Multi-Omic Data Interpretation to Repurpose Subtype Specific Drug Candidates for Breast Cancer

Triple-negative breast cancer (TNBC), which is largely synonymous with the basal-like molecular subtype, is the 5th leading cause of cancer deaths for women in the United States. The overall prognosis for TNBC patients remains poor given that few treatment options exist; including targeted therapies (not FDA approved), and multi-agent chemotherapy as standard-of-care treatment. TNBC like other complex diseases is governed by the perturbations of the complex interaction networks thereby elucidating the underlying molecular mechanisms of this disease in the context of network principles, which have the potential to identify targets for drug development. Here, we present an integrated “omics” approach based on the use of transcriptome and interactome data to identify dynamic/active protein-protein interaction networks (PPINs) in TNBC patients. We have identified three highly connected modules, EED, DHX9, and AURKA, which are extremely activated in TNBC tumors compared to both normal tissues and other breast cancer subtypes. Based on the functional analyses, we propose that these modules are potential drivers of proliferation and, as such, should be considered candidate molecular targets for drug development or drug repositioning in TNBC. Consistent with this argument, we repurposed steroids, anti-inflammatory agents, anti-infective agents, cardiovascular agents for patients with basal-like breast cancer. Finally, we have performed essential metabolite analysis on personalized genome-scale metabolic models and found that metabolites such as sphingosine-1-phosphate and cholesterol-sulfate have utmost importance in TNBC tumor growth

30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data

Background: There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods: This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results: In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions: This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients

Adaptation of Statistics Anxiety Scale to Turkish: Validity and Reliability Study

The aim of this study is to adapt the Statistics Anxiety Scale (SAS) developed by Vigil-Colet et al. (2008) to Turkish. This study is expected to fill an important gap in the literature since no valid and reliable specific statistics anxiety scale developed or adapted in Turkish for undergraduate students in the literature is available. The sample consists of a total of 439 university students, 258 women and 181 men, studying at Diizce University. The construct validity of the Turkish form of SAS was examined by EFA and DFA. Also, for the criterion validity, a different statistics anxiety scale whose validity and reliability tested was used. As a result of EFA, a three-dimensional structure was obtained as in the structure of the original scale. According to the CFA results, which is the second analysis for construct validity, all fit index results of the model were at an acceptable level. Thus, the CFA results supported the three-factor structure obtained from EFA findings. As a result of the reliability analysis, the Cronbach's Alpha internal coefficients of the SAS and its subscales and, the Guttman and Spearman-Brown internal consistency coefficients of Split-Half Reliability methods were quite high and above the limit of 0.70. For item discrimination, items have good discrimination by obtaining all values above 0.30 lower limit in the results. When the results of the study are evaluated as a whole, the SAS form adapted to Turkish can be used as a guiding scale to measure the statistics anxiety of undergraduate students.WOS:00069088420001

Experimental Craniofacial Composite Tissue Allotransplantation (CCTA) Models in Rats

Rats are the most frequently used animals in composite tissue allotransplantation (CTA) studies and most craniofacial composite tissue transplantation models are described in rats. During the last 10 years, a total of 8 different craniofacial composite tissue allotransplantation (CCTA) models have designed and developed in rats. These models include full face/scalp transplants, hemiface transplants, composite hemiface/calvarium transplants, rat maxilla allotransplants, composite osteomusculocutaneous hemiface/mandible/tongue flap transplants, composite midface allotransplants, total osteocutaneous hemifacial allotransplantation model and composite face and eyeball allotransplant model with optic nerve. All these models provide a basic and scientific foundation for future success in CTA in the clinical setting. This review presents different experimental models of CCTA in rats which are relevant to observed in clinical scenario cases of severe facial deformities. [Arch Clin Exp Surg 2012; 1(3.000): 181-187

A Review of the Prevention and Treatment of Hypertrophic Scars: Part I Clinical Aspects

The therapeutic management of hypertrophic scars remains challenging. Numerous methods have been described for the treatment of hypertrophic scars but, to date, the optimal treatment method has not been established. The aim of this review is to discuss the therapeutic modalities in the light of current literature, and to guide regarding the choice of treatment methods for physicians. The surgical and non-surgical treatment and prevention methods of the hypertrophic scars were reviewed and some recommendations for physicians who try to treat or prevent the hypertrophic scar were developed under cover of current literature and our personal experiences. A lot of therapeutic modalities have been described for the hypertrophic scars so far, but there is no absolute curative method alone. The most appropriate method or methods should be selected according to the patient and #8217;s needs and properties of the scar. The therapists can benefit from our review when they select the most appropriate method or methods for treatment of hypertrophic scars. [Arch Clin Exp Surg 2012; 1(4.000): 237-248

A Review of the Prevention and Treatment of Hypertrophic Scars: Part II. Experimental Studies

The understanding of the pathophysiological events of wound healing is very important to carry out the prevention or treatment of hypertrophic scars. Wound healing is a complex process consisting of the overlapping events, and the researchers have focused on the pathophysiology of the scar formation. The purpose of this article is to review the recent experimental studies about hypertrophic scars, and to analyze the substances focused on by recent experimental studies. We analyzed the researches for new hopeful treatment modalities as well as the substances that are important to wound healing in the second part of this extensive review. The researchers have tried to find a way to scarless wound healing, and it seems likely that new therapies will be available within the next few years. [Arch Clin Exp Surg 2013; 2(1.000): 49-58

Mediation role of work engagement in the effect of healthcare professionals' perception of organizational trust and organizational support on perception of organizational cynicism

The aim of this study is to investigate the mediating role of work engagement in the effect of healthcare workers' perceptions of organizational trust and organizational support on organizational cynicism. A total of 306 healthcare workers participated in the research. Data was collected using scales for organizational trust, organizational support, organizational cynicism, and work engagement. Confirmatory factor analysis was conducted to validate the structure of the scales. The study employed PATH analysis to determine the mediating role of work engagement. The data were analyzed using SPSS and AMOS software. The findings established a negative relationship between perceptions of organizational trust and organizational support with organizational cynicism, which is partially mediated by the level of work engagement. Additionally, the study identified a negative relationship between the level of work engagement and organizational cynicism. Conversely, the study concluded that perceptions of organizational trust and support have a positive impact on work engagement levels. This research makes a significant contribution to understanding the effects of healthcare workers' perceptions of organizational trust and support on organizational cynicism and work engagement. Furthermore, these results could provide a valuable foundation for developing effective strategies in the management and practice of health organizations.Artvin UniversityNo Statement Availabl