Secondary aortoenteric fistula or erosion (SAEFE), an abnormal connection between the aorta and gastrointestinal tract, is a rare but critical complication after abdominal aortic aneurysm repair. Most SAEFEs occur between the aorta or proximal graft anastomosis and the duodenum, and occurrence between the iliac graft and small intestine is rare. Standard SAEFE management involves graft removal and extra-anatomical bypass. However, this is extremely invasive and has a high mortality rate. We encountered a rare case of SAEFE with no sign of infection, which was successfully treated by ligating the iliac graft to reduce mechanical pulsatile stress and bleeding following the retroperitoneal approach. It has been reported that 90% of SAEFEs are aortoduodenal, 7.4% are aortojejunal, and 4.3% are aortoileal. To the best of our knowledge, few papers have discussed iliac graft to ileal fistula, and there is no report describing the surgical management of this condition. We encountered a rare case of SAEFE that was treated by ligating the distal limb of the graft 4 years after the aortic reconstruction.Secondary aortoenteric fistula or erosion (SAEFE) is a life-threatening, spontaneous erosion and irregular communication between the graft and the gastrointestinal tract after surgical repair of abdominal aortic aneurysm. The reported incidence of SAEFE including graft-enteric fistula is 0.6%–1.6% after aortic reconstructions.A 72-year-old man complaining of repeated gastrointestinal bleeding was transferred to our institution. He had a history of abdominal aortic aneurysm and aortic reconstruction using a vascular prosthesis at another hospital. Computed tomography (CT) imaging showed no active bleeding and adhesion between the right iliac graft and the small intestine .The diagnosis of SAEFE is not necessarily easy as no typical symptoms have been identified. Gnus et al. described 24 patients with SAEFE; 16 of which presented with symptoms of gastrointestinal bleeding, 6 with hemorrhagic shock, 4 with septic shock, 8 with abdominal pain, 4 with back pain, and 8 with a pulsatile abnormal mass. Some reports recommend complete graft resection as treatment of SAEFE with infection and establishment of extra-anatomical circulation. However, if the adhesion is dense, a broad range of adhered small intestine resections are required, and this can cause some various complications, such as the short bowel syndrome. Contrarily, Shindo et al. reported spontaneous closure of graft-duodenal fistula without any surgical fistula closure. This report suggested that if infection was controllable during the pre- and post-operative period, then there is a possibility of spontaneous closure of the fistula. In our case, the patient did not show any sign of infection; therefore, we decided to perform simple ligation of the iliac graft to reduce pulsatile stress. The postoperative course was uneventful without recurrent hemorrhage or infection. This finding supports the hypothesis that gradual mechanical stress can cause bowel erosion. This suggests that if SAEFE is caused by erosion of the small intestine, simple ligation of the graft to reduce the pulsatile stress is effective treatment if the patient shows no signs of infection.The management of SAEFE varies and is dependent on the patient’s condition, with complete resection of the fistula being a standard treatment option. Nevertheless, the surgical mortality rates of SAEFE remains high. Several reports have argued that SAEFEs can be divided into two groups: direct communication between the graft and intestinal lumen and periprosthetic fistula due to an eversion of an intestinal loop.We successfully performed surgical repair of SAEFE without any signs of infection before the occurrence of life-threatening bleeding using simple ligation of the iliac graft. If there is no sign of infection, this less invasive surgical treatment may be an effective alternative to removal of the whole graft and intestine.


Hydnocarpus hainanensis Merr. is an evergreen tree with a height of 6–12 m and a diameter at breast height of 50 cm. It is distributed in Guangxi, Guizhou, Hainan, South of Yunnan Province of China. Here, we report and characterize the complete plastid genome sequence of H. hainanensis in an effort to provide genomic resources useful for promoting its conservation and systematics research. The plastome of H. hainanensis is found to possess a total length 163,330 bp with the typical quadripartite structure of angiosperms, containing two inverted repeats (IRs) of 26,870 bp, a large single copy (LSC) region of 91,510 bp and a small single copy (SSC) region of 18,080 bp. The plastome contains 111 genes, consisting of 78 unique protein-coding genes , 29 unique tRNA genes  and four unique rRNA genes . The overall A/T content in the plastome of H. hainanensis is 63.70%. The phylogenetic analysis indicated that H. hainanensis is close to Salix rorida within Malpighiales. The complete plastome sequence of H. hainanensis will provide a useful resource for the conservation genetics of the one species as well as for the phylogenetic studies of Achariaceae. Hydnocarpus hainanensis is an evergreen tree with a height of 6–12 m and a diameter at breast height of 50 cm. It is distributed throughout the evergreen broad-leaved forests having altitudes that range from 300 to 1800 m in Guangxi, Guizhou, Hainan, South of Yunnan Province in China . This is the first report of a complete plastome for the H. hainanensis.H. hainanensis is sampled from Diaoluo Mountain , which is a National Nature Reserve of Hainan, China. The voucher specimens  are deposited in the Herbarium of the Institute of Tropical Agriculture and Forestry (HUTB), Hainan University, Haikou, China.In this study, Q ≤ 5) bases are filtered out using NGSQC-Toolkit v2.3.3 (Patel and Jain Idseia polycarpa (NC_032060.1) . The annotation is corrected with DOGMA  of 26,870 bp, a large single copy (LSC) region of 91,510 bp and a small single copy (SSC) region of 18,080 bp. The plastome contains 111 genes, consisting of 78 unique protein-coding genes , 29 unique tRNA genes  and four unique rRNA genes . Among these gene, one pseudogene , 13 genes  possessed a single intron and three genes  had two introns. The gene rps12 is found to be trans-spliced, as is typical of angiosperms. The overall A/T content in the plastome of H. hainanensis is 63.70%, in which the corresponding value of the LSC, SSC, and IR region is 66.10%, 69.50%, and 57.50%, respectively.The plastome of Averrhoa carambola  as outgroup. The phylogenetic analysis indicated that H. hainanensis is closer to Salix rorida than other taxa within Malpighiales (H. hainanensis will provide a useful resource for the conservation genetics of the species as well as for the phylogenetic studies of Achariaceae.We used RAxML (Stamatakis ighiales . Most no


Journal of Cannabis Research, sponsored by the Institute of Cannabis Research at Colorado State University - Pueblo and published with the assistance of Springer Nature, one of the world’s largest and most prominent academic publishers. One question immediately comes to mind: Why do we need this new journal now? I appreciate the opportunity to answer this question.I am proud and excited to introduce a brand new scholarly journal, the Academic inquiry about the cannabis plant, its products, and their effects has increased exponentially over the past several decades. This increase has occurred in all fields, from the plant biology and agriculture of the cannabis plant and the biomedical science underlying cannabinoids and the endocannabinoid system, to the health and public health effects of cannabis use and the regulation and socioeconomic impact of the cannabis industry . Up to now, the publications generated by this academic inquiry tend to be scattered across hundreds of journals in dozens of different academic fields. This dispersion makes it difficult for anyone to keep abreast of advances in more than a few aspects of cannabis science and to publish broadly multidisciplinary work that does not fit neatly into one topic.Our new journal aims to overcome this limitation, with 10 topic sections that cover the entire range of cannabis-related science, as outlined above. Our editorial board includes more than 30 distinguished scientists and scholars from diverse fields. They work in 9 countries on 5 continents, so that the journal will encompass international points of view. The goal is not only to publish high-quality scholarly work, but also to foster and publish multi-disciplinary syntheses and cross-cultural analyses that will advance the field. To this end, the journal will publish reviews and commentaries, as well original research presenting newly generated data.I believe that the 4 papers appearing in our inaugural issue well illustrate the breadth of our intended coverage. One paper , for improving our journal in the future.


