Cold to Hot: Tumor Immunotherapy by Promoting Vascular Normalization Based on PDGFB Nanocomposites.

Immunotherapy is a promising cancer therapeutic strategy. However, the "cold" tumor immune microenvironment (TIME), characterized by insufficient immune cell infiltration and immunosuppressive status, limits the efficacy of immunotherapy. Tumor vascular abnormalities due to defective pericyte coverage are gradually recognized as a profound determinant in "cold" TIME establishment by hindering immune cell trafficking. Recently, several vascular normalization strategies by improving pericyte coverage have been reported, whereas have unsatisfactory efficacy and high rates of resistance. Herein, a combinatorial strategy to induce tumor vasculature-targeted pericyte recruitment and zinc ion-mediated immune activation with a platelet-derived growth factor B (PDGFB)-loaded, cyclo (Arg-Gly-Asp-D-Phe-Lys)-modified zeolitic imidazolate framework 8 (PDGFB@ZIF8-RGD) nanoplatform is proposed. PDGFB@ZIF8-RGD effectively induced tumor vascular normalization, which facilitated trafficking and infiltration of immune effector cells, including natural killer (NK) cells, M1-like macrophages and CD8+ T cells, into tumor microenvironment. Simultaneously, vascular normalization promoted the accumulation of zinc ions inside tumors to trigger effector cell immune activation and effector molecule production. The synergy between these two effects endowed PDGFB@ZIF8-RGD with superior capabilities in reprogramming the "cold" TIME to a "hot" TIME, thereby initiating robust antitumor immunity and suppressing tumor growth. This combinatorial strategy for improving immune effector cell infiltration and activation is a promising paradigm for solid tumor immunotherapy.

A gene-based score for the risk stratification of stage IA lung adenocarcinoma.

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

Changes in effective connectivity during the visual-motor integration tasks: a preliminary f-NIRS study.

BACKGROUND: Visual-motor integration (VMI) is an essential skill in daily life. The present study aimed to use functional near-infrared spectroscopy (fNIRS) technology to explore the effective connectivity (EC) changes among brain regions during VMI activities of varying difficulty levels. METHODS: A total of 17 healthy participants were recruited for the study. Continuous Performance Test (CPT), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and Beery VMI test were used to evaluate attention performance, executive function, and VMI performance. Granger causality analysis was performed for the VMI task data to obtain the EC matrix for all participants. One-way ANOVA analysis was used to identify VMI load-dependent EC values among different task difficulty levels from brain network and channel perspectives, and partial correlation analysis was used to explore the relationship between VMI load-dependent EC values and behavioral performance. RESULTS: We found that the EC values of dorsal attention network (DAN) → default mode network (DMN), DAN → ventral attention network (VAN), DAN → frontoparietal network (FPN), and DAN → somatomotor network (SMN) in the complex condition were higher than those in the simple and moderate conditions. Further channel analyses indicated that the EC values of the right superior parietal lobule (SPL) → right superior frontal gyrus (SFG), right middle occipital gyrus (MOG) → left SFG, and right MOG → right postcentral gyrus (PCG) in the complex condition were higher than those in the simple and moderate conditions. Subsequent partial correlation analysis revealed that the EC values from DAN to DMN, VAN, and SMN were positively correlated with executive function and VMI performance. Furthermore, the EC values of right MOG → left SFG and right MOG → right PCG were positively correlated with attention performance. CONCLUSIONS: The DAN is actively involved during the VMI task and thus may play a critical role in VMI processes, in which two key brain regions (right SPL, right MOG) may contribute to the EC changes in response to increasing VMI load. Meanwhile, bilateral SFG and right PCG may also be closely related to the VMI performance.

The Association of Salivary Flow Rate and Sleep Quality among Head and Neck Cancer Survivors after Radiotherapy.

BACKGROUND: Head and neck cancer survivors suffer from xerostomia and sleep disturbances after radiotherapy, both of which affect their quality of life. This study aimed to explore the role of salivary flow in the oral health and sleep quality of head and neck cancer survivors. METHODS: We recruited 120 head and neck cancer survivors who were experiencing symptoms of dry mouth or sleep disturbances post-radiotherapy from a dental clinic. We gathered their socio-demographic and clinical data, measured their salivary flow rate, and recorded their dry mouth score using the summated xerostomia inventory. Additionally, a dentist collected the DMFT (Decayed, Missing, and Filled Teeth) index. The Pittsburgh Sleep Quality Index was employed to assess their sleep quality. RESULTS: In this study, xerostomia was observed in nearly 80% of the cancer survivors. The concurrent prevalence of sleep disturbance and xerostomia was at 55%. After five years post-radiotherapy, there was a significant improvement observed in both the quality of sleep (p = 0.03) and the stimulated salivary flow rate (p = 0.04). Additionally, these improvements were noted to have commenced from the third year onwards. A significant association was found between stimulated salivary flow and dry mouth scores with poor sleep quality (p <  0.05). CONCLUSIONS: We recommend that dental professionals prioritize managing both dental and mental health issues equally for head and neck cancer survivors who have undergone radiotherapy within the past 3 years.

