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Panfacial fractures are challenging for craniofacial surgeons. Aside from involving multiple subunits, they also lack the reliability of a useful landmark of the facial skeleton. Properly, reducing and fixing palatal fracture to re-establish the premorbid maxillary dental arch is important. This was a retrospective study conducted from 2015 to 2020. All patients underwent computed tomography (CT) scan for surgical planning of orthognathic surgery due to either esthetic or occlusion concerns. The classification of occlusion was recorded as class I, II, and III. The parameters measured on CT were the distance between the midpoint of the supra-orbital foramen/notch (IS), mesio-buccal cusp tips (IB), central fossa (IC), palatal cusp tips (IP), and the midpoint of the palatal marginal gingiva (IM) of the bilateral maxillary first molars. The IS was compared with the IB, IC, IP, and IM. The results were analyzed by using one-way repeated measurement analysis of variance. Eighty-seven patients (36 men and 51 women) were included in the study. There were 13 patients of class I malocclusion, 8 of class II malocclusion, and 66 of class III malocclusion. The IS was comparable to the IC in all three groups. The IS can predict the IC, regardless of the patient's occlusion, and can be subsequently used to decide the width of maxillary dental arch in panfacial fracture management. Further studies are necessary to obtain more definite results.

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.

Purpose: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue.Methods: We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan–Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis.Results: This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p=0.694), cirrhotic patients (p=0.753), non-cirrhotic patients (p=0.146), patients with alpha-fetoprotein (AFP) >20 ng/ml (p=0.562), patients with AFP ≤20 ng/ml (p=0.967), patients with Edmondson grade 1 or 2 (p=0.615), patients with Edmondson grade 3 or 4 (p=0.825), patients positive for hepatitis B surface antigen (HBsAg; p=0.308), in patients positive for anti–hepatitis C virus (HCV) antibody (p=0.781), or patients negative for both HBsAg and anti-HCV antibody (p=0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio [HR]: 1.338; 95% confidence interval [CI]:0.737–2.431; p=0.339).Conclusion: No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Purpose Tumor size, number, alpha-fetoprotein (AFP), and cirrhosis are well-known prognostic factors in patients with hepatocellular carcinoma (HCC) undergoing liver resection (LR). We aimed to develop a preoperative model to predict overall survival (OS) in these patients based on these variables.Methods Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B HCC were enrolled.Results Among 743 enrolled patients, 193 (26.0%) patients had a low tumor burden score (TBS) ( 7.9). Multivariate analysis showed that TBS (low: referent; medium: HR = 2.91; 95% CI: 1.62–5.24; p p p = 0.015), and cirrhosis (absence: referent; presence: HR = 1.88, 95% CI: 1.30–2.73, p Conclusion We have developed a simple preoperative model that performs better in predicting OS than the BCLC system.

Supplementary Table 1, Figures 1-7, Methods from hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress

Human hPuf-A/KIAA0020 was first identified as a new minor histocompatibility antigen in 2001. Its zebrafish orthologue contains six Pumilio-homology RNA-binding domains and has been shown to participate in the development of eyes and primordial germ cells, but the cellular function of hPuf-A remains unclear. In this report, we showed that hPuf-A predominantly localized in the nucleoli with minor punctate signals in the nucleoplasm. The nucleolar localization of hPuf-A would redistribute to the nucleoplasm after the treatment of RNA polymerase inhibitors (actinomycin D and 5,6-dichlorobenzimidazole riboside) and topoisomerase inhibitors [camptothecin (CPT) and etoposide]. Interestingly, knockdown of hPuf-A sensitized cells to CPT and UV treatment and cells constitutively overexpressing hPuf-A became more resistant to genotoxic exposure. Affinity gel pull-down coupled with mass spectrometric analysis identified PARP-1 as one of the hPuf-A interacting proteins. hPuf-A specifically interacts with the catalytic domain of PARP-1 and inhibits poly(ADP-ribosyl)ation of PARP-1 in vitro. Depletion of hPuf-A increased the cleaved PARP-1 and overexpression of hPuf-A lessened PARP-1 cleavage when cells were exposed to CPT and UV light. Collectively, hPuf-A may regulate cellular response to genotoxic stress by inhibiting PARP-1 activity and thus preventing PARP-1 degradation by caspase-3. Cancer Res; 71(3); 1126–34. ©2011 AACR.

