Analysis of Loudness Discomfort Level Tests in Tinnitus Patients.

INTRODUCTION: We aimed to investigate the clinical significance of loudness discomfort level (LDL) test in tinnitus patients and its relationship with pure-tone audiometry, tinnitogram and questionnaires. METHODS: We retrospectively reviewed the medical records of 320 tinnitus patients who visited a tertiary university hospital's tinnitus clinic and completed LDL tests between March 2020 and December 2022. Epidemiological data and psychoacoustic test results were collected. RESULTS: LDL showed no significant differences between frequencies for both ears. Mean LDL did not correlate with mean pure-tone average or hearing thresholds at each frequency. The hearing loss group had higher LDL at 8 kHz compared to the normal hearing group (p<0.01). Objective sound intolerance was found in a quarter, correlating with subjective hyperacusis, anxiety, and depression. Weak negative correlations were found between most of questionnaire's scores and LDL on the left side. Tinnitus loudness weak negatively correlated with LDL at most frequencies, except 8 kHz. DISCUSSION/CONCLUSION: Our findings suggest a notable association between LDL levels and emotional factors in tinnitus patients, rather than with auditory thresholds. While lateralized differences in LDL responses were observed, specifically on the left side, these preliminary results do not confirm a causal link and thus do not warrant changes to current clinical testing protocols without further research.

Machine learning model for circulating tumor DNA detection in chronic obstructive pulmonary disease patients with lung cancer.

Background: Patients with chronic obstructive pulmonary disease (COPD) have a high risk of developing lung cancer. Due to the high rates of complications from invasive diagnostic procedures in this population, detecting circulating tumor DNA (ctDNA) as a non-invasive method might be useful. However, clinical characteristics that are predictive of ctDNA mutation detection remain incompletely understood. This study aimed to investigate factors associated with ctDNA detection in COPD patients with lung cancer. Methods: Herein, 177 patients with COPD and lung cancer were prospectively recruited. Plasma ctDNA was genotyped using targeted deep sequencing. Comprehensive clinical variables were collected, including the emphysema index (EI), using chest computed tomography. Machine learning models were constructed to predict ctDNA detection. Results: At least one ctDNA mutation was detected in 54 (30.5%) patients. After adjustment for potential confounders, tumor stage, C-reactive protein (CRP) level, and milder emphysema were independently associated with ctDNA detection. An increase of 1% in the EI was associated with a 7% decrease in the odds of ctDNA detection (adjusted odds ratio =0.933; 95% confidence interval: 0.857-0.999; P=0.047). Machine learning models composed of multiple clinical factors predicted individuals with ctDNA mutations at high performance (AUC =0.774). Conclusions: ctDNA mutations were likely to be observed in COPD patients with lung cancer who had an advanced clinical stage, high CRP level, or milder emphysema. This was validated in machine learning models with high accuracy. Further prospective studies are required to validate the clinical utility of our findings.

Traumatic Neuroma in the External Auditory Canal.

Traumatic neuroma is the reparative proliferation of axons and Schwann cells at the proximal end of a severed nerve following injury or surgery. Traumatic neuromas with or without clinical symptoms have rarely been reported in the external auditory canal. A 50-year-old woman with a history of trauma visited our otorhinolaryngology clinic with a 7 × 5-mm mass localized on the anterior wall of the external auditory canal. The mass was easily removed via surgical excision and was histopathologically diagnosed as a neuroma. No signs of recurrence were observed after excision. Herein, the authors present this case, along with a review of the literature.

Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma.

Purpose: The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear. Materials and Methods: We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes. Results: Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression. Conclusion: Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.

Initial Response to Combination Therapies for Tinnitus: Lessons Learned From a Retrospective Analysis.

OBJECTIVE: To investigate the initial reduction of tinnitus effects by combining common therapies applicable in general otology clinics and establishing optimal treatment strategies. STUDY DESIGN: Retrospective cohort study. SETTING: A tertiary university hospital. PATIENTS: Patients with nonpulsatile subjective tinnitus who visited the hospital between January and December 2022. INTERVENTIONS: Combination therapies consisting of at least one of the directive counseling based on the neurophysiological model, hearing aids, medication, and/or neuromodulation were performed. MAIN OUTCOME MEASURES: Tinnitus Handicap Inventory (THI) questionnaire at both their initial visit and 1-month follow-up. RESULTS: A total of 151 patients were enrolled. THI improvement of 20 points or more was observed in 31.8% of participants. One-way analysis of variance revealed that counseling had a significant reduction in THI, whereas neuromodulation, medication, and hearing aids did not. THI improvement was significantly associated with received counseling, severity of initial THI, and mean loudness discomfort level. Hearing aids and neuromodulation were not significant prognostic factors for improvement. CONCLUSION: Counseling alone is the best treatment for most patients with tinnitus. There will be other patients with tinnitus that, in addition to counseling, would benefit from hearing aids, medications, and/or certain forms of neuromodulation.