Carbonized Polymer Dots with Controllable N, O Functional Groups as Electrolyte Additives to Achieve Stable Li Metal Batteries.

Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to decompose in cycling. Herein, in order to guide the homogeneous deposition of Li+ , carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M-CPDs) and hydrothermal (H-CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic-N, pyrrolic-N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li+ through electrostatic interaction effectively guide the uniform Li dispersion and limit the "tip effect" and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li+ in the electrolyte is formed, which induces faster Li+ diffusion/transfer. As expected, H-CPDs achieve the ultra-even Li+ transfer. The corresponding Li//LiFePO4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M-CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices.

Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer.

INTRODUCTION: This study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Primary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. RESULTS: Of the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. CONCLUSIONS: Heterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

Relationships between sensory integration and the core symptoms of attention-deficit/hyperactivity disorder: the mediating effect of executive function.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by executive function deficits and functional alterations in sensory integration. The present study aimed to investigate the relationship between ADHD core symptoms, executive function, and sensory integration in children with ADHD. A total of 228 children with ADHD were recruited for our study. The Sensory Organization Test (SOT) and Child Sensory Integration Scale (CSIS) evaluated the sensory integration ability from lab-based and scaled-based perspectives, respectively. Three core components of executive functions (inhibition, working memory, and set-shifting) were assessed using both lab-based tests and the relevant factors from the behavior rating inventory of executive function (BRIEF). Partial correlation analysis was performed to explore the correlation of sensory integration with EF and ADHD core symptoms. Based on the observed significant correlation, bootstrap analyses were further conducted to explore the potential mediating effect of EF on the relationship between sensory integration and ADHD core symptoms. ADHD symptoms and EF were significantly correlated with CSIS scores; no factors were significantly correlated with SOT performance. In detail, the vestibular-balance score was negatively correlated with both inattention and hyperactivity/impulsivity symptoms, while the hyper-sensory and proprioception scores were negatively correlated with only inattention symptoms. For the scaled-based EF, vestibular-balance was negatively correlated with inhibition and working memory, and the hyper-sensory score was negatively correlated with shift factor. No correlation was found for the lab-based EF tests. The subsequent mediation analysis found that inhibition partially mediated the relationship between vestibular balance and hyperactivity/impulsivity symptoms. Working memory completely mediated the relationship between vestibular-balance, hyper-sensory, proprioception, and inattention symptoms. These results were well validated in an independent sample. Our present findings demonstrated that the functional alteration in basic sensory integration might be associated with impairments of executive functions and then lead to the behavioral expression of ADHD. The present findings might provide a new perspective to understand the occurrence of ADHD symptoms and potential precise intervention methods.

Retrospective analysis of primary intraosseous malignancies in mandible and maxilla in a population of Taiwanese patients.

BACKGROUND/PURPOSE: Due to the rarity and diversity of primary intraosseous malignancies in jawbones, we aimed to evaluate the clinicopathological features and discuss the findings of our collected cases with the literatures. METHODS: Twenty-nine patients (2000-2020) diagnosed with primary central malignancies of jawbones were selected from the database of Oral Pathology Department in our institution. Clinical features, radiographic appearance, and histopathological diagnosis of the 29 cases were analyzed. RESULTS: Twenty-nine patients aged between 19 and 84 years (average, 57.4 years) with a male to female ratio of 1.2:1 were included. The most frequent site was the mandibular body and ramus, followed by the posterior maxilla and mandibular symphysis. The most common diagnosis was osteogenic sarcoma (n = 13), followed by odontogenic carcinoma (n = 7), hematologic malignancies (n = 5), salivary gland malignancies (n = 2), and neurogenic sarcomas (n = 2). The most frequent symptoms were swelling, pain, paresthesia of lower lip, and mobile tooth. Radiographically, they usually presented as ill-defined osteolytic to osteoblastic lesions depending on the amount of ossification. Wide excision comprising partial maxillectomy and segmental mandibulectomy were the most common therapeutic methods. CONCLUSION: Despite the rarity of primary central malignancies in jawbones, the clinical features may mimic infectious process or benign lesions. Detailed history-taking, clinical and imaging examination and awareness of the patient's signs and symptoms combining with the histopathological inspection are important for early diagnosis and improved prognosis. The current data contributes a useful basis for clinical investigation regarding intraosseous malignancies occurring in the jawbones.