Purpose The updated 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines recommend liver resection (LR) for single hepatocellular carcinoma (HCC) of any size, i.e., American Joint Committee on Cancer (AJCC) 7th edition image-defined stage 1. This study aimed to develop a model to preoperatively predict the survival of patients with HCC undergoing LR beyond the updated BCLC resection criteria. Methods Three hundred and three patients undergoing LR for HCC beyond the updated BCLC resection criteria between 2011 and 2017 were identified from the cancer registry database of our institution. A model to predict overall survival (OS) was developed and patients were classified using risk scores. Results Multivariate analysis of five-year OS identified three variables—AJCC 7th edition image-defined stage (stage 3 vs. 2; HR = 1.618; 95% CI = 1.061–2.467; p = 0.025), alpha-fetoprotein level (≥ 400 vs. < 400 ng/ml; HR = 1.837; 95% CI = 1.252–2.697, p = 0.002), and cirrhosis (presence vs. absence; HR = 1.569; 95% CI = 1.092–2.254; p = 0.015)—as independent prognostic factors of survival, which were used to formulate risk scores. Patients were divided into low-, medium-, and high-risk groups; their five-year OS was 86%, 56%, and 36% (p p = 0.001), respectively. Conclusion We developed a simple model that can preoperatively predict the survival of patients with HCC who are candidates for LR beyond the updated BCLC resection criteria.

This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality.

Purpose: Tumor necrosis is a significant risk factor affecting patients’ prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). Only one previous study has used a model incorporating tumor necrosis to predict tumor recurrence after LR in patients with a solitary HCC of ≤ 3.0 cm. We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. Methods: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features—tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis—were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram’s performance was evaluated using calibration plots with bootstrapping. Results: Early tumor recurrence was observed in 161 (21.3 %) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. Conclusion: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Many studies on the recurrence of pressure ulcers after surgical reconstruction have focused on surgical techniques and socioeconomic factors. Herein, we aimed to identify the risk factors of the associated comorbidities for pressure ulcer recurrence. We enrolled 147 patients who underwent pressure ulcer reconstruction and were followed up for more than three years. The recurrence of pressure ulcers was defined as recurrent pressure ulcers with stage 3/4 pressure ulcers. We reviewed and analyzed systematic records of medical histories, including sex, age, associated comorbidities such as spinal cord injury (SCI), diabetes mellitus (DM), coronary artery disease, cerebral vascular accident, end-stage renal disease, scoliosis, dementia, Parkinson's disease, psychosis, autoimmune diseases, hip surgery, and locations of the primary pressure ulcer. Patients with recurrent pressure ulcers were younger than those without. Patients with SCI and scoliosis had higher odds, while those with Parkinson's disease had lower odds of recurrence of pressure ulcers than those without these comorbidities. Moreover, the decision tree algorithm identified that SCI, DM, and age < 34 years could be risk factor classifiers for predicting recurrent pressure ulcers. This study demonstrated that age and SCI are the two most important risk factors associated with recurrent pressure ulcers following surgical reconstruction.

We evaluated whether combining the radiographic tumor burden score (TBS) and alpha-fetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2. Among 743 patients, 193 (26.0%) patients had a low TBS (7.9). Those with a TBS ≤ 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or ≥ 400 ng/mL (p < 0.001). A multivariate analysis using TBS ≤ 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175–3.623; p = 0.012) or ≥ 400 ng/mL (HR: 6.570; 95% CI: 3.684–11.719; p < 0.001) were independent predictors of OS. In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

Background: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. Materials and methods: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. Results: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). Conclusions: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.

