Targeted deep sequencing reveals genomic alterations of actinic keratosis/cutaneous squamous cell carcinoma in situ and cutaneous squamous cell carcinoma.

Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer-related genes with a median coverage of 515× for AK (N = 9), CIS (N = 9), cSCC lesions (N = 13), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK/CIS. Driver mutations were found in TP53 (81%), NOTCH1 (32%), RB1 (26%) and CDKN2A (19%). All AK/CIS and cSCC lesions (93.5%), except two, harboured TP53 or NOTCH1 mutations, some of which were known oncogenic mutations or reported mutations in normal skin. RB1 driver mutations were found in CIS/cSCC (36.4%) but not in AK. CDKN2A driver mutations were found more frequently in cSCC (30.8%) than in AK/CIS (11.1%). Among recurrent (≥3 samples) CNAs (gain in MYC and PIK3CA/SOX2/TP63; loss in CDKN2A and RB1), MYC (8q) gain and CDKN2A (9p) loss were more frequently detected in cSCC (30.8%) than in AK/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK/CIS and cSCC. Our study revealed that AK/CIS lesions harbour prevalent TP53 or NOTCH1 mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK/CIS lesions.

Psychological Stress in Parents of Children with Atopic Dermatitis: A Cross-sectional Study from the Korea National Health and Nutrition Examination Survey.

Atopic dermatitis is a chronically relapsing inflammatory skin condition that has profound impacts on quality of life of patients and their family. The aim of this study is to investigate the psychological stress in parents of children with atopic dermatitis in Korea, using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included parents of participants under 19 years of age (970 with atopic dermatitis and 5,733 without atopic dermatitis after excluding those who meet the exclusion criteria) from the 2009 to 2012 KNHANES. The psychological stress state was evaluated with the following four questionnaire items: self-perception of stress, depressed mood, suicidal ideation, and diagnosis of depression by a physician. After adjusting for age, gender, education level, occupation, and marital status, logistic regression analyses indicated that mothers of children with atopic dermatitis had a higher frequency of stress perception (adjusted odds ratio (aOR) 1.46 (95% confidence interval (95% CI) 1.22-1.74), p < 0.01) and suicidal ideation (aOR 1.40 (95% CI 1.1-1.79), p < 0.01) than those without atopic dermatitis. In contrast, fathers of children with atopic dermatitis did not show a significant difference in all items compared with those of children without atopic dermatitis. Understanding the psychological stress in parents of children with atopic dermatitis is important for clinicians, since evaluation, management and support for parents, especially mothers, of children with atopic dermatitis are required.

Impact of COVID-19 on ophthalmic medical access during successive waves: Demographics, disease factors, and wave locations.

BACKGROUND: The coronavirus disease (COVID-19) pandemic significantly impacted medical care, including ophthalmology. This study aimed to identify factors associated with reduced ophthalmic medical access during the pandemic. METHODS: This nationwide population-based cohort study analysed South Korean health insurance claims data from January 2019 to November 2021. Outpatient visits and surgeries for age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal detachment during the two pandemic waves were compared with those in the non-pandemic period. Poisson regression was used to estimate incidence rate ratios and changes in outpatient visits and surgeries between waves concerning patient age, sex, residential location, and health insurance type. RESULTS: Outpatient visits for five eye diseases decreased in the first wave (0.733-0.985, P < 0.001). In the second wave, only outpatient visits for age-related macular degeneration, cataract, and glaucoma decreased (0.754, 0.878, and 0.874, respectively, all P < 0.001). Age-related macular degeneration, cataract, and glaucoma surgeries were significantly reduced in the first wave (0.829, P < 0.001; 0.836, P < 0.001; 0.904, P = 0.030, respectively). Age-related macular degeneration (0.852) and cataract (0.716) surgeries dropped in the second wave. Women and elderly (>65 years) patients curtailed outpatient visits and surgeries more throughout the pandemic and were less resilient during the second wave. Wave location was also related to outpatient visits and surgeries. CONCLUSIONS: The COVID-19 pandemic decreased outpatient visits and surgeries for eye diseases, with more significant impact on women, older patients, and those residing near wave locations. These findings can inform healthcare policies to minimise future pandemic impacts on healthcare delivery.