The functional impairment of different subtypes and occupational states in euthymic patients with bipolar disorder.

BACKGROUND: The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients. METHODS: A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively. RESULTS: Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups. CONCLUSION: Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.

Clinical manifestations of oral lymphomas - Retrospective study of 15 cases in a Taiwanese population and a review of 592 cases from the literature.

BACKGROUND/PURPOSE: Due to the rarity of oral lymphoma (OL), we aimed to evaluate the clinical features of OL and discuss these findings in light of the literature. METHODS: English language literature (1980-2019) related to OL was searched in two electronic databases. Patients (2000-2019) diagnosed with OL were also selected from the database of the Oral Pathology Department in our institution. The clinical features, radiographic appearance, and histopathological diagnosis in these selected cases from publications and our institution were then analyzed. RESULTS: 607 cases of OL (15 in our institution and 592 from literature) in patients aged between 0 and 92 years (average, 51.8 years) with a male to female ratio of 1.6:1 were included. The most common diagnosis was diffuse large B-cell lymphoma (n = 205), followed by Burkitt lymphoma (n = 72) and T-cell lymphoma (n = 37). The most frequent site was the gingiva, followed by palate, maxilla, mandible, tongue and buccal mucosa. The most frequent symptoms were swelling, ulceration, paresthesia, mobile tooth and pain. Radiographic findings included ill-defined osteolytic lesion, thickening of the periodontal ligament, loss of lamina dura and tooth displacement. CONCLUSION: Despite the rarity of extranodal lymphomas in oral cavity, their occurrence may be part of disseminated disease. Detailed history-taking, clinical and imaging examination and awareness of the patient's signs and symptoms are important for early diagnosis and an improved prognosis. The current data form a useful basis for clinical investigation and teaching regarding lymphoma occurring in the oral cavity.

Protective Effects of Tyrosol against LPS-Induced Acute Lung Injury via Inhibiting NF-κB and AP-1 Activation and Activating the HO-1/Nrf2 Pathways.

Tyrosol (Tyr) is a natural antioxidant that displays anti-oxidant and anti-inflammatory properties. The present study aimed to investigate the effect and mechanism of Tyr on lipopolysaccharide (LPS)-induced acute lung injury (ALI). In a mouse model, we found that pretreatment with Tyr significantly improved survival rate, attenuated lung permeability, ameliorated histopathological alterations, reduced expression of the inflammatory mediators and improved expression of the antioxidant enzyme. Further study revealed that Tyr markedly inhibited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation at both in vivo and in vitro levels. To investigate the underlying mechanism, we examined the impact of Tyr on the heme oxygenase (HO)-1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway in vivo and in vitro. The results showed that Tyr significantly improved the expression of HO-1 and the activation of Nrf2. This study offers novel evidence to support the efficacy of Tyr against ALI, which helps to clarify the underlying causes of the therapeutic effects behind Tyr.

Retrospective analysis of nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions in a population of Taiwanese patients.

OBJECTIVE: We aimed to evaluate nonendodontic periapical lesions clinically misdiagnosed as endodontic periapical pathoses in a population of Taiwanese patients. MATERIALS AND METHODS: Cases (2000-2014) of histopathological diagnoses of nonendodontic periapical lesions were retrieved from all cases with a clinical diagnosis of radicular cyst, apical granuloma, or apical periodontitis in the institution. These cases were regarded as misdiagnosed nonendodontic periapical lesions, of which the types and frequencies, in addition to the demographic data, were determined. RESULTS: Four thousand and four specimens were clinically diagnosed as endodontically associated pathoses, of which 118 cases (2.95%) received a histopathological diagnosis of a nonendodontic pathologic entity, the most frequent lesion being keratocystic odontogenic tumor (KCOT, n = 38, 32.20%), followed by fibro-osseous lesion (n = 18, 15.25%), and dentigerous cyst (n = 13, 11.02%). Nine malignant lesions in the periapical area [squamous cell carcinoma (n = 7, 5.93%), adenoid cystic carcinoma (n = 1, 0.85%), and Langerhans cell histiocytosis (n = 1, 0.85%)] were also noted. CONCLUSIONS: A wide variety of histopathological diagnoses, including benign odontogenic and non-odontogenic cystic and tumorous lesions and infectious diseases, as well as malignant lesions, was noted in these 118 cases of nonendodontic periapical lesions. Squamous cell carcinoma was the most predominant malignancy of nonendodontic periapical lesions misdiagnosed as apical periodontitis lesions from imaging examination overlooking the clinical findings. CLINICAL RELEVANCE: The current data form a useful basis for clinicopathological investigation and educational teaching regarding nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions.

