An extended Cox model showed that each one percent increase of the FRS significantly increased the risk of chronic graft failure by 4% . This association remained significant after adjustment for potential confounders, including eGFR . Adding the FRS to eGFR resulted in a higher AUC in a receiver operating curve  than eGFR alone , and an improvement in the model likelihood ratio statistic . These results suggest that a combination of the FRS and eGFR improves risk prediction. The easy to determine and widely available FRS has clinical potential to predict chronic graft failure in RTR.Predicting chronic graft failure in renal transplant recipients (RTR) is an unmet clinical need. Chronic graft failure is often accompanied by transplant vasculopathy, the formation of de novo atherosclerosis in the transplanted kidney. Therefore, we determined whether the 10-year Framingham risk score (FRS), an established atherosclerotic cardiovascular disease prediction module, is associated with chronic graft failure in RTR. In this prospective longitudinal study, 600 well-characterised RTR were followed for 10 years. The association with death-censored chronic graft failure ( ThereDue to the post-transplantation increase in cardiovascular risk, there is rather extensive literature concerning CVD prediction in RTR using traditional risk stratification ,9,10. InHowever, with respect to chronic graft failure, no consensus has been reached regarding prediction models, although there is a clear clinical need for such an approach given the poor 10-year graft survival. A successfully validated risk prediction module would also allow to tailor targeted intervention approaches, e.g., with pharmacotherapy, to prolong graft survival. Although the overall cardiovascular status of RTR is mostly poor, the allograft often has a normal vascular make-up at the time of transplantation. As chronic rejection is frequently accompanied by de novo atherogenesis, we hypothesise that the FRS as a commonly applied cardiovascular risk score could also serve to stratify RTR at risk of developing chronic graft failure.All RTR with a normally functioning renal graft for at least one year who visited the outpatient clinic in the University Medical Centre Groningen (UMCG) between August 2001 and July 2003 were invited to join the study. Exclusion criteria were overt congestive heart failure, endocrine abnormalities except diabetes mellitus, and cancer other than cured skin cancer. Of the 847 eligible patients, 606 opted to participate in the study (72%). The baseline characteristics showed no difference between participants and the original cohort, making it an accurate representation of the whole. Out of the 606 patients, five had to be excluded due to insufficient data to calculate the Framingham risk score, and one patient was lost to follow-up. Patients were followed for a median period of 10 years. The study was approved by the local Medical Ethics Committee (METc2001/039), and is in accordance with the Declaration of Helsinki. All included subjects gave written informed consent. The TxL-IRI Biobank and Cohort Study is registered at ClinicalTrials.gov with identifier NCT03272854.Diabetes was defined as a fasting plasma glucose ≥7.0 mmol/L or the use of antidiabetic medication, in accordance with ADA guidelines .After an 8–12 h fasting period, blood was drawn and routine laboratory measurements were conducted, as previously described . GlucoseThe main predictor of this study was the 10-year Framingham cardiovascular risk score, which was calculated using the 10-year cardiovascular risk algorithm of the Framingham Heart Study ,16. The Renal transplant recipients were divided into three pre-defined groups based on the FRS, namely “low risk” (<10%), “intermediate risk” (10–20%) and “high risk” (≥20%), as established in earlier studies ,18. Diffp < 0.05). In order to account for the varying effect of the FRS over time, an extended Cox model was used. A time varying covariate (TVC) was computed, therefore rendering the proportional hazards assumption obsolete [A multivariable Cox regression analysis was performed to calculate the hazard ratio (HR), with 95% confidence intervals (CI), for chronic graft failure. However, the Schoenfeld residuals test was significant, indicating a violation of the proportional hazard assumption , Class I HLA antibodies, Class II HLA antibodies, acute rejection and estimated glomerular filtration rate (eGFR). Factors that are included in the calculation of the FRS were not adjusted for.The contribution of the FRS to risk prediction was assessed. ROC curves were computed for the TVC of the FRS, eGFR and a combined model of both the eGFR and FRS in order to assess the prognostic value of these variables for chronic graft failure. Considering the time-varying aspect of the Framingham risk score, the ROC curves were made with the FRS as a function of time. Furthermore, due to the nested nature of the analysis, the addition of the FRS to the eGFR was assessed using likelihood ratio statistics.p-value of <0.05 is considered statistically significant. In order to avoid a type-1 error p-values were corrected using the Bonferroni-Holm method [A m method . All staIn this prospective longitudinal study, the FRS was assessed as a potential clinical tool for predicting graft failure in 600 renal transplant recipients. A total of 81 patients (14%) experienced chronic graft failure during the 10-year follow-up. Graft failure occurred due to chronic allograft dysfunction in 50% of patients, chronic allograft nephropathy in 39%, return of primary disease in 4%, acute rejection in 2% and a vascular event in 2%. In 3% of patients, the cause of graft failure was unknown. During the follow-up period, 128 patients (21.3%) died.n = 155), medium , and high  risk, and differences between baseline characteristics were assessed (p < 0.001), likely also due to the inclusion of diabetes and total cholesterol as parameters in the FRS. A high body weight, BMI and higher levels of hs-CRP were also associated with a higher FRS (p < 0.001). The number of patients using proliferation inhibitors was highest in the low-risk group (p = 0.021). Graft function declined with increasing FRS, though this association was stronger for eGFR (p < 0.001) than for creatinine clearance (p = 0.02).Analyses were conducted by dividing patients into the predefined FRS categories of low , a multivariable extended Cox model was carried out, including a TVC of the FRS. Cumulative hazard ratios showed that participants with a higher FRS experienced a greater incidence of graft loss (p = 0.001). A univariable extended Cox regression , indicating a 4% increased risk of developing graft failure over the course of 10 years, per percentage increase in the FRS. The HR of the TVC was 0.99 , indicating that the risk decreases by 1% per year. Adjusting for Hba1c and concentration of insulin , the underlying primary kidney disease (model 3), hs-CRP (model 4) or use of calcineurin inhibitors, proliferation inhibitors and daily prednisolone dose (model 5) did not considerably alter this association. Adjusting for time on haemodialysis, proteinuria, time between transplantation and baseline, acute rejection, type of renal transplantation Class I HLA antibodies, Class II HLA antibodies and post-transplantation duration of oliguria  or eGFR , p < 0.001) did also not considerably alter the association. The association of the FRS with chronic graft failure remained significant in a fully adjusted model , p = 0.040). These results show that even when considering a substantial number of prevailing risk factors, the FRS remained to be prospectively associated with graft failure. Furthermore, additional analysis showed that patient age, systolic blood pressure, smoking and concentration of HDL-C contributed most to the association of the FRS with chronic graft failure , “intermediate risk” (10–20%) and “high risk” (>20%).p < 0.001, p < 0.001, p < 0.001, p < 0.001). These results indicate that using the FRS together with eGFR significantly improves risk prediction of chronic graft failure.Next, ROC curves for the FRS, eGFR, and a combination of eGFR and FRS were computed. The FRS ROC curve showed a fair degree of separability, and can therefore serve as a suitable predictor for graft failure (AUC = 0.66, Receiver operating curves for A. the Framingham risk score, B. eGFR and C. the Framingham risk score and eGFR combined. Abbreviations: eGFR, estimated glomerular filtration rate; AUC, area under the curve.Our results show that the 10-year cardiovascular FRS is significantly associated with chronic graft failure. Although chronic graft failure is driven by a combination of different insults, de novo atherosclerosis manifesting as TV is believed to be a significant contributor. The data indicate that every percent increase in the FRS leads to a 4% increased risk of developing chronic graft failure over the course of 10 years. In the adjusted model, taking all of the most common risk factors into account this association drops to 3%. Furthermore, the hazard decreases by 1% every year. When combining eGFR and the FRS in a ROC curve, the predictive value increases substantially.Currently, there is no consensus on clinical risk prediction for chronic graft failure in RTR. There have been studies that looked at a variety of potentially useful predictors of graft failure such as serum creatinine, eGFR, proteinuria, acute rejection, acute tubular necrosis, carotid-femoral pulse wave velocity, and use of immunosuppressants. However, most of the conducted research is not readily clinically implementable .A major contributing factor to chronic graft failure is transplant vasculopathy, where lesions closely resembling classical atherosclerosis damage the vascular make-up of the transplanted graft ,7. The FA well-established risk factor to predict chronic graft failure is eGFR . For thiAn advantage of using the FRS is that, in general, all components included in the FRS are susceptible to pharmacotherapy. The dependency of sustained graft functioning on the FRS indicates that, to a certain extent, modifiable risk factors underlie chronic graft failure. Intervention trials would be required to confirm such reasoning. Proper risk stratification has the potential to extend the average 10-year survival of renal grafts, putting less patients in need to consequently being re-transplanted, thereby overall contributing to an increased availability of donor kidneys.Taken together, the results of this study demonstrate that the FRS has clinical potential as a predictive tool to identify renal transplant recipients at risk of chronic graft failure. Due to the low costs and broad availability of the measurements included in the FRS, implementing the use of the FRS in daily clinical practice is realistic. Effective risk stratification combined with the potential for therapeutic intervention could conceivably contribute to prolonged survival of renal donor grafts.


