Development of a simulation system for femoroacetabular impingement detection based on 3D images.

Image-based criteria have been adopted to diagnose femoroacetabular impingement (FAI). However, the overlapping property of the two-dimensional X-ray outlines and static and supine posture of taking computed tomography (CT) and magnetic resonance imaging images potentially affect the accuracy of the criteria. This study developed a CT image-based dynamic criterion to effectively simulate FAI, thereby providing a basis for physicians to perform pre-operative planning for arthroscopic surgery. Post-operative CT images of 20 patients with satisfactory surgical results were collected, and 10 sets of models were used to define the flexion rotation centre (FRC) of the three-dimensional FAI model. First, let these 10 groups of models simulate the FAI detection action and find the best centre offset, and then FRC is the result of averaging these 10 groups of best displacements. The model was validated in 10 additional patients. Finally, through the adjustment basis of FRC, the remaining 10 sets of models can find out the potential position of FAI during the dynamic simulation process. Rotational collisions detected using FRC indicate that the patient's post-operative flexion angle may reach 120° or greater, which is close to the actual result. The recommended surgical range of the diagnostic system (average length of 6.4 mm, width of 4.1 mm and depth of 3.2 mm) is smaller than the actual surgical results, which prevents the doctor from performing excessive resection operations, which may preserve more bones. The FRC diagnostic system detects the distribution of FAI in a simple manner. It can be used as a pre-operative diagnosis reference for clinicians, hoping to improve the effect and accuracy of debridement surgery.

The use of customized 3D-printed mandibular prostheses with pressure-reducing device: A clinical trial.

BACKGROUND: Segmental bone defects of the mandible result in the complete loss of the affected region. We had incorporated the pressure-reducing device (PRD) designs into the customized mandible prostheses (CMP) and conducted a clinical trial to evaluate this approach. METHODS: Seven patients were enrolled in this study. We examined the association among the history of radiotherapy, the number of CMP regions, the number of chin regions involved, and CMP exposure. RESULTS: We included five men and two women with an average age of 55 years. We excised tumors with an average weight of 147.8 g and the average weight of the CMP was 68.5 g. No significant difference between the two weights was noted (p = 0.3882). Three patients received temporary dentures and the CMP remained stable in all patients. CONCLUSION: The use of PRD in CMP may address the previous challenges associated with CMP, but further research is necessary.

Use of customized 3-dimensional printed mandibular prostheses with a dental implant pressure-reducing device in mandibular body defect: A finite element study performing multiresponse surface methodology.

Background/purpose: Segmental body defects of the mandible result in the complete loss of the affected region. In our previous study, we investigated the clinical applicability of a customized mandible prosthesis (CMP) with a pressure-reducing device (PRD) in an animal study. In this study, we further incorporated dental implants into the CMP and explored the use of dental implant PRD (iPRD) designs. Materials and methods: By employing a finite element analysis approach, we created 4 types of CMP: CMP, CMP with iPRD, CMP-PRD, and CMP-PRD with iPRD. We developed 2 parameters for the iPRD: cone length (CL) in the upper part and spring pitch (SP) in the lower part. Using the response surface methodology (RSM), we determined the most suitable structural assignment for the iPRD. Results: Our results indicate that CMP-PRD had the highest von Mises stress value for the entire assembly (1076.26 MPa). For retentive screws and abutments, CMP with iPRD had the highest von Mises stress value (319.97 and 452.78 MPa, respectively). CMP-PRD had the highest principal stress (131.66 MPa) in the anterior mandible. The iPRD reduced principal stress in both the anterior and posterior mandible. Using the RSM, we generated 25 groups for comparison to achieve the most favorable results for the iPRD and we might suggest the CL to 12 mm and the SP to 0.4 mm in the further clinical trials. Conclusion: Use of the PRD and iPRD in CMP may resolve the challenges associated with CMP, thereby promoting its usage in clinical practice.

Comparison of the transverse cranial base dimension in different craniofacial skeletal relationships: A cone-beam computed tomography study.