To investigate the anti-carcinogenic effect of metronomic Celecoxib  against hepatocellular carcinoma (HCC) in the perspective of metastasis, spontaneous hepatocarcinogenesis, cancer invasion, proliferation, and stemness in vivo and in vitro.Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to cause anti-carcinogenic effects for HCC in suprapharmacological doses. However, the effects of metronomic Celecoxib treatment on HCC cells remain unclear.in vivo chemopreventive effect of metronomic Celecoxib (10mg/kg/d) was investigated by the syngeneic HCC implantation model and spontaneous hepatocarcinogenesis in HBV-transgenic(HBVtg) mice individually. HCC cell lines were treated by either suprapharmacological (100 μM) or metronomic (4 μM) Celecoxib therapy. Anti-carcinogenic effects were evaluated using cell invasion, cancer proliferation, angiogenesis, and phenotype of cancer stem/progenitor cells (CSPC). The molecular mechanism of metronomic Celecoxib on HCC was dissected using Luciferase assay.The In vivo metronomic Celecoxib exerted its chemopreventive effect by significantly reducing tumor growth of implanted syngeneic HCC and spontaneous hepatocarcinogenesis in HBVtg mice. Unlike suprapharmacological dose, metronomic Celecoxib can only inhibit HCC cell invasion after a 7-day course of treatment via NF-κB/MMP9 dependent, COX2/PGE2 independent pathway. Metronomic Celecoxib also significantly suppressed HCC cell proliferation after a 7-day or 30-day culture. Besides, metronomic Celecoxib reduced CSPC phenotype by diminishing sphere formation, percentage of CD90+ population in sphere cells, and expression of CSPC markers.Metronomic Celecoxib should be investigated clinically as a chemopreventive agent for selected high-risk HCC patients . Preventhe world . Nearly he world . Thus, pMetronomic use of chemotherapy  is well known to reduce the drug-related adverse effect and the risk of developing acquired drug resistance in cancer therapy . SimilarIncreased expression of COX-2 or nuclear factor-kappa B (NFκB) was in association with carcinogenesis in HCC clinically , 13. Cel6/implantation site) cells were implanted into bilateral flanks of C57BL/6 mice . Then, the mice received therapy consecutively for 36 days. During the treatments, we measured the body weight and subcutaneously implanted tumor size by the previous protocol  in animal experiments, which were approved by the China Medical University Committee of Laboratory Animal Welfare. We purchased Hepa1-6 cells for the syngeneic HCC model from ATCC , and modified the tumor development protocol from the previous report . We fed th days of pup mice. After genotyping to confirm HBVtg genotype, the mice were randomly assigned to two groups  or placebo (n = 16 sites) as protocol   or placebo (n = 9) as protocol and harvested liver for measurement after sacrificing them  and clinically available  doses of Celecoxib for 2 or 7 days. As shown in Celecoxib is a selective inhibitor of COX-2, which generates PGE2 that stimulates cell invasion, proliferation, and migration behavior in hepatoma cells . TherefoTo obtain more profound insights into the role of metronomic Celecoxib in NFκB-mediated invasiveness of HCCs, we assessed NFκB luciferase reporter activity after 7-day Celecoxib treatment. Results showed that low-dose (4 µM) Celecoxib treatment significantly suppressed the NFκB promoter activity  of Celecoxib significantly inhibited HCC cell viability compared with control cells for a 2-day incubation period , Celecoxib significantly attenuated sphere formation in HCC cells  and primary hepatocarcinogenesis . The mechanistic model of metronomic celecoxib on HCC suppression to prevent post hepatectomy surgery recurrence is illustrated in To our best knowledge, this is the first study to provide pre-clinical in vivo mice models, the conversion rate of drugs between human and mice is around 1 to 12  on tumor invasion, proliferation, angiogenesis, and metastatic potential. Under metronomic Celecoxib treatment, tumor invasion, proliferation, and metastatic potential were significantly reduced. Our results corresponded well to the previous researches, where Celecoxib suppresses cell viability by inhibiting cell proliferation and colony formation, although previous researches mainly investigated Celecoxib at supra-pharmacological concentration . Unlike in vivo study, we investigated the effect of metronomic Celecoxib on in vivo tumor growth of HCC with either homogenous or heterogeneous genetic backgrounds using two different animal models. We found a significant reduction in tumor regrowth of seeded syngeneic HCC while treating with metronomic Celecoxib compared to placebo. The implanted Hepa1-6 HCC cell line is derived from C57L mice with homogenous genetic background and widely accepted for studying in vivo tumor growth and metastasis of HCC in immunocompetent environment (th week) after low-dose DEN  administrated to HBVtg mice. This model is more clinically relevant and more like secondary chemoprevention to reduce progression to HCC from underlying chronic viral hepatitis ; National Health Research Institution (NHRI-EX109-10705BI); and China Medical University/Hospital .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To evaluate facial profile changes promoted by polymethyl methacrylate (PMMA) cement graft to reduce excessive gingival display due to hyperactivity of the elevator muscles of the upper lip during smiling. 1) and at least 6 months postoperatively (T2). Differences between T1 and T2 were verified by Wilcoxon test, and the correlation between the thickness of the graft and facial profile changes was statistically evaluated by Spearman’s Coefficient test. The significance level was set at p< 0.05.  Eleven patients  presenting gingival smile that were treated with PMMA cement grafts in a private clinic were selected for this retrospective study. Three angular and ten linear cephalometric facial profile measurements were performed preoperatively  and the labial component of the nasolabial angle showed statistically significant differences (p= 0.04), with higher values in T2. No correlations were found between the graft thickness and the statistically significant facial profile changes (p> 0.05).  The nasolabial angle (The PMMA bone cement graft projected the upper lip forward, thereby increasing the nasolabial angle without affecting the nasal component. No correlations between the graft thickness and the facial profile changes were detected. These factors occur separately or in combination,-23-25 An internal bevel incision followed by a reflected full-thickness flap is performed until exposure of the subnasal depression. The PMMA bone cement is indicated by the manufacturer for use in fixing orthopedic prostheses to bone tissue. It is manipulated (powder and liquid) and adapted to the region of interest. After polymerization, the PMMA graft is fitted with drills, for better volume and conformation. Two screw fixations are used to immobilize the PMMA graft in the subnasal depression. Sutures are inserted and removed 10 days later.23-25Recently, a new surgical technique for the management of the gingival smile was proposed by Naldi et al.23-25 However, there is still no information about the impact of this technique on the changes in facial profile. Thus, the aim of the present study was to test the null hypothesis that PMMA cement implanted to manage the gingival smile is not able to introduce changes in facial profile at rest. In addition, this study also aimed to determine whether a correlation exists between the thickness of the bone cement and a possible change in facial profile.PMMA is biocompatible and effective for reduction of the gingival smile; in addition, complications or adverse reactions, such as implant or bone resorption in the recipient region, were not reported in the medium term.The research protocol of this retrospective study was reviewed and approved by the Research Ethics Committee of the Federal University of Goiás . The STROBE guidelines for observational studies were followed.1) and at least six months after surgery (T2) from 11 patients submitted to surgical implantation of grafts based on PMMA.The sample initially comprised 38 patients submitted to the implantation of bone cement based on PMMA  at a private clinic in the city of Goiânia, Goiás, Brazil. The same surgeon operated all the patients, between November 2007 and April 2012. Among the initial sample, 11 met the inclusion criteria. All were women, aged from 20 to 43 years. The inclusion criteria were as follows: patients with gingival smile due to hyperactive muscles, treated with bone cement graft; 18 years-old or older; presence of pre- and postsurgical cephalometric radiographs with relaxed lips. The cases of hyperactivity of the elevator muscle of the upper lip involved both functional and morphological evaluation. Firstly, patients presented with high lip dynamics and, secondly, with a major subnasal depression that allows the upper lip to lodge during a spontaneous smile. The exclusion criteria were: poor image quality; cleft lip or cleft lip and palate; craniofacial syndromes; and other surgical interventions that could change the soft and hard tissues of the face during the period of study. For this study, cephalometric radiographs had been taken prior to treatment (T1 and T2 with an enlargement factor near to 1.0645 (6.45 percent). The patients were in a standing position and adequately protected, with the teeth in centric occlusion, lips in relaxed position, and Frankfurt plane parallel to the floor. Radiographic films were developed in an automatic processor .The cephalometric radiographs  were taken using the same cephalostat at TFacial profile was outlined by hand, on acetate paper in a darkened room, by the same experienced and calibrated investigator. A prior calibration was performed with three cephalometric radiographs traced twice by the same investigator, with an interval of two weeks. After confirmation of excellent concordance (ICC > 0.90), the overall sample was measured. The cephalometric tracing was composed by the anterior contour of the maxilla, symphysis, maxillary central incisors, external auditory canal and lower border of the orbit, besides the soft tissue profile , Tab. 1.1 and T2 were traced and measured twice, with a one-month interval, by the same investigator. Systematic errors were evaluated with the intraclass correlation coefficient (ICC). Excellent concordance between the two measurements at T1 and T2 was found , resulting in no systematic errors.To determine the reliability of the cephalometric method, all 11 cephalometric radiographs from T1, T2, and T1-T2 changes revealed the presence of both nonnormal distribution (Kolmogorov-Smirnov test) and no homogeneity of variances (Levene’s test) for all the variables. T1 and T2 variables were compared with the Wilcoxon signed-rank test. Correlations between possible statistically significant differences at T1, T2 and T1-T2 changes and the thickness of the graft (A-Grf) were verified with Spearman’s Coefficient test. The significance level was set at p< 0.05. SPSS 17.0 for Windows  was used for the statistical analysis. The power of the study was based on the sample size available and measurements that present statistically significant differences.The preliminary assessment of data at T1 and T2 angular and linear measurements were found for the nasolabial angle (Pn.Sn.Ul) (p= 0.03) and the labial component of the nasolabial angle [(Sn-Ul).Sn hor] (p= 0.04). The overall changes can be summarized by a representative superimposed cephalometric tracings before (T1) and after (T2) surgical treatment . Spearman’s Coefficient test showed no statistically significant correlations (Tab. 4).The thickness of the graft (A-Grf) ranged from 4 to 7 mm. Correlation analysis was performed to determine whether there was a correlation between the thickness of the graft (A-Grf) and facial profile changes. The correlation test was performed only for the measurements that were statistically significant. TThe calculation of the test power was based on the average and standard deviation of the nasolabial angle (Pn.Sn.Ul) and the labial component of the nasolabial angle [(Sn-Ul).Sn hor]. Considering an alpha level of 5%, the sample size (n = 11), and a clinically meaningful difference of 10 degrees to the nasolabial angle, and 8% for the labial component of the nasolabial angle, the power calculation was 0.83 and 0.87, respectively.Many techniques have been developed for treating gingival smiles. However, there is a lack of studies related to cephalometric changes provided by these techniques. Therefore, this original study investigated the cephalometric changes that occurred due to the use of bone cement based on PMMA. The null hypothesis was rejected, since cephalometric alterations in the nasolabial angle and the labial component of the nasolabial angle were observed with the use of the bone cement based on PMMA. All patients who were available and met the inclusion criteria were evaluated. The power calculation indicated adequate power for statistical inferences.,,---A gingival smile is reported as being unattractive by dentists and lay people.