Feature selection and modelling methods for microarray data from acute coronary syndrome

Acute coronary syndrome (ACS) represents a leading cause of mortality and morbidity worldwide. Providing better diagnostic solutions and developing therapeutic strategies customized to the individual patient represent societal and economical urgencies. Progressive improvement in diagnosis and treatment procedures require a thorough understanding of the underlying genetic mechanisms of the disease. Recent advances in microarray technologies together with the decreasing costs of the specialized equipment enabled affordable harvesting of time-course gene expression data. The high-dimensional data generated demands for computational tools able to extract the underlying biological knowledge. This thesis is concerned with developing new methods for analysing time-course gene expression data, focused on identifying differentially expressed genes, deconvolving heterogeneous gene expression measurements and inferring dynamic gene regulatory interactions. The main contributions include: a novel multi-stage feature selection method, a new deconvolution approach for estimating cell-type specific signatures and quantifying the contribution of each cell type to the variance of the gene expression patters, a novel approach to identify the cellular sources of differential gene expression, a new approach to model gene expression dynamics using sums of exponentials and a novel method to estimate stable linear dynamical systems from noisy and unequally spaced time series data. The performance of the proposed methods was demonstrated on a time-course dataset consisting of microarray gene expression levels collected from the blood samples of patients with ACS and associated blood count measurements. The results of the feature selection study are of significant biological relevance. For the first time is was reported high diagnostic performance of the ACS subtypes up to three months after hospital admission. The deconvolution study exposed features of within and between groups variation in expression measurements and identified potential cell type markers and cellular sources of differential gene expression. It was shown that the dynamics of post-admission gene expression data can be accurately modelled using sums of exponentials, suggesting that gene expression levels undergo a transient response to the ACS events before returning to equilibrium. The linear dynamical models capturing the gene regulatory interactions exhibit high predictive performance and can serve as platforms for system-level analysis, numerical simulations and intervention studies

Laparoscopic resection of gastric GISTs. Where do we stand now? A single-centered experience

Introduction. Gastrointestinal stromal tumors (GISTs) represent a rare type of gastrointestinal neoplasms. Resection with negative margins has been established as a mainstay treatment, but laparoscopic resections are still open to debate. Material and method. This retrospective study was conducted at a single institution, with data collected over 2 years (01.01.2017-01.01.2019). The variables examined were age, tumor location with regard to the gastric wall, the results of the intraoperative endoscopy, intraoperative and postoperative complications, the surgical technique, and histopathological reports. Results. We identified 12 relevant cases, of which 8 were females and 4 males. The average tumor diameter was 2.3 cm. The majority of the lesions were located on the anterior gastric wall (8 cases), on the small curvature (2 cases), and in the pyloric region (2 cases). Intraoperative endoscopy was performed successfully in 10 cases in order to identify the lesions and guide the resection. The average operative time was 120 minutes and the average hospital stay was 5 days. The gastric wall with the lesion was resected using an Ultrasonic device, a 2-cm oncological safety margin was preserved. Conclusion. Complete surgical resection independent from the tumor size represents the current optimal treatment. From a surgical point of view, these tumors must be considered malignant and the surgeon must respect principles of oncological surgery. Maintaining tumor integrity at dissection is critical for the patient’s long-term prognosis. Laparoscopic resection independent of the tumor size is feasible

Can intraoperative manometry influence the outcome of the surgical treatment of achalasia?

Introduction. Achalasia is defined as incomplete or even absent relaxation of the lower esophageal sphincter secondary to the chronic degeneration of unspecified etiology of the myenteric nerve plexus. Material and method. The retrospective study extended over 1 year. The collected variables were: age, sex, type of surgical intervention, intraoperative manometry results, and postoperative complications. Results. We identified 8 patients. The mean operative time was 100 minutes. The use of manometry determined an increase in time of 30 to 40 minutes. Manometry was successfully achieved in all cases, although in one case the sensor could not pass through the lower esophagus, so a prior pneumatic dilation was required. Manometry has proven useful during fundoplication as it offers a direct view of the pressure produced when knots set at 12 - 15 mmHg with a length of 4-5 cm were tightened. Of the 8 patients, 6 required an increase in the length of the resection of the esophagus after the results of the intraoperative manometry were reviewed. Conclusion. In our opinion, after reviewing our experience and the literature data, intraoperative manometry should become a standard procedure in the laparoscopic treatment of achalasia

Laparoscopic resection of gastric GISTs. Where do we stand now? A single-centered experience

Introduction. Gastrointestinal stromal tumors (GISTs) represent a rare type of gastrointestinal neoplasms. Resection with negative margins has been established as a mainstay treatment, but laparoscopic resections are still open to debate. Material and method. This retrospective study was conducted at a single institution, with data collected over 2 years (01.01.2017-01.01.2019). The variables examined were age, tumor location with regard to the gastric wall, the results of the intraoperative endoscopy, intraoperative and postoperative complications, the surgical technique, and histopathological reports. Results. We identified 12 relevant cases, of which 8 were females and 4 males. The average tumor diameter was 2.3 cm. The majority of the lesions were located on the anterior gastric wall (8 cases), on the small curvature (2 cases), and in the pyloric region (2 cases). Intraoperative endoscopy was performed successfully in 10 cases in order to identify the lesions and guide the resection. The average operative time was 120 minutes and the average hospital stay was 5 days. The gastric wall with the lesion was resected using an Ultrasonic device, a 2-cm oncological safety margin was preserved. Conclusion. Complete surgical resection independent from the tumor size represents the current optimal treatment. From a surgical point of view, these tumors must be considered malignant and the surgeon must respect principles of oncological surgery. Maintaining tumor integrity at dissection is critical for the patient’s long-term prognosis. Laparoscopic resection independent of the tumor size is feasible

Can intraoperative manometry influence the outcome of the surgical treatment of achalasia?