Clinical Features of Non-Lateralized Tinnitus.

BACKGROUND: We aimed to analyze and confirm the clinical features of patients with non-lateralized tinnitus and to identify clues that can be used in their management. METHODS: Data from 469 patients who visited a university hospital complaining of tinnitus between March 2020 and December 2021 were reviewed. The patients' medical histories, Tinnitus Handicap Inventory, Beck Depression Inventory, and numerical rating scale scores on tinnitus awareness, annoyance, loudness, and effect on life, audiological profiles, and quantitative electroencephalography findings were documented. RESULTS: Forty-nine (10.4%) patients had non-lateralized tinnitus. They were older and had a shorter duration of symptoms (13.91 ± 34.16 months) than patients with bilateral tinnitus (duration: 39.15 ± 80.82 months) (P -lt; .05). The accompanying symptoms, Tinnitus Handicap Inventory scores, and numerical rating scale scores were not significantly different between the 2 groups (P -gt; .05). Patients with non-lateralized tinnitus had worse hearing at 12 kHz on the left side than those with unilateral tinnitus. Hearing asymmetry was least common in non-lateralized tinnitus (n=11/49, 10.4%), followed by bilateral tinnitus (n=54/198, 42.2%) and unilateral tinnitus (n=97/222, 47.3%) (P-lt; .001). Regarding quantitative electroencephalography, there were significant differences in the absolute power of the theta, alpha, beta, gamma, and total frequency bands based on tinnitus lateralization (P -lt; .001). CONCLUSION: Non-lateralized tinnitus can be perceived in elderly patients with symmetric and extended high-frequency hearing loss before habituation is achieved at an early stage of tinnitus. However, there was no difference in the questionnaire scores and accompanying symptoms; therefore, it may not be worth managing non-lateralized tinnitus separately from tinnitus in the ear.

Exploring the origins of decreased sound tolerance in tinnitus patients.

This study aimed to confirm the characteristics of auditory function alterations in tinnitus patients with concomitant decreased sound tolerance (ST) and provide insights for developing tailored therapeutic approaches. A retrospective analysis was conducted on patient records from a tertiary university hospital's tinnitus clinic between March 2020 and June 2023. Demographic attributes and audiological profiles were reviewed. Patients were categorized into Group 1 if loudness discomfort level test outcomes were 77 dB or below, measured using an average of frequencies from 250 Hz to 8 kHz. The remaining patients were allocated to Group 2. Among the 434 tinnitus patients, 115 (26.5%) demonstrated decreased ST and were classified as Group 1. This group exhibited higher DPOAE amplitudes (p < 0.001), shortened latency, and decreased threshold of ABR wave V bilaterally (p < 0.05). No significant disparities were observed in gender, age, tinnitus handicap inventory, visual analog scale, and pure-tone audiometry results except subjective hyperacusis. Binary logistic regression analysis utilizing the forward conditional method revealed that the difference between groups was independently linked to DPOAE response at 7,277 Hz on the left side [B = 0.093, p < 0.001, EXP(B) = 1.07, 95% CI = 1.044-1.153]. Increased DPOAE amplitude and shorter and decreased ABR wave V in tinnitus patients with decreased ST might suggest a possible association with lesions in or around the superior olivary complex or higher central auditory pathway, potentially linked to the inhibition of medial olivocochlear efferents.

Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence.

Soybean (Glycine max) is an important ingredient of cuisines worldwide. While there is a wealth of evidence that soybean could be a good source of macronutrients and phytochemicals with health-promoting effects, concerns regarding adverse effects have been raised. In this work, we reviewed the current clinical evidence focusing on the benefits and risks of soybean ingredients. In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM. However, soybean had adverse effects on certain types of drug treatment and caused allergies. In sum, this work provides useful considerations for planning clinical soybean research and selecting dietary protein sources for human health.

DNA methylation biomarkers distinguishing early-stage prostate cancer from benign prostatic hyperplasia.