The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole. Several aortic stent-graft designs are available commercially, and in this study, we show that our implicit effective stent membrane (ESM) approach to modelling open cell and braided stents provides similar results to lengthy explicit simulations that are required to deal with the complex contact/buckling issues that arise during the crimp and deployment steps of the procedure. In the case of OSR, the diseased section of the aorta is removed and replaced with a synthetic vessel. The graft, generally fabricated from polyethylene terephthalate or Dacron, comprises of tightly woven or knitted fibres with high tensile strength . An MRI-based subject-specific aortic model  or the Dacron enforced diameter limit (DEDL). The fully expanded Nitinol stent geometry is taken to be the stress-free reference configuration.ing Fig. a. To accWe begin by performing a simulation of the crimp and deploy of a Nitinol stent-graft (SG) ring, using the inbuilt Abaqus/Standard Superelastic shape-memory material definition  modelling approach for efficient analysis of graft performance: Owing to the considerable computational cost of modelling complex geometric details of stent-graft geometries (e.g. braided stent designs or closed cell stent designs), we next present a homogenised stent-graft model that can be calibrated such that the radial force (RF) versus diameter (D) relationship is identical to that of a full stent (SG) model described above. A phenomenological constitutive law is developed and implemented in a user material subroutine (UMAT) so that the following features of a full device are replicated: the initial high-stiffness regime during loading; the low stiffness loading plateau; the initial unloading regime; the low stiffness unloading plateau. For the remainder of this paper, we refer to this homogenised device modelling approach as the effective stent membrane (ESM). The graft material only contributes mechanically once the DEAL is reached; during the crimp and deployment (up until the DEAL is reached), the graft is in a wrinkled/buckled state between the stent struts. Due to the extremely high stiffness of the graft material  An equilibrium zero-pressure configuration is computed, whereby the cross-sectional area of the vessel reduces to Ae, such that the internal tensile circumferential stress due to elastin pre-stretch and SMC contractility is in equilibrium with the compressive circumferential stress generated in the matrix. 3.) The lumen pressure is increased from zero up to the peak systolic value (117 mmHg). The pressure increases through a sub-physiological pressure regime (SPPR). At the diastolic pressure, Pd, (73 mmHg) the computed lumen area is denoted Ad. The pressure is then increased through the physiological pressure range (PPR) up to the peak systolic value, Ps (117 mmHg), at which point the computed area is denoted As. As illustrated in the pressure–area curve above, based on our MRI measurements, the PPR is characterised by a high-compliance regime (HCR) up to a transition pressure, Pt, followed by a low compliance regime (LCR) up to the peak of systole. In Figure t). Excellent agreement is observed between the predicted volume fractions of wall constituents along the aorta and histological investigations by the same authors on cadaveric aortae , which compares favourably with the experimental study of Hallock and Benson (1937) who found an As/Ad = 1.09 for the 71–78-year-old cohort. For comparison, the same study reports an As/Ad = 1.39 for the 20–24-year-old cohort, compared to an As/Ad = 1.42 in our healthy 26-year-old male volunteer.Figure  Fig. r. . An equi Fig. r. . An equiThe solution procedure for the FE simulations is as follows. As described in  of the untreated artery in the systole pressure range. Analyses reveal that the primary effect of deployment of the Nitinol stent is to expand the artery so that collagen fibres are in the high-stiffness regime throughout the entire cardiac cycle. The fact that the device does not significantly alter the pressure–area slope from the native LCR slope can be explained by considering the circumferential stress–strain path computed during the crimp-deployment history of the device, as shown in Fig. in vivo nonlinear aortic compliance was captured using the physical based constitutive law outlined in Sect. In Fig. In the patient-specific case, a longer stent graft consisting of four stent rings, is considered. Figure We next use the validated ESM modelling approach to investigate the influence of device over-sizing, device positioning, and native vessel age on the post-implantation changes in the aortic pressure–area relationship.Influence of Oversizing—Model development: The effect of EVAR device oversizing on the pressure–area relationship at Plane 6 (mid descending thoracic aorta) is investigated using the subject-specific aortic model. Clinical guidelines recommend 10–20% oversizing for aortic stent-grafts  may have two negative drawbacks: (1) the device may not reach the unloading plateau when deployed, in which case it will exhibit a higher tangent stiffness and the effective vessel compliance will be lower than the native LCR; (2) the device may not fit in a standard delivery catheter, or it may fracture during crimping. However, insufficient oversizing may be catastrophic. As an example, we illustrate in Fig. The influence of the DEAL should be emphasized. As described above, the 20% oversized device reaches the DEAL at a lumen pressure of 93 mmHg, so the device becomes effectively, infinitely stiff and the vessel area remains constant as the pressure is increased to the peak-systolic value (i.e. the compliance is near zero in this regime). 2 for the native vessel, versus ΔA = 28 mm2 post-implantation, representing an 86% reduction). Simulations also reveal the critical importance of device oversizing in highly compliant proximal sections: as shown in Fig. Figure 2 for the native vessel, versus ΔA = 13 mm2 post-implantation, representing an 65% reduction).Figure The relationship between vessel compliance and device design is further elucidated in Fig. The Nitinol stent-graft device expands the artery wall into a new equilibrium configuration which exceeds the transition strain of the vessel, meaning that the artery is now in the low-compliance regime (LCR) where the high stiffness of straightened collagen fibres governs the mechanical behaviour of the wall, and the high-compliance regime (HCR) at diastolic pressure is eliminated.The stent-graft unloads from the crimped configuration during deployment and operates along the unloading plateau between diastole and systole. The direct effective stiffness of the implant is negligible compared to the high stiffness of the artery wall in the LCR. As a result, the pressure–area relationship post-stenting between diastole and systole follows that of the local LCR slope of the aorta.Provided the Nitinol device increases its diameter sufficiently during deployment so that it reaches the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel. Each oversized device considered in this study is found to exert approximately the same radial force because all devices reach the unloading plateau. Additionally, the radial compliance  on the unloading plateau is negligible compared to the LCR slope of the native artery.We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in latter portion of systole.Our study suggests that oversizing is more important proximally, while stiffer distal vessels do not require as much oversizing. The implanted section follows the local LCR slope for the entire cardiac cycle, and as a result, the effective compliance change in diastole is more pronounced in proximal sections where the difference between the HCR and LCR of the native vessel is greatest.Device deployment in a pathologically stiffened (‘Old’) artery (in which the collagen transition strain and elastin content are both decreased) does not strongly alter the lumen pressure–area curve. Furthermore, oversizing of the device has a negligible effect on the lumen pressure–area curve.This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of the aorta. Specifically, the influence of device implantation on the pressure–area curve of the vessel is analysed. The study uncovers a number of fundamentally important, and previously unreported, insights that should be of critical concern for device design and clinical practice.in vivo and in vitro, report that the deployment of self-expanding stent-grafts reduces aortic wall compliance  throughout the entire cardiac cycle. The high stiffness of the stretched/straightened collagen fibres governs the mechanical behaviour of the wall in both diastole and systole. Furthermore, as the implant unloads from the crimped configuration during the deployment step, it operates along the unloading plateau between diastole and systole, and therefore, the direct effective stiffness of the implant is negligible compared to the high stiffness of the artery wall in the LCR. As a result, the pressure–area relationship between diastole and systole follows that of the local LCR slope of the aorta. The deployment of the device merely expands the vessel diameter so that collagen in the vessel wall is in the high-stiffness regime throughout the cardiac cycle and the compliance of the vessel itself is decreased during diastole. Several studies, both in vivo area change during a cardiac cycle  on the unloading plateau is negligible compared to the LCR slope of the native artery; therefore, the device itself does not significantly contribute to the overall compliance of the section. Rather, the device merely stretches the collagen in the vessel wall into a straightened stiff configuration, thus eliminating the HCR associated with wavy collagen in diastole. Our study provides an explanation for the observations of an experimental study by Nauta et al. , where pInsufficient device oversizing has catastrophic consequences including device migration and endoleak, resulting in pulsation, dilation and rupture of the aneurysmal wall Chuter . We showTo the best of the author’s knowledge, this is the first study to report the Dacron enforced area limit (DEAL), and its implications on vessel biomechanics. The role of the graft is to: (1) de-pressurize the aneurysm wall leading to a reduced risk of rupture; (2) hold the stent rings together; and (3) act as a conduit for blood and pressure transfer. When the device is being deployed, the graft itself does not contribute mechanically until the DEAL is reached due to it being in a crimped/buckled configuration which provides no outwards radial force. Once the DEAL is reached, however, the high stiffness of the Dacron material (~ 3 GPa) results in an effective zero-compliance of the device, whereby negligible area increase will occur for a given pressure increase. Guan et al.  report nin vivo nonlinear compliance curves can be captured with a similar degree of accuracy for the homogeneous and trilayered wall models . As the behaviour of the wall follows the local LCR slope due to straightened collagen  arteries results in a less pronounced effect on the pressure–area curve than the healthy control case. Furthermore, oversizing has a negligible effect on the pressure–area curve as the baseline stiffness in the old aorta is higher resulting in an almost identical diastolic equilibrium configuration following deployment. This result provides an explanation for the observation by Nauta et al.  that theSeveral experimental studies, in addition to clinical trials, show that stent-grafts increase the pulse wave velocity (PWV) of the aorta  and finite deformations. In our patient-specific finite element model, we also incorporate heterogeneity in mechanical properties, in addition to contact mechanics at the device–vessel interface.Thoracic endovascular aortic repair (TEVAR) and abdominal endovascular aortic repair (EVAR) are associated with reduced early perioperative morbidity and mortality compared to open surgical repair. However, this early gain is diminished at long-term follow-up, primarily due to an upsurge in cardiovascular complications, mainly related to the graft material (Sultan et al. in vivo nonlinear pressure–area curve, such that the aortic wall loses its HCR and operates only in the LCR throughout the entire cardiac cycle postoperatively. The test-bed developed in this study can be used to design the next-generation devices and to guide clinical intervention so that post-operative complications including device migration and cardiac mortality can be reduced.In this study, the effect of stent-graft deployment in a patient-specific aorta is investigated, where mechanical properties of the vessel are calibrated from (Concannon et al.