Repression of a chromatin modifier aggravates lipopolysaccharide-induced acute lung injury in mouse.

Local inflammatory responses and alveolar epithelial cells (AECs) apoptosis are both important for the development of the acute lung injury (ALI), a clinically important complication causing high morbidity and mortality, but little is known about the molecular mechanisms underlying the pathogenesis. Herein, we showed for the first time that expression of Metastasis-associated protein 1 (MTA1), a master transcriptional regulator with the ability to regulate divergent cellular pathways by modifying the acetylation status of crucial target genes, was up-regulated in the alveolar cells of the Escherichia coli lipopolysaccharide (LPS)-induced murine ALI model. Inhibition of MTA1 expression by in vivo siRNA treatment exacerbated the pathology of LPS-induced ALI, by selectively promoting the expression of NF-κB-regulated inflammatory cytokines. Moreover, ablation of MTA1 expression promoted the LPS-induced apoptosis in AEC II cells, leaving AEC I cells unaffected. These data collectively underscore an alveolar facet of this important chromatin modifier, which may represent as a novel regulator and a new therapeutic target for the treatment of ALI.

Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2.

BACKGROUND: Successful drug treatment for ischemia--reperfusion-induced lung injury remains a major clinical problem. Melatonin (MT) is a hormone that is principally synthesized in the pineal gland. It has been shown to exhibit a variety of functions including anti-inflammatory and antioxidant effects. Previous reports on N-myc downstream-regulated gene (NDRG)2 have suggested that it is involved in cellular differentiation, development, antiapoptosis, anti-inflammatory cytokine, and antioxidant. The objective of this study was to test whether MT, a novel NDRG2 activator, can protect against intestinal ischemia-reperfusion-induced lung injury (IIRI). MATERIALS AND METHODS: IIRI was induced in rats by occlusion of the superior mesenteric artery for 60 min, and the occlusion was then released for reperfusion. Rats were randomly divided into six groups as follows: control group; MT group; IIRI group; IIRI+5 mg/kg MT group; IIRI+15 mg/kg MT group; and IIRI+25 mg/kg MT group. The effects of MT on intestinal ischemia-reperfusion-induced lung pathologic changes, inflammatory cytokines release, myeloperoxidase and superoxide dismutase activities, and malondialdehyde level were examined. In addition, the NDRG2 activation in lung tissues was detected by Western blot analysis. RESULTS: MT pretreatment attenuated edema and the pathologic changes in the lung. MT also decreased the levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-8 in bronchoalveolar lavage fluid. In addition, MT markedly prevented IIRI-induced elevation of malondialdehyde and myeloperoxidase levels, as well as reduction of superoxide dismutase activity. Furthermore, the expression of NDRG2 was activated by MT pretreatment in lung tissues. CONCLUSIONS: The present study demonstrates that MT exerted protection against IIRI-induced oxidative stress. The potential mechanism of this action may attribute partly to the activation of NDRG2 expression.

Retrospective study of oral and maxillofacial lesions in older Taiwanese patients.

OBJECTIVE: The aim was to provide information regarding oral and maxillofacial (OMF) lesions in an older Taiwanese population. BACKGROUND: The rate of increase of older people in Taiwan is expected to be rapid. OMF lesions are very frequent in the older population, but no studies have been performed on these lesions in Taiwan. MATERIALS AND METHODS: OMF cases (between 2000 and 2011) in geriatric patients (≥60 years of age) with records of age, sex and histological diagnoses were retrieved from the Oral Pathology Department of our institution. These lesions were classified into four main categories: tumour/tumour-like reactive lesions, cystic/pseudocystic lesions, inflammatory/infective lesions and other miscellaneous lesions. RESULTS: Six thousand seven hundred and twenty-six lesions were collected from a total of 39 503 OMF lesions in older Taiwanese patients in this study. Most of these lesions were distributed in the inflammatory/infective group, followed by tumour/tumour-like reactive lesions. Squamous cell carcinoma was the most common lesion, and, additionally, there was a high frequency of oral potentially malignant disorders. CONCLUSIONS: The present study showed trends similar to previous reports from other countries. However, some detailed information was different, perhaps due to the different criteria and different geographic distribution. Worthy of note, our results indicated that screening for oral potentially malignant disorder and oral malignancy in the older population is essential.

