Recent studies showed that ABO‐adjusted calculated panel reactive antibody (ABO‐cPRA) may better reflect the histocompatibility level in a multi‐ethnic population, but such data in Asians is not ...available. We developed an ABO‐adjusted cPRA metric on a cohort of waitlist kidney transplant patients (n = 647, 99% Chinese) in Hong Kong, based on HLA alleles and ABO frequencies of local donors. The concordance between the web‐based ABO‐cPRA calculator and the impact on kidney allocation were evaluated. The blood group distribution for A, B, O and AB among waitlist kidney candidates were 26.2%, 27.5%, 40.1%, and 6.1%, and their chances of encountering incompatible blood group donors were 32.6%, 32.4%, 57.6%, and 0%, respectively. There is poor agreement between web‐based ABO‐cPRA calculator and our locally developed metrics. Over 90% of patients showed an increase in cPRA after ABO adjustment, most notably in those with cPRA between 70% and 79%. Blood group O patients had a much greater increase in cPRA scores after adjustment while patients of blood group A and B had similar increment. 10.6% of non‐AB blood group waitlist patients had ABO‐cPRA elevated to ≥80%. A local ABO‐adjusted cPRA metric is required for Asian populations and may improve equity in kidney distribution for patients with disadvantageous blood groups. The result from the current study potentially helps other countries/localities in establishing their own unified ABO‐cPRA metrics and predict the impact on kidney allocation.
Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of ...A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation.
OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation.
IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation.
A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.
Abstract Teeth segmentation for periapical raidographs is one of the most critical tasks for effective periapical lesion or periodontitis detection, as both types of anomalies usually occur around ...tooth boundaries and dental radiographs are often subject to noise, low contrast, and uneven illumination. In this paper, we propose an effective scheme to segment each tooth in periapical radiographs. The method consists of four stages: image enhancement using adaptive power law transformation, local singularity analysis using Hölder exponent, tooth recognition using Otsu's thresholding and connected component analysis, and tooth delineation using snake boundary tracking and morphological operations. Experimental results of 28 periapical radiographs containing 106 teeth in total and 75 useful for dental examination demonstrate that 105 teeth are successfully isolated and segmented, and the overall mean segmentation accuracy of all 75 useful teeth in terms of (TP, FP) is (0.8959, 0.0093) with standard deviation (0.0737, 0.0096), respectively.
Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial ...cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.
Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the ...bladder function preservation and adverse effects analysis.
Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis.
The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 l
Underlying endothelial dysfunction (EnD) may present in the early stage of ED or psychogenic ED. We retrospectively evaluated 191 ED patients with effective nocturnal penile tumescence and rigidity ...(NPTR) recording, including detailed medical and psychosexual history, International Index of Erectile Function-5 and vascular parameter. All patients were allocated into psychogenic and organic groups according to the NPTR test. Brachial artery flow-mediated dilation (FMD) was used to diagnose EnD, and ED patients were classified into two groups: non-EnD (FMD10) and EnD (FMD<10). General and vascular parameters were compared between psychogenic and organic groups, and non-EnD and EnD groups with ED were compared in terms of NPTR parameters. In all, 48.7% and 51.3% patients were diagnosed as psychogenic and organic ED, respectively. 73.1% of the psychogenic patients had EnD and 39.8% organic patients had normal endothelial function. In all parameters, only the FMD value showed significant difference between psychogenic and organic ED groups (8.26±2.57 vs 9.16±2.76, P=0.020). No statistical difference was founded in NPTR parameters between non-EnD and EnD groups (P>0.05). In conclusion, NPTR cannot effectively identify the underlying vasculogenic ED from psychogenic ED. Psychogenic causes may cause or aggravate EnD in these ED patients with normal NPTR.
Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally ...identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.
In this study, a hybrid sequential data assimilation and probabilistic collocation (HSDAPC) approach is proposed for analyzing uncertainty propagation and parameter sensitivity of hydrologic models. ...In HSDAPC, the posterior probability distributions of model parameters are first estimated through a particle filter method based on streamflow discharge data. A probabilistic collocation method (PCM) is further employed to show uncertainty propagation from model parameters to model outputs. The temporal dynamics of parameter sensitivities are then generated based on the polynomial chaos expansion (PCE) generated by PCM, which can reveal the dominant model components for different catchment conditions. The maximal information coefficient (MIC) is finally employed to characterize the correlation/association between model parameter sensitivity and catchment precipitation, potential evapotranspiration and observed discharge. The proposed method is applied to the Xiangxi River located in the Three Gorges Reservoir area. The results show that: (i) the proposed HSDAPC approach can generate effective 2nd and 3rd PCE models which provide accuracy predictions; (ii) 2nd-order PCE, which can run nearly ten time faster than the hydrologic model, can capably represent the original hydrological model to show the uncertainty propagation in a hydrologic simulation; (iii) the slow (Rs) and quick flows (Rq) in Hymod show significant sensitivities during the simulation periods but the distribution factor (α) shows a least sensitivity to model performance; (iv) the model parameter sensitivities show significant correlation with the catchment hydro-meteorological conditions, especially during the rainy period with MIC values larger than 0.5. Overall, the results in this paper indicate that uncertainty propagation and temporal sensitivities of parameters can be effectively characterized through the proposed HSDAPC approach.
•HSDAPC is developed for uncertainty quantification of hydrologic models.•PCM-based TEDPAS is derived for revealing parameter sensitivities.•The association between sensitivity and catchment conditions is identified.•The case study demonstrate the efficiency of the HDAPC approach.
Heat generated during implant osteotomy might lead to osteonecrosis and delayed bone repair, thus resulting in impaired early osseointegration and fixation of bone-anchoring devices. In this study, ...we proposed to overcome heat-induced injury to bone by fabricating core-shell polymeric biodegradable microspheres encapsulating a mitogenic factor, platelet-derived growth factor (PDGF), and a differentiation factor, simvastatin, in a simultaneous or sequential release profile. Microspheres encapsulating bovine serum albumin (BSA), PDGF, simvastatin, PDGF-in-core with simvastatin-in-shell, and simvastatin-in-core with PDGF-in-shell were delivered to fill standardized osteotomy sites on edentulous ridges of rat maxillae under irrigated or non-irrigated conditions. In the absence of irrigation, significant reduction of cell viability and increase in inflammation and sequestrum formation without evidence of osteogenesis were observed. Both PDGF and simvastatin deliveries facilitated cell viability and reduced osteonecrosis. Localized osteogenesis was seen under simvastatin treatment, while generalized but primitive osteogenesis was noted in PDGF-treated osteotomy sites. In addition, sequential PDGF-simvastatin delivery further augmented osteogenesis and promoted bone maturation. The results suggested that sequential PDGF-simvastatin delivery was an effective modality to prevent heat-induced complications and facilitate bone apposition after implant osteotomy, potentially favoring the early fixation of bone-anchoring devices and oral implant osseointegration.
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