Background: DNA methylation markers are considered robust diagnostic features in various cancer types, as epigenetic marks are commonly altered during cancer progression. Differentiation between benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PCa) is clinically difficult, relying on the information of the patient's symptoms or levels of prostate-specific antigen. Methods: A total of 42 PCa patients and 11 BPH patients were recruited. Genomic DNA was purified from tissues and used for the library preparation of the target-enriched methylome with enzymatic conversion and a Twist 85 Mbp EM-seq panel. Paired-end sequencing (150 bp) was performed using NovaSeq 6000 or NextSeq 550. After quality control, including adapter trimming and de-duplication of raw sequencing data, differential methylation patterns were analyzed between the BPH and PCa groups. Results: We report DNA methylation patterns existing between BPH and PCa. The major finding is that broad hypermethylation occurred at genic loci in PCa tissues as compared to the BPH. Gene ontology analysis suggested that hypermethylation of genic loci involved in chromatin and transcriptional regulation is involved in cancer progression. We also compared PCa tissues with high Gleason scores to tissues with low Gleason scores. The high-Gleason PCa tissues showed hundreds of focal differentially methylated CpG sites corresponding to genes functioning in cancer cell proliferation or metastasis. This suggests that dissecting early-to-advanced-grade cancer stages requires an in-depth analysis of differential methylation at the single CpG site level. Conclusions: Our study reports that enzymatic methylome sequencing data can be used to distinguish PCa from BPH and advanced PCa from early-stage PCa. The stage-specific methylation patterns in this study will be valuable resources for diagnostic purposes as well as further development of liquid biopsy approaches for the early detection of PCa.

Short-Term Effect of Adjunctive Transcranial Random Noise Stimulation on Idiopathic Sudden Sensorineural Hearing Loss and Tinnitus: A Preliminary Study.

BACKGROUND: Transcranial random noise stimulation has previously been used to manage tinnitus. This study assessed the feasibility of adjuvant transcranial random noise stimulation with conventional steroid treatment for idiopathic sudden sensorineural hearing loss with or without tinnitus. METHODS: Prospective, randomized, single-blind study was conducted in Eulji University hospital. Twenty-four patients with idiopathic sudden sensorineural hearing loss were admitted for treatment between March 2019 and February 2020. The study group received 4 sessions of adjuvant transcranial random noise stimulation (frequency band: 0.1-100 Hz; target, T7/T8; duration: 20 minutes), while the control group received only conventional treatment. Hearing levels at admission, discharge day (day 7), and 4 weeks later and clinical characteristics were assessed. The primary outcome measure was hearing improvement at 4 weeks after neuromodulation. The secondary outcome measure was the presence of tinnitus at 4 weeks. RESULTS: The mean hearing thresholds improved significantly over time (P < .05). Although initial hearing levels did not differ between the 2 groups, the study group had a significantly better hearing at 4 weeks after discharge (P > .05). A significant interaction was also observed between the mean hearing thresholds at various timepoints and transcranial random noise stimulation (P=.001). However, the persistence of tinnitus after treatment did not differ irrespective of the allocation groups. CONCLUSION: Adjuvant transcranial random noise stimulation seems to be a potential treatment option for hearing restoration in patients with idiopathic sudden sensorineural hearing loss without serious complications. However, transcranial random noise stimulation does not seem to alleviate tinnitus.

Evaluation of the efficacy and safety of conventional and interlaminar full-endoscopic decompressive laminectomy to treat lumbar spinal stenosis (ENDO-F trial): Protocol for a prospective, randomized, multicenter trial.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

Orobol, 3'-hydroxy-genistein, suppresses the development and regrowth of cutaneous SCC.

Chronic solar ultraviolet exposure is a major risk factor for cutaneous squamous cell carcinoma (cSCC), which is the second most common type of skin cancer. Our previous data showed that total protein and phosphorylation levels of T-LAK cell-originated protein kinase (TOPK) were enhanced in solar-simulated light (SSL)-induced skin carcinogenesis and overexpressed in actinic keratosis (AK) and cSCC human skin tissues compared to those in matched normal skin. Thus, targeting TOPK activity could be a helpful approach for treating cSCC. Our data showed that orobol directly binds to TOPK in an ATP-independent manner and inhibits TOPK kinase activity. Furthermore, orobol inhibited anchorage-independent colony formation by SCC12 cells in a dose-dependent manner. After discontinuing the treatment, patients commonly return to tumor-bearing conditions; therefore, therapy or intermittent dosing of drugs must be continued indefinitely. Thus, to examine the efficacy of orobol against the development and regrowth of cSCC, we established mouse models including prevention, and therapeutic models on the chronic SSL-irradiated SKH-1 hairless mice. Early treatment with orobol attenuates chronic SSL-induced cSCC development. Furthermore, orobol showed therapeutic efficacy after the formation of chronic SSL irradiation-induced tumor. In the mouse model with intermittent dosing of orobol, our data showed that re-application of orobol is effective for reducing tumor regrowth after discontinuation of treatment. Moreover, oncogenic protein levels were significantly attenuated by orobol treatment in the SSL-stimulated human skin. Thus, we suggest that orobol, as a promising TOPK inhibitor, could have an effective clinical approach to prevent and treat the development and regrowth of cSCC.