Introduction. Achalasia is defined as incomplete or even absent relaxation of the lower esophageal sphincter secondary to the chronic degeneration of unspecified etiology of the myenteric nerve plexus. Material and method. The retrospective study extended over 1 year. The collected variables were: age, sex, type of surgical intervention, intraoperative manometry results, and postoperative complications. Results. We identified 8 patients. The mean operative time was 100 minutes. The use of manometry determined an increase in time of 30 to 40 minutes. Manometry was successfully achieved in all cases, although in one case the sensor could not pass through the lower esophagus, so a prior pneumatic dilation was required. Manometry has proven useful during fundoplication as it offers a direct view of the pressure produced when knots set at 12 - 15 mmHg with a length of 4-5 cm were tightened. Of the 8 patients, 6 required an increase in the length of the resection of the esophagus after the results of the intraoperative manometry were reviewed. Conclusion. In our opinion, after reviewing our experience and the literature data, intraoperative manometry should become a standard procedure in the laparoscopic treatment of achalasia

Efficient error control in 3D mesh coding

Our recently proposed wavelet-based L-infinite-constrained coding approach for meshes ensures that the maximum error between the vertex positions in the original and decoded meshes is guaranteed to be lower than a given upper bound. Instantiations of both L-2 and L-infinite coding approaches are demonstrated for MESHGRID, which is a scalable 3D object encoding system, part of MPEG-4 AFX. In this survey paper, we compare the novel L-infinite distortion estimator against the L-2 distortion estimator which is typically employed in 3D mesh coding systems. In addition, we show that, under certain conditions, the L-infinite estimator can be exploited to approximate the Hausdorff distance in real-time implementation

Unmodifiable variables related to thyroid cancer incidence

The incidence of thyroid cancer is significantly different between male and female patients. Thyroid cancer is also the only form of cancer where age can be considered a staging variable. Identifying biological prognostic factors such as age or sex is important as it helps select an optimal personalized therapy. The present analysis is an observational, prospective study that enrolled all patients with thyroid disease who were operated upon at a single center. The study aimed to determine the most frequent age at presentation, the predominance of one sex over the other, the incidence of malignant thyroid disease, and the relative risk for each sex to develop thyroid carcinoma. The incidence of thyroid carcinoma was higher for women than for men, with a higher relative risk in the female subgroup. Incidence was also highest in the 50-60-year-old group. Given that studies show better survival for women and for younger patients, even when presenting with advanced disease, compared with older, male patients, such prognostic indicators should be a factor in the treatment decision

Functional radical cervical dissection for differentiated thyroid cancer: the experience of a single center

There is ongoing debate regarding the role of neck dissection in differentiated thyroid cancer, about its usefulness in elective settings, and the increased costs regarding morbidity and operative time. This retrospective study aimed to determine the rate of metastases in cervical lymph nodes, to examine the morbidity of this surgery, and to assess whether a pattern of distribution of tumor cells concerning neck lymphatic compartments exists. The most frequent type of cancer to metastasize was papillary cancer, the majority of patients were young with a median of 30 years, predominantly females. Differentiated thyroid cancer frequently metastasizes to the central and lateral compartments of the neck. The morbidity is minimal in a high-volume center. Radical neck dissection is safe and feasible in selected patients with confirmed invaded or enlarged lymph nodes due to differentiated thyroid cancer, and postoperative complications are minimal if the anatomy is correctly identified and the cases strictly selected

Does sex of the patient play a role in survival for MSI colorectal cancer?

Microsatellite instability (MSI) is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center study which included 122 colorectal cancer patients who were tested for MSI using immunohistochemistry. The trial included patients with stage II to IV colorectal cancer, treated in the Prof. Dr. Agrippa Ionescu Emergency Hospital, Bucharest, Romania. Follow-up data were collected during a 24-month period. The study attempted to determine whether differences exist in overall survival for MSI (microsatellite instability) vs. MSS (microsatellite stable) colorectal cancer and to ascertain whether sex of the patient influences prognosis in MSI patients, irrespective of stage or treatment. Results demonstrated no significant differences in survival for MSI vs MSS colorectal patients, and patients’ gender proved not to influence the outcome in MSI patients

Unmodifiable variables related to thyroid cancer incidence

The incidence of thyroid cancer is significantly different between male and female patients. Thyroid cancer is also the only form of cancer where age can be considered a staging variable. Identifying biological prognostic factors such as age or sex is important as it helps select an optimal personalized therapy. The present analysis is an observational, prospective study that enrolled all patients with thyroid disease who were operated upon at a single center. The study aimed to determine the most frequent age at presentation, the predominance of one sex over the other, the incidence of malignant thyroid disease, and the relative risk for each sex to develop thyroid carcinoma. The incidence of thyroid carcinoma was higher for women than for men, with a higher relative risk in the female subgroup. Incidence was also highest in the 50-60-year-old group. Given that studies show better survival for women and for younger patients, even when presenting with advanced disease, compared with older, male patients, such prognostic indicators should be a factor in the treatment decision