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases.

BACKGROUND: Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data. METHODS: Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR. RESULTS: After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59-0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54-0.88 and HR 0.74; CI 0.55-0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62-0.98). CONCLUSIONS: In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Current Issues in Treatment of Parotid Gland Cancer and Advanced Surgical Technique of Robotic Parotidectomy.

PURPOSE OF REVIEW: This paper analyzed previous research data to identify the most important issues to be considered during treatment of parotid gland cancer (PGC) and reviewed recent advancements in techniques in parotid surgery. RECENT FINDINGS: For successful treatment of PGC, a preoperative surgical plan should be designed with consideration of the histologic characteristics and anatomical complexity of the tumor, and the functional and anatomical integrity of the facial nerve should be carefully inspected during surgery and damage to the nerve minimized. The need for adjuvant radiotherapy should be determined based on intraoperative findings and pathologic findings of the specimen after surgery. Surgery and radiotherapy are the main treatment options for PGC. To optimize treatment outcomes for PGC, the extent of surgery should be decided according to histologic characteristics and extent of tumor resection, and use of adjuvant radiotherapy should be considered based on risk stratification.

Leukaemia Cutis: Clinical Features and Outcomes of 56 Patients.

Leukaemia is a malignant neoplasm of the haematopoietic system. Cutaneous manifestations of leukaemia are called leukaemia cutis, and are regarded as a sign of poorer prognosis and shorter survival time. A single-institution retrospective review was performed of medical records of patients diagnosed with leukaemia cutis in the dermatology department of Seoul St Mary's Hospital between January 2012 and April 2021. Fifty-six cases with cutaneous leukaemic involvement and underlying haematological malignancy were included (40 acute myelogenous leukaemia, 8 acute lymphoblastic leukaemia, 3 chronic myeloid leukaemia, 2 chronic lymphocytic leukaemia, and 3 myelodysplastic syndrome). Male-female ratio 1.9:1, mean age at diagnosis 45.8 years. Plaques (28%) and papules (27%) were the most common skin lesions, followed by patches (18%) and nodules (16%). Mean time from diagnosis of leukaemia to development of leukaemia cutis was 12.3 months. Forty-six patients (84%) died during the 7-year follow-up; mean time from diagnosis of leukaemia cutis to death was 5.4 months. The results suggest that leukaemia cutis is associated with poor outcomes in patients with leukaemia. Comprehensive skin examination of these patients may help diagnose leukaemia cutis early, enabling prompt treatment.

Controllable fabrication of silver-deposited polyurethane acrylate nanopillar array film as a flexible surface-enhanced Raman scattering (SERS) substrate with high sensitivity and reproducibility.

A controllable method for fabricating flexible surface-enhanced Raman scattering (SERS) substrates is demonstrated by depositing silver onto a flexible nanopillar array film. The flexible nanopillar array film was cost-effectively prepared by replicating an anodic aluminum oxide (AAO) template with UV-curable polyurethane acrylate (PUA) over a large area. Then, the deposition of silver was done by an Ar-assisted thermal evaporation. In the deposition process, the partial pressure of Ar was optimized because it has a significant influence on the SERS intensity through the microstructural changes of silver deposited on PUA nanopillars. In addition, the increase in the nanopillar diameter and height enhanced the SERS intensity obtained at 785-nm excitation because of the increased number of hot spots. However, the agglomeration of Ag-deposited nanopillars, which is caused by high aspect ratios, negatively affected the SERS performance in terms of intensity and standard deviation. The optimized Ag-deposited nanopillar array film with nanopillar diameters and heights of 80 nm and 200 nm exhibited excellent SERS sensitivity and signal reproducibility with stable mechanical flexibility. For application in food and biomedical analysis, it was used for detecting saccharin and peptide and showed a good linear relationship between the SERS intensity and concentration. These findings demonstrate the suitability of our method for the controllable fabrication and optimization of flexible SERS substrates with high sensitivity and reproducibility.

Linear Vertigo in Benign Paroxysmal Positional Vertigo: Prevalence and Mechanism.

