Clinically relevant postoperative pancreatic fistula (CR-POPF) can significantly affect the treatment course and outcome in pancreatic cancer patients. Preoperative prediction of CR-POPF can aid the ...surgical decision-making process and lead to better perioperative management of patients. In this retrospective study of 108 pancreatic head resection patients, we present risk models for the prediction of CR-POPF that use combinations of preoperative computed tomography (CT)-based radiomic features, mesh-based volumes of annotated intra- and peripancreatic structures and preoperative clinical data. The risk signatures were evaluated and analysed in detail by visualising feature expression maps and by comparing significant features to the established CR-POPF risk measures. Out of the risk models that were developed in this study, the combined radiomic and clinical signature performed best with an average area under receiver operating characteristic curve (AUC) of 0.86 and a balanced accuracy score of 0.76 on validation data. The following pre-operative features showed significant correlation with outcome in this signature (Formula: see text) - texture and morphology of the healthy pancreatic segment, intensity volume histogram-based feature of the pancreatic duct segment, morphology of the combined segment, and BMI. The predictions of this pre-operative signature showed strong correlation (Spearman correlation co-efficient, Formula: see text) with the intraoperative updated alternative fistula risk score (ua-FRS), which is the clinical gold standard for intraoperative CR-POPF risk stratification. These results indicate that the proposed combined radiomic and clinical signature developed solely based on preoperatively available clinical and routine imaging data can perform on par with the current state-of-the-art intraoperative models for CR-POPF risk stratification.
To examine the comparative robustness of computed tomography (CT)-based conventional radiomics and deep-learning convolutional neural networks (CNN) to predict overall survival (OS) in HCC patients. ...Retrospectively, 114 HCC patients with pretherapeutic CT of the liver were randomized into a development (n = 85) and a validation (n = 29) cohort, including patients of all tumor stages and several applied therapies. In addition to clinical parameters, image annotations of the liver parenchyma and of tumor findings on CT were available. Cox-regression based on radiomics features and CNN models were established and combined with clinical parameters to predict OS. Model performance was assessed using the concordance index (C-index). Log-rank tests were used to test model-based patient stratification into high/low-risk groups. The clinical Cox-regression model achieved the best validation performance for OS (C-index 95% confidence interval (CI) 0.74 0.57-0.86) with a significant difference between the risk groups (p = 0.03). In image analysis, the CNN models (lowest C-index CI 0.63 0.39-0.83; highest C-index CI 0.71 0.49-0.88) were superior to the corresponding radiomics models (lowest C-index CI 0.51 0.30-0.73; highest C-index CI 0.66 0.48-0.79). A significant risk stratification was not possible (p > 0.05). Under clinical conditions, CNN-algorithms demonstrate superior prognostic potential to predict OS in HCC patients compared to conventional radiomics approaches and could therefore provide important information in the clinical setting, especially when clinical data is limited.
Background and Objectives. Most performance theories were tested under controlled laboratory settings and offer therefore only limited transferability to real-life situations. E-sport competitions ...offer a relatively controllable while at the same time competitive setting, and our aim was to examine different influencing factors on competitive performance. Design and Methods. Salivary cortisol was measured immediately before, after, and 30 minutes after a game of 23 computer players during e-sport tournaments. The players answered the Flow Short Scale, which consists of the two subdimensions “flow experience” and “anxiety” subsequent to their game. The performance was assessed by the result of each player’s game (win or loss). Results. Mean cortisol levels increased significantly during the game but response patterns were inconsistent. Winners and losers differed significantly in anxiety with winners showing higher anxiety levels. After dividing the sample into three groups of different cortisol response patterns, significant differences in performance and anxiety were found, with low to moderate levels of cortisol being associated with the highest performance and anxiety. Conclusions. A low to moderate physiological arousal and a simultaneously high level of anxiety represent a favorable state for achieving optimal performance during e-sports. Anxiety seems to exert a stronger influence on performance than physiological arousal.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is projected to be the second leading cause of cancer-related death by 2030. Despite extensive knowledge and ...insights into biological properties and genetic aberrations of PDAC, therapeutic options remain temporary and ineffective. One plausible explanation for the futile response to therapy is an insufficient and non-specific delivery of anticancer drugs to the tumour site.
Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed against the cell cycle-specific serine-threonine-kinase, Polo-like kinase-1 (siPLK1-StAv-SPIONs), could serve a dual purpose for delivery of siPLK1 to the tumour and for non-invasive assessment of efficiency of delivery in vivo by imaging the tumour response. siPLK1-StAv-SPIONs were designed and synthesised as theranostics to function via a membrane translocation peptide with added advantage of driving endosomal escape for mediating transportation to the cytoplasm (myristoylated polyarginine peptides) as well as a tumour-selective peptide (EPPT1) to increase intracellular delivery and tumour specificity, respectively.
A syngeneic orthotopic as well as an endogenous cancer model was treated biweekly with siPLK1-StAv-SPIONs and tumour growth was monitored by small animal MRI. In vitro and in vivo experiments using a syngeneic orthotopic PDAC model as well as the endogenous LSL-Kras
, LSL-Trp53
, Pdx-1-Cre model revealed significant accumulation of siPLK1-StAv-SPIONs in PDAC, resulting in efficient PLK1 silencing. Tumour-specific silencing of PLK1 halted tumour growth, marked by a decrease in tumour cell proliferation and an increase in apoptosis.
Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC.
Purpose
Postpancreatectomy hemorrhage (PPH) is one of the leading causes of mortality after pancreatic resection. Late onset PPH is most often treated using a transarterial approach. The aim of this ...study was to analyze risk factors for in-hospital mortality after endovascular treatment.
