were used in the study . The morphological study included 60 adult patients of both sexes who had undergone the surgery in the period 2002-2006. The first group comprised patients operated on one level (L4/L5 and L5/ S1), and the second included patients operated on two levels (L3/ L4/L5; L4/L5/S1 and L5/S1/S2). Using lateral radiographs, after digitalization, the height of intervertebral disc space (HD), angle between vertebral bodies (A) and translation (T) were measured. RESULTS: Comparing preoperative and postoperative values, statistically significant difference has been found for HD in the first group and HD and A in the second group. In neither groups there was statistically significant difference for T, which is one of radiological signs of segmental instability. The comparison of postoperative values for both groups has not shown any statistically significant difference. CONCLUSIONS: The standard lumbar discectomy on two levels has not shown more pronounced morphological changes or changes suggesting an increased risk of segmental instability as compared to one level discectomy.

[Chronic epidural haematoma mimicking meningioma]. / Hronicni epiduralni hematom dijagnosticiran kao meningeom.

The study presents a rare case of organised chronic epidural haematoma that imitated a meningioma. A patient was admitted to the Department of Neurology of the Cantonal Hospital Zenica due to loss of consciousness and right hemiparesis. Non-contrast Computed Tomography (CT) scan had shown an expansive intracranial process in the left parietal region which was radiologically diagnosed as a meningioma. During the operation a linear skull fracture and organised chronic epidural haematoma were found.