Background/purpose: In comparing the cranial base's size, most cephalometric studies focused on the length and angle in the anteroposterior direction. However, investigating the anterior, middle, and posterior cranial base's transverse dimensions is challenging. This study aimed to investigate the transverse dimensions of the cranial base in different craniofacial skeletal patterns and sexes using cone-beam computed tomography (CBCT). Materials and methods: A total of 210 adults (105 males and 105 females), including three different skeletal relationships, were included in the study. The cranial base dimensions were measured on a three-dimensional image structure rendered by CBCT. Statistical methods included the Kappa statistic for analysis of consistency and reproducibility and the independent t-test for differences in cranial base dimensions between sexes. A general linear model (GLM) was used to compare the transverse size of the cranial base among skeletal Class I, II, and III groups. The Pearson correlation coefficient explored the correlation among the cranial base dimensions. Results: The cranial base dimensions did not differ significantly between skeletal Class I, II, and III. The more prominent cranial base size was found in males than females, except for the crista galli length (CGL) and cribriform ethmoid plate width (CEPW). The cranial base dimensions did not differ significantly between different skeletal relationships. Most dimensions have significant correlations in the middle and the posterior cranial base. Conclusion: The cranial base's transverse dimensions in Taiwanese adults show no significant differences between craniofacial skeletal relationships. In the middle and posterior cranial base, transverse measurements reveal significant sexual dimorphism.

Functional Fitness Norms of Community-Dwelling Older Adults in Southern Rural Taiwan: A Cross-Sectional Study.

BACKGROUND: Physical activity (PA) and functional fitness (FF) are crucial for promoting independent living and healthy aging in older adults. However, there is a lack of normative values for the Senior Fitness Test (SFT) among older adults (aged 55-90) living in southern rural Taiwan, particularly in the Chiayi region, which has been relatively underserved in terms of health-related resources compared to northern Taiwan. PURPOSE: This study aimed to determine the age- and gender-specific normative fitness scores for a large representative population of community-dwelling older adults in southern rural Taiwan. METHODS: A cross-sectional descriptive study was conducted to obtain normative FF scores for 3332 community-dwelling elderly people (1057 men and 2275 women) in Chiayi, through the implementation of functional fitness tests across 72 Chiayi communities. The developed normative data served as a reference for exercise prescription for the elderly in southern Taiwan. RESULTS: The study showed that the average normative values of all functional fitness tests declined significantly with increasing age (p < 0.05). Sex differences were also found in all measures of FF tests, with elderly women scoring significantly better than men on flexibility (scratch back: -1.34 ± 9.03 vs. -6.54 ± 11.07; chair sit and reach: 6.56 ± 9.44 vs. 0.56 ± 10.40) (p < 0.05), while men scored significantly higher than women on strength (grip strength: 30.83 ± 8.06 vs. 21.82 ± 5.32; bicep curl: 19.25 ± 5.44 vs. 17.64 ± 4.98) (p < 0.05). Furthermore, four FF normative scores in southern rural Taiwan were found to be significantly higher than their counterparts living in northern Taiwan. CONCLUSION: These findings contribute positively to the evaluation of fitness levels among older adults in southern rural Taiwan and provide a concrete reference for developing sound PA programs for this population. The results suggest that strategies aimed at promoting increased participation in PA among older adults need to consider age-, sex-, and region-specific factors.

Maturation of the Female Pharyngeal Airway from Adolescence to Adulthood.