Methods
Between 2012 and 2017, patients who were treated endovascular due to PPH were identified from a retrospective analysis of a database. Risk factors for mortality were identified by univariate analysis.
Results
In total
,
52 of the 622 patients (8.4%) underwent endovascular treatment due to PPH. The primary technical success achieved was 90.4%. In 59.6% of patients, bleeding control was achieved by placing a stent graft and in 40.4% by coil embolization. The primary 30-day and 1-year patency of the placed covered stents was 89.3% and 71.4%, respectively. The 60-day mortality was 34.6%. The reintervention rate was higher after stent graft placement compared to coiling (39.3% vs. 21.1%,
P
= 0.012). In the univariate analysis the need for reintervention was associated with a higher in-hospital mortality (21.2% vs. 7.7%,
P
= 0.049). The use of an antiplatelet agent was associated with a decreased in-hospital mortality in the univariate (11.5% vs. 25%,
P
= 0.024) and multivariate analysis (HR 3.1, 95% CI 1.1-9,
P
= 0.034), but did not increase the risk of rebleeding.
Conclusion
Endovascular management of delayed PPH has a high technical success rate. Stent graft placement showed a higher reintervention rate. The need for reintervention was associated with a higher in-hospital mortality but did not differ between coiling and stent graft placement.
Background Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have ...revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. Methods This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8.sup.th edition (AJCC8), HPV status, treatment modality (surgery (+ or - radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. Results With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (+ or - R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). Conclusion Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies. Keywords: Human papillomavirus (HPV), Oropharyngeal squamous cell carcinoma (OPSCC), Gender, Epidemiology, Survival, Prognosis
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Understanding individual growth in commercially exploited fish populations is key to successful stock assessment and informed ecosystem‐based fisheries management. Traditionally, growth rates in ...marine fish are estimated using otolith age‐readings in combination with age‐length relationships from field samples, or tag‐recapture field experiments. However, for some species, otolith‐based approaches have been proven unreliable and tag‐recapture experiments suffer from high working effort and costs as well as low recapture rates. An important alternative approach for estimating fish growth is represented by bioenergetic modelling which in addition to pure growth estimation can provide valuable insights into the processes leading to temporal growth changes resulting from environmental and related behavioural changes. We here developed an individual‐based bioenergetic model for Western Baltic cod (Gadus morhua), traditionally a commercially important fish species that however collapsed recently and likely suffers from climate change effects. Western Baltic cod is an ideal case study for bioenergetic modelling because of recently gained in‐situ process knowledge on spatial distribution and feeding behaviour based on highly resolved data on stomachs and fish distribution. Additionally, physiological processes such as gastric evacuation, consumption, net‐conversion efficiency and metabolic rates have been well studied for cod in laboratory experiments. Our model reliably reproduced seasonal growth patterns observed in the field. Importantly, our bioenergetic modelling approach implementing depth‐use patterns and food intake allowed us to explain the potentially detrimental effect summer heat periods have on the growth of Western Baltic cod that likely will increasingly occur in the future. Hence, our model simulations highlighted a potential mechanism on how warming due to climate change affects the growth of a key species that may apply for similar environments elsewhere.
A bioenergetic model, which includes in‐situ knowledge of distribution and food intake, allows tracing (seasonal) growth patterns of cod. The model shows that summer heat periods can lead to negative energy turnover, ultimately resulting in reduced growth and potentially in a reduced reproductive potential. A detrimental effect that may occur more often in the future in the course of ongoing climate change.
The rapid evolution of Industrial Computed Tomography (CT) continues to raise the bar for high-resolution, accurate, and precise imaging tools. Developing effective micro CT test patterns is key to ...meeting these expectations. This study presents XRnanotech's advanced MicroCT test target, engineered using micro- and nano-fabrication technologies, including electron beam lithography. There are several variants; one set features various lines and spaces with dimensions as small as 200 nm and a gold contrast height of 1.5 µm for high contrast. Another set features a contrast height of approximately 4 µm, with the smallest feature sizes of 300 nm and 400 nm, respectively. The paper highlights its performance metrics, ultimately demonstrating how this innovation advances the potential of MicroCT testing.
The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid ...gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.
The purpose of this study was to test whether the 8th edition of the AJCC/UICC TNM staging system (UICC) precisely differentiates between stages and reflects disease outcome in human papilloma virus ...(HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).
OPSCC patients that were diagnosed between 2000 and 2016 were included in this analysis and HPV status was determined by combined DNA and p16 testing. Stratification was done according to 7th and 8th UICC staging rules. Incidence trends of HPV-associated tumorigenesis, 5-year overall survival (OS) according to tumor stages as well as the influence of therapy and prognostic factors toward the outcome were calculated using Kaplan-Meier method and Cox proportional-hazards model.
A significant increase 2000;
= 8/39 (21%)-2015;
= 17/32 (53%);
= 0.002 in HPV-associated OPSCC was seen in the observation period. Together, 150/599 (25.0%) of the patients had HPV-driven OPSCC and 64.7% of curative treatments in all OPSCC patients included upfront surgery of the primary and the neck. 7th edition staging rules led to no discrimination in all respective four UICC stages in HPV OPSCC underlining the need for new staging rules. However, only discrimination between stages I vs. II and III vs. IV was significant in our patients with HPV-OPSCC (94.4 vs. 77.5%;
= 0.031 and 63.9 vs. 25.0%;
= 0.013), and stages II vs. III did not differ in OS rates (
= 0.257), when applying the new staging rules. For HPV-negative OPSCC, significant outcome differences were only seen between UICC stages III vs. IV (57.6 vs. 35.2%;
= 0.012).
While the 7th edition of UICC shows invalid discrimination between stages, the 8th edition is more suitable for HPV-associated carcinoma. Due to lack of differentiation between stages II and III further adaption is essential.
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