Ultrafast prediction of somatic structural variations by filtering out reads matched to pan-genome k-mer sets.

Variant callers typically produce massive numbers of false positives for structural variations, such as cancer-relevant copy-number alterations and fusion genes resulting from genome rearrangements. Here we describe an ultrafast and accurate detector of somatic structural variations that reduces read-mapping costs by filtering out reads matched to pan-genome k-mer sets. The detector, which we named ETCHING (for efficient detection of chromosomal rearrangements and fusion genes), reduces the number of false positives by leveraging machine-learning classifiers trained with six breakend-related features (clipped-read count, split-reads count, supporting paired-end read count, average mapping quality, depth difference and total length of clipped bases). When benchmarked against six callers on reference cell-free DNA, validated biomarkers of structural variants, matched tumour and normal whole genomes, and tumour-only targeted sequencing datasets, ETCHING was 11-fold faster than the second-fastest structural-variant caller at comparable performance and memory use. The speed and accuracy of ETCHING may aid large-scale genome projects and facilitate practical implementations in precision medicine.

The Tinnitus Handicap Inventory is a better indicator of the overall status of patients with tinnitus than the Numerical Rating Scale.

OBJECTIVES: The Tinnitus Handicap Inventory (THI) and Numerical Rating Scale (NRS) for awareness, annoyance, loudness, and effect on life are two of the most commonly used questionnaires for patients with tinnitus. This study aimed to determine whether these two questionnaires can comprehensively evaluate the patient's condition and which questionnaire is better as a primary endpoint for tinnitus. MATERIALS AND METHODS: Data from 90 patients who visited a university hospital with subjective, non-pulsatile tinnitus and without a history of any psychiatric disorders were reviewed between March 2020 and May 2022. The patients' medical histories, audiological profiles, questionnaires including the THI and NRS, Beck Depression Inventory (BDI), Beck Anxiety Depression (BAI), Hospital Anxiety-Depression Scale (HAD), and the Brief Encounter Psychosocial Instrument (BEPSI) were analyzed. RESULTS: The THI had a moderately positive correlation with the NRS for effect on life, annoyance, and loudness. It also had a low positive correlation with the BDI, HAD-A, BEPSI, and BAI. Considering annoyance and loudness, the NRS did not correlate with the other questionnaires, except for the THI (p > 0.05). The NRS for tinnitus awareness correlated with most audiological profiles. The ROC curve analysis revealed that the THI significantly predicted depression, anxiety, and stress. Conversely, none of the four NRS items significantly predicted these psychiatric problems (p > 0.05). CONCLUSIONS: Using the THI as a primary endpoint after interventions rather than the NRS is more reasonable because the THI covers the emotional, functional, and catastrophic aspects of tinnitus, although not the audiological status. To compensate for this, the auxiliary use of NRS for awareness should also be considered.

Clinical Findings That Differentiate Co-Occurrence of Hyperacusis and Tinnitus from Tinnitus Alone.