-23-25 It is not clear how much of this reduction in gingival display may be due to the PMMA graft, since the graft has been associated with aesthetic crown lengthening.The PMMA bone cement is marketed in Brazil and registered at the National Sanitary Surveillance Agency (ANVISA) valid until 2028. Its preliminary indication was intended for orthopedic medical surgeries. In the present study, a PMMA graft was proposed to fill the major subnasal depression observed in some patients with gingival smile. The graft was able to fill this depression, resulting in reduced gingival display. It was hypothesized that this depression contributes to the lack of lip support and, when smiling, the lip tends to contract, shorten, and become lodged in this depression.-However, it should be borne in mind that the technique has been shown to be effective in reducing the gingival smile. Clinical reports have demonstrated the stability and biocompatibility of the PMMA graft in the medium term .,,In Medicine, PMMA bone cement grafts have been used in cranioplasty, with high stability and a low complication rate.The pioneering objective of this study was to evaluate the impact of PMMA bone cement grafts to manage the gingival smile in facial profile at rest, thereby enabling the understanding of some of the possible side effects of this intervention. The hypothesis that a PMMA graft was able to introduce cephalometric changes in facial profile was accepted.The cephalometric results of this study demonstrated that the graft does not cause many significant changes in the facial profile. However, a small protrusion of the upper lip, promoting a slight increase of the nasolabial angle, without affecting the nasal component, was verified. It is important to highlight as a limitation of this study that the cephalometric method is a static and lateral evaluation. Frontal and functional evaluations still require investigation.32 Compared to maxillary impaction, a PMMA bone cement graft can be advantageous, since it does not seem to induce major changes in facial physiognomy, and have a low risk of neurosensory deficit and bleeding, as described for orthognathic surgery.33 However, the PMMA graft may not be the treatment of choice for resolving cases of gingival smile whose etiology is excessive vertical growth of the maxilla with greater severity.Cephalometric analysis has been conducted to evaluate facial changes due to other surgical procedures. Maxillary impaction changed the vertical and anteroposterior maxilla position, leading to nasal protraction, upper lip retraction due to retraction of the maxillary incisors, and soft tissue movement of the chin.--Compared to other treatment options to manage hyperactivity of the upper lip, it is important to point out that the effect of PMMA graft is not temporary, as has been described for the approach with injection of botulinum toxin.There was no correlation between the PMMA graft thickness and the facial profile changes. This may be explained by the small variability in the thickness of the grafts, which ranged from 4 to 7 mm. Even so, results of this study indicate a slight and long-term change in facial profile with PMMA bone cement. The PMMA graft added volume to the upper lip, projecting it forward. This facial profile change may be considered unpleasant for some patients, and therefore, this should be considered for the indication of the technique. Studies regarding patients’ perceptions about the treatment of gingival smile with PMMA grafts and to clarify many other aspects involved in the technique are necessary.This was a retrospective study with the main sample selected from clinical files. The selection of the sample was possible due to the availability of records of cases treated by means of the surgical procedure under analysis. No control group was used due to ethical reasons, and the comparison was performed between before and after the surgical procedure. Statistical difference found only for the nasolabial angle may be due to the fact that the sample was too small and unable to reveal the actual results related to type II error. However, the high power obtained for this inference makes it reliable. The 2-D cephalometric measurements confirmed good reproducibility, and a 3-D evaluation was not the scope of this study. Moreover, the decision to submit these patients to higher X-ray exposures was not justified. The female sample limited the generalization of the data, however, there is no biological reason to find difference between the sexes.» The PMMA bone cement graft to manage the hyperactive musculature during gingival smile projected the upper lip forward about 1mm, increasing the nasolabial angle without affecting the nasal component.» No correlations between the implant thickness and the facial profile changes was detected.


Little is known about the in vivo forces and stresses on grafts used in anterior cruciate ligament (ACL) reconstruction. The aims of this study were to evaluate and compare the forces and stresses on grafts used in anatomical single-bundle ACL reconstruction at different locations of the femoral footprint  during a lunge motion.Establish subject-specific finite element models with different graft’s tunnel loci to represent the primary ACL reconstructions. A displacement controlled finite element method was used to simulate lunge motions (full extension to ~ 100° of flexion) with six-degree-of-freedom knee kinematics data obtained from the validated dual fluoroscopic imaging techniques. The reaction force of the femur and maximal principal stresses of the grafts were subsequently calculated during knee flexion.Increased and decreased graft forces were observed when the grafts were located higher and lower on the femoral footprint, respectively; anterior and posterior graft placement did not significantly affect the graft force. Lower and posterior graft placement resulted in less stress on the graft at higher degrees of flexion; there were no significant differences in stress when the grafts were placed from 0° to 30° of flexion on the femoral footprint.The proposed method is able to simulate knee joint motion based on in vivo kinematics. The results demonstrate that posterior to the centre of the femoral footprint is the strategic location for graft placement, and this placement results in anatomical graft behaviour with a low stress state. Anterior cruciate ligament (ACL) reconstruction is a technical procedure. Femoral tunnel positioning is one of the most critical steps to achieve successful ACL reconstruction and is still being discussed by researchers . BecauseThe graft force needs to be considered to restore normal ACL function. Measuring the forces on native ACLs continues to be one of the greatest challenges in assessing the biomechanics of the knee joint. To overcome this challenge, investigators have proposed a technique involving the isolation of the tibial attachment of the cruciate ligament by creating a bone plug and attaching a load sensor to measure the native ACL force in cadaveric knees , 6. ThisTherefore, this study used displacement controlled finite element analysis combined with dual fluoroscopic imaging techniques to evaluate the effects of placing the graft at different locations on the femoral footprint after anatomical single-bundle ACL reconstruction via lunge simulations. The results from this study may help surgeons to gain a better understanding of the influence of grafts placed at different femoral tunnel locations in terms of the forces and stresses and contribute to the current literature by providing biomechanical information on ACL reconstruction.This study was approved by our institutional review board, and informed consent was obtained by the subject. One healthy volunteer  was recruited for this study. The subject had a right dominant limb and no history of knee injuries, surgeries or systemic diseases. Physical examinations (Lachman test and pivot shift test) were performed to rule out knee pathologies. The motion of the right knee was analysed  and dual fluoroscopic imaging techniques have been described in detail previously , 11. SimLocal femoral and tibial coordinate systems were established before the imaging procedure. The femoral origin was located at the midpoint of the geometric centre axis, a line connecting the centres of the spheres fit to the lateral and medial posterior femoral condyles, representing the mediolateral axis. The anteroposterior axis was perpendicular to the plane defined by the geometric centre axis and the femoral shaft. The proximodistal axis was set to be perpendicular to the two other axes. The tibial origin was the projection point of the femoral origin on the tibial plateau. In order to make the calculated kinematic data easier to be applied in the finite element analysis subsequently, the three axes of the tibial coordinate system were parallel to the femoral coordinate system Fig. a. The 3DThe femoral bony landmarks  were identified and used to determine the femoral footprint of the ACL , 3 Fig.a. TwentyC1 is the neo-Hookean constant and D is the inverse of the bulk modulus k = 1/D  [The bones were considered shells and defined as rigid bodies. The grafts were considered solids and were defined as nearly incompressible, transversely isotropic hyperelastic neo-Hookean materials with the following strain-energy function: 0.00687) . A free 0.00687) . The conTo replicate the ACL reconstruction completely, a model at 20° of knee flexion and an initial graft tension of 80 N were used , 19. TheP < 0.05 was considered significant.Analysis of variance (ANOVA) with repeated measures and the least significant difference (LSD) post hoc tests were used to detect statistically significant differences in the data. The within-subject factor was defined as the flexion angle. The between-subjects factor was defined as the location. At each tested flexion angle, the data from different groups were skewed distributed. Thus, we used two nonparametric tests for the comparison, the Kruskal–Wallis and Mann–Whitney U nonparametric tests were used to assess the differences across the different locations and to compare between pairs of the three locations if significant effects were detected. All analyses were performed in SPSS , and P < 0.001). At high degrees of flexion, the high location led to a consistently larger force; the middle location led to anatomical graft behaviour similar to that of a normal knee, while the low location led the graft force to decrease early to nearly zero. No significant differences in the graft force were found when the graft was placed in the anterior–posterior direction (P = 0.971)  Table. . The staP < 0.001) but not in the anterior–posterior direction (P = 0.104) (Table P = 0.037)  Table . The staPreviously, researchers have used displacement controlled finite element analysis to study the biomechanics of ACL during knee flexion , 17, 20.In term of the model construction, most of the previous studies constructed the ACL graft as a single cylindrical solid , 21, 22.The most important finding of the present study is that the strategic femoral location for anatomical single-bundle ACL reconstruction is posterior to the centre of the footprint. These findings can be explained by the forces and stresses on the grafts. When restoring a normal ACL force–flexion curve, a lower level of stress on the graft is beneficial to prevent graft injury. Traditionally, the focus of ACL reconstruction has been on placing grafts in the most isometric manner, which can prevent the windshield wiper effect and is favourable for tendon-bone healing , 27. A nMultiple cadaveric studies have been conducted to investigate the graft force during passive flexion–extension. These studies used the force–flexion curve as an indicator to evaluate different ACL reconstruction techniques , 30. It Large stresses on the graft and stresses close to the femoral or tibial tunnels were thought to be closely related to graft injuries and the widening of tunnels after surgery , 32. GivThis study has several limitations. The entire range of motion was not studied. Hyperextension and flexion angles beyond 100° of flexion were not analysed. Only a lunge activity was used, and other functional activities, such as walking and ascending stairs, should be considered. Comparing the current results with the literature was not easy because there is no standard method for modelling and performing simulations. Therefore, the attachment points of the graft were identified by the bony landmarks individually. There was a concern that the radiation would be harmful to the subject. According to the record, the cumulative radiation dose was within the safety level and could be markedly reduced in future study . FurtherThis study used dual fluoroscopic imaging and CT-based finite element modelling to estimate forces and stresses of grafts for anatomical single-bundle ACL reconstruction. The results of this study confirm that posterior to the centre of the femoral footprint is the strategic location for graft placement, and graft placement in this location results in anatomical graft behaviour with a low level of stress. This information may help surgeons optimize anatomical single-bundle ACL reconstruction or revision. Additional computational analyses and clinical studies are necessary to verify the practical significance of this conclusion.