BACKGROUND: The present study aimed to investigate developmental changes in the female pharyngeal airway from adolescence to adulthood, considering variations in the anatomical structures related to the airway dimensions. METHODS: Lateral cephalograms of 214 females were analyzed and categorized into five developmental stages: early adolescence (10-13 years), middle adolescence (14-17 years), late adolescence (18-21 years), early adulthood (22-30 years), and middle adulthood (31-50 years). The focus of the analysis included the point A-Nasion-point B (ANB) angle, tongue pharyngeal airway space (TPS), epiglottis pharyngeal airway space (EPS), soft palate airway space (SPS), and the horizontal and vertical positions of the hyoid bone. RESULTS: The ANB angle exhibited significant variation across groups, being significantly larger in the early-adolescence group (4.22°) compared to the middle-adolescence, late-adolescence, and early-adulthood groups. The TPS and EPS were significantly shorter in the early-adolescence group. Negative correlations were observed between the ANB angle and the lengths of the pharyngeal airway spaces (SPS, TPS, and EPS). The horizontal and vertical positions of the hyoid bone remained stable after middle adolescence. CONCLUSION: The maturation of the ANB angle and pharyngeal airway in females seems nearly completed during middle adolescence (14-17 years). Additionally, a significant and negative correlation was identified between the ANB angle and the lengths of various pharyngeal airway spaces (SPS, TPS, and EPS). The horizontal and vertical positions of the hyoid bone showed stability after middle adolescence.

The effects of laser acupuncture dosage at PC6 (Neiguan) on brain reactivity: a pilot resting-state fMRI study.

Previous studies indicated that laser acupuncture (LA) may effectively treat various medical conditions. However, brain responses associated with LA intervention have not been fully investigated. This study is focused on the effect of LA with different energy density (ED) in brain using resting-state functional magnetic resonance imaging (fMRI). We hypothesized that different ED would elicit various brain responses. We enrolled healthy adults participants and selected bilateral PC6 (Neiguan) as the intervention points. LA was applied, respectively, with ED of 0, 7.96, or 23.87 J/cm2. Two 500-s resting-state fMRI scans were acquired before and after intervention, respectively. The functional connectivity (FC) was calculated between autonomic nerve system-regulation associated brainstem structures and other brain regions. Compared to other dosages, the FC between rostral ventrolateral medulla and orbitofrontal cortex has more enhanced; the FC between caudal ventrolateral medulla, nucleus of the solitary tract/nucleus ambiguus, and dorsal motor nucleus of the vagus and somatosensory area has more weakened when ED was 23.87 J/cm2. Different dosages of LA have demonstrated varied regions of FC changes between regions of interest and other brain areas, which indicated that variations in EDs might influence the clinical efficacy and subsequent impacts through distinct neural pathways within the brain.

Correlation between facial asymmetry of skeletal class III jaw relationship and morphology of the temporomandibular joint: A cone beam computed tomography study.

Background/purpose: Facial asymmetry is a common dentofacial deformity especially in skeletal Class III jaw relation. The purpose of this study was to evaluate the condylefossa relationship of Taiwanese people in skeletal Class III jaw relation with or without facial asymmetry by CBCT image. Materials and methods: CBCT images were collected from Kaohsiung Medical University Hospital and then divided into symmetric Class III group (Menton [Mn] deviation â‰¦ 4 mm) and asymmetric Class III group (Menton [Mn] deviation > 4 mm). Maxilla deviation, upper and lower dental midline deviation, joint space, condylar axial angle and condylar volume was measured. Independent t test was used for comparison between groups, and paired t test was applied for comparison between both condyles within each group. The Pearson correlation coefficient was used to analyze the correlation between skeletal midline deviations and joint morphology. Results: No significant difference was found in joint space between groups or between sides within each group, but we can find a significant difference in axial condylar angle easurement which was greater on the non-deviation side of condyle. Significant lesser condylar volume was also found on the deviation side in asymmetric group. There had a significant positive correlation between Mn point deviation, geometric center difference and condylar volume ratio. Conclusion: These results demonstrated that in the side with greater mandibular growth potential, the axis rotation in axial plane would be greater. In the side with lesser mandibular growth potential, the total condyle volume would be lesser, even though with large variation.

Efficacy assessment of laser Doppler imager in diagnosing the pulp vitality after dental trauma.