Machine learning has many attractive theoretic properties, specifically, the ability to handle non predefined relations. Additionally, studies have validated the clinical utility of mpMRI for the detection and localization of CSPCa (Gleason score ≥ 3 + 4). In this study, we sought to develop and compare machine-learning models incorporating mpMRI parameters with traditional logistic regression analysis for prediction of PCa (Gleason score ≥ 3 + 3) and CSPCa on initial biopsy.A total of 688 patients with no prior prostate cancer diagnosis and tPSA ≤ 50 ng/ml, who underwent mpMRI and prostate biopsy were included between 2016 and 2020. We used four supervised machine-learning algorithms in a hypothesis-free manner to build models to predict PCa and CSPCa. The machine-learning models were compared to the logistic regression analysis using AUC, calibration plot, and decision curve analysis.P < 0.05). However, the CART illustrated best calibration for PCa (SSR = 0.027) and CSPCa (SSR = 0.033). The ANN, SVM, RF, and LR for PCa had higher net benefit than CART across the threshold probabilities above 5%, and the five models for CSPCa displayed similar net benefit across the threshold probabilities below 40%. The RF  and SVM  for PCa and CSPCa spared more unnecessary biopsies than logistic regression  at 95% sensitivity for detection of CSPCa.The artificial neural network (ANN), support vector machine (SVM), and random forest (RF) yielded similar diagnostic accuracy with logistic regression, while classification and regression tree  had significantly lower diagnostic accuracy than logistic regression (AUC = 0.894 and 0.917) in prediction of PCa and CSPCa  yielded similar diagnostic accuracy and net benefit, while spared more biopsies at 95% sensitivity for detection of CSPCa, compared with logistic regression. However, no method achieved desired performance. All methods should continue to be explored and used in complementary ways. Prostate cancer (PCa) is the most common malignancy of the male reproductive system, with over one million cases and 358 989 deaths in 2018  to fall in between 0 and 1, and entered as continuous variables. The mpMRI parameters were entered as dummy variables, and biopsy results were entered as binary variables.The machine learning models were fit using the packages in R (version 3.6.2). The ANN is based on biological neural networks and composed of interconnected groups of artificial neurons . And it All data cleaning and analyses were conducted using R statistical software (Version 3.6.2). Diagnostic accuracy of the models was evaluated using the area under the ROC curve (AUC). The 95% confidence interval (CI) and comparisons of AUCs were determined using the method of DeLong et al. . PerformP < 0.001), tPSA , and PSAD , while lower f/tPSA  and prostate volume  compared with no-PCa  biopsied before December 31, 2018 were used as training cohort, and the remaining patients  were used as validation cohort. Table P < 0.05); Whilst the pairwise comparison of AUCs were insignificant amongst ANN, SVM, RF, and LR models for PCa and CSPCa, respectively (each P > 0.05) , RF (AUC = 0.897 for PCa and AUC = 0.916 for CSPCa), LR (AUC = 0.894 for PCa and AUC = 0.917 for CSPCa), and ANN (AUC = 0.891 for PCa and AUC = 0.911 for CSPCa) models outperformed CART (AUC = 0.834 for PCa and AUC = 0.867 for CSPCa) model in diagnostic accuracy , followed by SVM (SSR = 0.049), LR (SSR = 0.063), ANN (SSR = 0.091), and RF (SSR = 0.125)  .Clinical consequences of using machine learning-assisted models at given sensitivity, including the number of biopsies that could be spared and the number of PCa by Gleason score that would be missed were displayed in Table 5) Table . Additio5) Table . At 95% 5) Table . HoweverIn our study, we developed, validated, and compared the machine learning-assisted models with LR analysis to predict PCa and CSPCa among patients with serum tPSA ≤ 50 ng/ml, using the same variables and population. The ANN, SVM, and RF models yielded similar diagnostic accuracy and net benefit with LR, and CART had lower diagnostic accuracy than LR in prediction of PCa and CSPCa. However, the CART model illustrated best calibration for PCa and CSPCa. And the SVM and RF models for PCa and CSPCa spared more biopsies than LR at 95% sensitivity for detection of CSPCa.PCa was detected in 20% of the subjects with serum tPSA in the gray zone 4–10 ng/ml) in our study (data not shown). This was similar with the PCa detection rates of the same group of patients in Singapore 21%) [% [21], J ng/ml inA growing body of literatures have validated the clinical utility of mpMRI in the detection and localization of CSPCa . HoweverFor prediction of PCa, ANN has become  one of the fastest growing and most effective machine-learning algorithms . TheoretAnother three machine-learning algorithms  were developed to predict PCa and CSPCa in our study. Some studies showed that RF algorithms outperformed LR model in the fields of identifying peripheral artery disease and mortality risk , predictOur study developed and compared machine-learning models with LR analysis to predict PCa and CSPCa. The SVM and RF models yielded similar diagnostic accuracy and net benefit with LR, while spared more unnecessary prostate biopsies than LR model at 95% sensitivity for detection of CSPCa. CART model illustrated best calibration for the prediction of PCa and CSPCa. Our study did not have sufficient power to draw conclusion that machine-learning models outperformed traditional LR analysis in prediction of PCa and CSPCa. All methods should continue to be used and explored in complementary ways.


