Present research deals with exposure of granular starch to the accelerated electron of 5.5 MeV energy in order to examine: (i) the temperature evolution in starch within an irradiation process and (ii) the indirect effects generated in starch by radiation-induced heating. The temperature evolution in potato and corn starches within the irradiation process was investigated by placing two different sensors inside each starch batch and recording the temperature simultaneously. Each starch batch was sampled into distinct location sectors of different absorbed radiation levels. The output effects in each sample were analyzed through physicochemical properties such as moisture content, acidity and color attributes. The outcomes showed that a starch temperature profile had different major stages: (i) heating during irradiation, (ii) post-irradiation heating, up to the maximum temperature is reached, and (iii) cooling to the room temperature. A material constant with signification of a relaxation time was identified by modeling the temperature evolution. Changes of the investigated properties were induced both by irradiation and radiation-induced heating, depending on the starch type and the batch sectors. Changes in the irradiated batch sectors were explained by irradiation and radiation-induced heating whereas changes in the sector of non-irradiated starch were attributed only to the heating. Starch is one of the most widespread natural polymers, being composed of two different fractions: amylose (linear fraction) and amylopectin (branched fraction). Starch is used in various food and non-food applications such as pharmaceuticals and biomedical products, packaging materials, textiles, adhesives, etc. Native starch has limited functionality in technological applications due to its poor processing properties such as high viscosity, tendency for retrogradation, lack of thermal stability. However, it has a range of very significant advantages being a cheap, renewable, non-toxic, and widely available biodegradable raw material . Thus, tElectron beam irradiation is widely used in material processing, involving both chemical and thermal effects. The chemical effects due to ion and free radical generation ,8 are coFurthermore, in the present work, we aimed out to show the evolution of temperature in granular starch subjected to an irradiation process. At the same time, the presence of indirect effects produced in starch by electron-beam induced heating was highlighted. For this purpose, starches from two different botanical sources, potato and corn, were exposed to an accelerated electron field in a selected irradiation setup (geometry and irradiation parameters). For both types of starch, the temperature was measured simultaneously at two points in the batch. The analysis of batches was performed by sampling them into three distinct location sectors and evaluating some physicochemical properties such as moisture content, pH and color attributes. The findings of this work are relevant for any research related to the irradiation of starch-based materials, especially whenever the research results are transferred at a large scale. An important advantage in the radiation application comes from the possibility of irradiating samples with large dimensions, but in this case the cooling process is more difficult and unforeseen thermal effects can occur.Potato starch  and corn starch  used in the experiments were purchased from Sigma-Aldrich Company .r = 37 mm from the beam axis at a distance of 220 mm from accelerator window exit. The maximum dose rate of 𝒟o = 12 kGy/min in the beam center, on the irradiation sample surface, was reached by using a mean beam intensity of 4 µA. The sample irradiation was carried out for a period of 435 s, at the room temperature (22 ± 1 °C) and ambient pressure in air.The irradiation of starch powder in solid state was performed in static mode by using an e-beam generated by a linear accelerator ALID-7 of energy of 5.5 MeV . The electron accelerator facility is of traveling-wave type which uses microwaves in the S-band at 2.99 GHz propagating in a disk-loaded tube of about 2 m long, and the microwaves are produced by an EEV-M5125 type magnetron delivering 2 MW of power in pulses of 4 μs ,15. The 3 for both types of starch. Consequently, the maximum depth of electrons in starch determined according to the ISO/ASTM 51649:2002(E) [maxP = 55 mm. The box had the radius R = 65 mm and the height H = 100 mm and its symmetry axis coincided with the e-beam axis during irradiation. Two temperature sensors  were placed inside the starch batch: S1 on the e-beam axis and S2 at r = 37 mm from the axis. Both sensors were located at a depth of 55 mm, which is equal to the maximum depth of the electrons in starch, in order to avoid that these sensors directly absorb heat/energy from the radiation field.The starch powder was placed in a cylindrical cardboard box  so that :2002(E)  was PmaxThe temperature values were simultaneously recorded by both sensors during starch irradiation and after irradiation, namely during the heating due to the radiation field as well as during the cooling toward room temperature.h = 40 mm  at 105 °C for 45 min.w/v) concentration were then allowed to stand at room temperature (25 ± 1 °C). After cooling, pH was measured at 25 ± 1 °C with an inoLab® 7110 pH-meter .Starch samples were mixed in distilled water by magnetic stirring on bath water at 85 °C for 30 min, and the mixtures of 1% (w/v) concentration were then allowed to stand at room temperature (25 ± 1 °C). After cooling, the UV-Vis spectra of the samples were recorded in a Cary 100 Bio spectrophotometer . Colorimetric features of the samples were measured in absorbance in the visible region (360–830 nm), for standard illuminant D65 (daylight source), observer angle of 10° (perception angle of a human observer). The colorimetric attributes expressed as CIELCH parameters  were analyzed by using the Color Application of Cary Win UV v. 3.10 software .Starch samples were mixed in distilled water by continuously magnetic stirring on bath water at 85 °C for 30 min, and the mixtures of 1% , and InfoStat versión 2018 [p ≤ 0.05 was considered as statistically significant.The results reported are expressed by means of values ± standard deviation of triplicate determinations. The processing of experimental data was performed using OriginPro 8.1 , Microsoftt = 435 s, (ii) post-irradiation heating, up to the maximum temperature is reached, and (iii) cooling to the room temperature. This finding is consistent with the fact that the heat continues to propagate in starch for a while, in connection with the place where the sensors are placed, after the irradiation process is stopped and before the cooling process begins [potato and S1corn, but even more visible in the second sensor, S2potato and S2corn. This differentiation of behavior can be attributed to the different thermal properties of these two types of investigated starch.The evolution of the temperature recorded by the two sensors, for each type of starch, during irradiation and cooling is presented in s begins . The maxpotato compared to 38 °C in S1corn after 435 s. Also, the potato starch continued to heat up post-irradiation for a longer time than corn starch, visible in both sensors. Therefore, the potato starch needed 364 s to reach the maximum temperature in S1 while the corn starch needed only 216 s. Conversely, the maximum temperature was higher for corn starch compared to the potato starch, with 1 °C in S1, and with 2 °C in S2. However, the time to reach the peak temperature in S2 appeared to be comparable for the two starches, but this maximum was maintained much longer for potato starch than corn starch. In this way, the last stage started later with lower values for potato starch than corn starch, in both sensors. The cooling curves showed an exponential trend, so that the temperatures for potato starch and corn starch in the first sensor, S1potato and S1corn, respectively, overlapped quite well, especially after about 2000 s. Also, in the second sensor, the cooling process was similar for the two starches after about 5000 s.During the irradiation stage, the potato starch had a lower heating rate than corn starch, reaching a temperature of 36 °C in S1T is the temperature in each sensor during cooling process (°C), T0 is a temperature parameter (°C), which depends on both the maximum temperature and the time considered as the beginning of the cooling process, t is the time (s), τ0 is a parameter that has the signification of a relaxation time (s), namely the time required for starch to decrease the temperature to the equilibrium temperature e times.By analyzing the cooling curves, it can be noticed that their evolution followed an exponential law, in each sensor:τ0 obtained by fitting the experimental data of the cooling process are displayed for each starch and each sensor in the first row of 0 estimated in this way can characterize the starch thermal behavior, but also it depends on the geometry characterizing the starch at the time of temperature measuring.The values of T is the temperature in each sensor after irradiation stopping (°C), iT (°C), iτ (s) and Δt (s) are parameters that characterize the post-irradiation heating, t is the time (s), T0 is a temperature parameter, associated with the temperature at which the cooling started, τ0 is the parameter with significance of relaxation time (s).On the other hand, we were able to find a function that also describes the evolution of the starch temperature for post-irradiation heating process:τ0 found for the cooling process, we determined the other parameters that best fit (R2) the experimental data for the post-irradiation heating processes, and the values obtained are shown in T0 is the difference from the room temperature to the maximum value reached in each sensor, and iτ can express the time required to reach the maximum temperature after irradiation in each sensor. iT and Δt take values that describe the temperatures in sensors when the irradiation is off as well as the shape of the curves around the maximum value. The parameters i, τiT, and Δt depend more on the irradiation geometry (S1 vs. S2) than on the type of starch . Note that even though τ0 and iτ depend on the starch type and geometry, the values of their difference τ0 − iτ are not significantly different. This finding suggests that τ0 − iτ could be a material constant, and the starch relaxation time could actually have values around 5800 s.Keeping the values of p > 0.05) affected in the Edge compared to that of the control samples. A decrease in moisture content was observed in the Center and Adjacent sectors compared to the control samples for both starches. However, corn starch showed a drastic