This study aimed to determine the prevalence and mechanism of linear vertigo reported by the patients during the attacks of benign paroxysmal positional vertigo (BPPV). We prospectively evaluated the characteristics (rotational vs. linear) of positional vertigo in 70 patients with posterior and horizontal canal BPPV using a questionnaire allowing multiple choices. In patients with linear vertigo, we further assessed the directionality of linear vertigo. We adopted the velocity-storage model to explain the occurrence and direction of linear vertigo in these patients with BPPV. Patients reported only rotational vertigo in 46 (46/70, 65.7%), only linear vertigo in 10 (14.3%), and both rotational and linear vertigo in 14 (20%). The patients experienced fear from rotational vertigo in 54 (54/70, 77.1%) and from linear vertigo in 20 (20/70, 28.6%). The direction of linear vertigo was concordant with the direction of inertial acceleration predicted by the velocity-storage model. Patients with BPPV may experience linear as well as rotational vertigo during the attacks. This linear vertigo may be ascribed to centrally estimated inertial acceleration.

Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus E7 from Suppressing Interferon-Stimulated Genes.

Human papillomavirus (HPV) in high-risk groups is known to suppress the type I interferon (IFN) signaling pathway leading to the transcription of interferon-stimulated genes (ISGs), which have many antiviral functions. However, the effects of HPV on the action of various ISGs in low-risk groups are not fully understood. We aimed to investigate whether antiviral ISGs are expressed in transfected keratinocytes with type 2 HPV (HPV-2) E7. The mRNA and protein expressions of ISGs and type I IFN signaling pathway components were evaluated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and/or immunohistochemistry. Compared with normal skin, mRNA expression of all ISGs in HPV-2 positive cutaneous warts was significantly decreased (p < 0.05). In comparison with empty vector transfection, E7 transfection significantly down-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly up-regulated by E7 siRNA transfection (p < 0.05). Interestingly, epigallocatechin-3-gallate (EGCG) pretreatment up-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly down-regulated by E7 transfection (p < 0.05). Our results demonstrate that EGCG is a potential candidate for cutaneous wart prevention.

Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

BACKGROUND: Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. METHODS: We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. RESULTS: All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-ß signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). CONCLUSION: Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.

Correction: Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. METHODS: We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model. RESULTS: We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73-4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2 = 97.49%). CONCLUSION: In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.

Comparison of Surgical Outcomes of Robotic and Conventional Approaches in Patients with Pre- and Poststyloid Parapharyngeal Space Tumors.

BACKGROUND: Benefits and drawbacks of robotic surgical approaches for parapharyngeal space (PPS) tumors remain undetermined. The purpose of this study is to compare surgical outcomes of PPS tumor patients who underwent robotic surgery with those of patients who received conventional surgical treatment. PATIENTS AND METHODS: We retrospectively analyzed clinicopathologic data from 136 patients who underwent surgical removal of PPS tumors via conventional or robotic approaches. RESULTS: We identified PPS tumors in pre- and poststyloid regions in 87 (64%) and 49 (36%) patients, respectively. There were 48 (35.3%) pleomorphic adenomas, 36 (26.5%) schwannomas, and 24 (17.6%) paragangliomas. Conventional surgical techniques were performed in 83 patients, and robotic surgical approaches were administered to 53 patients. Transcervical-parotid and transcervical approaches were most commonly performed in conventional surgery, while transoral and retroauricular approaches were the preferred surgical methods in robotic surgery for pre- and poststyloid PPS tumors, respectively. Robotic surgery resulted in less estimated blood loss during poststyloid PPS tumor surgery. Postoperative cranial nerve complications were noted in 36 of 83 cases (43.4%) in the conventional surgery group and in 17 of 53 cases (32.1%) in the robotic surgery group. Intraoperative tumor spillage of pleomorphic adenoma showed no significant differences between the two groups (13.6% in conventional vs. 15.4% in robotic surgery). The mean follow-up time was 4.9 ± 3.4 years, and recurrences were observed in two patients during follow-up without a significant difference between the two groups (4.5% in conventional vs. 3.8% in robotic surgery). CONCLUSIONS: Robotic surgery in PPS tumors is feasible through transoral, retroauricular, or combined approaches and provides treatment outcomes comparable to those of conventional open surgery.

Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer.

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.

Height Is Associated with Dyslipidemia in Korean Premenopausal Women: Data from the Korea National Health and Nutrition Examination Survey.

BACKGROUND: The association between height and cardiovascular disease (CVD) has been reported in epidemiological studies for decades; however, the mechanism for this relationship is still unclear. We previously reported that dyslipidemia was associated with adult height in Korean men without CVD. OBJECTIVES: This study explored the potential -relationship between height and dyslipidemia in premenopausal women. METHODS: This study used data from the 2007-2016 Korea National Health and Nutritional Examination Survey (KNHANES). We identified 16,361 premenopausal women aged ≥19 years without a history of CVD (myocardial infarction/stroke) or cancer. Fasting total cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels were measured. Dyslipidemia was further classified as hypercholesterolemia (total cholesterol level ≥240 mg/dL or treatment with lipid-lowering medications), hypertriglyceridemia (triglyceride level ≥200 mg/dL), and low HDL-C (HDL-C level <40 mg/dL). Subjects were divided into four groups by their height (<155, 155-159.9, 160-164.9, and ≥165 cm), and the prevalence of dyslipidemia was compared. RESULTS: Multiple regression analysis revealed that short premenopausal women had a higher likelihood of hypercholesterolemia (ptrend = 0.002), hypertriglyceridemia (ptrend = 0.010), and low HDL-C (ptrend = 0.002) when adjusted for age, comorbidities, waist circumference, health-related habits, and economic status. CONCLUSION: There was a dose-dependent correlation between adult height and adverse lipid profile in premenopausal Korean women who did not have CVD. This finding could serve as further evidence that dyslipidemia can be a link between shortness and CVD.

Preserved Serotonergic Activity in Early-Onset Parkinson's Disease.

BACKGROUND: Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson's disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment. METHODS: A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson's Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications. RESULTS: The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, -0.61 ± 0.61: -1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, -1.457 ± 1.078: -0.904 ± 0.812, p = 0.0018). CONCLUSIONS: Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.

Coronectomy of Mandibular Third Molar: Four Years of Follow-Up of 130 Cases.

Inferior wisdom teeth extraction surgery may have some complications that, in some cases, could be prevented by a correct diagnosis and minimal surgery. Coronectomy is a technique used for wisdom teeth surgery where only the crown is extracted and the root/roots are left in situ. This procedure may be controversial, but it could limit the common risks of the extraction procedure. Nowadays, the indication and contraindication of this technique are debated, and clinicians normally extract the entire tooth. The following case series includes the data and follow-up radiographs of 130 patients who received a coronectomy, reporting the safety of the procedure. After a mean follow-up period of four years, no complications occurred. A total of 13 patients showed mobile roots but had no complications or symptoms. The roots migrated in a mesial or coronal direction in 31 patients; in 4 cases, they were removed because of patient preference. Coronectomy is a useful oral surgical procedure in certain complicated cases of mandibular wisdom tooth extraction.

Corneal topography and angle parameters after laser iridotomy combined with iridoplasty assessed by dual Scheimpflug analyzer.

PURPOSE: To investigate the changes in corneal topography including parameters such as corneal curvature and corneal aberrations, along with anterior chamber angle (ACA) after laser iridotomy (LI) combined with peripheral iridoplasty (PI) using dual Scheimpflug analyzer. METHODS: In this prospective observational study, dual Scheimpflug analyzer images were acquired before and 1 week after LI plus PI. Corneal curvature of both axial and instantaneous maps from anterior and posterior surface, respectively, and total corneal power (TCP) were acquired. These corneal parameters from three zones (central, middle, and peripheral) and total corneal wavefront aberration, trefoil, and coma were obtained. The ACA from four quadrants, anterior chamber depth (ACD), anterior chamber volume (ACV), and intraocular pressure (IOP) were also inspected. RESULTS: ACD increased significantly from 2.15 ± 0.25 to 2.18 ± 0.24 mm (P = 0.002). ACV and ACA from all four quadrants increased significantly after the laser treatment (all P < 0.05). IOP decreased significantly from 16.9 ± 3.1 to 14.7 ± 2.9 mmHg following LI plus PI (P = 0.000). No significant changes were detected in corneal axial and instantaneous curvature from three zones on the anterior and posterior corneal surface after LI plus PI (all P > 0.05). The TCP, total corneal wavefront aberration, trefoil, and coma also revealed no significant changes after the laser procedure (all P > 0.05). CONCLUSIONS: Treatment with LI combined with PI did not affect the corneal topographic parameters from both anterior and posterior surfaces. However, LI plus PI improved ACA parameters significantly and effectively.