The operational performance of cantilever composite structures can benefit from both stiffness tailoring and geometric design, yet, this potential has not been fully utilized in existing studies. The present study addresses this problem by simultaneously optimizing layer and taper angles of cantilever laminates. The design objective is selected as minimizing the average deflection of the tip edge subjected to shear loads while keeping the length and total volume constant. The plate stiffness properties are described by lamination parameters to eliminate the possible solution dependency on the initial assumptions regarding laminate configuration. The responses are computed via finite element analyses, while optimal design variables are determined using genetic algorithms. The results demonstrate that the plate aspect ratio significantly influences the effectiveness of stiffness tailoring and tapering as well as the optimal layer and taper angles. In addition, concurrent exploitation of the lamination characteristics and plate geometry is shown to be essential for achieving maximum performance. Moreover, individual and simultaneous optimization of layer and taper angles produce different optimal results, indicating the possible drawback of using sequential approaches in similar composite design problems. Engineering structures are typically designed in geometries that yield optimal deformation behavior under operating loads. One particular group of structures whose shape can be optimized to improve load-carrying performance is the tapered cantilevers, which are used in various applications such as propeller and turbine blades  or aircrCantilever plates made of fiber-reinforced composites have also been extensively studied since their operational responses can be altered by modifying the fiber angles and stacking sequence of the layers. For example, Kılıc et al.  investigThere are several studies that consider cantilever laminated plates that are tapered along their length. For instance, Franco Correia et al.  minimizeIn the design of fiber-reinforced composites, the optimal solutions can depend on the initial assumptions on the laminate arrangement such as number layers and layer thicknesses. As a remedy, the lamination parameters approach was introduced to determine globally optimal laminate configurations . This foThere are also available studies that use lamination parameters in the design of cantilever composites. For instance, Hammer et al.  used an As shown in the literature review, the deformation mechanics of tapered cantilever laminated plates has been broadly studied. However, to the best of the author’s knowledge, concurrent optimization of geometrical tapering and laminate stiffness has not been previously addressed using direct layer angles or lamination parameters. Studies that involve the use of lamination parameters within topology optimization  are alst), lengths (l), and surface areas (A). The width of the rectangular plate is denoted by w. Distributed shear loads with total magnitude F are applied to the tip of the plates.N is the number of layers, The laminate stiffness properties are described by means of lamination parameters, which are non-dimensional variables that govern the integral stiffness characteristics . The stu1 and V3 ,34, whic1 and V3 (1)V1V3=The values of the lamination parameters are constrained by the following relations :(2)−1≤V1Using the longitudinal modulus  follows :(3)U1U2UIn terms of lamination parameters and material invariants, the constitutive matrix relating in-plane strains to stresses is stated as (4)Cp=U1essed as (5)Ct=56The material properties of the graphite/epoxy laminae used in the present study are given in The solutions are computed by finite element analyses that are performed using in-house software. The plates are discretized with linear 4-node isoparametric shell elements with three translational and two rotational degrees of freedom at each node. The formulation details for this first-order shear deformable element can be found in .K) is obtained. One should note that previously obtained constitutive matrices (f) is defined by equally distributing the total in-plane shear force over the nodes at the tip. Then, K and f are modified to impose fixing boundary conditions at the clamped end. Finally, the nodal displacement vector (u) is calculated by solving the following global system of equations:Through elemental stiffness matrix generation, domain discretization, and assembly procedures, the nodal stiffness matrix , stiffness-tailored rectangular (ST-R), and stiffness-tailored tapered (ST-T)) and four different aspect ratios  and two extreme nominal aspect ratios (The deflection profiles differ significantly with both panel design and aspect ratios. For late see . The tapRaising the  as well ,10. ThisThe deflection contours also facilitate interpreting the growing effectiveness of all optimized designs with increasing aspect ratio. The low aspect ratio plates behave intrinsically stiffer due to the larger proportion of the fixed edge length. This characteristic disrupts the development of a regular deformation field along the plate length. A greater aspect ratio increases the relative length of the free edges potentially boosting the improvements that can be attained through optimization.In this study, layer and taper angles of cantilever composite plates were concurrently optimized. The analyzed plates were subject to in-plane shear loads, and the average tip displacement was minimized as the design objective. The plate stiffness properties were modeled using lamination parameters to circumvent the solution dependency on the initial assumptions on the laminate configuration. The effectiveness of stiffness tailoring and tapering as well as the optimal layer and taper angles were investigated for several panel aspect ratios.The optimal lamination parameters appeared at the lower boundary of the feasible domain for the studied problem. Since these points require especially orthotropic angle-ply laminates in the stacking-sequence retrieval, corresponding layer angles were also determined. Optimal taper and layer angles both decreased with increasing plate aspect ratio.The optimization results showed that internal stiffness properties and plate geometry should both be exploited to minimize the deflection. In addition, the individually optimal layer and taper angles did not remain unchanged when they were simultaneously optimized. This result signifies the possible downside of using sequential optimization approaches in composite design studies. Moreover, tapering alone was found to be more effective than sole stiffness tailoring for low plate aspect ratios, while an opposite condition was observed for a large aspect ratio. However, the individual effectiveness of both approaches improved with the increasing aspect ratio.Future work may address concurrent stiffness tailoring and tapering optimization in multi-axial loading scenarios. In addition, multi-objective optimization studies can be conducted to observe the conforming or conflicting behavior of different performance metrics.


The reported clinical scenarios presented two patients, one managed with a prefabricated abutment and the other with a customized abutment, and both patients were pleased with the outcome. However, from a professional viewpoint, the esthetic outcome using the custom zirconia abutment was superior to that using the prefabricated titanium abutment. The reported clinical scenarios presented two patients, one managed with a prefabricated abutment and the other with a customized abutment, and both patients were pleased with the outcome. However, from a professional viewpoint, the esthetic outcome using the custom zirconia abutment was superior to that using the prefabricated titanium abutment. The patThe need for a simultaneous bone graft during the implant therapy was explained to the patient, who agreed to the procedure after being informed of her options. A Kirkland type flap was performed, and a single implant with a diameter of 3.2 mm and length of 11.5 mm  was placed. A bone graft  was placed, and a membrane  with three screws  secured the bone graft into position. The soft tissue flap was repositioned, and vertical and horizontal mattress suturing techniques provided closure . A polymethylmethacrylate  Adhesive Interim prosthesis (E‐max CAD‐CAM milled block—lithium disilicate glass‐ceramic—Ivoclar Vivadent) was cemented onto the lingual surface of tooth #9 and cantilevered on #10. The provisional prosthesis was kept completely out of occlusion during the healing time.After 2 months, another provisional restoration  was fabricated directly onto the implant to help contour the soft tissue. Provisional restoration contours were modified every 2 weeks for 2 months, at which time the soft tissue provided an ideal gingival architecture. An impression abutment  was placed, and a final impression was made with polyvinyl silane in heavy and light body consistency . A prefabricated abutment  was evaluated in the mouth, and contours were evaluated.  on the abutment. The patient was satisfied with the final results and she received a night guard to protect her teeth and the dental restoration. At the 4‐year follow‐up, the patient was still pleased with the result.  of the patient was taken, and a three‐dimensional evaluation was completed (4.5.9 Blue Sky Plan). The assessment found sufficient bone in the area that provided the ideal position for the implant and followed the curvature of the adjacent teeth. The patient was also offered the option of having soft tissue graft on the facial gingival recession of tooth #11, which the patient accepted. The diagnostic wax‐up was superimposed on the CBCT to fabricate a surgical guide for the ideal position of the implant .An implant with a 3.0 mm diameter and a length of 11.5 mm was placed  on site #10. Soft tissue auto‐grafts taken from the palate were placed on the facial surface of tooth #11 using non‐resorbable sutures . The non‐resorbable sutures, along with resin composite, were placed on the facial surface of tooth #11 to help hold the tissue in position . Next, a screw‐retained provisional restoration, made using polymethylmethacrylate, for tooth #10 was placed in position. The contour of the provisional restoration was modified every other week for 2 months to construct an ideal gingival architecture. Once the tissue obtained the desired shape, a final impression was made.A zirconia with titanium base abutment and porcelain fused to zirconia crown were fabricated. The custom titanium base abutment was placed in the mouth, and contours were evaluated. Figure  A retrac3The ideal three‐dimensional placement of the implant results in optimal support and stability for the surrounding hard and soft tissues.For proper decision‐making, the clinician must predict how different gingival phenotypes could react to implant‐related therapy.At the 4‐year follow‐up for both clinical cases presented here, the soft tissue levels reminded stable without any reduction. This can be attributed to the development of these techniques. Implant placement and bone grafting techniques have evolved and made surgical results more predictable for clinicians. It is clear both from earlier reports and from these cases that if these two procedures are performed appropriately, patient satisfaction can be obtained. As a result, three‐dimensional implant planning, implant position, and surgical management for soft tissue are more important than the type of abutment.However, from a professional view point, the esthetic outcome was much better for the implant therapy using a customized zirconia abutment than for that using a prefabricated titanium abutment due to the darkened soft tissue in the latter case. It goes without saying that this is due to the influence of the abutment color. Although the problem is at a level that does not bother the patient, these cases confirmed that, considering the color of the material, the use of zirconia offers a superior prognosis for the restoration. Further, the restorative procedures involved in implant therapy in the esthetic zone present challenges in soft tissue management beyond those of color.4In these two cases, both prefabricated titanium and custom zirconia abutments were successfully used to achieve the desired esthetic outcomes over 4 years. Properly planned and precisely placed implants and gingival management can be achieved using either prefabricated titanium or custom zirconia abutments. However, the esthetic outcome in implant therapy for a maxillary lateral incisor using a custom zirconia abutment was better and faster than that using a prefabricated titanium abutment.The authors declare that there is no conflict of interest regarding the publication of this article.GGP and CAJ contributed to concepts and manuscript editing. CARR and YT contributed to design. SA and CCF contributed to definition of intellectual content. AA and AT contributed to manuscript editing. AT and CCF contributed to literature search and manuscript review.The patients described were fully informed on the method and the purpose of the case report. Written consent to participate and for publication was obtained by the patients and is available upon request.All authors have confirmed during submission that patients' consents have been signed and collected in accordance with the journal's patient consent policy.