Article submissions to The Gerontological Society of America’s high impact scientific journals continue to increase each year which has led to editors becoming more selective about which articles are accepted for publication. The purpose of this session is to describe how to efficiently and successfully navigate the process of determining which journal is the best fit for your manuscript. Objectives of the workshop include guidance in: (1) understanding the differences in scope and features of each journal; (2) determining which journal is most appropriate for the topic and methods of your manuscript; (3) appreciating how to use journals’ Instructions to Authors to your benefit, and (3) conveying the scientific contribution of your article to the journal.


Findings from psychological research are usually difficult to interpret for non-experts. Yet, non-experts resort to psychological findings to inform their decisions . Thus, the communication of psychological research to non-expert audiences has received increasing attention over the last years. Plain language summaries (PLS) are abstracts of peer-reviewed journal articles that aim to explain the rationale, methods, findings, and interpretation of a scientific study to non-expert audiences using non-technical language. Unlike media articles or other forms of accessible research summaries, PLS are usually written by the authors of the respective journal article, ensuring that research content is accurately reproduced. In this study, we compared the readability of PLS and corresponding scientific abstracts in a sample of 103 journal articles from two psychological peer-reviewed journals. To assess readability, we calculated four readability indices that quantify text characteristics related to reading comprehension . Analyses of variance revealed that PLS were easier to read than scientific abstracts. This effect emerged in both included journals and across all readability indices. There was only little evidence that this effect differed in magnitude between the included journals. In sum, this study shows that PLS may be an effective instrument for communicating psychological research to non-expert audiences. We discuss future research avenues to increase the quality of PLS and strengthen their role in science communication. Scientific journal articles in psychology are usually difficult to understand for non-experts. Yet, psychological findings influence decision-making processes in various domains, ranging from individual-level decisions  to legislation . Thus, there has been an increasing interest in “translating” psychological findings for non-expert audiences . This enTo date, research on PLS has largely focused on the biomedical literature –9. HowevWhether psychological researchers comprehensibly summarize findings may depend on the psychological discipline. For example, a journal article in cognitive psychology may be more difficult to summarize understandably than a journal article from a more applied discipline . Additionally, the instructions and guidance for writing PLS provided by journals may influence whether PLS are comprehensibly written or not.As a proxy for text comprehensibility , readability indices  are frequently used. For example, the Cochrane Collaboration, an independent international organization that produces high-quality and accessible systematic reviews to inform evidence-based health decision making, recommends the Simple Measure of Gobbledygook (SMOG ) to assePrevious research on differences in readability between PLS and scientific abstracts has focused on Cochrane systematic reviews and has produced mixed findings. Cochrane systematic reviews synthesize and appraise evidence to inform health decisions using systematic and reproducible methods. These reviews either focus on the harms and benefits of interventions in healthcare (intervention reviews) or on the accuracy of diagnostic tests for diagnosing a particular disease (diagnostic test accuracy reviews). A recent investigation found lower SMOG scores (indicating better reliability) for a sample of 156 PLS of Cochrane systematic reviews compared to the corresponding scientific abstracts . RegardiIn psychology, PLS are supposed to enable non-experts to understand and draw conclusions from research findings. Thus, they should exhibit a higher readability than traditional scientific abstracts. The aim of the present study was to compare the readability of scientific abstracts and PLS in psychology based on reproducible readability indices.To identify psychological peer-reviewed journals that provide PLS, we conducted an explorative web-based search in June 2019 and contacted experts from different psychological disciplines. Various journals include a brief statement  regarding the public significance of an article . Other journals  provide non-technical summaries explicitly directed at other researchers rather than non-expert audiences. We have identified only two psychological peer-reviewed journals with PLS, whose length and content correspond to that of the corresponding scientific abstracts and which are aimed at non-experts: Archives of Scientific Psychology and the Journal of Social and Political Psychology. Archives of Scientific Psychology is the American Psychological Association’s (APA) open-access journal publishing articles from all psychological disciplines. The Journal of Social and Political Psychology is an online open-access journal (without author fees) publishing articles with different methodical and theoretical perspectives at the intersection of social and political psychology. The editors of Archives of Scientific Psychology ask authors to provide a PLS for the educated public describing the study and its relevance for societal or psychological problems. Additionally, the editors offer assistance in writing PLS, if necessary. For the Journal of Social and Political Psychology, a PLS is optional, but strongly encouraged. The editors of the Journal of Social and Political Psychology ask authors to provide a PLS for lay audiences to increase the visibility of their work beyond the respective discipline and beyond academia more generally. To structure PLS, the Journal of Social and Political Psychology provides mandatory sub-headings: 1. Background, 2. Why was this study done, 3. What did the researchers do and find, 4. What do these findings mean.Overall, we retrieved 103 PLS and corresponding scientific abstracts in February 2020 . To retrieve the scientific abstracts and PLS from Archives of Scientific Psychology, we used PsycINFO. We retrieved the scientific abstracts and PLS from the Journal of Social and Political Psychology from the journal’s database on the PsychOpen GOLD platform operated by the Leibniz Institute for Psychology Information (ZPID). Prior to calculating readability indices, we removed the standardized sub-headings  from the PLS of articles in the Journal of Social and Political Psychology as not discarding them would have biased resulting readability indices.nwsy> = 3 is the number of words with three syllables or more and nst is the number of sentences. The FRES is based on average sentence length and the number of syllables per word. Higher FRES scores indicate better reliability. We calculated the FRES with the following formula: nsy is the number of syllables, and nw is the number of words. The FKRS is also based on average sentence length and number of syllables per word. Lower FKRS scores indicate better readability. We calculated the FKRS as nwd is the number of "difficult" words not matching the Dale-Chall list of 3,000 "familiar" words [In accordance with the Cochrane Collaboration’s recommendation , we usedon study . Higher r" words .http://doi.org/10.23668/psycharchives.2768, http://dx.doi.org/10.23668/psycharchives.2723. We deleted all scientific abstracts and PLS for Archives of Scientific Psychology from the data set prior to uploading. This was due to PsycINFO's copyright policy. The scientific abstracts and PLSs can be found via the DOIs we provided.We conducted a 2 (abstract type) × 2  mixed analysis of variance (ANOVA) with abstract type  as within-factor, journal  as between-factor and the SMOG as dependent variable. A significant main effect of abstract type indicates that scientific abstracts and PLS differ in readability. A significant main effect of journal indicates that there is a difference between the two journals regarding the readability of PLS and scientific abstracts. A significant interaction of abstract type and journal indicates that differences in readability between the articles’ scientific abstracts and PLS are more accentuated in one journal compared to the other journal. As follow up analyses, we conducted one-way ANOVAs with abstract type  as within-factor and the SMOG as dependent variable for each journal separately. To test the robustness of our analyses, we repeated all analyses with the FRES, the FKRS, and the NDCRF as dependent variables. Our data and scripts are available via the PsychArchives repository:, SD = 44.00) for scientific abstracts and 277.96 words (SD = 153.81) for PLS. r = .33, p < .001). The four readability indices were highly correlated .The average text length was 183.04 words  = 18.47, p < .001, ηp2 = .16. The main effect of journal did not reach statistical significance, indicating that there was no significant difference between the two journals in the readability of scientific abstracts and PLS, F = 0.88, p = .349, ηp2 = .01. Moreover, the interaction effect of abstract type and journal did not reach statistical significance, F = 1.26, p = .264, ηp2 = .01. This finding indicates that the difference in readability between an article’s scientific abstract and PLS did not differ significantly between the two journals. Follow-up one-way ANOVAs with abstract type  as within-factor confirmed the significant effect of abstract type for each journal separately, F = 5.80, p = .019, ηp2 = .08 for Archives of Scientific Psychology and F = 20.86, p < .001, ηp2 = .37 for the Journal of Social and Political Psychology.A 2 (abstract type) × 2  mixed ANOVA with abstract type  as within-factor, journal  as between-factor, and the SMOG as dependent variable revealed a significant main effect of abstract type, indicating that PLS are easier to read than scientific abstracts, F = 44.30, p < .001, ηp2 = .31 for the FRES, F = 13.63, p < .001, ηp2 = .12 for the FKRS, and F = 55.58, p < .001, ηp2 = .36 for the NDCRF. For Archives of Scientific Psychology, follow-up one-way ANOVAs with abstract type as within-factor confirmed a better readability of PLS compared to scientific abstracts for the FRES  = 10.16, p = .002, ηp2 = .13) and the NDCRF  = 20.97, p < .001, ηp2 = .24), but not for the FKRS  = 3.13, p = .082, ηp2 = .05). For the Journal of Social and Political Psychology, follow-up one-way ANOVAs with abstract type as within-factor confirmed a better readability of PLS compared to scientific abstracts for the FRES  = 53.89, p < .001, ηp2 = .61, the FKRS  = 24.71, p < .001, ηp2 = .41), and the NDCRF  = 