decrease (p ≤ 0.05) of moisture content only in the Center. At the same time, the potato starch, with a higher moisture content, suffered (p ≤ 0.05) the highest loss, of over 20% in the Center. It is noteworthy that potato starch showed a higher moisture loss than corn starch for each sector, which can be explained by the origin of different botanical sources and, implicitly, their different structural arrangement.The moisture content for the starch sampled from the three considered locations  was evaluated for each type of starch (potato and corn) together with the corresponding control samples. The results presented in T0. Thus, these values are associated with the maximum temperature reached in the sensors assigned to these location sectors. The different temperatures measured in a sensor for investigated samples could be explained by their different specific heat capacities, pc. It is well known that the specific heat capacity pc of a sample is directly related to its moisture content. Considering that pc = 3.35 u + 0.84 (kJ kg−1 K−1) [u = u%/100 is the mass ratio of water in starch (kg kg–1), the specific heat capacity values pc were determined as shown in The starch dehydration could be explained by a water vapor transport that accompanied the cooling process which occurred by heat dissipation from the Center to the Edge. Moisture content losses in the Center and Adjacent sectors are in accordance with the estimated values for the temperature parameter g−1 K−1) , where up ≤ 0.05) of pH values for all investigated location sectors in comparison to the control sample (The native starches had an acidic character with a pH around 5.5 for both starches. Both starches showed the reduction (l sample . Althougp ≤ 0.05) in pH value for potato starch can be totally attributed to a thermal phenomenon, even if it was a small one. This different behavior of the two types of starch can be attributed to their different amylose content. It is known that the thermal properties of starches from different botanical sources are influenced not only by the structural features, but the amylose content or amylopectin/amylose ratio, which leads to higher or less thermal stability of starch polymers [p ≤ 0.05) in its pH value due to the heating in the Edge can be explained.On the other hand, only potato starch had a significant reduction in pH value in the Edge in comparison to control sample. However, it should be noted here that the Edge sector was considered free of radiation, but with a small temperature variation, which led us to believe that the difference  → 100 (white)), chroma (saturation) C* is the quantitative component of the color while hue h° is the qualitative component of color, being expressed in degrees: 0° (red), 90° (yellow), 180° (green), 270° (blue). In these terms, native potato starch showed higher values of L* and C* than native corn starch. In other words, the potato starch had greater transparency and saturation in comparison to corn starch that showed the tendency of its color to grey. Instead, the hue h° had similar values indicating the same slightly yellowish color hue for both native starches.In the CIE (p ≤ 0.05) for the parameters that characterize the color space L*C*h° compared to the corresponding native counterparts. However, the corn starch from Edge showed values of color parameters similar to those of its native counterpart.In our experiment, it was observed that the samples from the considered location sectors, for both starches, showed modified values Although the color parameter evolution in opposite directions was noted for both potato and corn starches in the Adjacent and Center, all samples of both starches showed an intensification in terms of lightness by irradiation . SimilarC* decreased significantly while the hue h° tended to green by moving from the red-yellow quadrant (0–90°) to the yellow-green one (90–180°) for the sample from the Center. In contrast, for corn starch , indicating the red-yellowish color trend.In the case of potato starch a, the chn starch b, the coIn this study of the chromatic attributes, as in the case of pH, it was noticed that the potato starch from Edge showed significant changes compared to its native counterpart. Therefore, once again, it was found that potato starch, unlike corn starch, was affected by a thermal phenomenon induced by irradiation in a location sector (Edge) considered free of radiation.Based on all these results and observations, it can be stated that radiation-induced heating can affect the physicochemical properties of starches, depending on their botanical source, moisture content, amylopectin/amylose content, and thermal sensitivity.The temperature profiles recorded in starch samples showed three major stages: (i) heating during irradiation, (ii) post-irradiation heating, up to the maximum temperature is reached, and (iii) cooling to the room temperature.The maximum values of temperatures reached and the heating rates were different for both starches in the studied location sectors. However, the cooling rates were similar for both starches in each location sector thermally studied.The evolution of the measured temperatures was modeled as a function of the parameters that depend on the starch type and the location sector considered inside the batch. Based on this modeling, a material constant having the significance of a relaxation time was identified with values around 5800 s.Dehydration and changes in the values of the specific heat capacity, pH and color parameters of the starch were noticed due to the irradiation and radiation-induced heating, depending on the starch type and the batch sectors. The changes in the irradiated batch sectors  could be explained by irradiation and radiation-induced heating. On the other hand, the changes in the sector where the starch was practically not irradiated could be attributed only to the heating. Although the reached temperatures here were lower than in the other batch sectors, these changes cannot be ignored.The temperature evolution in two different granular starches (potato and corn) within an electron beam irradiation process was investigated. Also, the indirect effects that occurred in starch by radiation-induced heating were studied by sampling each starch batch into distinct location sectors having different absorbed radiation levels . The main findings of this study are:Therefore, for a heat-sensitive material like starch, specific experimental precautions are required to prevent the temperature rise and dehydration due to irradiation whenever indirect consequences are not desired. Moisture-containing materials may undergo a dehydration process by irradiation as a result of the transport of water vapors. At the same time, some thermal characteristics such as specific heat capacity can modify considerably due to the very high value of the water heat capacity. Our findings are of practical use for any experimental design in which the radiation-induced direct and indirect effects in the moisture-containing materials should be taken into consideration. When simulating processes due to irradiation, such as Monte Carlo method, it is necessary to take into account such variations in temperature and moisture content that can occur in a material. Thus, the main challenge in this research field is the enhanced control and mitigation of the radiation-induced thermal effects in order to enable the desired chemical effects on starch-based materials. Future work in the field should be performed to differentiate the effects induced in starch directly by irradiation from those developed indirectly by radiation-induced heating.


The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients  remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring  is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients. Government Information on Organ Donation and Transplantation: https://optn.transplant.hrsa.gov/news/annual-record-trend-continues-for-deceased-organ-donation-deceased-donor-transplants). At the same time, 1269 keratoplasties were performed in Poland compared to 1180 SOTs (Poltransplant: https://www.poltransplant.org.pl/statystyka_2020.html).The cornea is the most frequently transplanted solid tissue. In 2020, the Eye Bank Association of America distributed 66,278 tissues for keratoplasty compared to 33,309 solid organ transplants (SOTs) performed in 2020 in the United States . After 8 years of follow-up, the survival rates are 73% and 32%, respectively (p < 0.001)  keratoplasties are chosen. The technique of corneal suturing does not affect the rejection rate, but it is recommended to hide the knot under the surface of the donor’s cornea because if it is in the patient's own cornea, it is more likely that irritation will stimulate vascular growth , blood transfusion, or pregnancy (Worthington et al. In 1969 it was demonstrated that antibodies directed against MHC antigens are the main cause of rejection in SOT (Patel and Terasaki For many years, the T cell response was considered predominant in SOT but it is now known that the humoral response is the main cause of acute graft loss Terasaki . The preThere are different mechanisms underlying corneal graft rejection. Animal studies on B cell-deficient and complement-deficient mice showed that it can occur in the absence of complement-fixing antibodies (Goslings et al. In summary, allospecific antibodies are not always the cause of corneal graft decompensation but indeed can cause serious graft damage in a complement-dependent or complement-independent manner. Furthermore, there are four types of corneal graft rejection: acute or chronic, each of which can be cellular- or antibody-mediated. Of course, overlapping types are also possible. Specific approaches should be applied depending on the type of rejection.DSA monitoring has become a mainstay of AMR risk stratification in SOT recipients; however, it is not routinely performed after keratoplasties. Establishing a link between pre-transplant sensitization or development of antibodies de novo, and individualized decision making in this patient population requires large, prospective randomized clinical trials with the use of modern DSA detection methods. At present, it seems reasonable to stratify the immunological risk for graft rejection in cornea recipients based on pre-existing DSA. Further adjustments of IS could follow such stratification.Systemic IS in patients after high-risk keratoplasty seems to improve graft survival but rejection episodes still occur in up to 40% of grafts after 5 years (Chow et al. The impact of DSA on corneal graft rejection still remains unknown but determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection and lead to personalized treatment for this group of transplant recipients.