The starch and starch/fiber mixtures were characterized by pasting and flow measurements as well as by viscoelastic and textural analysis. The pasting properties showed a greater BH effect (0.2%) on the gelatinization of PS than WPS. The starch gels and starch fiber mixtures showed biopolymer gel behavior. In the WPS/BH pastes, a smaller increase in hardness was noted compared to PS/BH.The aim of this study was to investigate the impact of fiber from buckwheat hull waste (BH) on the pasting, rheological, and textural properties of 4% and 5% ( Starches belong to the hydrocolloid family and are used in a wide range of products either as raw materials or as food additives. Due to their amylose content, native starches have undesirable properties, such as gel retrogradation or syneresis during storage, which limits its applicability .The food industry is now focused on designing new foods that are based on natural and health-promoting raw materials. In such foods, an additional advantage may be the use of by-products incurred from the agri-food processing. Changes in food texture can be achieved by adding hydrocolloids or dietary fibers, which, in small quantities bind water and can the control structure and texture of stored products ,3,4.From a technological point of view, dietary fiber is one of the most preferred additives in the food industry. Due to their water binding capacity, gel forming ability, texturizing and thickening effects, fiber can improve the texture, sensory characteristics, and shelf-life of foods with starchy ingredients . Dietaryo-methylglucuronoxylan)  a. (2020) .w/w BH developed higher 0T and ηmaxT values than the samples that only contained potato starch. An increase in T0 due to the addition of compounds such as hydrocolloids or fibers was also reported by Adamczyk et al. (2020) [maxη) and lower or no statistically significant differences in viscosity at 95 °C (95°Cη) compared to plain potato starch (maxη by 18.9% (4% PS) and 28.2% (5% PS) and by 4.2% (4% WPS) and 6.2% (5% WPS). Such a tendency indicates a reduction in the swelling rate of the native starch granules, something that was also claimed by Ragaee and Abdel-Al. (2006) [maxη value of waxy potato starch in the presence of fiber was observed in our previous study [PS and WPS (3.8–4.8%) samples with 0.2% . (2020) , and Yil. (2020) . The preo starch . The rep. (2006) . In the us study  explaineus study .minη) of blends with BH that also had a lower starch content (4%) was increased with BH was added, but conversely, at higher concentrations (5%)—minη decreased.The minimum viscosity values (50°Cη) in relation to the minη. The minη values for WPS/BH were close to the viscosity for the control sample (WPS). In the case of PS, only slight influence on the 50°Cη was reported after the addition of the BH. After being cooled, PS created less viscous systems in 4% PS/BH and more viscous systems in 5% PS/BH blends.It was determined that the viscosity of the WPS and WPS/BH pastes did not increase greatly in the tested samples after then had been cooled to 50 °C  [The breakdown parameter (BD) describes the tendency of starch to resist shear force during heating and the stability of the final product . We note. (2002) , the glu0T and an increase in the maxη of starch blends against a control sample (fiber-free). Such a distinct influence of fiber on the rheological properties of starch results, among other factors, from differences in the content of soluble (SDF) and insoluble fractions (IDF) in the fiber. In the case of fiber applied by Yildiz et al. (2013) [Buckwheat fiber had a greater effect on the gelatinization profile of native potato than it did on waxy starch. Similar results were observed in our previous work , where a. (2013) , TDF con. (2013) ,30,31,32The parameters of the rheological model that was used to describe the experimental curves are provided in −1 within 600 s) and decreasing (shear rate from 300 to 0 s−1 within 600 s) shear rates were able to be fitted to an Ostwald–de Waele model very well (R2 = 0.977–0.999).The studied pastes exhibited non-Newtonian, shear-thinning properties. The flow curves that were determined at increasing (shear rate from 0 to 300 sK) of the PS and WPS increased with the paste concentration (4% and 5%). However, the presence of buckwheat hulls in the starch pastes decreased this value by about 50%. For example, the 4% blends PS and PS/BH had 0.96 and 0.51 Pa∙sn, whereas the 4% blends of WPS and WPS/BH had 2.06 and 1.07 Pa∙sn, respectively (in the range of increasing shear rates from 0 to 300 s−1) (−1), there was tendency for the impact of the buckwheat hulls to be similar, with the main difference being that the coefficient K was characterized by higher values .The consistency coefficient (300 s−1) . A simil300 s−1) . In the n) for the up curves showed shear-thinning properties (n < 1) for both the increasing and decreasing shear rates. The shear-thinning behavior was common for starch pastes [n parameter, and there was a non-significant increase in the 5% WPS.The flow index . The values of the thixotropy and anti-thixotropy hysteresis loop areas  were calculated by summing the areas of particular trapeziums between the “up” and “down” hysteresis loop curves and are presented in The starch pastes showed hysteresis loop (expressed as the area between the “up” and “down” flow curves) . The curIn both the native and waxy potato starch pastes, the replacement of 0.2% starch with the addition of BH caused a reduction in the shear stress . The sheG′ value exceeded the G” value in the whole frequency sweep range. In the starch gels, both of the moduli were frequency dependent because the values of G’ and G” over the whole frequency range increased when the angular frequency increased [G’ showed a spectrum that was parallel to G”; moreover, no crossover was observed between them throughout the experiment when the frequency varied from 0.1 to 10 Hz . In general, the replacement of starch with the addition of buckwheat hulls slightly reduced the values of G′ and G″ compared to the control samples .Additives such as hydrocolloids or fiber modify the dynamic spectra of starch, and different trends can be observed . The preS pastes a,b. In tS pastes a,b. Thesδ) is a rheological parameter that is associated with the energy lost per cycle divided by the energy stored per cycle (G″/G′). In this way, values of tan δ < 1 indicate that the behavior of the material is elastic and tan δ > 1 indicates viscous properties [δ values for all studied gels were smaller than 1, indicating predominantly elastic behavior (δ) of the 4% normal and waxy potato starch-BH gels was higher than tan δ of the plain starch gels. The same tendency was observed for 4% waxy potato starch-BH mixture, but the effect was more predominant. These results indicated that 4% PS/BH, 4% WPS/BH and 5% WPS/BH mixtures were less elastic than control samples (plain starch gels). The values of tan δ being close to 1 at this frequency suggested that samples were more liquid-like, because the values of G′ and G" was very close from each other. An opposite effect was observed for the 5% native potato starch–BH sample; the tan δ of the starch-BH gels was lower than the tan δ of the control sample (5% PS). The effect was more pronounced in the frequency range between 0.1 and 1.0 Hz. A less pronounced effect was noted at higher frequencies (between 1.0 and 10 Hz), where the tan δ for the starch pastes and their mixtures with BH was at the same level. These results indicate that the 5% native starch–BH gel was more elastic than the control sample.The loss tangent , the hardness of the gels was higher than that of the fresh gels after 1 day of storage, independent of the starch concentration.0). The hardness values  of the gels increased with the storage time (1 day and 7 days), but the effect was more significant in the case of the native starch. The PS-alone gels (4% and 5%) showed a more noticeable increase in the gel hardness over time than the WPS-alone gels.The effect of BH fiber on the hardness values of the gels was not statistically significant for the fresh gels  . In the The rheological and textural properties of potato starch pastes and gels were influenced by buckwheat hull fiber. The presence of BH in mixtures comprising native potato starch increased the initial pasting temperature and decreased the maximum viscosity, leading to the starch granule swelling less and the gelatinization of the starch becoming reduced; as a result of this, less amylose leached from the starch granules. The antagonistic interaction between BH and amylose was confirmed by examining the impact of fiber on the rheological properties of WPS. In cases where there was a limited amount of amylose, the effect of the added fiber turned out to be much smaller.−1 within 600 s) and decreasing (shear rate from 300 to 0 s −1 within 600 s) shear rates were able to be fit to an Ostwald–de Waele model very well and showed loop hysteresis. The normal potato starch and the blends of normal potato starch with BH were characterized with one type of loop (anticlockwise), while in the waxy potato starch samples and WPS with BH had a mixed characteristic—clockwise/anticlockwise course. On the other hand, the addition of buckwheat hulls to the starch pastes showed smaller areas between the flow curves; therefore, these PS/BH pastes showed greater rheological stability than the WPS/BH systems did, especially when compared to the control samples . Native starch paste (4%) was characterized as having total surface area values (466.8 Pa/s) that were twice as high as those of waxy starch (195.9 Pa/s). In the case of the 5% PS pastes, the area of the hysteresis loop was three times larger (1180.9 Pa/s) than it was for the 5% WPS pastes (382.9 Pa/s). The rheological results that were obtained showed that the native starch–BH gel was more elastic than the control sample. In the WPS/BH gels, a smaller increase was noted in the hardness value compared to PS/BH gels, suggesting the influence of BH on the starch retrogradation process. In summary, BH had a greater effect on the pasting, flow, and textural properties of native potato starch than it did on waxy starch and showed stronger interaction with amylose than with amylopectin. Our results indicate that buckwheat hulls, an agricultural by-product, can be used as an additive in starch-based food to enrich the amount of fiber that is present in the product. Therefore, this research may be important for the design of starch-based foods that are enriched with TDF by-products and that have a desirable texture and high storage stability as well as foods with beneficial health properties. Moreover, interesting rheological properties create the possibility for the mixtures obtained in this study to be used in a wide range of applications, e.g., in the development of biodegradable composites, which may be used as films, coatings, and other packaging materials in the future.The studied pastes exhibited non-Newtonian, shear-thinning properties. The flow curves at the increasing (shear rate from 0 to 300 s