Background/purpose: This is the first paper evaluating the efficacy of laser Doppler imager in diagnosis of pulpal vitality. The purpose of this study was to evaluate and compare the diagnostic benefits of laser Doppler imaging and electric pulp test (EPT) in dental trauma. Materials and methods: Seven patients were selected for pulp vitality evaluation in Kaohsiung Medical University Hospital between 2018 and 2019. EPT and laser Doppler imager evaluation were performed for patients with traumatic injury to teeth. Statistical methods included the Kappa consistency test and the chi-square test. In addition, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used. Results: There was a significant difference in Doppler flow values between the severe trauma group and the mild trauma group, regardless of patient self-reported symptoms (P = 0.043) or physicians' diagnostic classification (P = 0.018). For an EPT instrument, the Kappa coefficient was 0.67 and 1-year pulpal status findings were highly consistent (P < 0.001). Using a Doppler instrument, the Kappa coefficient was 0.85. According to the ROC curve, the AUC for EPT was 0.94, the AUC for Doppler was 1, and the optimal cut-off value was 31.55, indicating that both were superior diagnostic tools. Conclusion: Both laser Doppler imager and EPT can be used as tools for diagnosing traumatic pulp necrosis. Doppler imaging instruments allow for a more timely and accurate assessment of pulp vitality in dental trauma. In the future, ongoing research and related training are necessary for interpretation of Doppler data.

Locating the Mandibular Lingula Using Cone-Beam Computed Tomography: A Literature Review.

This study aimed to review the literature on adult mandibular lingula (ML) locations and related distances determined using cone-beam computed tomography (CBCT). A search was conducted for studies on CBCT using the following databases: PubMed, Web of Science, and Embase. The search results were limited to studies published between 1970 and 2021. The inclusion criteria were the investigation of ML location, CBCT, and participants aged ≥18 years. Eligible studies were examined for the distances from the lingual tip to the anterior ramus border, posterior ramus border, sigmoid notch, inferior ramus border, and occlusal plane. Eight studies on CBCT qualified for inclusion in the study. The mean distances from the ML to the anterior ramus border were 15.57 to 20 mm. In most of these, the ML was located above the occlusal plane. No significant differences were observed in the location and related distances for the ML among patients of different sexes, ethnicities, or skeletal patterns.

Morphological Study of the Mandibular Lingula and Antilingula by Cone-Beam Computed Tomography.

The patterns of the lingula and antilingula are crucial surgical reference points for ramus osteotomy. Cone-beam computed tomography (CBCT) provides three-dimensional images, and patient radiation dose is significantly lower for CBCT than for medical CT. The morphology of the mandibular lingula and antilingula of ninety patients (180 sides) were investigated using CBCT. The lingula were classified as having triangular, truncated, nodular, and assimilated shapes. The antilingula were classified as having hill, ridge, plateau, and plain shapes. The patients' sex, skeletal patterns (Classes I, II, and III), and right and left sides were recorded. The most to least common lingula shapes were nodular (37.8%), followed by truncated (32.8%), triangular (24.4%), and assimilated (5%). The most to least common antilingulae were hill (62.8%), plain (18.9%), plateau (13.9%), and ridge (4.4%) patterns, respectively. The lingula and antilingula had identical patterns on both sides in 47 (52.2%) and 46 patients (51.1%), respectively. Sex and skeletal pattern were not significantly correlated to lingula and antilingula shapes. No significant correlation was observed between lingula and antilingula shapes.

Condylar and ramus volume in asymmetric and symmetric skeletal class III malocclusion: A cone-beam computed tomography study.