Magnetic-resonance-imaging-based predictive models (MRI-PMs) improve the MRI prediction of clinically significant prostate cancer (csPCa) in prostate biopsies. Risk calculators (RC) provide easy individual assessment of csPCa likelihood. MRI-PMs have been analysed in overall populations of men suspected to have PCa, but they have never been analysed according to the prostate imaging-report and data system (PI-RADS) categories. Therefore, the true clinical usefulness of MRI-PMs regarding the specific PI-RADS categories is unknown.p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories.A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort ( Prostate cancer (PCa) suspicion is established from prostate-specific antigen (PSA) serum elevation and/or abnormal digital rectal examination (DRE), while its diagnosis is confirmed with a prostate biopsy . The claOur main objective was to design a new web-RC for csPCa likelihood, derived from a developed MRI-PM in the metropolitan area of Barcelona, Spain. The RC calculator will provide the novel option of selecting the csPCa probability threshold to facilitate future external validations and outperformances in specific PI-RADS categories. The specific objectives were: i. to develop the Barcelona MRI-PM; ii. to externally validate the developed model in a representative cohort of the Barcelona metropolitan area; iii. to design a friendly and free available web-RC with the PCa probability threshold selection allowed; and iv. to analyse the MRI-PM performance regarding PI-RADS categories in the development and external validation cohorts.The development cohort was formed of 1987 men with suspected PCa who had serum PSA > 3 ng/mL and/or abnormal DRE and were referred to our early PCa detection program from the primary care system. All men were scheduled for pre-biopsy multipa-rametric MRI (mpMRI), and thereafter, underwent guided and/or systematic biopsies from 1 to 4 weeks later, between 1 January 2016 and 31 December 2019, in one academic institution (VHH) of the metropolitan area of Barcelona, Spain. Data were collected in a prospective database according to the standards of reporting for MRI-targeted biopsy studies (START) . WrittenThe external validation cohort comprised 946 men with suspected PCa who were retrospectively selected in two other academic institutions (PSM and GTIPH) and were representative of the metropolitan area of Barcelona, Spain. The criteria of PCa suspicion, the period of recruitment, and the diagnostic approach were the same as in the development cohort.MRI scans were acquired using a 3-tesla scanner with a standard surface phased-array coil. Magneto Trio  equipment was used for the development cohort and Diamond Select Achieva 3.0-TX  and Nova Dual  were used for the external validation cohorts. The acquisition protocol included T2-weighted imaging (T2W), diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging, according to the guidelines of the European Society of Urogenital Radiology. Two expert radiologists in each institution analysed images using the PI-RADSv.2.0, and in cases with multiple PI-RADS category lesions, the highest PI-RADS was selected for the model . ProstatAll men underwent a 2- to 4-core transrectal ultrasound (TRUS), cognitive-fusion guided biopsies for all PI-RADS > 3 lesions, and a 12-core TRUS systematic biopsy. Men with PI-RADS < 3 underwent a 12-core TRUS systematic biopsy. All biopsies were performed by one experienced urologist in each institution using the BK Focus 400 ultrasound scanner  for the development cohort, and the Siemens Acuson 150  and the Sonolite Antares  for the external validation cohort.Biopsy samples were sent separately to local pathology departments, where two expert uro-pathologists analysed them, assigning them an International Society of Uro-Pathology (ISUP) grade group when PCa was detected. csPCa was defined when ISUP grade > 2 was founded .The independent ability to predict csPCa of PI-RADSv.2.0 (1–5), age (years), ethnicity (Caucasian vs. others), serum PSA level (ng/mL), prostate volume (mL), DRE , PCa family history (no vs. first-degree relatives), and biopsy type  was explored. PSAD was not directly included as a predictor because of the need for previous calculation, and due to having an area under the curve for csPCa detection of 0.892 and 0.897 when serum PSA and prostate volume were the predictors (data not shown).CsPCa detection rates and avoidable prostate biopsy rates.Descriptive statistics for the development and external validation cohorts were analysed and compared with the Chi-square and Mann–Whitney U tests. Binary logistic stepwise regression analysis of csPCa candidate predictors was performed for the model development. Continuous variables were modelled as linear or nonlinear predictors using restricted cubic splines. Calibration of the predictive model was assessed in both cohorts. Discrimination power was determined using the receiver operating characteristic (ROC) curve and the area under the curve (AUC), and clinical utility was determined using the clinical utility curve (CUC), which explored the potential rates of missed csPCa detection and avoidable prostate biopsies. The net benefit of the mpMRI- and MRI-based predictive model over biopsying all men was evaluated with a decision curve analysis (DCA). AUCs and specificities for 90% sensitivity to csPCa of the MRI and MRI-based predictive model in the development and external validation cohorts were compared with the DeLong and Chi-square tests, respectively. After selecting the threshold with 95% sensitivity to csPCa, the overall performances of the MRI and MRI-based predictive model were compared, and a sub-analysis—after stratifying by PI-RADS < 3, 3, 4 and 5—was performed. Sensitivity, specificity, positive and negative predictive values, and accuracy of rates of avoidable biopsies and potentially undetected csPCa were analysed. For the external validation, transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statements were followed. Statistical analyses were computed using R programming language v.4.0.3  and SPSS v.24 .p < 0.001). We also noted higher abnormal DRE, PCa family history, and repeat prostate biopsy rates in the external validation cohort (p < 0.001). The prostate volume was similar in both cohorts (p = 0.559). The Caucasian race was predominant in both cohorts (p = 0.738). Different case-mixes of PI-RADS categories existed between both cohorts (p < 0.001). We noted no significant increase in csPCa in the external validation cohort (p = 0.054), and a significant increase in iPCa (p < 0.001). The overall detection rate of csPCa was 36.9% in the development cohort, and regarding PI-RADS categories, 4.1% of men had PI-RADS < 3, 15.3% of men had PI-RADS 3, 52.4% of men had PI-RADS 4, and 83.4% of men had PI-RADS 5. The overall detection rate of csPCa was 40.8% in the external validation cohort, and regarding PI-RADS categories, 10.9% of men had PI-RADS < 3, 20.4% of men had PI-RADS 3, 51.9% of men had PI-RADS 4, and 84.0% of men had PI-RADS 5.The characteristics of development and external validation cohorts are summarised in Logistic regression analysis showed age, serum PSA, DRE, prostate volume, PCa family history, type of biopsy, and PI-RADSv2.0 as independent predictors of csPCa , and a fThe ROC curves of mpMRI and MRI-PM in the development cohort are presented in p = 0.011). The efficacies of the mpMRI-PM were higher than those of mpMRI (p < 0.001) at 85%, 90%, and 95% sensitivities. At 90% sensitivity, the specificity of mpMRI was 56.8% (95% CI: 53.6–60.0) and that of MRI-PM was 69.5%  (The AUC of the mpMRI increased from 0.842 (95% CI: 0.822–0.861) to 0.902 (95% CI: 0.880–0.914) of MRI-PM in the development cohort , the real incidence is approximately 25%; thus, the model underestimates real csPCa occurrence. The intercept (0.261) and slope (0.815) show this disagreement, which is probably due to a 4% higher csPCa incidence (40.8 vs. 36.9%) in the cohort .p < 0.001). The AUC of MRI-PM in the external validation cohort was 0.858 (95% CI: 0.833–0.883) while it was 0.897 (95% CI: 0.880–0.914) in the development cohort (p = 0.009) (p < 0.001)  and the shiny library. The designed RC incorporates the novel option of selecting the csPCa probability threshold, and it is freely available at https://mripcaprediction.shinyapps.io/MRIPCaPrediction/ (accessed on 23 November 2020).The validated nomogram was implemented in a web-diagnostic tool using RStudio v.1.2.5001 , 4.3% and 6.5% would be biopsied, respectively, in the developed and external validation cohorts, detecting 33.3% and 18.2% of existing csPCa, respectively. In these low and intermediate PI-RADS categories, the absolute number of undetected csPCa is low due to the limited number of existing csPCa that did not reach rates higher than 5–10% of all detected csPCa.External validations in populations where predictive models are going to be used are essential, and accessible and friendly RC are needed to avoid the cumbersome and time-consuming use of nomograms ,12. A noWe developed a new MRI-PM for csPCa and externally validated it, initially in the same metropolitan area. An accessible and friendly RC was designed for its easy and widespread use. The novelty of selecting the csPCa probability threshold may be helpful in new external validations and to modulate the desired sensitivity to csPCa in each PI-RADS category. Rather than limitations, we believe that local reporting by experienced radiologists following PI-RADS v.2 ; local eA new MRI-PM for csPCa was developed to improve and individualise the selection of candidates for prostate biopsy in the metropolitan area of Barcelona, Spain. An associated web-RC incorporates the option to select the csPCa probability threshold, which may improve further external validations and outperformances in specific PI-RADS categories. The developed MRI-PM was able to detect 95% of existing csPCa, avoiding 40% of prostate biopsies in our overall population. However, the analysis regarding PI-RADS categories shows that the developed MRI-PM outperforms in PI-RADS < 3.


Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer mechanisms of metronomic therapy are antiangiogenesis and immunomodulation, which have been demonstrated in several delicate in vitro and in vivo experiments. In contrast to the traditional maximum tolerated dose (MTD) dosing of chemotherapy, metronomic therapy possesses comparative efficacy but greatlydecreases the incidence and severity of treatment side-effects. Clinical trials of metronomic anticancer treatment have revealed promising results in a variety cancer types and specific patient populations such as the elderly and pediatric malignancies. Oral cavity squamous cell carcinoma (OCSCC) is an important health issue in many areas around the world. Long-term survival is about 50% in locally advanced disease despite having high-intensity treatment combined surgery, radiotherapy, and chemotherapy. In this article, we review and summarize the essence of metronomic therapy and focus on its applications in OCSCC treatment. Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide, comprises heterogenous groups of tumors arising from the oral cavity, oropharynx, hypopharynx, and larynx . In Taiw2 every 3 weeks) is generally considered a gold standard regimen [2) is deemed as a highly toxic regimen because it has significant side-effects such as nephrotoxicity, ototoxicity, and neurotoxicity [The most important chemotherapeutic agent in OCSCC treatment is platinum. In platinum-based concurrent chemoradiotherapy or palliative chemotherapy, administration of the maximum tolerated dose (MTD) of cisplatin cytotoxic agents at more frequent intervals (no prolonged drug-free breaks) . InitialNeoangiogenesis takes a central role during the growing phase of the primary tumor and supports the establishment of distant metastatic deposits. It has long been proposed as a potential target in cancer treatment ,56. ChemDuring the process of carcinogenesis and tumor progression, cancer cells may evade the immunosurveillance through the release of cytokines , and interleukin-6) and recruitment of precancerous immune cells (such as regulatory T cell (Treg), myeloid derived suppressor cells (MDSC), and tumor associated macrophage-2) . Studies+, CD44+, or CD133+; alone or combined expression) [Cancer cells, like their normal counterparts, contain a minority portion of cells that possess the ability of self-renewal and differentiation. These specific cancer cells are called cancer stem cells (CSCs), which are detected mainly with the expression of specific cell surface markers (CD24ression) . CSCs haression) ,80. A feression) ,82,83. Vression) . IncorpoH tetrazolium bromide assay. However, functional evaluations revealed that oral cancer treatment with more frequent 5-FU dosing  showed the highest expression of TSP-1 (antiangiogenesis molecule) and lowest expression of VEGF and CD44 (CSC marker). In the in vivo xenograft model, the usual S-1 schedules were 4weeks on followed by 2 weeks off and 2weeks on followed by 1weekoff, which were the same as the standard regimens in human. The metronomic dosing was 1dayon followed by 1dayoff. The results revealed that all three regimens resulted in similar tumor volume reductions. The nude mice in the two standard regimen groups had a lower weight than those in the metronomic treatment group. The xenograft tumors in the metronomic treatment group showed increased TSP-1 and decreased VEGF expression, which was consistent with the findings of the in vitro study. In addition, a reduction in CD44 expression was observed. The number of endothelial cells (based on CD31 expression) and the micro vessel density (MVD) both decreased in the metronomic treatment group tumors. The results of S-1 treatment in an oral tongue cancer model revealed that metronomic dosing resulted in comparable tumor inhibition. Considering the proof-of-concept viewpoint, metronomic dosing of S-1 demonstrated antiangiogenesis and cancer stem cell elimination effects. According to our knowledge, a variety of compounds extracted from traditional Chinese medicine possess anticancer effects [Cordyceps sinensis, alone or in combination with radiotherapy for 8 weeks. No weight loss was observed, and the hematological, renal, and hepatic functions were preserved [Although metronomic therapy has been applied in clinical trials or daily oncological practice, only one chemotherapeutic agent, S-1, has been tested completely in both in vitro and in vivo models. S-1 is composed of three compounds. One compound is a 5-fluorouracil (5-FU) prodrug, tegafur. The other two are gimeracil (inhibits the 5-FU degradation) and oteracil  . In an i effects . Some of effects ,91,92,93In the past two decades, the concept of metronomic therapy was translated into real practice, and clinical trials have finally proven its effectiveness and better tolerability in a variety of cancers ,95,96,972/day for 1 year, and another 40 patients were observational controls. The 4year disease-free survival (DFS) of the metronomic group versus the control group was 85.6% and 75.9% (p = 0.02). Simultaneously, they performed laboratory correlation by detecting the change in CEP  cells, a marker of angiogenesis activity. The results revealed that patients treated with metronomic UFUR had a significant reduction in the detectable viable CEP cells, which might implicate an antiangiogenesis mechanism behind the survival benefits. The toxicities were mild and manageable, with skin rash (5%) being the most common side-effect, followed by hematological side-effects (2.5%) and nausea/vomiting (2.5%) [p = 0.0008) and 57% versus 41%  in the metronomic and control groups, respectively. In addition, longer UFUR treatment duration (≥12 months) and higher dose (300–400 mg/day) contributed to better survival benefits. The metronomic UFUR treatment seemed to decrease the occurrence of distant metastasis  compared with no UFUR treatment. Moreover, the toxicities were mild and well-tolerated, with skin rash (3.5%) being the most common side-effect. Another study used low-dose S-1 as adjuvant chemotherapy in locally advanced HNSCC patients [2; 50 mg/day for 1.25 m2 ≤ BSA < 1.5 m2; 60 mg/day for BSA ≥ 1.5 m2) and was administered for 2 years. Forty-three (82.7%) patients received S-1 continuously for 2 years without dose reduction. Hematological toxicity was found in 98.1% of the patients; however, only two (3.8%) patients were grade 3. Nonhematological toxicity was found in 15 (28.8%) patients, and all cases were grade 1. The 3year DFS and OS rates were 82.6% and 94%, respectively.Three studies used metronomic fluorouracil drugs in adjuvant/maintenance therapy. Lin et al. conducted a prospective cohort study and reported that 80 OCSCC patients with stage III–IVa (T3–T4a and/or N0–N1) diseases received curative intent surgery. Forty patients received metronoic UFUR (each capsule contains tegafur 100 mg and uracil 224 mg) with a fixed dose of tegafur 150 mg/mg (2.5%) . Hsieh eg (2.5%)  conductepatients . The stu2)) in recurrent/metastatic HNSCC patients. The metronomic chemotherapy consisted of weekly oral methotrexate  and daily celecoxib (200 mg twice daily) [p = 0.014) and OS  compared with the cisplatin arm. Moreover, the response rate (RR) and clinical beneficial rate were better in the metronomic arm compared with the cisplatin arm: 12.3% versus 1.9% and 54.4% versus 32.1%, respectively. Fewer grade 3–4 adverse events were noted in the metronomic arm compared with the cisplatin arm , without statistical significance [2). Overall, 418 patients  were included in the per-protocol analysis. At a median follow-up of 15.73 months, the primary endpoint, median overall survival, was 7.5 months in the oral metronomic chemotherapy group compared with 6.1 months in the intravenous cisplatin group . Grade 3 or higher adverse events were observed in 37(19%) of 196 patients in the oral metronomic chemotherapy group versus 61(30%) of 202 patients in the cisplatin group [2 and found 9 mg/m2 to be the OBD. Overall, 91 patients were enrolled in the study. The median PFS and OS were 4.6 and 7.17 months, respectively. The overall best RR was 42.9%, which was superior to the second line treatment (RR = 2.2–13.6%) in platinum-refractory HNSCC [Three studies examined the effectiveness and toxicity profiles using metronomic therapy in recurrent/metastatic OCSCC patients. Patil et al. conducted a prospective randomized phase II clinical trial, comparing metronomic chemotherapy with single agent (three-weekly cisplatin (75 mg/me daily) . MTX is e daily) . Celecoxe daily) ,109. A tificance . Due to in group . This wain group . The regved in 37% of 196 ry HNSCC . The mosOur data review revealed that metronomic therapy does achieve comparable disease control rate in OCSCC and has a favorable toxicity profile compared with standard systemic chemotherapy, such as platinum. However, more solid and high-level evidence  is required to consolidate the role of metronomic therapy. In addition, we found that the optimal metronomic dosage for OCSCC is not well defined. Pharmacodynamic and pharmacokinetic analysis of the metronomic dosing might provide valuable information for determining the optimal dose ,113,114.Antiangiogenesis and immunomodulation are the two main mechanisms of action of metronomic therapy . As far Oral squamous cell carcinoma is a heterogenous disease with a high unmet medical requirement. The cure rate and accompanied complications have not improved despite high-intensity treatment. Metronomic therapy provides an alternative treatment choice in contrast to traditional chemotherapy. Its mechanism of action is as follows: angiogenesis inhibition, immunomodulation, and overcoming drug resistance. A comparative disease control rate and superior toxicity profile are its advantages. It is widely applicable in clinical patient care. However, randomized phase III trials comparing it with the standard care are required to demonstrate its effectiveness. We can anticipate that more studies focusing on metronomic therapy with novel agent combination, such as immunotherapy, will be conducted in the future and translated into clinical treatment benefits.


This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft.  Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts' cardiac electrical and mechanical functions. However, the durability of effect, immune response, and  hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. p < 0.05) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles.  The epicardially placed tissue graft therapy improved ( This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option. NCT04696328).Heart failure (HF) with reduced ejection fraction carries a mortality of over 30% within five years of the initial hospitalization , 2. WhilA previous study from our laboratory demonstrated that tissue-engineered (TE) cardiac grafts composed of human neonatal dermal fibroblasts seeded on bioabsorbable scaffolds induced angiogenesis and increased myocardial blood flow in rodents with HF after myocardial infarction (MI) . In addiin vitro electrophysiologic and mechanical characterization of the TE graft both in vitro and in vivo. HiPSC-CMs were utilized in this study rather than rodent or murine iPSC-CMs because this study was designed as a preclinical evaluation of a novel therapeutic that is being optimized for clinical implementation. We hypothesized that implanting these TE cardiac grafts onto the epicardium of immune-competent rats in HF would result in improvements in cardiac function and that durability would persist despite the transient nature of the implant.The goals of this study were to (1) confirm the reproducibility of a previous hiPSC-CM TE graft study , (2) tesThree weeks after permanent left coronary ligation, chronic heart failure (CHF) rats were randomly assigned to either TE graft treatment or untreated CHF for seven weeks. Rats assigned to untreated CHF underwent the second surgical approach without graft treatment. Prior to surgical implantation, each graft was removed from the incubator and transferred to a 35-millimeter dish and rinsed in 1x phosphate-buffered saline. The chest was reopened via partial left thoracotomy, and one graft was implanted over the infarcted area, bridging healthy to healthy myocardium. The graft was secured using 3-4 simple interrupted suture stitches for the periphery of the graft and a single simple stitch for the center of the graft.P/V) relationship curves were obtained within ten minutes of induced cardiac arrest and analyzed for dead volume, stiffness constants, left ventricular (LV) pressure, and standardized volume analyses [Three diastolic pressure-volume  and at weeks 1, 3, and 7 post-graft implantation.