As biodegradable and eco-friendly bio-resources, polysaccharides from a wide range of sources show steadily increasing interest. The increasing fossil-based production of materials are heavily associated with environmental and climate concerns, these biopolymers are addressing such concerns in important areas such as food and biomedical applications. Among polysaccharides, high amylose starch (HAS) has made major progress to marketable products due to its unique properties and enhanced nutritional values in food applications. While high amylose-maize, wheat, barley and potato are commercially available, HAS variants of other crops have been developed recently and is expected to be commercially available in the near future. This review edifies various forms and processing techniques used to produce HAS-based polymers and composites addressing their favorable properties as compared to normal starch. Low toxic and high compatibility natural plasticizers are of great concern in the processing of HAS. Further emphasis, is also given to some essential film properties such as mechanical and barrier properties for HAS-based materials. The functionality of HAS-based functionality can be improved by using different fillers as well as by modulating the inherent structures of HAS. We also identify specific opportunities for HAS-based food and biomedical fabrications aiming to produce cheaper, better, and more eco-friendly materials. We acknowledge that a multidisciplinary approach is required to achieve further improvement of HAS-based products providing entirely new types of sustainable materials. Polysaccharides are used in a wide array of applications, e.g., food products, biofuels, pharmaceutical industry, and biomaterials. They can be classified at multiple levels depending on their applications such as structure, physical properties, function, and chemical composition. Polysaccharides can be produced from a diversity of sources but are mainly derived from higher plants from which cellulose, starch, and pectin are derived and from animal sources where chitin and chitosan are derived. The diversity of polysaccharide-providing sources that could produce a substance of choice as starting materials that can be modified and used in many applications. The main polysaccharides by volume are cellulose, starch, chitin and pectin  1]..1].Starch is one of the most abundant biopolymers on earth is starch. It is widely commonly used in food, pharmaceutical, paper, plastic, textile, and cosmetic industries in liquid dispersions granule, film, or gel forms. Starch is a granular energy reserve composed of amylose (AM) and amylopectin (AP). AM is a mainly linear polymer consisting of α  linked D-glucopyranosyl units while AP is a branched polymer of α-D-glucopyranosyl units primarily linked by  bonds with branches resulting from  linked D-glucopyranosyl units. Most methods for chemical modification of starch depends on the intrinsic reactivity of the hydroxyl groups.The structure of starch granules can be categorized into four hierarchally levels, ranging of scale from nm to mm . Level 1Based on the botanical origin and genetic background, the composition of AM and AP varies. Starch granules similarly contain various amounts of proteins, lipids, ashes and phosphates. Lipids such as phospholipids tend to form single helical complex with AM, resulting in stability of starch molecule and reducing swelling and water-binding capacity.The AM: AP ratio, the length of α-glucan chains, and the branching degree of amylopectin define the structure and the functionalities of starch granules from different plant species. The AM present in the starch affects its physiochemical, and functional properties including altered solubility and reduced swelling. Thus, AM can be utilized to modify specific properties of starch making it useful in structure applications.Starch has been the subject of intensive research over many decades, resulting in a massive number of published studies on physical, biochemical and chemical properties, uses and functionality. In the present review, we aim to provide a concise discussion on HAS applications and forms relevant to its functionality with emphasis on biomaterials and its interactions with other natural polysaccharides.Chemical and physical treatments are usually used to modify starch functionalities like etherification or esterification to meet the industrial requirements . In addiHAS is typically directly produced in specific mutants or engineered crops where key enzymes have been knocked out in the crop . For exaHAS, has a non-optimal structure for generating chain-entangled matrices, which is important for e.g., bioplastics applications, due to the presence of highly branched amylopectin providing too short chain segments for stable double-helical junction zones to be formed . HoweverExamples of HAS include the commercially available HAS of corn including Hylon V (50% AM), Hylon Vll (70% AM), Gelose 50 (50% AM), Gelose 70 (70% AM), Gelose 80 (80% AM), and the recently produced barley AM (99% AM). HAS gelatinizes at higher temperatures as normal starch due to the long linear AM and AP chains that tend to entangle and crystallize. Due to its unique functionality including high gel forming capacity and resistance to dietary degradation, HAS is an important ingredient for low carb nutrition and raw material for bio plastics production . For futThe linear structure of AM permits complex formation with various host molecules. Generally, the AM inclusion complex acts in the form of a single left-handed helix termed V-type crystalline polymorph as revealed by wide-angle X-ray diffraction that is caused by amylose guest molecular hydrophobic interactions. The guest molecule are included in the cavity of AM helices or in between the helices, depending on the structure of the molecule which suggest the potential of encapsulating of food flavor compounds through interactions with polysaccharides .The branched nature of the AP molecules in HAS is the main cause of the well-ordered semi-crystalline nature of the starch granule while amylose is regarded as more or less amorphous. To produce starch films, it is essential to convert the semi crystalline form to a completely amorphous state. Starch is not a thermoplastic material in its native state, but in the presence of a plasticizer e.g., glycerol or sorbitol, water, high temperatures (90–180 °C), and shear it becomes a thermoplastic . Hence, Starch films can be fabricated using two main approaches based on wet and dry processing. Both methods destroy the granular semi-crystalline form, resulting in quite wide differences in such as permeability and mechanical properties of the films. The dry process depends on the thermoplastic properties of starch induced by extrusion, where starch is heated in low water content 10–40% above its glass transition temperature (Tg). This method is mainly viable for industrial level manufacturing . For theControlling film texture is a main problem in production of starch films and the use of proper raw material is decisive in this respect. As an example, films made of pure AP (named waxy) become too brittle, due to the resin stiffness resulting in reduced expansions of the blown films. An additional problem is the formation of, double walled films due to sticky extrudates . AlternaAs compared to normal-and waxy starch, HAS requires higher gelatinization temperature and moisture than normal starch to produce films by extrusion. However, as an effect of the high thermo-resistivity, HAS films shows better thermal and mechanical properties compared to their low AM counterparts. This is attributed to entanglement of long linear AM chains and partly retain granular structures in HAS films, which act as a self–reinforcement . ProcessTo improve the functionality of HAS-based materials, blending with other biopolymers such as chitosan can be performed. For example, a study revealed the extrusion of HAS (70% AM) with chitosan blends generating higher stability with the addition of 5 and 10% of chitosan. The blended extrudates showed a homogenous surface with no agglomeration of chitosan and a reduction in mechanical properties due to chitosan plasticity effect .Mechanical properties of bioplastics film including Young’s modulus (E), tensile strength (TS) and percentage of elongation at break (EAB) depend on film composition and nature of components . Starch The AM:AP ratio is an important factor influencing the mechanical properties of such materials, especially since amylose affects the degree of crystallinity and entanglement. Increased AM content is typically related to an increase in tensile strength and a decrease in strain . This isBrittleness is generally due to the amorphous regions of AM why plasticizers must be included to enhance plasticity. Alternatively, blending with other biopolymers and synthetic polymers such as PVA can improve the mechanical properties while maintaining the biodegradability.The tensile strength increases as AM content increases although this relation is not linear . FactorsThe presence of nano-fillers e.g., nano-clay in Hylon VII enhances the mechanical properties, which is credited to the mechanical resistance exerted by the nano-clay itself. Theoretically, the complete dispersion of the clay as nano-layers in the polymer optimizes the number of available reinforcing elements for carrying an applied load. The link between the large surface area of the clay and the polymer matrix facilitates stress transfer from the matrix to the nano-filler, resulting in this tensile improvement .w/w and insufficient content of these plasticizers may lead to an anti-plasticization effect, e.g., adding 15% of glycerol to barley AM-only (99% AM) composite films reinforced with cellulose nanofibers (CNF), shown reduction at EAB. This phenomena was reverted by adding 25% of glycerol which significantly increased the EAB  [OAc]) as a plasticizing agent and glycerol on using Gelose 80 (AM 82%). Gelose 80 is known to be very resistant towards gelatinization and thereby shows