67.48, p < .001, ηp2 = .66 for the NDCRF) separately. In sum, these findings suggest that the readability of PLS is higher than the readability of scientific abstracts across all included readability indices and in in both included journals. The main effect of journal did not reach significance for any of the readability indices, F = 2.01, p = .159, ηp2 = .02 for the FRES, F = 0.39, p = .534, ηp2 = .00 for the FKRS, and F = 0.52, p = .474, ηp2 = .01 for the NCDRF. The interaction effect of abstract type and journal reached statistical significance for the FRES  = 6.28, p = .014, ηp2 = .06), but not for the FKRS  = 1.65, p = .202, ηp2 = .02) or the NCDRF  = 1.64, p = .203, ηp2 = .02). Thus, there is only little evidence that the magnitude of the difference in readability between an article’s scientific abstract and the corresponding PLS differs between the two journals.In a set of 2 (abstract type) × 2  mixed ANOVAs with abstract type as within-factor and journal as between factor, we found significant main effects of abstract type for the three additional readability indices, This study showed that PLS in two psychological peer-reviewed journals are easier to read than scientific abstracts. This effect was evident for each of the two journals and replicated across all readability indices. Thus, psychological researchers seem to be able to communicate their findings in a language more accessible for non-experts compared to the language used in scientific abstracts. Against the background of the increasing relevance of science communication , this fiAlthough we could only include two psychological journals in this study, the finding that PLS are easier to read than scientific abstracts might generalize beyond these journals across different disciplines of psychology. This assumption is supported by the great variety in content and methods of articles published in both included journals. Thus, editors of journals from all psychological disciplines might consider encouraging authors to submit a PLS together with their journal articles.This study has several limitations. First, we did not assess actual information extraction by non-experts. Thus, the text characteristics quantified in this study might be unrelated to non-experts’ comprehension of PLS and scientific abstracts. However, assessing the SMOG is consistent with the Cochrane Collaboration’s recommendation  and quanAgainst the background of the increasing importance of science communication, this study showed that, in two psychological peer-reviewed journals, author-written PLS are easier to read than scientific abstracts. We hope that this finding aids in strengthening the role of study authors as “public communicators”  of their


Allograft kidney transplantation has become a treatment of choice for patients with end-stage renal disease (ESRD), and post-transplant diabetes mellitus (PTDM) has been associated with impaired patient and graft survival. Taiwan has the highest incidence and prevalence rates of ESRD with many recipients and candidates of kidney transplantation. However, information about the epidemiologic features of PTDM in Taiwan is incomplete. Therefore, we aimed to investigate the prevalence and incidence of PTDM with subsequent patient and graft outcomes.Using the Taiwan National Health Insurance Research Database (NHIRD), 3663 kidney recipients between 1997 and 2011 were enrolled. We calculated the cumulative incidences of diabetes mellitus (DM) after transplantation. Cox proportional hazards model with competing risk analysis was used to calculate the hazard ratio (HR) and 95% confidence intervals (CI) between three targeted groups . The outcomes of primary interest were the occurrence of graft failure excluding death with functioning graft, all-cause mortality, death with functioning graft and major adverse cardiovascular events (MACE) including myocardial infarction (MI), cerebrovascular accident (CVA) and congestive heart failure (CHF). Subgroup analysis for graft failure excluding death with functioning graft, MACE and all-cause mortality was performed, and interaction between PTDM and recipient age was examined.interaction < 0.01) with higher risk in recipients with PTDM aged younger than 55 years . A trend (pinteraction = 0.06) of age-modifying effect on the association between PTDM and all-cause mortality was also noted with higher risk in recipients with PTDM aged younger than 55 years.Of 3663 kidney transplant recipients, 531 (14%) had pre-existing DM and 631 (17%) developed PTDM. Compared with non-DM group, the PTDM and DM groups exhibited higher risk of graft failure excluding death with functioning graft , MACE , all-cause mortality , and death with functioning graft . Both PTDM and DM groups had increased cardiovascular disease-related mortality , cancer-related mortality , and infection-related mortality  compared with non-DM group. The subgroup analyses showed that the add-on risks of MACE and mortality from PTDM were mainly observed in patients who were younger and those without associated comorbidities including atrial fibrillation, cirrhosis, CHF, and MI. Age significantly modified the association between PTDM and MACE (pIn the present population-based study, the incidence of PTDM peaked within the first year after kidney transplantation. PTDM negatively impacted graft and patient outcomes. The magnitude of cardiovascular and survival disadvantages from PTDM were more pronounced in recipients aged less than 55 years. Further trials to improve prediction of PTDM and to prevent PTDM are warranted. End-stage renal disease (ESRD) is a leading cause of morbidity and mortality worldwide. Taking care of patients with ESRD caused great expenditure and has become a financial burden to healthcare system , 2. AccoWe conducted a retrospective cohort study with longitudinal data from the NHIRD. The NHI program is a nationwide, compulsory healthcare program covering approximately 99.9% of Taiwan’s population, which stood at approximately 23.37 million people in 2014. Before 2000, diagnoses in claims data were coded with A codes, followed by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes thereafter. The NHIRD involves comprehensive healthcare information on insured patients, comprising disease diagnoses, inpatient orders, outpatient visits, drug prescriptions, and registries of beneficiaries with specific conditions, but it does not include laboratory data. The requirement to obtain informed consent was waived because data in the NHIRD that could identify specific patients are scrambled and encrypted before being released to researchers. However, consistent data encryption makes linking and continuously following all claims belonging to the same patient within the NHIRD feasible. The study protocol was approved by the Institutional Review Board, Chang Gung Medical Foundation, Taiwan (IRB No: 201900806B0).In the NHI program, patients with specific chronic conditions, including organ transplantation, ESRD, malignancies, were qualified for a catastrophic illness certificate. To qualify for a certificate, a patient’s condition must be repeatedly verified by a peer review group based on clinical evidence, pathologic findings, and laboratory data. The Registry for Catastrophic Illness Patient Database (RCIPD) is an NHIRD subset composed of certificated patients’ data, including those receiving kidney transplantation or maintenance dialysis.Figure Diseases were detected using A codes before 2000 or ICD-9-CM diagnostic codes after 2000. The covariates were age, sex, place of residence, income levels, occupations, comorbidities, Charlson comorbidity index (CCI), medications, rejection, cytomegalovirus (CMV) infection and initial dialysis type.Comorbidities were identified when reported for more than two outpatient visits or one inpatient stay within the previous year of index date. Comorbidities included malignancy, hypertension, hyperlipidemia, cerebrovascular accident (CVA), myocardial infarction (MI), CHF, atrial fibrillation (AF), peripheral artery disease, chronic obstructive pulmonary disease (COPD), liver cirrhosis, hepatitis B (HBV) infection and hepatitis C (HCV) infection. Most diagnostic codes used for these comorbidities had been validated in previous NHIRD-based studies , 11. MedThe outcomes of primary interest were all-cause mortality, death with functioning graft, the occurrence of graft failure excluding death with functioning graft, and MACE including MI, CHF and CVA. Graft failure was defined as returning to hemodialysis or peritoneal dialysis after kidney transplant for more than 90 days. Components of MACE was detected based on the principal diagnosis of an emergency visit or hospitalization. Mortality was defined as withdrawal from the NHI program. Given that the association between DM status and mortality may be modified by events that occur after graft loss, death with functioning graft was also included as a primary endpoint, defined as the mortality group with elimination of those who had been on maintenance hemodialysis continuously for more than 3 months before death. The secondary outcomes were cardiovascular diseases-related, infection-related and cancer-related death. These outcomes were detected based on the principal or secondary diagnosis of an emergency department visit or hospitalization. Components of cardiovascular diseases were detected based on the principal diagnosis of any emergency visit or hospitalization, most of these diagnostic codes for which have been previously validated , 13. AllThe descriptive statistics of demographic and clinical information at the date of transplantation were stratified by non-DM, PTDM and DM groups. The difference between groups was estimated by Chi square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. The temporal trends of incidence rates of DM prior to and after kidney transplantation were calculated by each year. The Cox proportional hazards model was used to estimate the risk of incident DM after transplantation using demographic and clinical variables in the patients without history of DM while adjusting for the covariates. Since some studies revealed that the major impact of diabetes status on graft survival was not due to rejection but to death instead , it is cThe incident DM status after transplantation was time-dependent rather than a fixed categorical variable, which violated the assumption of Cox proportional model. Therefore, the Simon and Makuch method and Mantel-Byar test, rather than the traditional Kaplan–Meier method and log-rank test, were used to draw survival curves for the non-DM, PTDM and DM groups. To clarify the association between the occurrence of PTDM and outcomes, we stratified the risks of primary interests by era. Risks of graft failure excluding death with functioning graft, MACE and overall mortality in 0–3 years and > 3 years after transplantation were calculated. From the time-dependent Cox model with consideration of the competing risk of death and inverse probability of treatment weighting (IPW) using the propensity