μL of plasma to one million cells in a 100 μL suspension. The presence of rat anti-fibroblast primary antibodies and rat anti-hiPSC-CM primary antibodies was confirmed using conjugated secondary mouse anti-rat IgM and goat anti-rat IgG antibodies, respectively, each linked to a fluorophore .Plasma was analyzed to quantify total nonspecific IgM and total nonspecific IgG using sandwich enzyme-linked immunosorbent assay . To assess the graft-specific IgG response, serially collected plasma samples were tested by flow cytometry. In brief, plasma from CHF rats and graft-treated rats was decomplemented for thirty minutes in a 56°C water bath prior to incubation with hiPSCs-CMs or fibroblasts (viability confirmed using Zombie Violet) at a ratio of 1 The TE graft described in this study is composed of a cellularized bioabsorbable polyglactin 910 knitted mesh. The meshes are cut into 1.6 cm diameter circular disks. The 1.6 cm disks are placed into the base of a 24-well plate and inoculated with human neonatal dermal fibroblasts and hiPSC-CMs in a ratio between 1 : 1 and 1 : 2, respectively. The hiPSC-CMs are terminally differentiated and express >95% cTnT and display contractions 24 hrs after integration into the grafts. The grafts can be manufactured easily in large batches. The grafts adhere tightly to the heart and are secured in place with 2-3 spot sutures.Fura 4 florescent indicator, and mechanical displacement was quantified using MuscleMotion image analysis software [The TE grafts were assessed for intracellular calcium concentration flux and mechanical contraction at increasing rates of depolarization (1 hertz/60 beats per minute to 3 hertz/180 beats per minute) with the CellOPTIQ® platform. Intracellular calcium was quantified optically using software . Thapsigsoftware .in vivo procedures has been provided for reference , CHF (n = 5), and graft-treated CHF (n = 7)  . The P/VAll evaluated LV sections were from equal ventricular heights, ensuring appropriate comparison between short-axis sections. Randomly selected graft-treated CHF sections revealed smaller ventricular cavity diameters, increased ventricular anterior wall thickness, and increased anterior wall myocyte densities as compared to randomly selected untreated CHF controls .n = 10) and graft-treated CHF rats (n = 8) at baseline  and between CHF rats (n = 5) and graft-treated rats (n = 8) at 21 days post-graft therapy . No significant IgM differences were observed at all other time points. There were no differences in the level of detectable IgG between CHF and graft-treated CHF rats.Total IgM and IgG antibody response was quantified using ELISAs . There wn = 7-8, 58.7 ± 11.8% positive hiPSC-CMs). These antibodies were not detected in the plasma of the untreated CHF group. Beyond seven days post-graft implantation, the graft-specific antibodies steadily increased over the duration of the study up to the study endpoint and at seven weeks post-graft implantation   . No grafFive days after the initiation of coculture, engineered grafts contracted spontaneously and synchronously at 71 ± 7 beats-per-minute during culture  was used to depict unipolar voltage electrograms, which revealed clear depolarization and repolarization waveforms . The larn = 8) revealed a physiologic shortening of the R-R interval relative to baseline (n = 8) (99.8 ± 0.4 milliseconds (ms) versus 106.9 ± 0.4 ms, p < 0.0001). Furthermore, electrograms revealed a physiologic shortening of the QT interval  with isoproterenol (n = 6), relative to baseline (n = 3). Changes in the electrogram amplitude between electrogram waveforms is likely due to differences in adhesion forces between the hydrophobic array and the engineered cardiac graft from differing amounts of culture media in the petri dish (n = 4) revealed a physiologic prolongation of the QS-QS interval  as well as a physiologic prolongation of the QT interval .Pharmacologic challenge with isoproterenol  expressed increased levels of connexin 43 (Cxn43), kinase insert domain receptor (KDR), smooth muscle actin (SMA), sarcomeric alpha actinin (SAA), cluster of differentiation 56 (CD56), and platelet-derived growth factor receptor-α (PDGFRA) compared to a fibroblast-only graft that did not contain hiPSC-CMs  confirm the reproducibility of a previous hiPSC-CM TE graft study , (2) tesin vivo timeline was increased from three weeks to seven weeks  was not observed  in the treatment of HF as described by Pfeffer et al. in 1985 . SpecifiTo better understand the impact of the immune-competent model, we conducted a preliminarily evaluation of the humoral immune response. Total IgM and IgG titers  showed ein vitro electrophysiologic and mechanical characterization of the engineered graft was performed. Preliminary assessment of the engineered graft with light microscopy showed rapidly spontaneous and synchronous mechanical activity (Supplemental Video In vitro pharmacologic challenges to the engineered graft showed that the hiPSC-CMs are capable of appropriate physiologic responses to beta-adrenergic receptor agonism and antagonism (An tagonism . Furthertagonism . The sartagonism .An additional control group consisting of CHF rats that received hiPSC-CM-free grafts, that is only the polyglactin 910 knitted mesh and the human neonatal dermal fibroblasts, would have provided additional experimental clarity. However, a previously completed study described such a graft's effect as angiogenic without facilitating improvements in hemodynamic parameters .In addition, no assay regarding the survival rate of implanted hiPSC-CMs was performed in this study. Nonetheless, our previous publication revealed that no xenografted hiPSC-CMs survived beyond 21 days post-implantation . Due to Finally, one of the stated goals of this study was to provide a preliminary characterization of the humoral immune response following TE graft therapy. Though the goal was accomplished using total and graft-specific IgM and IgG titers, it is necessary to acknowledge that evaluation of the innate immune response in the target organ would have provided a more comprehensive perspective regarding transplanted cell fate and microenvironment quality. Regardless of the exact local innate response, the transplanted cells are known to be cleared within 21 days of transplantation .In vitro assessment of the graft revealed an electrophysiologic and mechanical phenotype consistent with hiPSC-CMs, but a complex messenger RNA profile suggesting rich soluble factor secretion.This TE cardiac graft seeded with hiPSC-CMs and human dermal fibroblasts improved LV systolic and diastolic functions on invasive hemodynamic assessment. Our data illustrate the advantages of using a TE scaffold to deliver hiPSC-CMs to treat CHF as opposed to direct cell injection into the heart or down the coronary arteries. The TE graft enables the cells to remain in contact with the epicardial surface of the heart, which has been shown to be a hub for cardiac regeneration. Another advantage of a TE graft is the ability to place the graft directly on the scar tissue. This is contrasted with direct cell injection, where it is not always clear where the cells are injected, and the cells may be rapidly washed out of the heart. These improvements in cardiac function occurred in the presence of a detectable immune response against the graft, specifically an increasing donor-specific antibody titer that peaked 21 days post-implantation of the xenograft.


Buccal mucosa is a great choice for urethroplasty for urethral stricture repair because of ease of harvesting, pliability of the graft, and minimal donor site morbidity. These procedures are performed at our institution as a combined case with Pediatric Otolaryngology and Urology. Harvesting buccal mucosal grafts in younger patients is more technically challenging due to limited oral cavity access and smaller area available for tissue harvest, but is able to be performed safely and with limited morbidity with the addition of parotid duct cannulation and use of retraction sutures to the graft harvest technique. This retrospective case series reports harvest technique, outcomes, and complications of children and young adult males undergoing buccal or lower lip mucosal graft harvesting to repair congenital urethral strictures. Outcome measures were perioperative bleeding, trismus, pain, numbness, parotid duct injury and lip deformity. Six patients underwent nine harvest procedures. Technique modifications included application of anterior graft margin stay sutures to help stabilize the graft mucosa and cannulation of the parotid duct with lacrimal probes to avoid duct injury and to maximize graft size. Overall, buccal mucosal graft harvesting is a well-tolerated procedure with minimal complications using proper harvest technique. Hypospadias is one of the most common congenital defects of the external male genitalia, affecting one in 250 male newborns. This requires surgical repair by a pediatric urologist. The rate of post-repair strictures varies based on surgical technique, ranging from 6-50% . DependiAfter nasotracheal intubation, a bite block was placed and the anterior tongue was retracted with a 2-0 silk suture. The parotid duct was cannulated with a 00 lacrimal probe that was left in place during dissection. Lidocaine 1% with 1:100,000 epinephrine was injected into the submucosa. The graft size was outlined with a marking pen, taking care to mark at least one centimeter (cm) posterior to the oral commissure . Graft length and width ranged from: 2 to 8 cm and 2 to 3.5 cm, respectively. The average time to follow-up was 15 days after surgery  of the patients reported mild tenderness. The remainder of the patients reported no pain. No patient experienced postoperative bleeding; 1/6 (17%) patients reported temporary numbness; 1/6 (17%) patient reported temporary trismus. The patient who reported trismus was a 27-year-old smoker and also had a benign leukoplastic lesion on the contralateral buccal mucosa that was biopsied at the time of graft harvesting. His trismus resolved three months post operatively with normal interincisal opening on physical exam. No patients reported or had evidence of parotid duct injury or parotitis. One patient had a combined labial and buccal graft in order to obtain a longer graft.Our results show there is minimal morbidity with our modified technique for buccal mucosa graft harvesting in pediatric and young adult patients. The two main technique modifications made to safely maximize graft size and avoid graft and harvest bed injury were parotid duct cannulation and stay suture placement, which have not been described in prior studies.The parotid duct was cannulated before injection and marking of the graft. To our knowledge, no prior study has described cannulation of the parotid duct prior to harvesting. One study described parotid duct injury with subsequent ductal stenosis in two patients after buccal mucosal graft harvesting . Two of Second, the application of stay sutures to the anterior margin of the graft during harvest is also important. This helps in manipulation of the graft during dissection and avoids damage to the graft with forceps during harvesting. It is also helpful in taking a thin, pliable graft allowing for excellent traction to separate the submucosa from the buccal musculature. Avoidance of deep dissection may be important for better healing, less pain and scarring as well as avoidance of sensory nerve damage.Fabbroni et al. described a similar technique where the graft was marked out to avoid the parotid duct however, the parotid duct was not cannulated . In addiComplete closure of donor sites is controversial and may contribute to scar formation and increased perioperative pain. All of our patients had complete mucosalization of the donor site at their six-week post-operative appointment. The donor site healed well with secondary intention. Placing absorbable, interrupted sutures along the graft harvest wound edges to reduce the size of the defect seems to help reduce the defect size. All patients were able to tolerate regular diet within 24 hours after surgery, despite two patients reporting mild tenderness. Wong et al. published a prospective study comparing primary closure versus secondary intention in patients who underwent buccal mucosal graft harvesting . PatientBuccal mucosa is a very useful graft for reconstruction for urethral stricture, and is harvested at our institution by the pediatric otolaryngologist for use by the pediatric urologist. This allows for a two-team approach to this reconstruction, which likely allows for decreased operative time. However, we were unable to fully examine this in our study as we did not have any cases where the graft was not harvested by otolaryngology.Buccal mucosa is a very useful graft for reconstruction for urethral stricture, and is harvested at our institution by the pediatric otolaryngologist for use by the pediatric urologist. Although parotid duct injury is a rare complication, it can cause significant morbidity. This can be avoided with no additional morbidity by duct cannulation and palpation during graft marking and elevation. The addition of anterior graft margin stay sutures is helpful in harvesting a thin, even graft and helps avoid trauma to the graft and to the buccal musculature, which helps reduce long-term complications of scarring and trismus. Overall, buccal mucosal graft harvesting is a well-tolerated procedure with minimal complications using proper harvest technique.