Background/purpose: Among the craniofacial structures, the mandible is the only bony structure with movable joints. Each part (including condyle process, coronoid process, and ramus) of mandible would interaction with the muscles and proceed different osteogenesis progress. The objective of this study was to evaluate the mandibles with symmetric and asymmetric skeletal Class III jaw relations by quantifying differences in the condyle process, coronoid process and ramus on CBCT (Cone-beam computer tomography) images. Our hypothesis was that CBCT would reveal no voluminal differences between deviated and non-deviated mandibular segments in asymmetric skeletal Class III. Materials and methods: CBCT imagines were collected from dental department, KMUH and then divided into symmetric Class III group (Menton deviation < 4mm) and asymmetric Class III group (Menton deviation≧4mm). The mandibular structure would be segmented to ramus, condylar and coronoid process. Each volume was measured. Independent t test was used for comparison between groups, and paired t test was applied for comparison between both segmented parts within each group. Results: Significant differences between deviation and non-deviation sides in the asymmetric group were found in condylar and ramus segments for volumetric quantitative measurements. There has no significant difference in ramus parts between groups. Significant greater condylar volume was found in non-deviation side of asymmetric group. Conclusion: The results demonstrated that in the side with greater mandible growth potential, the condylar and the ramus volume would be greater as well. CBCT is a useful and accurate modality for quantification and evaluation of mandibular asymmetry.

Non-Contrast-Enhanced MR Arteriography of Potential Living-Related Liver Donor: Using Contrast Enhanced CT Arteriography as Standard Reference.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the primary modalities to assess donors' vessels before transplant surgery. Radiation and contrast medium are potentially harmful to donors. PURPOSE: To compare the image quality and visualization scores of hepatic arteries on CTA and balanced steady-state free-precession (bSSFP) non-contrast-enhanced MRA (NC-MRA), and to evaluate if bSSFP NC-MRA can potentially be a substitute for CTA. STUDY TYPE: Prospective. POPULATION: Fifty-six consecutive potential living-related liver donors (30.9 ± 8.4 years; 31 men). FIELD STRENGTH/SEQUENCE: 1.5T; four bSSFP NC-MRA sequences: respiratory-triggered (Inhance inflow inversion recovery [IFIR]) and three breath-hold (BH); and CTA. ASSESSMENT: The artery-to-liver contrast (Ca-l) was quantified. Three radiologists independently assigned visualization scores using a four-point scale to potential origins, segments, and branches of the hepatic arteries, determined the anatomical variants based on Hiatt's classification, and assessed the image quality of NC-MRA sequences. STATISTICAL TESTS: Fleiss' kappa to evaluate the readers' agreement. Repeat measured ANOVA or Friedman test to compare Ca-l of each NC-MRA. Friedman test to compare overall image quality and visualization scores; post hoc analysis using Wilcoxon signed-rank test. P-value <0.05 was considered statistically significant. RESULTS: Inhance IFIR Ca-l was significantly higher than all BH bSSFP Ca-l (0.56 [0.45-0.64] vs. 0.37 [0.29-0.47] to 0.41 [0.23-0.51]). Overall image quality score of BH bSSFP TI1200 was significantly higher than other NC-MRA (4 [4-4] vs. 4 [3 to 4-4]). The median visualization scores of almost all arteries on CTA were significantly higher than on NC-MRA (4 [3 to 4-4] vs. 1 [1-2] to 4 [4-4]). The median visualization scores were all 4 [4-4 ] on Inhance IFIR with >92.3% observed scores ≥3, except the segment 4 branch (3 [1-4], 53.6%). The identification rates of arterial variants were 92.9%-97% on Inhance IFIR. DATA CONCLUSIONS: Although CTA is superior to the NC-MRA, all NC-MRA depict the donor arterial anatomy well. Inhance IFIR can potentially be an alternative image modality for CTA to evaluate the arterial variants of living donors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Bilateral theta-burst stimulation on emotional processing in major depressive disorder: A functional neuroimaging study from a randomized, double-blind, sham-controlled trial.