score, the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated for the associations between DM groups and interested outcomes.The propensity scores used for IPW were estimated with generalized boosted regression models and considered the demographics, CCI, comorbidities prior and after transplantation, plus medications . The subTable Figure The risk factors of PTDM among 3132 patients without DM prior to transplantation were shown in Additional file Table Table interaction) between PTDM status and age were 0.463 for graft failure excluding death with functioning graft, 0.01 for MACE, and 0.06 for all-cause mortality.To further verify whether the effect of PTDM was consistent among different clinical situations, we performed pre-specified subgroup analyses for graft failure excluding death with functioning graft, MACE and all-cause mortality, as shown in Table In the present study, we conducted a retrospective cohort analysis with longitudinal data from the NHIRD. The key findings of the present study were as follows: (i) PTDM incidence peaked in the first year post-transplant; (ii) the presence of DM (pre-existing or incident) was associated with higher risks of all-cause mortality, MACE and graft failure excluding death with functioning graft; (iii) the adverse effects of PTDM on MACE and patient survival were observed exclusively in those who were relatively young and with less comorbidities.PTDM, also known as new-onset diabetes after transplantation (NODAT), is a common complication of kidney transplantation. Due to the lack of standards regarding the definition of diagnosis, it was once difficult to estimate the incidence rate of PTDM precisely. A review of literature reported the incidence of PTDM ranged widely between 10 and 74% . In 2003Since pre-transplant DM has been associated with inferior transplant outcomes , there iWith respect to the negative influence of PTDM on graft function, our study showed that the PTDM group exhibited a significantly higher risk of graft failure excluding death with functioning graft compared with the non-DM group even after competing risk analysis serving as death-censoring investigation. The study published by Miles et al. showed PTDM was associated with impaired long-term renal allograft function and survival, though it did not provide the information about death-censoring analysis . AnotherTo verify whether the deleterious effects of PTDM on patient and graft survival were consistent among patients with different underlying clinical conditions, we performed subgroup analyses for graft failure excluding death with functioning graft, MACE and all-cause mortality. In patients under the age of 55 years, PTDM correlated with a significantly higher risk of MACE and a trend of higher mortality risk, while in those over the age of 55 years with PTDM had shown neither difference in MACE nor death. Our results shared similarities with some earlier studies: A retrospective study in the United Kingdom revealed that patient survival was adversely affected by both pre-existing diabetes and by PTDM, particularly in those with an age less than 55 years. However, the cause of death was not identified in the study . SimilarConcerning the detrimental effect of PTDM on patient survival and possibly graft survival, there have been plenty of studies evaluating the potential measures to prevent PTDM, including lifestyle modification –34, sterAdmittedly, our research had some limitations. First, our study was subject to flaws inherent in retrospective analysis, such as the reporting bias and erroneous data. Second, because NHIRD does not provide information about all patient characteristics related to our primary interest, certain well-established risk factors including donor factors and human leukocyte antigen (HLA) matching were inevitably veiled. Third, because NHIRD does not include laboratory data, our study was limited by lack of information needed to completely meet the diagnostic criteria of the consensus guidelines. The alternative solution was to filter all the diagnoses made and recorded by clinicians and to examine whether they matched the logic behind the consensus recommendations. In the present study, the diagnosis of DM was established by documented ICD diagnostic codes and use of anti-diabetic agents so as to match the follow-up nature of guideline diagnosis. Although there was risk that we might have excluded some patients presenting with only mild hyperglycemia after transplantation, the rationale behind the way we defined PTDM can be justified by one study showing that being diagnosed with PTDM may be of unique prognostic value rather than just having hyperglycemia . HoweverTo the best of our knowledge, this study is the first to provide Taiwanese population-based information about the differences in graft and patient survival outcomes among kidney transplant recipients who were stratified by DM status. In a large cohort of patients from the nationwide registry data, we found that the incidence of PTDM peaked within the first year post kidney transplantation. PTDM was associated with worse patient and graft outcomes, with the magnitude of cardiovascular and survival disadvantages from PTDM more pronounced in recipients aged less than 55 years. Although the reasons for these associations have not been disclosed, the results of our research could be a useful aid for decision makers in establishing a personalized surveillance and treatment programs.Additional file 1. Additional figure and tables.


Grafting is a common practice for vegetative propagation and trait improvement in horticultural plants. A general prerequisite for successful grafting and long term survival of grafted plants is taxonomic proximity between the root stock and scion. For the success of a grafting operation, rootstock and scion should essentially be closely related. Interaction between the rootstock and scion involves complex physiological-biochemical and molecular mechanisms. Successful graft union formation involves a series of steps viz., lining up of vascular cambium, generation of a wound healing response, callus bridge formation, followed by vascular cambium formation and subsequent formation of the secondary xylem and phloem. For grafted trees compatibility between the rootstock/scion is the most essential factor for their better performance and longevity. Graft incompatibility occurs on account of a number of factors including of unfavorable physiological responses across the graft union, transmission of virus or phytoplasma and anatomical deformities of vascular tissue at the graft junction. In order to avoid the incompatibility problems, it is important to predict the same at an early stage. Phytohormones, especially auxins regulate key events in graft union formation between the rootstock and scion, while others function to facilitate the signaling pathways. Transport of macro as well as micro molecules across long distances results in phenotypic variation shown by grafted plants, therefore grafting can be used to determine the pattern and rate of recurrence of this transport. A better understanding of rootstock scion interactions, endogenous growth substances, soil or climatic factors needs to be studied, which would facilitate efficient selection and use of rootstocks in the future. Protein, hormones, mRNA and small RNA transport across the junction is currently emerging as an important mechanism which controls the stock/scion communication and simultaneously may play a crucial role in understanding the physiology of grafting more precisely. This review provides an understanding of the physiological, biochemical and molecular basis underlying grafting with special reference to horticultural plants. The scion becomes the new shoot system and the rootstock  forms the root system of the grafted plant. Scions are selected based on yield related traits and are generally grafted over specific rootstocks having the ability to survive the biotic and abiotic components of the environment. Rootstock mostly influences scion vigor and its water relations. Grafting is usually practiced in perennial horticultural trees with the main aim to reduce vegetative growth and shorten the juvenile period. Additional benefits of grafting include dwarf tree structures to increase the planting density per unit area and hence productivity simultaneously with minimal investments in orchard cultural practices like pruning, pest and foliar disease control. For an efficient root system to develop the rootstock and scion compatibility plays a crucial role  and 40 to 90% in apple (cv. Anna on MM106) with increasing benzylaminopurine (BAP) concentration from 0 to 2.0 mg/L. Patharnakh shoot tips were propagated in vitro on Kainth rootstock. Graft success and vigor was found to be maximum by following wedge grafting method and using 5–10 mm scions and M2 (MS liquid media +20 g/l sucrose) media  media . Hetero-e) media . Comparae) media . Gene exe) media . Studiese) media . This inArabidopsis micrograft system is 7–12 days , growth of the roots gets resumed at this stage around 5 DAG, and at 7 DAG xylem vessels get re-joined. By analyzing the pattern of cell division and tissue regeneration at the graft junction it was observed that cells at first showed an asymmetrical pattern of cell division and differentiation but as soon as a contact establishes between the stock and scion, they tend to lose this asymmetry and the vascular connection gets re-established  and Arabidopsis thaliana (At) have been reported where the growth of Nb scion was slow but distinct at the same time  was also higher in rootstock. Additionally, the scion and stock were found to have a moderately higher concentration of total phenolic compounds with high antioxidant activity. Differences in concentration of CGs, primarily prunasin, was found to be responsible for the incompatibility between Prunus persica and Prunus mume  encouraged phloem differentiation, but higher levels brought about the differentiation of xylem. Similarly, in grafting trials, auxins are an essential group of elements resulting in the formation of compatible graft unions  stimulates cytokines which triggers the formation of callus at the graft junction. Simultaneously, auxin gets transported basipetally and due to the lack of vascular connectivity, its flow across the union is hampered, resulting in its accumulation above the graft interface and low concentration at the bottom junction. Auxin accumulation, along with ethylene signaling, triggers the expression of Arabidopsis NAC domain containing protein 71 (ANAC071) above the graft union, and simultaneously inhibits the expression of RAP2.6L as well as Jasmonic acid biosynthesis. Beneath the graft, the depleted auxin levels trigger the biosynthesis of Jasmonic acid and expression of RAP2.6L. The expression of ANAC071 and RAP2.6L prompts cell division around the graft junction. Auxin, in collaboration with gibberellins and cytokinins, stimulates differentiation of cells, resulting in formation of vascular connection and re-joining between both junctions, thereby