Various types of zirconia are widely used for the fabrication of dental implant superstructures and fixtures. Zirconia–alumina composites, such as ATZ and NanoZR, are adequate for implant fixtures because they have excellent mechanical strength in spite of insufficient esthetic properties. On the other hand, yttria-stabilized zirconia has been used for implant superstructures because of sufficient esthetic properties. They are classified to 12 types with yttria content, monochromatic/polychromatic, uniform/hybrid composition, and monolayer/multilayer. Zirconia with a higher yttria content has higher translucency and lower mechanical strength. Fracture strength of superstructures strongly depends on the strength on the occlusal contact region. It suggests that adequate zirconia should be selected as the superstructure crown, depending on whether strength or esthetics is prioritized. Low temperature degradation of zirconia decreases with yttria content, but even 3Y zirconia has a sufficient durability in oral condition. Although zirconia is the hardest dental materials, zirconia restorative rarely subjects the antagonist teeth to occlusal wear when it is mirror polished. Furthermore, zirconia has less bacterial adhesion and better soft tissue adhesion when it is mirror polished. This indicates that zirconia has advantageous for implant superstructures. As implant fixtures, zirconia is required for surface modification to obtain osseointegration to bone. Various surface treatments, such as roughening, surface activation, and coating, has been developed and improved. It is concluded that an adequately selected zirconia is a suitable material as implant superstructures and fixtures because of mechanically, esthetically, and biologically excellent properties. The number of types of dental zirconia has increased over the past two decades ,3,4,5,6,2), three crystal phase systems  transform with temperature, with the monoclinic phase being stable at room temperature. When zirconia is solidly dissolved in yttrium (Y), calcium (Ca), magnesium (Mg), cerium (Ce), or other ions with a larger ionic radius than that of zirconium (Zr), the tetragonal and cubic phase systems become stable at room temperature . H. H27]. HSince the translucency was further improved, the anterior teeth did not need to be veneered with porcelain, and a monolithic zirconia anterior crown became possible. In this way, the translucency of dental zirconia has been dramatically improved . In 2015Furthermore, since 2016, polychromatic and hybrid composition multilayer (M3Y-5Y), which are laminates of TZP and PSZ with different compositions and characteristics, have been provided. On the other hand, zirconia using high-strength PSZ (4Y) e, which ® (Densply Sirona), making it possible to fabricate high-translucent and high-strength prosthetics in a short sintering time.The zirconia pre-sintered body used in the laboratory is mainly in the form of a disc with a diameter of 98 mm and a thickness of 16 to 35 mm , but theAs mentioned above, various types of yttria-stabilized dental zirconia are marketed one after another by each company , and zirWhen the yttria content is high, there are many cubic phases and the translucency is high, but the strength is inferior because there are few tetragonal phases that contribute to the strength. The translucency of 5Y is improved by 20 to 25% compared to that of 3Y, but the flexural strength is reduced by 40 to 50% . Therefore, the higher the translucency, the lower the strength. This contradictory relationship must be fully considered when applying zirconia to dental restorations. In other words, 3Y, which has high strength but low translucency, can be applied to long-span bridges, but is not suitable for anterior tooth crowns. On the other hand, 5Y and M5Y, which have low strength but high translucency, cannot be applied to long-span bridges, but can be applied to anterior tooth crowns and veneers. In the case of the polychromatic and hybrid composition multilayer type, such as M3Y-5Y, the application case of 5Y having low strength is dominant. On the other hand, both 4Y and M4Y are applicable to cases of all sites in sufficient terms of strength and translucency.® by Dental Direkt GmbH and One4All® by Metoxit AG. It implies that both 4Y and M4Y can be applied to any cases of any sites.In Europe and the United States, there is a strong need to use zirconia as a long-span overdenture, and both 4Y and M4Y are preferred. The intention is also reflected in the product names, e.g., DDcube ONE−6/°C, and there is no significant difference depending on the yttria content. This is because there is no crystal transformation in this temperature range and the coefficient of thermal expansion mainly depends on the strength of the atomic bond. The bulk density of zirconia is about 6, and there is no significant difference depending on the yttria content.Thermal properties of zirconia are extremely specific, and among dental restorative materials, zirconia has extremely low thermal conductivity . The coefficient of thermal expansion in the range of 25 to 500 °C is around 10 × 10Translucency of zirconia is clearly lower than glass ceramics . In the Zirconia shows higher radio-opacity than titanium and aluminum. Between the two types of zirconia, the radio-opacity of NanoZR is slightly lower than that of 3Y-TZP . This isThe hardness of dental zirconia is almost constant, although their flexural strengths decrease with the yttria contents . ZirconiIn addition, the fracture toughness values of 5Y decrease by about 50% from that of 3Y with the cubic phase content due to the increasing of yttria content  33]. Fr. Fr33]. The fracture toughness value is an index of impact strength, and a low fracture toughness value means a low impact strength. Therefore, considering that the strength of 5Y dental restoration is inferior to that of 3Y, it is necessary to consider making the 5Y restoration thicker than 3Y. Nevertheless, 5Y has higher flexural strength and higher fracture toughness than glass–ceramic materials such as lithium disilicate .® and Procera® crowns] after aging in a chewing simulator in comparison with a conventional titanium implant restored with porcelain-fused-to-metal (PFM). They reported that there was no significant difference between the PFM crown group and the Procera® group. Furthermore, they also reported that the fracture strength of two-piece cylindrical zirconia implants  after aging in a chewing simulator in comparison with a conventional titanium implant restored with PFM crown  by MTT assay for 24 h and 72 h. Smooth zirconia (Zr-S) showed the highest value in both elapsed times, and cell proliferation grew significantly faster than other surfaces. In addition, smooth zirconia (Zr-S) spread cells most evenly on the sample surface [Yamano et al.  evaluate surface . TherefoZirconia has high strength, but as mentioned above, its polished surface is hydrophobic and is classified as a bioinert material. However, hydrophilicity is desired as an implant fixture to be bonded to living hard tissue.Therefore, surface modification is required, but it has not been established yet. Furthermore, it is feared that these treatments may cause a decrease in strength, which is an advantage of zirconia. The increase in toughness of zirconia with sandblasting involves the crystal transformation from tetragonal to monoclinic crystals. When other substances enter the surface layer, this transformation behavior becomes hard to occur and the strength unavoidably decreases. Many methods have been proposed to resolve this contradiction and balance the degree of strength reduction with the improvement of biocompatibility ,74,75,76Zirconia is hydrophobic when mirror polished, but it can be improved to some extent by surface roughness, such as grinding and sandblasting. The authors examined the MTT assay of MC3T3-E1 cells cultured on pure titanium, alumina, 3Y-HA, and NanoZR plates . The num® treatment, and has reported that it showed the same osteosynthesis as the SLA® treatment of titanium [Zirconia implant fixtures have rapidly become commercially available, mainly in Europe. Many products are only sandblasted on the surface, but some are acid-treated. Since zirconia has high acid resistance, it is treated with heated hydrofluoric acid ,82. Stratitanium ,84.2 and Er:YAG lasers did not cause such damage. However, it has been reported that the CO2 laser improves hydrophilicity and improves the adhesion of human osteoblasts (hFOB) [The effect of laser irradiation on zirconia varies greatly depending on the type of laser. We reported that the surface of zirconia was blackened and cracked by Nd:YAG laser irradiation . CO2 ands (hFOB) . In addis (hFOB) ,88.® [® from Nobel Biocare, and it has been confirmed that it is equivalent to Ti-Unite® in the differentiation of osteoblasts on the surface [A method of forming a porous zirconia layer on the surface by applying a zirconia slurry containing a foaming agent to the surface of calcined zirconia and firing has been reported. It has been reported that implants were made in the femur and cervical bone of rabbits to obtain good binding , new bone mass, and connective tissue equivalent to those of Nobel Biocare’s Ti-Unite® . This po surface ,91. ThisAlthough UV irradiation of titanium is effective, the bioactivation treatment effect of irradiation of zirconia is often negative ,93.It has been reported that it is possible to clean the prosthesis before it is placed in the oral cavity and activate its properties, and it is effective in improving the bond between zirconia and the resin adhesive . By impr−6/K for zirconia and 8.5 × 10−6/K for titanium. Therefore, surface activation coating treatment by heating is applied to zirconia, including the glass coating used for titanium. Kim et al. have reported a method of coating the surface of zirconia with fluoroapatite using the sol–gel method [Zirconia has properties close to metals among ceramics, and titanium has properties close to ceramics among metals. For example, the coefficient of thermal expansion is close to 10.1 × 10l method . Howeverl method  have repl method  bake bio2, borax Na2B4O7 10H2O, and tricalcium phosphate Ca3(PO4)2 as the basic composition of glass and dissolved and pulverized to prepare the glass powder. In the composition containing a large amount of tricalcium phosphate, hydroxyapatite is precipitated in the glass. This glass was made into a paste and applied to zirconia and fired to form a film. The adhesive strength between glass and zirconia depends on the borax content [The authors used silica SiO content . The amo content .Phosphate compounds are highly reactive with zirconia, and when heated in contact with them, they react with yttrium added to stabilize zirconia to produce yttrium phosphate . As a reDental zirconia continues to increase and is classified into 12 species in the yttria system alone. They are classified with yttria content, monochromatic/polychromatic, uniform/hybrid composition, and monolayer/multilayer.Higher yttria content zirconia has higher translucency and lower mechanical strength. Fracture strength of superstructures strongly depends on the strength on the occlusal contact region. Therefore, adequate zirconia should be selected as the superstructure crown, depending on whether strength or esthetics is prioritized.Low temperature degradation of dental zirconia decreased with yttria content, but even 3Y zirconia has a sufficient durability in oral condition.Although zirconia is the hardest dental materials, zirconia restoratives rarely wear the antagonist teeth when it is mirror polished.Zirconia has less bacterial adhesion and better soft tissue adhesion when it is mirror polished. Therefore, zirconia has advantageous for implant superstructures.Zirconia–alumina composites, such as ATZ and NanoZR, are adequate for implant fixtures because they have excellent mechanical strength in spite of insufficient esthetic properties.Zirconia is required for surface modification to obtain osseointegration to bone. Various surface treatments, such as roughening, surface activation, and coating, have been developed and improved.The present review classified the various dental zirconia and summarized their properties for implant superstructures and fixtures as follows:Therefore, it is concluded that an adequately selected zirconia is a suitable material as an implant superstructure and fixture because of its mechanically, esthetically, and biologically excellent properties.