AIM: Bilateral theta-burst stimulation (biTBS; intermittent TBS over the left dorsolateral prefrontal cortex [DLPFC] and continuous TBS over the right DLPFC) has demonstrated efficacy in improving symptoms in patients with major depressive disorder (MDD). However, the underlying brain mechanisms remain unknown. The authors aimed to investigate the antidepressant efficacy of biTBS monotherapy and its effects on the brain responses measured by functional magnetic resonance imaging (fMRI) during emotional processing in MDD. METHODS: The authors conducted a double-blind, randomized, sham-controlled trial of patients with MDD who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode. Recruited patients were randomly assigned to 10 biTBS monotherapy or sham stimulation sessions. The fMRI scans during performing emotional recognition task were obtained at baseline and after 10 sessions of treatment. Depressive symptoms were assessed using the 21-item Hamilton Rating Scale for Depression at baseline and the weeks 4, 8, 12, 16, 20, and 24 week. RESULTS: The biTBS group (n = 17) exhibited significant decreases in depression scores compared with the sham group (n = 11) at week 8 (70% vs 40%; P = 0.02), and the significant differences persisted during the 24-week follow-up periods. At week 4, when the treatment course was completed, patients in the biTBS group, but not in the sham group, exhibited increased brain activities over the left superior and middle frontal gyrus during negative emotional stimuli. CONCLUSION: The authors' findings provide the first evidence regarding the underlying neural mechanisms of biTBS therapy to improve clinical symptoms in patients with MDD.

Stepwise Dual-Target Magnetic Resonance-Guided Focused Ultrasound in Tremor-Dominant Parkinson Disease: A Feasibility Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) has been applied successfully in treating refractory tremors in Parkinson disease (PD). It generates a precise thermal ablation in a specific nucleus or tract, such as ventral intermediate nucleus (VIM) or pallidothalamic tract (PTT). Despite a single lesion improving parts of the PD symptoms, the feasibility and efficacy of a stepwise dual-lesion in VIM and PTT are yet to be explored. METHODS: Three patients with tremor-dominant PD (aged 60.7 ± 6.0 years) received dual-target MRgFUS treatment with a series of primary and secondary outcome measures. The VIM and PTT were navigated based on individual magnetic resonance imaging planning of the brain. The primary outcome measures were the off-status Clinical Rating Scale for Tremor and Unified Parkinson's Disease Rating Scale part III (UPDRS-III). The secondary outcome measures included UPDRS I, II, IV, Hohen and Yahr score, Neuropsychiatry Inventory, Quality of life in PD Rating Scale, Non-Motor Symptoms Scale, and Clinical Global Impression. The baseline data were compared with those acquired 1 day and 1 month following the treatment. RESULTS: The severity of tremor and motor deficits represented by Clinical Rating Scale for Tremor-part B and UPDRS III were significantly improved (P < 0.05 by nonparametric Mann-Whitney U tests) after dual-target ablations. The nonmotor symptoms investigated by UPDRS II and Non-Motor Symptoms Scale also showed significant improvement at the 1-day and 1-month follow-up. There was no adverse effect except temporary procedure-related headache and dizziness during the treatment. CONCLUSIONS: Stepwise dual-lesion targeting VIM and PTT is a safe and effective MRgFUS therapeutic strategy for patients with PD.

The Dosage Effect of Laser Acupuncture at PC6 (Neiguan) on Heart Rate Variability: A Pilot Study.

Laser acupuncture (LA) has been more applicated in the clinical practice with good responses, but the dosage and parameter settings are still inconsistent with the arguments. This study is focused on the effect of LA on heart rate variability (HRV) with different energy density (ED). Based on the Arndt-Schulz law, we hypothesized that the effective range should fall within 0.01 to 10 J/cm2 of ED, and settings above 10 J/cm2 would perform opposite or inhibitory results. We recruited healthy adults in both sexes as subjects and choose bilateral PC6 (Neiguan) as the intervention points to observe the HRV indexes changes by an external wrist autonomic nerve system (ANS) watch on the left forearm. The data from the ANS watch, including heart rate, blood pressure, and ANS activity indexes, such as low frequency (LF), high frequency (HF), LF%, HF%, LF/HF ratio, and so on, were analyzed by the one-way ANOVA method to test the possible effect. In this study, every subject received all three different EDs of LA in a randomized order. After analyzing the data of 20 subjects, the index of HF% was upward and LF/HF ratio was downward when the ED was 7.96 J/cm2. Otherwise, the strongest ED 23.87 J/cm2 performed the opposite reaction. Appropriately, LA intervention could affect the ANS activities, with the tendency to increase the ratio of parasympathetic and decrease the ratio of sympathetic nerve system activities with statistically significant results, and different ED interventions are consistent with Arndt-Schulz law with opposite performance below and above 10 J/cm2.