restoring auxin symmetry. Gibberellins, in collaboration with auxin, stimulate emergence of tissues by means of cell expansion  together with increase in flavonoids concentration lead to the reduced auxin movement which correlates to the dwarfing stature of these rootstocks  through a pear graft union. The results show that only 4 to 10 days after micro-grafting, Pyrus-GAI could be transported endogenously and not just this but it could also be transported to a scion of 10–50-cm height in a 2-year-old tree. The results serve as a basis for improving rootstocks and controlling scion properties in trees by the application of portable mRNA to fruit tree grafting. Agronomically significant traits such as compatibility, short juvenile period, dwarf phenotypes and antivirus can be transferred to the scion by making use of the transmissible mRNA in a transgenic rootstock . Transport of GAI mRNA across the union took place 5 days after grafting, which points out the movement of GAI mRNA in both upward and downward direction  protein across the graft union  gets transported to long distances in the phloem and this process of transport is rather complex in nature controlled by the form of a tree, environmental conditions and nutrient concentration of the tree  (JA) linked with histone deacetylation and acetylation is a stress hormone produced at the graft interface. Histone deacetylases (HDACs) are induced by JA. Which suggest that PTMs and transcriptome reprogramming have a role in wound healing  . Jasmoni healing .Arabidopsis, SRNAs were found to move from shoot to root and vice versa and were found to be linked with DNA methylation as they are the key components of the RdDM pathway (The discovery of non-autonomous RNA has made a significant contribution in understanding epigenetic modifications . In Arab pathway . In geno pathway  signifyi pathway .Despite the fact that grafting technology has improved enormously, the long-standing survival of grafted plants is still to a certain extent unpredictable due to the incompatibility problems. However, a prior selection method can serve as an efficient means to foresee the future of a compatible combination way before any external symptoms appear. The effect of rootstock-scion interactions pertaining to growth, attainment of reproductive potential, fruit set, yield efficiency and quality characteristics of fruit crops is complex and poorly understood. A healthier understanding of rootstock scion interactions would aid in more effective selection and use of rootstocks in future. The latest technology of silencing transmissible RNA and its potential to regulate growth and stress responses has provided new opportunities to understand stock-scion relationships. On the basis of the results of different studies discussed in this review, it is now possible to make use of mobile mRNAs in grafting systems of fruit trees. Undeniably, there is great scope for the development of transgenic rootstocks, in fruit trees that carry transportable mRNAs which regulate key horticultural traits, such as disease and stress resistance properties or dwarfing growth habit. This kind of approach would not only improve the characteristics of scion using transmissible mRNA from a transgenic rootstock, but also might shun some of the disagreements regarding transgenic fruit production. The epigenetic modifications occurring at the graft site is one of the most important yet unexplored fields. Understanding methylation patterns, epigenetic markers and maintenance of these changes in different perennial crops is a very important field to explore in future research.AR and SM: conceptualization. AR and TB: software. GIH, KMB, MNA, PA, and AJ: validation. AR and SM: writing—original draft preparation. AR, SM, KMB, GIH, BAP, AAA, and PA: writing—review and editing. AR, SM, GIH, HAE-S, BAP, and PA: supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The purpose of the study was to determine the hardness and fracture toughness of dental yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) manufactured by digital light processing (DLP) technology to study its clinical prospects.  The experimental group was DLP-manufactured zirconia, and the control group was milled zirconia. The hardness was investigated under a range of test loads . Meyer's law was applied to describe the indentation size effect (ISE). Meanwhile, the PSR model and MPSR model were utilized to generate true hardness values. The cracks were observed to be induced by indentation under loads above 49.03 N, while the cracks showed the radial-median type under the load of 196.1 N, under which the fracture toughness was calculated.  The true hardness of DLP-manufactured zirconia was 1189 HV based on the PSR model and 1193 HV based on the MPSR model, a bit lower than that of milled zirconia. The fracture toughness was 3.43 ± 0.29 MPa√m, which showed no statistical difference with the milled zirconia.  The dental zirconia manufactured by the DLP 3D printing technique is similar to that manufactured by the conventional milling process in hardness and fracture toughness, thus having a promising future of clinical use. In recent years, yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) is widely used in dentistry due to its excellent biocompatibility and mechanical properties, as well as its satisfying aesthetics. Usually, the zirconia prostheses are manufactured by the numerically controlled milling process, while there still exist some problems . FirstlyWith the rapid development of three-dimensional (3D) printing techniques, 3D printing ceramics becomes a hot issue in prosthodontics. This technique builds parts layer by layer with no need for machining or mould, thus possessing the characteristics of high production efficiency, high usage rate of material, and unlimited printing shapes . TherefoAt present, there were a few studies on the mechanical properties of dental zirconia manufactured by 3D printing techniques. Lu et al. investigated that DLP-manufactured zirconia can achieve high flexural strength close to milled zirconia . Li et a2 with 25 μm each layer. Then, the debinding process was performed by putting the green parts into the debinding furnace under 100-450°C to remove organic parts. At last, the final sintering process was carried out on Y-TZP of the two groups by sintering them for 2 h at 1510°C with heating and cooling rates set at 300°C/h. All samples were observed under an optical microscope, and those without surface defects were selected for experiments. Before experiments, the samples were firstly ground with P400-P1200 SiC abrasive paper, followed by a polishing step with 9 μm-1 μm polishing slurry in a polishing machine .All experiments were performed on zirconia discs with dimensions of diameter 20.0 mm and thickness 2.0 mm. The control group was Y-TZP, which was milled out of presintered Y-TZP discs  by a CAD/CAM machine  (MILL group). The experimental group was Y-TZP manufactured by a DLP stereolithography printing machine  (DLP group), as is listed in d is the density (g/cm3), m1 is the mass of the dried specimen in air (g), m2 is the mass of the water-impregnated specimen in water (g), m3 is the mass of the water-impregnated specimen (g), and ρ is the density of water which equals to 0.9982 g/cm3. The surface morphologies of Y-TZP were observed by a scanning electron microscope . And the SEM images were used for analyzing the grain sizes using software ImageJ 1.52a . The crystalline phase structure was determined by an X-ray diffractometer , with a step size of 0.02° and a scan range of 10°-70°. Young's modulus was tested by an MHT3 microindentation tester. The maximum load was 10 N, and the holding time was 10 s. Young's modulus of each group was calculated by Indentation Software.To characterize the specimens, the density, grain size, crystalline phase, and Young's modulus were investigated. The density was measured by means of Archimedes' method using the calculationF is the applied load (N), d is the mean value of the indentation diagonals (mm), and α is the indenter's geometrical constant, which equals 0.1891.According to ASTM C1327-2015 , the Vicc (mm) and half of the indentation diagonal a (mm) were measured to calculate the c/a ratio. The crack type could thus be confirmed [c/a > 2.5, the crack shows the Palmqvist type, and when c/a < 2.5, the crack shows the radial-median crack type. The fracture toughness values were then calculated using the correct equation for the corresponding crack type.The fracture toughness was measured using the indentation fracture method. Based on the Vickers hardness tests above, the length of the crack induced by the indentation onfirmed . When c/As is shown in F, which is called the normal indentation size effect (ISE) [F is the load (N), K is a hardness constant, and d is the mean value of the indentation diagonal (mm). A linear regression analysis was conducted on ln F versus ln d to obtain the slope that represents Meyer's index n. The fitting curves are displayed in The average hardness values versus applied indentation loads are plotted in ct (ISE) . To verict (ISE) :(3)F=K∙a1 (N mm−1) is a constant related to elasticity and a2 (N mm−2) is a constant related to plasticity. These two values were calculated by linear regression carried out on F/d versus d  model and the modified proportional specimen resistance (MPSR) model were used to determine the true hardness. The PSR model is a modification of Meyer's law , and it us d see . The resa0 (N) related to the material characterization and surface treatment:The MPSR model is developed based on the PSR model , 16, whiF versus d to obtain a0, a1, and a2 (see T (HV) could be calculated by the following equation [Polynomial regression was applied to d a2 see , and theequation , 16:(6)As is shown in c (mm) and half of the indentation diagonal a (mm), the c/a ratio was calculated to be smaller than 2.5 under the load of 49.03 N and larger than 2.5 under the load of 196.1 N, while under the load of 98.07 N, the c/a ratio showed a mixture type (see KIC (MPa√m):F/(2a)2) (MPa), c is the crack length from the indentation center to the crack tip (mm), and E is Young's modulus of zirconia (GPa). The fracture toughness value was 3.43 ± 0.29 MPa√m for the DLP group and 3.44 ± 0.23 MPa√m for the MILL group. Student's t-test was conducted using the SPSS 22.0 software  to analyze the difference in KIC values between the two groups. The results indicated that there was no significant difference between DLP-manufactured zirconia and milled zirconia (P > 0.05). The indentation crack profiles of both groups are shown in According to the measurements of crack length type see . The fraThe results of this study show that the Vickers hardness of DLP-manufactured zirconia was statistically lower than that of milled zirconia while there was no statistical difference in fracture toughness between two groups of zirconia, thus rejecting the null hypothesis.In this study, the dental zirconia specimens were manufactured by two techniques. Since the 3D printing zirconia slurry