Supplemental material, sj-pdf-1-slr-10.1177_02676583231167790 for Phonolexical processing of Mandarin segments and tones by English speakers at different Mandarin proficiency levels by Yen-Chen Hao in Second Language Research

PURPOSE To evaluate the prevalence and extension of macrovascular invasion (MaVI) in a large cohort of hepatocellular carcinoma (HCC) patients and analyze the association between MaVI and overall survival (OS). METHODS From 2011 to 2018, 2540 patients with newly diagnosed HCC who were managed in our institution were enrolled in this retrospective study. Tumor invasion of the intrahepatic branches of the portal or hepatic veins was defined as peripheral MaVI. Tumor invasion of the main portal vein or inferior vena cava was defined as central MaVI. RESULTS MaVI prevalence was 16.2% (n = 411). Among patients with Barcelona Clinic Liver Cancer (BCLC) stage C and Child-Pugh class A, 165 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 13.2 months (95% confidence interval [CI]: 11.4-15.4) in the peripheral MaVI group and 6.6 months (95% CI: 3.6-9.5) in the central MaVI group (p

Replication stress causes replication fork stalling, resulting in an accumulation of single-stranded DNA (ssDNA). Replication protein A (RPA) and CTC1-STN1-TEN1 (CST) complex bind ssDNA and are found at stalled forks, where they regulate RAD51 recruitment and foci formation in vivo. Here, we investigate crosstalk between RPA, CST, and RAD51. We show that CST and RPA localize in close proximity in cells. Although CST stably binds to ssDNA with a high affinity at low ionic strength, the interaction becomes more dynamic and enables facilitated dissociation at high ionic strength. CST can coexist with RPA on the same ssDNA and target RAD51 to RPA-coated ssDNA. Notably, whereas RPA-coated ssDNA inhibits RAD51 activity, RAD51 can assemble a functional filament and exhibit strand-exchange activity on CST-coated ssDNA at high ionic strength. Our findings provide mechanistic insights into how CST targets and tethers RAD51 to RPA-coated ssDNA in response to replication stress., During replication stress, the RPA protein complex coats single-stranded DNA to preclude RAD51 loading. Here, the authors show how RPA and CST crosstalk to regulate RAD51 activity.

Purpose:The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. Methods: Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007–2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. Results: Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3 %) BCLC-A, and 69 (9.2 %) BCLC-B HCC; 81 (10.8%) had a high TBS (> 7.9), 474 (63.3%) a medium TBS (2.6–7.9), and 194 (25.9%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p< 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024–5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI =1.443–10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077–6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p< 0.001). Conclusion: The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

The ATP binding sites of many enzymes are structurally related, which complicates their development as therapeutic targets. In this work, we explore a diverse set of ATPases and compare their ATP binding pockets using different strategies, including direct and indirect structural methods, in search of pockets attractive for drug discovery. We pursue different direct and indirect structural strategies, as well as ligandability assessments to help guide target selection. The analyses indicate human RAD51, an enzyme crucial in homologous recombination, as a promising, tractable target. Inhibition of RAD51 has shown promise in the treatment of certain cancers but more potent inhibitors are needed. Thus, we design compounds computationally against the ATP binding pocket of RAD51 with consideration of multiple criteria, including predicted specificity, drug-likeness, and toxicity. The molecules designed are evaluated experimentally using molecular and cell-based assays. Our results provide two novel hit compounds against RAD51 and illustrate a computational pipeline to design new inhibitors against ATPases., This work was supported by Academia Sinica (P.C.), National Taiwan University (P.C.), Taiwan Ministry of Science and Technology (MOST 110-2326-B-002-012 to P.C), Scottish Funding Council (V.B.), and the Generalitat Valenciana and European Social Fund (APOSTD/2020/120 to V.B.).