Changes in Preexisting Temporomandibular Joint Clicking after Orthognathic Surgery in Patients with Mandibular Prognathism.

This study aimed to investigate the changes in preexisting temporomandibular joint (TMJ) clicking and the new incidence of TMJ clicking after orthognathic surgery. A total of 60 patients (30 men and 30 women) with mandibular prognathism underwent intraoral vertical ramus osteotomy (IVRO) for a mandibular setback. The setback amount and TMJ clicking symptoms (preoperative and one year postoperative) were recorded. To assess the risk of new incidence of TMJ clicking in asymptomatic patients, the cutoff value for postoperative mandibular setback was set at 8 mm. The left and right mandibular setbacks were 11.1 and 10.9 mm in men, respectively, and 10.7 and 10.0 mm in women, respectively. Thus, no difference in setback amount on either side was observed between the sexes. The improvement rate in patients with preexisting TMJ clicking was 69.2% (18 of 26 sides); the postoperative improvement rates were 71.4% (setback amount > 8 mm) and 60% (setback amount ≤ 8 mm). IVRO may reduce the severity of preexisting TMJ clicking. A high setback amount (>8 mm) may not be associated with a considerable increase in the risk of postoperative TMJ clicking.

Context-specific roles of diphthamide deficiency in hepatocellular carcinogenesis.

Diphthamide biosynthesis protein 1 (DPH1) is biochemically involved in the first step of diphthamide biosynthesis, a post-translational modification of eukaryotic elongation factor 2 (EEF2). Earlier studies showed that DPH1, also known as ovarian cancer-associated gene 1 (OVCA1), is involved in ovarian carcinogenesis. However, the role of DPH1 in hepatocellular carcinoma (HCC) remains unclear. To investigate the impact of DPH1 in hepatocellular carcinogenesis, we performed data mining from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. We found that reduced DPH1 levels were associated with advanced stages and poor survival of patients with HCC. Also, we generated hepatocyte-specific Dph1-deficient mice and showed that diphthamide-deficient EEF2 resulted in a reduced translation elongation rate in the hepatocytes and led to mild liver damage with fatty accumulation. After N-diethylnitrosamine (DEN)-induced acute liver injury, p53-mediated pericentral hepatocyte death was increased, and compensatory proliferation was reduced in Dph1-deficient mice. Consistent with these effects, Dph1 deficiency decreased the incidence of DEN-induced pericentral-derived HCC and revealed a protective effect against p53 loss. In contrast, Dph1 deficiency combined with Trp53- or Trp53/Pten-deficient hepatocytes led to increased tumor loads associated with KRT19 (K19)-positive periportal-like cell expansion in mice. Further gene set enrichment analysis also revealed that HCC patients with lower levels of DPH1 and TP53 expression had enriched gene-sets related to the cell cycle and K19-upregulated HCC. Additionally, liver tumor organoids obtained from 6-month-old Pten/Trp53/Dph1-triple-mutant mice had a higher frequency of organoid re-initiation cells and higher proliferative index compared with those of the Pten/Trp53-double-mutant. Pten/Trp53/Dph1-triple-mutant liver tumor organoids showed expression of genes associated with stem/progenitor phenotypes, including Krt19 and Prominin-1 (Cd133) progenitor markers, combined with low hepatocyte-expressed fibrinogen genes. These findings indicate that diphthamide deficiency differentially regulates hepatocellular carcinogenesis, which inhibits pericentral hepatocyte-derived tumors and promotes periportal progenitor-associated liver tumors. © 2022 The Pathological Society of Great Britain and Ireland.