used in this study was 3 mol% yttria partially stabilized tetragonal zirconia polycrystal (3Y-TZP), which is composed of similar contents to the commercial nontransparent zirconia , the ZenKIC values could easily be calculated according to empirical formulas based on the results of Vickers indentation tests. Although the KIC values determined by the indentation fracture method could just be used as approximations of true fracture toughness values, they were good indicators for comparing the fracture toughness between two materials.The hardness and fracture toughness of the DLP-manufactured zirconia were determined by the indentation technique, which is a standard method for determining the Vickers hardness  while noThe hardness was tested under a range of loads from 0.49 N to 196.1 N. The results revealed that both groups of zirconia had normal ISE, which was further verified by Meyer's law, indicating that the obtained results of hardness were apparent hardness dependent on the applied loads. The apparent hardness of DLP zirconia was a bit statistically lower than that of MILL zirconia for 2% at 0.49 N, 4% at 0.98 N, 3% at 1.96 N, 1% at 4.9 N, 4% at 9.81 N, 4% at 29.42 N, 4% at 49.03 N, 4% at 98.07 N, and 5% at 196.1 N. The PSR model and MPSR model were applied to obtain the true hardness, and the results showed that the true hardness of DLP zirconia was 5% lower than that of MILL zirconia. Research has shown that the Vickers hardness has a strong dependence on porosity and pore size . The harKIC values of zirconia were a bit lower than those of previous research studies [Zirconia stands out from other ceramics mainly due to its high fracture toughness, which is an important property for the clinical use of bridge frameworks, especially those with large spans. It differs from other brittle ceramic materials in that it would just generate clear indentations with cracks under large loads like metal materials do without any fracture or chipping . The tou studies , 28, whi studies . Althoug studies , it is aKIC values calculated by empirical formulas relying on indentation crack lengths could not be used as the true values of fracture toughness. Meanwhile, the dynamic mechanical properties like fatigue property and degeneration behavior need to be studied, and the biocompatibility, printing accuracy, and aesthetic performance also deserve exploration to provide an all-rounded theoretical basis for the clinical application of DLP-manufactured dental Y-TZP.Based on the previous research on the flexural strength of DLP-manufactured Y-TZP , this stThe DLP-manufactured zirconia is similar to milled zirconia in microstructure, including density, grain size, and crystalline phase compositionThe true hardness of DLP-manufactured zirconia is 5% lower than that of milled zirconia, which may be attributed to the existence of large pores on the surface of DLP zirconiaThere is no statistical difference in fracture toughness between DLP-manufactured zirconia and milled zirconia, which may be due to the highly similar microstructure of both groups of zirconiaDLP-manufactured dental zirconia can achieve the requirements of dental prostheses in basic mechanical propertiesAccording to the study above, the following conclusions can be drawn:


Surface Plasmon Resonance (SPR) is widely used in biological and chemical sensing with fascinating properties. However, the application of SPR to detect trace targets is hampered by non-specific binding and poor signal. A variety of approaches for amplification have been explored to overcome this deficiency including DNA aptamers as versatile target detection tools. Hybridization chain reaction (HCR) is a high-efficiency enzyme-free DNA amplification method operated at room temperature, in which two stable species of DNA hairpins coexist in solution until the introduction of the initiator strand triggers a cascade of hybridization events. At an optimal salt condition, as the concentrations of H1 and H2 increased, the HCR signals were enhanced, leading to signal amplification reaching up to 6.5-fold of the detection measure at 30 min. This feature enables DNA to act as an amplifying transducer for biosensing applications to provide an enzyme-free alternative that can easily detect complex DNA sequences. Improvement of more diverse recognition events can be achieved by integrating HCR with a phase-sensitive SPR (pSPR)-tested aptamer stimulus. This work seeks to establish pSPR aptamer system for highly informative sensing by means of an amplification HCR. Thus, combining pSPR and HCR technologies provide an expandable platform for sensitive biosensing. We. Wehttp:The procedure of probe immobilization and target hybridization was done first to anneal a gold film surface with deionized water to avoid non-specific binding and 20 mM 6-mercapto-1-hexanol (MCH)  to minimize generation of a secondary structure. Then, 1 uM initiator probe DNA was added for 1 h for a higher density of immobilization. Again, the gold film surface was cleaned with deionized water to further reduce non-specific binding. With the probe immobilized, DNA hybridization can then be measured by the pSPR system.We designed HCR sequences and anchored 1 μM 5′-end thiolated-initiator and 10 nM thiolated-10 thymine on the gold surface of the pSPR chip, and then introduced 1 μM of H1. Later, a mixture of 1 μM H1 and H2 was injected to enable HCR reaction. As the initiator was bound by H1, forming an initiator-H1 complex, H2 was then combined to the H1 tail, and H1 and H2 were bounded alternatively and repeatedly to form a double helix DNA complex structure, leading to signal amplification . A gradiTo verify the initiator, H1 and H2 DNA aptamers underwent HCR amplification. The 2% agarose gel electrophoresis experiment was performed in 1× sodium borate buffer (1× SB buffer) . Electrophoresis was done with a 100 V driving voltage (with MAJOR SCIENCE MP-100) at room temperature, using a 1× SB running buffer. The fluorescent dye used for imaging was Safe Green . The proportion of initiator, H1 and H2 was 5:5:0.25 to 5:5:10, and after 30 min of mixing, the HCR yield was from 100 bp to 2 kbp. In the gel electrophoresis experiment, the HCR chemistry was in free solution, the proportion of initiator, H1 and H2 was 5:5:0.25 to 5:5:10, while in pSPR, the initiator was anchored on a gold surface, a two-dimensional space with 10 mer Thymine spacers in between.We anchored the HCR initiator DNA aptamer on the SPR chip gold surface and added H1 and H2 sequences to amplify the HCR signal. A gradient of sodium chloride, 0.025 M NaCl, 0.05 M NaCl, 0.1 M NaCl and 0.2 M NaCl was injected into the fluidic system to become a calibration ruler for data normalization. Running buffer (1 × PBS + 1 MNaCl) was added to gain the baseline. At around 5000 s, 500 nM H1 was injected to form the H1-initiator complex. After one hour, running buffer was added to stop the reaction; the reaction was around 0.0001 ∆RIU. We then added 1 µM mixture of H1 and H2 to the system. As can be seen, the HCR reaction was around 0.0005 ∆RIU at 30 min. In the pSPR result, after 30 min of the initiator and H1 binding reaction and the 30 min washing step marks A, the time point of 30 min after the addition of H1 and H2 mixture marks B. (A + B)/A = 6.5, indicating a 6.5-fold of the detection measure at 30 min. There was no significant signal difference when only H1 was added A.By combining pSPR and DNA gel electrophoresis results, we were able to study the length of HCR product at the same reaction time of 30 min. We also compared the product length of HCR at 60 min, by pSPR and DNA gel electrophoresis. Initiator was 22 + 10 T = 32 mer, but only 22 mer reacted in the HCR process. H1 and H2 each had 44 mer, the combination of H1 and H2 makes 22 + 22 = 44, 22 × 6 + 22 = 154 bases, 22 × 7 + 22 = 176 bases B.Results of HCR reaction under different aptamer concentrations and ionic strength environment are shown in In the present work, a pSPR detection system based on HCR was developed for the amplification of DNA aptamers. We designed HCR sequences and anchored the 5′-end thiolated-10 thymine-initiator on the gold surface of the pSPR chip, and then we introduced H1 and H2 hairpin DNA aptamers to enable HCR reaction. As the initiator was bound by H1, forming an initiator-H1 complex, H2 was then combined to the H1 tail, and the H1 and H2 were bounded alternatively and repeatedly to form a double-helix DNA complex structure without an enzyme. Finally, as the concentration of H1 and H2 increased, the HCR signals were enhanced, leading to signal amplification.The HCR chemistry was in free solution in the gel electrophoresis experiment. The proportion of initiator, H1 and H2 was 5:5:0.25 to 5:5:10, while the initiator was anchored on the gold surface in pSPR, a two-dimensional space with 10 mer adenosine spacers in between.We designed HCR sequences, planted thiolated-initiator on the gold surface of the pSPR chip, and then introduced H1 and H2 to enable HCR. On the other hand, when thiolated H1 was first bound to the gold surface, HCR could not be activated followed by adding initiator and H2 in our setting. This is because the initiator is needed initially when the hairpin structure is unlocked, and the structure of HCR-initiator can be revealed and opened for the HCR reaction.The HCR response was most intense under a running buffer composition of 1.5 M NaCl in 1× PBS, as can be seen. Based on the data, at salt concentrations greater than or less than 1.5 M NaCl in 1× PBS, the HCR reaction was relatively smaller. We therefore conclude that, for pSPR-based HCR, there is an optimal salt concentration.Loop-mediated isothermal amplification (LAMP) has also observed these phenomena ,40,41,42In a previous study using microfluidics, higher SPR signals could be obtained with target concentrations from 10 nM to 100 nM where target signals can be detectable prior to HCR . During −17 M to 1.0 × 10−11 M.A recent advance of pSPR has been proposed to combine amplification cascades of catalyzed hairpin assembly (CHA) and HCR with the sensitive SPR responses of plasmonic gold nanorods . The proThus, the method of combining pSPR and HCR technologies provides an expandable platform for future direction of ultrasensitive biosensing.HCR is a high-efficiency enzyme-free DNA amplification process operated at room temperature, in which two stable species of DNA hairpins coexist in solution before the introduction of the initiator strand causes a cascade of hybridization events. Improvement of more diverse recognition events can be achieved by integrating HCR with pSPR-tested aptamer stimuli. This feature enables DNA to act as an amplifying transducer for biosensing applications. This work sets out a pSPR system for highly informative sensing using HCR for amplification and opens a new era of sensitive detection for various biological and medical conditions for pSPR biosensor technology. Possible future applications may include early diagnosis of cancer metastases, prognosis prediction and exosome profiling by tumor marker quantification.