Differences in theta coherence between spatial and nonspatial attention using intracranial electroencephalographic signals in humans.

A number of previous studies revealed the importance of the frontoparietal network for attention and preparatory top-down control. Here, we investigated the theta (7-9 Hz) coherence of the right frontoparietal networks to explore the differences in connectivity changes for the right frontoparietal regions during spatial attention (i.e., attention to a specific location rather than a specific feature) and nonspatial attention (i.e., attention to a specific feature rather than a specific location) tasks. The theta coherence in both tasks was primarily maintained at a preparatory state, decreases after stimulus onset, and recovers to the level of the preparatory state after the response time. However, the theta coherence of the frontoparietal network during spatial attention was immediately maintained after cue-onset, whereas for the case of nonspatial attention, it was immediately decreased after cue-onset. In addition, the connectivity of the right frontoparietal network, including the middle frontal gyrus and superior parietal lobe, were significantly higher for spatial attention rather than for nonspatial attention, suggesting that the dorsal parts of right frontoparietal network are more engaged in spatial-specific attention from the preparatory state. These findings also suggest that these two attention systems involve the use of different regional connectivity patterns, not only in the cognitive state, but in the preparatory state as well.

PI3Kδ Is a Therapeutic Target in Hepatocellular Carcinoma.

Class I phosphoinositide 3-kinase (PI3K) signaling is a major pathway in human cancer development and progression. Among the four PI3K isoforms, PI3Kα and PI3Kß are ubiquitously expressed, whereas PI3Kγ and PI3Kδ are found primarily in leukocytes. Until now, PI3K targeting in solid tumors has focused on inhibiting PI3Kα-mediated and PI3Kß-mediated cancer cell-intrinsic PI3K activity. The role of PI3Kδ in solid tumors is unknown. Here, we evaluated the effects of PI3Kδ using established hepatocellular carcinoma (HCC) cells, malignant hepatocytes derived from patients with advanced HCC, murine models, and HCC tissues using RNA sequencing, quantitative PCR, immunoblotting, immunofluorescence, microarray, liquid chromatography-tandem mass spectrometry, and kinase assay. We established a chemical carcinogenesis model of liver malignancy that reflects the malignant phenotype and the in vivo environment of advanced HCC. In this in vivo advanced HCC-mimic system using HCC cells treated with hydrogen peroxide (H2 O2 ), we showed that H2 O2 selectively increases PI3Kδ activity while decreasing that of other class I PI3Ks. Blocking PI3Kδ activity with a PI3Kδ inhibitor or small interfering RNA-mediated PI3Kδ gene silencing inhibited HCC-cell proliferation and dampened key features of malignant HCC, including the up-regulation of telomerase reverse transcriptase (TERT). Mechanistically, H2 O2 induced oxidative modification of the serpin peptidase inhibitor, serpin peptidase inhibitor (SERPINA3), blocking its ubiquitin-dependent degradation and enhancing its activity as a transcriptional activator of PI3Kδ and TERT. High PI3Kδ levels in HCC were found to correlate with poor survival rates, with human advanced HCC showing positive correlations between the protein levels of oxidized SERPINA3, PI3Kδ, and TERT. Thus, PI3Kδ plays significant roles in malignant liver tumors. Conclusion: Our data identify PI3Kδ inhibition, recently approved for the treatment of human B-cell malignancies, as a potential treatment for HCC.