PURPOSE: We aimed to assess the characteristics of patients with concurrent tinnitus and hyperacusis, determine the best audiological criteria for predicting hyperacusis, and confirm whether objective evidence of changes in the brain exists. MATERIALS AND METHODS: The medical records of patients with tinnitus who visited the hospital between March 2020 and December 2021 were reviewed. Data on accompanying hyperacusis, audiological profiles, and questionnaires including the Tinnitus Handicap Inventory (THI), Beck Depression Inventory, and numerical rating scale were analyzed. Resting-state quantitative electroencephalography (qEEG) using power spectral density (PSD) and event-related spectral perturbation (ERSP) were performed to objectively quantify changes in the brain. RESULTS: A total of 194 patients were analyzed. Among them, 51 (26.3%) reported combined subjective hyperacusis with tinnitus. However, the proportions widely varied from 7.4% to 68.4% based on three audiological criteria for assessment. A higher score on the THI questionnaire was independently associated with the co-occurrence of tinnitus and hyperacusis. Fair agreement was observed between subjective hyperacusis and the audiological criterion based on a loudness discomfort level (LDL) of ≤90 dB at two or more frequencies for the diagnosis of hyperacusis. An increased beta-PSD and decreased levels of gamma-PSD, all-ERSP, and delta-ERSP were observed in patients with hyperacusis (p<0.05). CONCLUSION: Patients with co-occurring tinnitus and hyperacusis had more severe tinnitus distress. An LDL of ≤90 dB at two or more frequencies may be applicable to predict accompanying hyperacusis in subjects with tinnitus, and qEEG also provides more objective information.

Measures of Subjective Tinnitus: What Does Visual Analog Scale Stand for?

BACKGROUND: Patients with tinnitus may have different severity levels of tinnitus distress. Visual analog scale (VAS) is a simple method to measure the extent of subjective distress caused by tinnitus. It includes ratings of tinnitus loudness, awareness, annoyance, and impact of tinnitus on life. PURPOSE: The purpose of this study was to evaluate what led to different distress levels in patients with bilateral tinnitus by analyzing the relationships among all subscales of VAS scores for tinnitus distress and the documented variables. RESEARCH DESIGN: This study was a retrospective cohort study. STUDY SAMPLE: The medical records of 268 patients who visited a tinnitus clinic between March and December 2020 were reviewed. DATA COLLECTION AND ANALYSIS: Epidemiologic characteristics, subjective tinnitus distress factors including tinnitus loudness, awareness, annoyance, and impact of tinnitus on life, questionnaire results including those from the Tinnitus Handicap Inventory (THI) and Beck Depression Inventory (BDI), and audiometric profiles were documented. Based on a bivariate analysis between variables and subtypes of subjective tinnitus distress, stepwise logistic regression was performed to identify potential influencing factors for aggravating each subtype. RESULTS: Data from a total of 122 patients with bilateral tinnitus were collected. The cohort included 77 males and 45 females with a mean age of 51.16 ± 13.50 years. Tinnitus loudness was associated with an accompanying headache (p < 0.001), the BDI score (p = 0.001), and the duration of tinnitus (p = 0.006). A high THI (p < 0.001) and an accompanying headache (p = 0.016) were both associated with tinnitus annoyance. Hearing thresholds at 250 Hz (p = 0.011) and 500 Hz (p = 0.002) on the left side were associated with an impact of tinnitus on life. The hearing threshold at 4 kHz on the left side alone was associated with tinnitus awareness (p = 0.013). CONCLUSION: Psychologic complaints are mainly associated with tinnitus loudness and annoyance. On the other hand, hearing loss is linked with tinnitus awareness and its impact on life. Thus, an individualized, sequential approach that considers different subtypes of tinnitus severity to assess subjective tinnitus distress is needed.

Accuracy of 3D printed models and implant-analog positions according to the implant-analog-holder offset, inner structure, and printing layer thickness: an in-vitro study.

PURPOSE: This study aimed to determine how the implant-analog-holder (IAH) offset, inner structure, and printing layer thickness influence the overall accuracy and local implant-analog positional changes of 3D printed dental models. METHODS: Specimens in 12 experimental groups (8 specimens per group) with different IAH offsets, inner structures, and printing layer thicknesses were printed in three dimensions using an LCD printer (Phrozen Shuffle) and digitized by a laboratory scanner (Identica T500). The trueness and precision of the printed model as well as the angular distortion, depth deviation, and linear distortion of the implant analog were evaluated using three-way ANOVA. RESULTS: The positional accuracy was significantly higher for IAH offsets of 0.04 mm and 0.06 mm than for one of 0.08 mm, for a hollow than a solid inner structure, and for a printing layer thickness of 100 µm than for one of 50 µm (all P<.001). CONCLUSIONS: The accuracies of the 3D printed models and the implant-analog positions were significantly affected by the IAH offset, inner structure, and printing layer thickness. CLINICAL SIGNIFICANCE: Given the observation of this study, premeditating the IAH offset of 0.06 mm, hollow inner structure, and printing layer thickness of 100 µm before printing can help clinicians reach the optimum overall printing accuracy and minimum the local positional changes of the implant-analogs.