The automated blister epidermal micrograft (ABEM) is a newly introduced surgical transplantation for refractory vitiligo. Comparative analysis of other surgical methods is lacking. We conducted a retrospective study to compare the efficacy, safety, and experience of ABEM with conventional suction blister epidermal graft (SBEG). A total of 118 anatomically based vitiligo lesions from 75 patients were included. The primary outcome was the degree of repigmentation; the patient and operator experience were evaluated. SBEG had a significantly greater incidence of repigmentation (p < 0.001), as measured by the Physician Global Assessment, as well as improvements in the Vitiligo Area Scoring Index, particularly on the face/neck area (p < 0.001). ABEM, on the contrary, had reduced donor harvest time, a better patient operative experience, and more significant Dermatology Life Quality Index improvements. In a subgroup of 38 lesions from ten patients who received both SBEG and ABEM concomitantly, there was no difference in the degree of repigmentation in the same recipient area. Overall, the degree of repigmentation for SBEG is higher than ABEM, especially in the mobilized region, and the cost is less expensive. On the contrary, ABEM requires less procedure learning curve and can supply a greater transplanting zone with shorter donor site recovery. Understanding the benefits and drawbacks of two blister grafting procedures is essential for optimal surgical outcomes for vitiligo grafting. The characteristic clinical features are white macules and patches with sharply circumscribed but irregular borders. Various modalities, both conventional and alternative, non-surgical and surgical, are used in the treatment. Vitiligo has a detrimental effect on a patient's quality of life due to social stigma and comorbidities6.Vitiligo is an acquired depigmentation of the skin caused by the complete loss of melanocytes. It affects approximately 0.5 to 2 percent of the general population7. Systemic steroids or immunosuppressants are used to halt the autoimmune destruction for rapidly progressive unstable lesions. Narrowband ultraviolet B phototherapy and monochromatic excimer laser can enhance melanocyte regeneration and immunomodulatory effect7. Patients suffering from stable recalcitrant lesions that have not responded to non-surgical methods may opt for surgical treatment using melanocyte transplant techniques7. The two most common types of procedures are tissue grafts and cellular grafts. Melanocyte-rich tissue grafting includes full-thickness, split-thickness, and suction blister grafts9. A novel automated epidermal harvesting technique that induces blister epidermal micrograft formation is now commercially available10.Vitiligo is one of the most complex dermatological conditions to manage. The recommended first-line treatment is topical steroids, either alone or in combination with topical calcineurin inhibitorsThis study aims to compare conventional suction blister epidermal graft (SBEG) with automated blister epidermal micrograft (ABEM) technique for patients with stable vitiligo in terms of efficacy, safety, and patient and operator experience. In addition, anatomical areas, including the face, trunk, limbs, and acral parts, were also analyzed. To our knowledge, this is the first study that compares two blister epidermal graft surgical methods for the treatment of stable vitiligo.We conducted a retrospective comparative trial from January 2017 to December 2020 in the Dermatology Department of Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. The protocol was approved by the Chang Gung Medical Foundation Institutional Review Board (No.: 202100274B0) before the initiation of the study. All of the research was carried out in accordance with the applicable rules and regulations.11.Patients were recruited from the practice of a single dermatologist in a tertiary medical center. The study included patients with stable vitiligo  who failed to respond to other therapies in the past two years. Stable vitiligo was defined as no deterioration of old lesions and no new lesions within a year. Exclusion criteria included keloidal tendency, active infections, pregnancy, lactation, bleeding diathesis, or any sign of unstable disease . The efficacy and safety of ABEM in segmental and non-segmental vitiligo from the same patients in this study has been investigated and reported in the literature13. This method requires creating a subepidermal bulla from the donor site by prolonged vacuum application; then, the roof is surgically removed and transplanted to the recipient site. A suction syringe without a plunger is applied to generate constant negative pressure on the donor site through a 3-way connector. An infrared lamp as a heating source was used to shorten the blistering time. The recipient site was prepared by ablation with Erbium: Yttrium–aluminium-garnet (Er: YAG) laser  with a 2-mm spot-sized handpiece at the average fluence of 6.3 J/cm2 for optimal graft adherence and uptake. The graft was then transferred after being modified to the proper size and shape and wrapped with a hydrocolloid dressing.Suction blister epidermal grafting is a low-cost, high-effective technique that results in complete repigmentation in 68–70% of cases15. With a negative pressure of − 400 to − 500 mmHg and a temperature of 37 to 41 °C, the device automatically produces suction micro domes and harvests epidermal micrografts with an area of 20–25 cm215. A silicone-coated nonadherent dressing  was used to transfer the epidermal micrografts perforated design helps fluid to drain from the micro blisters16. After preparing the recipient site with Er: YAG laser ablation, the graft was transferred to the recipient site and wrapped with a hydrocolloid dressing. All patients with ABEM and SBEG received topical tacrolimus 0.1% ointment after grafting procedure. 64%  with ABEM grafting and 55%  received excimer light and/or narrow band UVB phototherapy at least once per week after grafting.The automated blister epidermal micrograft  is a novel option, allowing patients to receive pain-free epidermal skin grafts with reduced donor site trauma Fig. 14,15. Wi17. The secondary outcome measure was the patient and operator experience evaluated by operative conditions, pain score, and change in the Dermatology Life Quality Index (DLQI)18. Adverse event was monitored and recorded.The primary outcome measure was the degree of repigmentation per lesion. The rate of repigmentation, identified as the area of pigments at the recipient site one year after initial treatment, was graded as very good (≥ 75%), good (50–74%), fair (25–49%), and poor (0–24%) using a Physician Global Assessment (PGA) scale. In addition, improvement in Vitiligo Area Scoring Index (VASI), a quantitative parametric score developed by Hamzavi et al., was used to assess the efficacyData were analyzed using the R software . The descriptive statistic was showed by mean, standard deviation (SD) for continuous variable and count, % for categorical variable.To compare the results, we used paired sample t-test, chi-square × 2 tests, or Fisher exact tests to compare the difference between various groups. A p-value less than 0.05 was considered statistical significance.Reviewed and approved by Chang Gung Medical Foundation IRB; approval #202100274B0.We obtained written informed consent from all participants.In the study, 118 anatomically based lesions from 75 patients with stable vitiligo were enrolled. 62 lesions received conventional suction blister epidermal graft (SBEG), and 56 lesions receiving automated blister epidermal micrograft (ABEM)  of the lesions in the SBEG group were scored as very good (≥ 75%); 5 (8%) as good (50–74%); 1 2%) as fair (25–49%); and 9 (15%) as poor (0–24%)  and to complete the whole procedure  than SBEG , and 75.81% achieved very good results (≥ 75% repigmentation), which is comparable to the degree of repigmentation in a meta-analysis by Ju et al.2 of area in a single harvesting. Hence, the treatment area for each grafting with ABEM is larger than of SBEG.In terms of operator experience, ABEM took significantly less time to harvest the blisters and complete the procedure than SBEG, making it more convenient and appropriate for ambulatory surgery. It allows reduced operation time, which is beneficial for both operators and patients, especially children who cannot withstand long harvesting. SBEG, on the other hand, takes longer and is less suitable for broad achromic surfaces. The rounded blisters collected from SBEG must be tailored to the vitiligo area, which is sometimes uneven in shape and can result in graft waste. Furthermore, the quality of harvested blister is occasionally unpredictable, and the operator needs to pay close attention to the orientation of blisters to avoid engraftment problems caused by upside-down grafting. The ABEM contains micrografts aligned on silicone dressing that can be readily tailored to match the shape of the transplanted area and generate 20–25 cmIn addition, when compared to SBEG, ABEM had better donor side outcomes, with patients experiencing significantly fewer side effects such as pain, donor site hyperpigmentation, and scarring. In ABEM, dotted repigmentation from the micrografts can be observed within one month and gradually expand centrifugally. Over time, the repigmentation confluent into a more homogenous pattern to cover the recipient area, with an optimal result at around a year after grafting Fig. . On the 23. ABEM has a higher yield of graft area (20–25 cm2) per harvest than SBEG, making it suitable for a larger recipient area. In the intra-individual study, there was little difference in repigmentation efficacy between SBEG and ABEM. Therefore, ABEM can be an alternative for individuals seeking a less painful and more convenient treatment modality. Furthermore, combining the two treatments to optimize the surgical outcome may be an option  at a single harvest, and a better operational experience, which includes a shorter procedure time, fewer donor side problems , and improved quality of life. Understanding the benefits and drawbacks of two blister grafting methods is crucial for optimal surgical results.To the best of our knowledge, this is the first study directly comparing the effect and safety for SBEG and ABEM. We found that stable vitiligo treated with SBEG had a significantly higher repigmentation rate than those treated with ABEM, particularly around lips, eyelids, and bony prominences. SBEG should be used on the face and neck because of its better efficacy and cost-effectiveness. ABEM, on the contrary, has some advantages, including better blister quality, a higher yield of graft area (20–25 cm