low processability. The study showed that [Emim] [OAc] was effective in a compression moulding process involving only minor shear treatment. In addition, scanning electron microscopy (SEM) analysis showed that [Emim] [OAc], as compared to glycerol, contributed to less granular remains. Hence, [Emim] [OAc] at low concentration efficiently disrupted the original granular B-type and V-type crystalline polymorphs and also prevented single or double helix formation is due to the strong interaction between starch hydroxyl group and acetate anion in [Emim][OAc] thus producing less V-type crystalline structures and increased the mobility of the amorphous starch .Starch films have excellent oxygen barrier properties due to their high ordered hydrophilic hydrogen-bonded network structure, in which AM and AP form partly tightly connected crystalline networks. Differences in the molecular arrangements of the starch, plasticizers, the microstructure, thickness of the films and different storage conditions has tremendous effects on the barrier properties. Generally, plasticized starch-based films show poor water vapor permeability (WVP) due to their hydrophilic nature and increases water diffusion rate within the film .9 g/ms Pa and it increased to 14.7 × 109 g/ms Pa with increased concentration of plasticizer. Films with glycerol had higher WVP than those of sorbitol ..47].The effect of hydrocolloids such as xanthan gum and guar gum on gel properties of HAS e.g., Hylon V (50% AM) and HAS (71% AM) showed that the presence of gums in HAS resulted in increased viscosities and suppressed swelling of starch granules as compared to a pure AP starch . Guar guRelevant for direct food applications is the capability of AM in HAS to form inclusion complexes with variety of flavor compounds. Importantly, the starch provides a matrix showing a decrease in flavor perception due to the starch-flavor inclusion complex formation. Size, hydrophobicity, water solubility and shape of the ligand contribute to the ability of the ligand to complex with starch . InteracWide-angle powder X-ray diffractograms of Hylon VII-fatty acids  complexes prepared at 30 °C, 50 °C, 70 °C displayed the typical V-type crystalline polymorph, the size of the formed crystals decreased, and the crystallinity degree increased as the preparation temperature of the complexed AM increased. SEM micrographs showed that presence of complexed crystals either in the form of lamella or in the form of spherulites. For example, thermogravimetric analysis (TGA) data (solid state) indicated that oleic acid was adequately protected in the form of complexes .Proteins has also an effect on AM-lipid complexes. Such multiple interactions are likely to be common in cooked starch-based foods and may influence their functionality but studies are limited .As opposed to fatty acids and alike, HAS nanoparticles showed lower encapsulation efficiencies (45%) towards anthocyanins compared to AP and normal starch nanoparticles . AP molecules with low degree of substitution favored the encapsulation efficiencies with anthocyanins by succinaylated nanoparticles. The nanoparticle-anthocyanin interaction occurred through electrostatic and hydrophobic staking interactions. The nano-capsule obtained from AP had the smallest particle size (<100 nm) .Bakery foods are starch-rich, which provide a good texture for consumers but are typically highly glycemic by containing high amounts of rapidly digestible starch (RDS) and slowly digestible starch (SDS), and a low amount of RS. Especially, high amounts of RDS has a great potential to induce an excessive postprandial glycemic response, obesity and cardiovascular disease. HAS flour can act as an efficient and highly palatable ingredient to substitute wheat flour (WF) for the preparation of novel starch-based food to improve RS content, and decrease glycemic index. For example, HAS (50% AM) added to cookies showed 10.1% of RS compared to 1.6% in a pure WF cookie . Bread cAM-only (99% AM) produced in barley exhibits low predicted glycemic index (pGI) due to suppressed starch digestibility. Substituting wheat flour with AM-only flour in a bread model provided a highly microbiota-modifying bread model with reasonably good baking properties  58]..58].Currently, many applications such as food packaging and drug delivery increasingly replace non-biodegradable materials with biodegradable natural raw materials. HAS is especially relevant as a safe, odor-less, robust, and biodegradable raw material for food packaging and food coating . EspeciaTo improve mechanical and barrier properties, several materials have been incorporated into HAS-based films resulting in blended composite films. The incorporation of cellulose nanocrystals (CNC) has been shown to provide a more homogeneous surface and increases the amorphous halo and reduce the crystallinity, which confirms the interaction of nanoparticles to glycerol molecules and limits AM-glycerol interaction. Dynamic mechanical analysis (DMA) of the HAS/CNC films suggested a hydrogen-bonded cellulose network within the starch matrix. Furthermore, the incorporation of CNC can shift the start of material degradation to higher temperatures . Castingw/w) as an enhancer to film preparation of chitosan-HAS (55% AM) in addition to glycerol. MC increases the film permeability and mechanical properties. Excessive increase of MC declines both the mechanical and the barrier properties due to the heterogeneous structure composite (Another example is the effect of methylcellulose (MC) 6% (omposite  62]..w/w) as w/v). At lower concentrations, phase separation was the main effect of KGM on HAS films while the linkage inhibition developed at high addition concentrations of KGM. The WVP values increased with more of KGM. This could be due to the incompatibility of the two polymers. The WVP result suggested that the composite film maybe not be suitable for application as high barrier film. The optimal content of KGM was 0.3%, where a homogeneous and compact structure was formed (Plasticized composite films based on HAS (85% AM) and konjac glucomannan (KGM) were developed to enhance morphological irregularities, which is typical for pure HAS-based packaging materials. The similarity in the linear structure of KGM and HAS makes it rather compatible with HAS. The HAS/KGM composite films were fabricated at KGM concentrations of 0.1–0.5% (s formed  63]. In. Inw/v).s formed . w/w) which was reflected in visible surface cracking in the SEM image. At a glycerol concentration of 5%, the thermal properties, and the TS were reduced and the EAB increased with increased glycerol content (For HAS (80% AM)/Chitosan plasticized films, TS values (3.44 MPa) were lower than that for HAS/KGM composite films . The EAB content  65]..w/w) whiHAS (72% AM) was used as a filler to enhance the gelation of gelatin films under different gelatinization conditions and at different concentrations. The presence of HAS increased the film integrity, transparency, thermal properties, water solubility, and thickness. Mechanical properties were improved with the gelatinized starch especially at 50% concentration. Water resistance was observed when HAS was gelatinized in hot alkaline media. The outcomes may serve as a platform to improve gelatin film performance and potentially extend applications of edible gelatin films in the food industry  66]..66].As described above, HAS films are biologically absorbable, non-toxic, and are good barriers to oxygen and semipermeable to carbon dioxide. Incorporation of active substances such as antimicrobial agents, plasticizers and lipids into HAS-based matrices allow controlling of the release behavior of the amount and the diffusion rate of the active substances . IncorpoHydroxyl propyl-HAS (80% AM) films functionalized with different contents of pomegranate peel (PGP) powder can be potentially used as a reinforcement and as an antimicrobial agent. All parts of pomegranate are widely reported as antioxidant as well as antibacterial. The pomegranate fruit peel being rich in phenolic compounds such as catechin, rutin and epicatechin . While tAs previously mentioned, most of the native starches are limited in their direct application due to it suboptimal mechanical properties, high water sensitivity, and poor long-term stability. This is also valid for HAS. To overcome these limitations HAS blended with other raw biomaterials may lead to new biodegradable biomedical scaffolds with potentially better properties that can be used in advanced applications such as within the medical and pharmaceutical fields .A comparative study investigated the properties of collagen with three different maize starches: waxy starch (0% AM), normal starch (27% AM) and HAS (72% AM). Blending collagen with starch at both low (10%) and high (50%) concentrations enhanced the mechanical strengths, HAS provided the highest strengths at both concentrations. AM small uniform granule created less heterogeneous films, providing strong interaction with the collagen fibers, whereas larger granules such as those found in the waxy and normal starch preparations disrupted the continuity of the collagen matrix and decreased the cohesive force between collagen fibers, which eventually decreased the mechanical strength. Films of waxy and normal starches were degraded following heating while HAS (72% AM) still maintained its granular shape. The addition of HAS increased the thermal stability, and reduce film solubility in water. Hence, HAS improved collagen film, providing a potential solution to address challenges facing e.g., collagen-based casing industry  70]..70].On the contrary, physical properties of extruded starch-based materials with different glycerol concentrations were examined using starch from two different botanical origins, amylomaize (70% AM) and potato (20% AM), after immersion in a physiological medium, as well in vitro cell effect and in vivo tissue response in a rat animal model. Potato starch samples with glycerol 20% and HAS (70% AM) samples without glycerol showed an elastic modulus of 1.5 and 9.8 MPa and only weak swelling in water, lasting stable for 30 days. Stabilization of the mechanical properties and geometry was due to the evolution of crystallinity in potato starch samples. The crystallinity of the potato starch samples with 20% glycerol increased the B-type crystallinity from 15% to 25% after 30 days of immersion. While the B-type crystallinity of HAS samples were disrupted by amylose-lipid complexes that led to the superimposition of the V-type pattern [In vivo implantation materials, the potato starch-based prototypes were integrated into the tissue with a limited inflammatory reaction, due to the presence of M2 macrophages that is generally allied with the implant healing. However, the HAS material induced a pathological foreign–body reaction at day 30 post implantation as revealed by granuloma formation, the presence of giant cells and macrophages going towards HAS degradation . This stFor bio-therapeutic applications, electrospun starch-based, core-sheath composite fibers, have been demonstrated to be promising delivery vehicles with the aim to improve the stability of live bacteria. The use of such composite fibers for encapsulation of viable probiotic cells showed that these fibers with mean diameters of 4.13 μm could be used as carriers to stabilize Lactobacillus paracasei cells, where the glycerol core can act as the cell suspension medium. The sheath solution was composed of 17% Hylon Vll dissolved in formic acid to produce starch formate. The core-sheath starch-formate/glycerol composite fibers were capable of retaining bacterial viability when stored at 4 °C and room temperature for up to 21 days . Considerable efforts are made to develop colon targeting drug systems, aiming at securing direct treatment of colon-related disorders and providing more precise strategies for chronotherapy for diseases that are sensitive to e.g., the circadian rhythm . EspeciaImprovements included heating of HAS to 80 °C during the aqueous film coating process (WO 2008/012573 A1), which prevented the release of drugs in the stomach or upper intestine, while the release was observed in the colon as an effect of specific degradation of the starch coating by the intestinal microbiota . HydroxyRecent efforts in the bone and tissue engineering field have been made to form bone scaffolds that mimic the structure and function of the bone. Preliminary examination of the effect of the chemical constitution of the composite was performed using hydroxyl apatite and printed by a solid freeform fabricator (SFF). Compared to cassava (15% AM) and potato (20% AM) starches composites with hydroxyapatite, corn starch (25% AM) improved the mechanical strength from 2.12 ± 0.77 MPa to 12.49 ± 0.22 MPa, which is more closely to the mechanical strength of natural cancellous bone .High AM content in the starch facilitates the hydroxyapatite to interact with the starch particles with hydrogen bonding. AM was proven to provide a biologically active reinforcement moiety of resorbable bone scaffolds through an interparticle and crystal interlocking mechanism , improviDevelopmental efforts have been attempted over many decades to use starch as a raw material for a wide range of applications. However, mainly due to its inefficient suboptimal mechanical behavior, difficulty in processability, and hydrophilicity, still limit the application of starches for many industrial uses. From the studies described in this review, it is evident that there are possibilities for the utilization of HAS providing some unique functionalities in a wide array of diverse applications. Different HAS polymers can provide solutions for a wide range of food, bio-composite, and biomedical applications. Most importantly, HAS can typically readily drop in at existing processing systems as a bulk, be easily available raw, biopolymer that can be fabricated into form of powder, foams, hydrogels and fibers and as a compatible component in bio composites. The review provides a comprehensive report on the HAS properties and the latest updates in different fields, which will further open up a plethora of challenges that need to be addressed by the research community.


This study examines the influence of organizational psychological capital on the performance of small and medium-sized companies (SMEs) during crises. We argue that SMEs use their intangible resources to cope with difficult situations such as the COVID-19 pandemic. Therefore, we investigate how organizational psychological capital impacts performance and creative innovation through such intangible resources, namely, organizational citizenship behavior, solidarity, and cooperation. Methodologically, we combine structural equation modelling and regression analysis on a dataset of 379 SMEs. Our results support the notion that organizational psychological capital positively influences creative innovation of SMEs and thus performance during crises. Our research contributes to the organizational behavior literature by showing that psychological resources of SMEs can strengthen performance in times of crisis and help to prepare for future ones. The COVID-19 pandemic has impacted our economic system tremendously and continues to be a threat, especially for small and medium-sized companies (SMEs). Our research shows that a shared positive thinking, namely, Organizational Psychological Capital, can be used by SMEs to counteract the negative effects of exogenous crises, such as the COVID-19 pandemic. Using a dataset of 379 SMEs, we highlight that organizational psychological capital positively affects creative innovations of SMEs and leads to better performance. Thus, the principal implication of our study is the fact that SMEs should place a stronger emphasizes on their organizational psychological capital and try to stay positive, as it will help them to come up with innovative ideas coping with the effects of the crisis, ultimately increasing their performance and survival rate. In early 2020, the world was hit by a global pandemic caused by the coronavirus   influence the SMEs ability to deal with the quickly changing reality during crisis and how those companies can use positive psychological resources to survive or even thrive in adverse circumstances. First empirical evidence by McKenny et al.  shows thComplementary to McKenny et al. , PearsonBesides the role of psychological resources, companies take actions which help them to thrive during crises. Many companies and individuals offered their support to assist those affected most by the situation to overcome those troublesome times. This assistance is usually called prosocial behavior Jonas, . For exaBesides the shown behaviors of SMEs, further research suggests that in crisis context those companies react in a more creative way to the emerging opportunities than larger companies  during crisis.In summary all these reasons have a common objective, to face the adversities created by the crisis and to cushion the impact of its effects. As OPC, and its underlying dimensions, reflect a company’s positive psychological state and a shared level of agency  in SMEs, the greater will be creative innovative activity during times of crisis.Besides that, we propose that also cooperation with stakeholders during the recent crisis impacts the creative innovation in SMEs. Due to resource scarcity, which implies a lack of resources and capabilities in SMEs, innovations can lead to the companies being overstretched . Lastly, we used a construct of 13 questions to measure creative innovation in the firm proposed by Zhou and George  developed and validated by Luthans et al. . In agreTo ensure that our analysis is not influenced by unobserved socio-demographic, company-related, or situational factors, we included several control variables in our analysis. First, we included company-related control variables such as the number of employees, as a measure of company size, and the age of the company in the analysis. Both, company size and company age, have already been shown to be related to performance  bootstrapping with a two-sided significance test at the 0.05 significance level.To analyze the formulated hypotheses, we use a structural equation model in this study. Since the constructs are latent and indirectly measured by indicator variables, by using this method, we are able to integrate these variables into the calculation Chin, . We are To inspect the reflective latent constructs, the metrics recommended by Hair et al. , OPC on cooperation  and OPC on solidarity , and thus confirm the first hypothesis. Likewise, a significant positive influence of OPC on creative innovation  is shown, which confirms the second hypothesis.Referring to our hypotheses, we found a positive significant influence of OCB on creative innovation , cooperation on creative innovation  and solidarity on creative innovation , significant positive influences were found, as hypothesized in the third hypothesis. Creative innovation itself also shows a positive impact on the company’s performance  during the crisis, which supports hypothesis four. Ultimately, the direct significant effect of OPC on the firm’s performance during crisis , parallel to indirect pathways via the mediators, confirms hypothesis five. For the whole mediation paths of OPC via OCB and via creative innovation on performance, we found a significant positive complimentary mediation. Likewise, for the path of OPC via cooperation and via creative innovation on performance. The indirect path which includes solidarity turned out to be not significant.For the further connections of To validate our results and to prove the robustness of our findings, we conducted some tests with alternative methodological approaches. First, we performed a confirmatory factor analysis to show how the individual items load on the latent constructs and how the factors separate themselves from each other in our model. We performed this analysis using AMOS with the maximum likelihood discrepancy function. The results of this confirmatory factor analysis are shown in Fig. For these validated constructs, we further calculated the mean indices for the factors and used them in ordinary least squares regressions to validate our model from the PLS-SEM. The correlations in Table The recent COVID-19 pandemic which hit the world in early 2020 poses huge challenges for companies around the globe  plays a crucial role in this perspective, as it not only directly influences creative innovation and performance but also plays a decisive role in fostering prosocial behaviors (OCB and solidarity), as well as cooperation with stakeholders, which in turn influence small-scale creative innovation during a crisis. By that we follow the call of POB researchers to use a positive psychology perspective (James et al., Even though the recent COVID-19 pandemic offers great potential to study the behavior of companies in prolonged global crisis situations each crisis is different in its nature (James et al., Our study also offers several implications for research and practice. As OPC is considered a state like resource (Luthans et al.,