The aim of this study was to evaluate the characteristics and eating quality of salted noodles that are incorporated with different formulations of flour. Up to 20% of wheat flour was substituted by composite flours of highly resistant starches, including heat moisture treatment corn starch (HMT-CS), high-amylose corn starch (Hylon VII), and green banana flour (GBF). The physical properties of dough, in conjunction with the eating quality and estimated glycemic index (EGI) of cooked salted noodles, were investigated in this study. The results concluded that the incorporation of GBF, HMT, and Hylon VII not only affected the water absorption and mixing tolerance of the dough, but also the maximum resistance to extension and extensibility in terms of the extensographic properties. Meanwhile, GBF, HMT, and Hylon VII incorporation significantly increased the resistant starch content and decreased the fat content of the noodle samples. The textural profile analyses of cooked salted noodles indicated that hardness, gumminess, chewiness, and shearing force increased; nevertheless, springiness declined with the increase in the proportion of flours from 10 to 20%. The sensory evaluation detected that wheat flour composited with 10% GBF and HMT flours could produce acceptable quality noodles as compared with normal typical control noodles. In the meantime, salted noodles incorporated with GBF, HMT-CS, and Hylon VII flour decreased the estimated glycemic index (EGI) dramatically. The result of this study concluded that incorporation of various sources of resistant starch flour could develop a low-GI noodle with good acceptability that may contribute to gastrointestinal health. The evolution of valued products has recently been a deliberate focus of the food industry. Consumers are challenging foods in terms of their traditional nutritional requirements, whereas additional health benefits, such as in nutraceutical foods, are anticipated from regular intake. Rich sources of resistant starch (RS) have commonly been applied in commercial food manufacturing in the last decades. RS is known as an important contributor to the maintenance of gastrointestinal health. It is recognized that incorporation of resistant starch in staple foods could be considered in order to increase the daily dietary fiber intake . VariousAsian noodles are a commonly eaten food, including udon and ramen noodles , as well as Chinese yellow alkaline noodles (Hokkien noodles). The rheological properties of salted noodles are closely correlated with the compositions of wheat flour used, a factor that has been broadly examined ,6. Due tBanana is one of the most imperative climacteric fruits in Taiwan, being a potential source of starch, and has value in terms of investigation due to its abundance, predominantly in tropical countries. Unripe or green banana starch is extremely impervious to digestion in rats and humans . PreviouA diet with high-amylose corn starch  and heat moisture treatment corn starch (HMT-CS) also contains a significant amount of RS, up to 46–50% of which can be offered as a nutraceutical food to satisfy consumer demand ,12. HeatNevertheless, to the best of our knowledge, no such material has been found to date regarding incorporation of HMT corn starch, Hylon VII corn starch, and green banana flour (GBF) to salted noodles. Hence, the goal of this current study was to apply several sources of RS-rich flours, such as HMT corn starch, Hylon VII corn starch, and green banana flour (GBF), to formulate a composited flour for dough and salted noodle preparation. The physicochemical properties, sensory quality, and glycemic index of the salted noodles were also evaluated in this study.The flour composition in this current study was formulated with different proportions of RS source flours, including the HMT, Hylon VII, and GBT , together with the wheat flour . All chemicals used were American Chemical Society (ACS)-certified chemical grade.Green banana (Musa padisiaca) was locally grown at a local farm at Nantou, Taiwan. Green banana was treated by the procedures of washing, peeling, dicing, and being air-dried by a hot air oven. The dried green banana was intermixed by a blender, generating a flour with consistent size by passing through a 100-mesh, which is 150 µm of sieve. The green banana flour (GBF) was put into a polyethylene zipper bag and stored in a freezer until further use.The moisture content of corn starch was guided to around 30% before further treatment. The samples were heated in a hot air oven at a temperature of 100 °C for a continuous 16 h. After the flour cooled down, the starch was air-dried to assure consistent moisture content (10%) ,16.High-amylose corn starch, namely, Hylon VII, was supplied by the National Starch and Chemical Company . The sample was stored in an air-tight container before further use.The proximate analyses for moisture, crude protein , and ash content (methods 08–01 and 08–17) of the wheat flour and salted noodles were accomplished in accordance with the method of the AACC (2000). Crude lipid (Method 30–25) was analyzed by using the Soxhlet method, while the crude fiber (method 32–20) was measured gravimetrically after chemical digestion and solubilization. The contents of moisture, crude protein, and ash of the wheat flour were 13.04, 10.98, and 0.39%, respectively.We added 2% of salt into the formulated flours. Next, mixing was carried out at low speeds with water for 5 min in a mixer, and it was continued by rolling into a dough sheet with around 3 mm of thickness. Folding and sheeting were consequently carried out. The dough sheet was put aside to rest for around 1 h, and it was passed through the sheeting rolls 3 times, gradually decreasing the gaps of the roll from 2.60 to 2.30 to 2.00 mm. The noodle strand was cut uniformly from the noodle sheet, and the organized noodles were stored in an air-tight container .A Farinograph , by referring to the standard method of AACC 54-21 (2000), was applied to investigate the rheological properties of the dough sample. Different formulations of HMT, Hylon VII, and GBT, at 0, 10, and 20%, respectively, together with wheat flour, were prepared before the examination. During the examination, the water absorption, arrival time, departure time, dough stability, peak time, and mixing tolerance index were investigated. Meanwhile, the flexible properties of the dough with different amounts of HMT, Hylon VII, and GBT were also measured by using an Extensograph , which was in reference to the standard method of AACC 54-10 (2000). After Farinograph measurements, the dough was cut into two parts and passed through the balling, followed by the mold unit of the Extensograph. The dough was rested for 45 min in the fermentation cabinet and was followed by stretching. The resistance to extension (BU) and extensibility (cm) were the parameters included in the test.A total of 100 mL of boiling water was prepared, and 10 g of salted noodles was cooked in for 5 min and drained. The cooked noodles were dried in a hot-air oven at a temperature of 115 °C, and the leftover solids were measured to calculate the cooking loss, which was stated as a percentage of the initial dry matter.The texture profiles of the cooked salted noodles were evaluated by a texture analyzer, with the TA-XT2 model, equipped with Stable Micro Systems. First, the noodle was cooked in 500 mL of boiling distilled water for 5 min, and then cold water was used to rinse the noodles for 1 min. Next, the cooked noodle sample was held by tension grips about 3 mm apart in the TA-XT2i and was extended at 0.8 mm/s until failure or breakdown. The maximum slope and the decrease in force on breaking was verified from the force (g)–displacement (mm) curve. The determination of tensile strength of the cooked noodle sample was carried out with modification .Five 6 cm long strands were arranged perpendicularly to the pasta blade probe on a flat aluminum platform base in order to determine the cutting force. The probe moved down through the noodle sample at a speed of 1 mm/s until it touched the platform base. The test was performed twice at different locations to acquire an average result.For the TPA study, six replications of the noodle sample were examined within 3 min after cooking and cooling. The noodles were positioned on a flat aluminum platform base, and a 3 mm diameter steel cylinder probe crushed the noodle sample to 70% of its original height at a speed of 2 mm/s. The characteristic of the noodle samples in terms of hardness, cohesiveness, springiness, gumminess, and chewiness were recorded from the force-time curves.Twelve panelist members made up of graduate students of the Food and Nutrition Department at Providence University were selected to be involved in the sensory evaluation of noodles with different formulations of HMT, Hylon VII, and GBT. Rating test training was carried out on the panelists to assure the panelists evaluated samples properly. A multi-sample comparison test was applied to assess the color, stickiness, cohesiveness, firmness, and overall acceptability of the noodle samples. The multi-sample comparison test of cooked noodles was assessed on a 9-point scale with 1 representing “extremely low” and 9 representing “extremely high”. The color of cooked noodles was evaluated in terms of whiteness on a 9-point scale, with 1 representing “extremely light” and 9 representing “extremely dark”. The overall acceptability test of cooked noodles was estimated on a 9-point scale, with 1 as the “lowest” and 9 as the “highest”. A hedonic scale was applied to evaluate the overall acceptability. The noodle samples were cooked in boiling distilled water for 5 min and cooled in drinking-grade tap water for 1 min before serving. Samples were served individually in a randomized order on plastic trays. Panelists were requested to rinse their mouths with deionized drinking water in the middle of testing each sample.Ground samples (100 mg) were placed in 2 mL of 2 M KOH and were continuously stirred in an ice/water bath for 20 min. To the solubilized starches, we added 8 mL of 1.2 M sodium acetate buffer (pH 3.8) and hydrolyzed them using 0.1 mL of α-amylase and 0.1 mL of amyloglucosidase . The mixture was mixed up thoroughly and incubated at 50 °C in water baths for 30 min. After centrifugation, the glucose content in the supernatant was measured by using a glucose oxidase-peroxidase (GOPOD) kit. Absorption was measured at a wavelength of 510 nm, and glucose concentration was converted into starch content by using a factor of 0.9. The TS content was converted from the content of glucose .A Megazyme Resistant Starch Assay Kit (AOAC Method. 2002.02) was used to measure the resistant starch (RS) content. Ground samples (100 mg) were hydrolyzed by 40 mg of α-amylase solution at 37 °C for 16 h. The hydrolysates were centrifuged, and the supernatants were removed. The residues were analyzed for starch as described above using amyloglucosidase from Aspergillus niger .In vitro starch digestibility in salted noodles was evaluated by using the method of Reshmi et al. (2020) with modifications . A total−kt), where C corresponds to the percentage of starch hydrolyzed at time t, C∞ represents the percentage of starch hydrolyzed after 180 min, k represents the kinetic constant, and t represents the time (min). The parameters C∞ and k were assessed for each type of starch and each formulation on the basis of the data obtained from the in vitro hydrolysis procedure. The areas under hydrolysis curves  were calculated. The percentage of total glucose release from each sample was calculated as the hydrolysis index (HI) to that of glucose released from white bread. The estimated glycemic index was calculated according to the equation of EGI = 39.71 + 0.549HI.The first order equation had the form C = C ∞  of salted noodles, showing that the highest EGI, 72.8, was in the control sample , followew/w), for example, the GBF, HMT flour, and Hylon VII flour, with wheat flour generates a dough with appropriate strength and extensible texture, allowing salted noodles to uphold a stiff and elastic form. Moreover, the nutritional value is subsequently enhanced, as the addition of resistant starch source flour with salted noodles resulted in more nutrient components with lower GI value. Furthermore, the 10% GBF noodles exhibited an EGI value of 62.8, as compared to the control sample (72.8). Even though increasing the amounts of resistant starch source flour used caused the cooking characteristics to deteriorate proportionally, supplementing salted noodles with 10% (w/w) resistant starch source flour (10% GBF) demonstrated equal overall acceptability in terms of sensory evaluation as compared with the control noodle sample.The incorporation of resistant starch source flour (10–20%,