Impact of removable dentures on oral health-related quality of life among elderly adults in Taiwan.

BACKGROUND: Although the use of removable dentures can improve oral function and esthetics for elderly people, compared to those who do not wear removable dentures, those wearing removable dentures could have worse oral health related-quality of life (OHRQoL). Additional information is required to assess which factors related to denture wearing influence the OHRQoL of elderly individuals. The purpose of this study is to evaluate the association between denture wearing and OHRQoL in a sample of elderly individuals in Taiwan. METHODS: The study population included 277 elderly people wearing removable dentures (mean age = 76.0 years). Using face-to-face interviews, we collected data on the participants' socio-demographic characteristics, dental care service usage (regular dental checkups, treatment during toothache, dental visits in the last year), and factors related to denture wearing (perceived oral pain, perceived loose denture, perceived oral ulcer, perceived halitosis, perceived dry mouth, and perceived total denture satisfaction scores). OHRQoL was measured using the Taiwanese version of the Geriatric Oral Health Assessment Index (GOHAI-T). The location and number of remaining natural teeth and the type of denture were also recorded. Hierarchical multiple regression analysis was performed using GOHAI-T scores as the dependent variable. RESULTS: All the predictors together accounted for 50% of the variance in GOHAI-T scores. Further, education level, number of natural teeth, denture status, perceived loose denture, perceived oral ulcer, and perceived total denture satisfaction scores had statistically significant influences on OHRQoL. When compared with other variables, factors related to denture wearing, especially perceived total denture satisfaction scores, had the greatest impact on GOHAI-T scores. CONCLUSIONS: Of the factors analyzed in this study, denture satisfaction was the strongest predictor of OHRQoL. This suggests that denture satisfaction is useful for assessing the effect of denture treatment on the OHRQoL of elderly individuals wearing removable dentures.

Malignant transformation in 5071 southern Taiwanese patients with potentially malignant oral mucosal disorders.

BACKGROUND: Oral cancers can be preceded by clinically evident oral potentially malignant disorders (OPMDs). The current study evaluated the rate and the time of malignant transformation in the various OPMDs in a cohort of patients from southern Taiwan. Parameters possibly indicative for malignant transformation of OPMDs, such as epidemiological and etiological factors, and clinical and histopathological features were also described. METHODS: We followed-up 5071 patients with OPMDs-epithelial dysplasia with oral submucous fibrosis, epithelial dysplasia with hyperkeratosis/epithelial hyperplasia, hyperkeratosis/epithelial hyperplasia, oral submucous fibrosis, lichen planus, and verrucous hyperplasia-between 2001 and 2010 for malignant transformation. RESULTS: Two hundred nineteen of these 5071 OPMD patients (202 men, 17 women; mean age: 51.25 years; range: 30-81 years) developed oral cancers (179 squamous cell carcinomas; 40 verrucous carcinomas) in the same sites as the initial lesions at least 6 months after their initial biopsies. The overall transformation rate was 4.32% (mean duration of transformation: 33.56 months; range: 6-67 months). Additionally, the mean time of malignant transformation was significantly shorter for lesions with than without epithelial dysplasia. The risk of malignant transformation was 1.89 times higher for epithelially dysplastic than non-dysplastic lesions. The anatomical site of OPMD and the presence of epithelial dysplasia were significantly associated with malignant transformation. The hazard rate ratio was 1.87 times larger for tongue lesions than for buccal lesions. CONCLUSION: Patients with OPMDs require long-term follow up.

Active shimming for a 25 T NMR superconducting magnet by spectrum convergence method.

In the design of ultrahigh field nuclear magnetic resonance (NMR) superconducting magnets, it typically requires a high homogeneous magnetic field in the diameter of spherical volume (DSV) to obtain high spectrum resolution. However, shimming technique presents challenges due to the magnet bore space limitations, as accurate measurement of magnetic field distribution is very difficult, especially for customized micro-bore magnets. In this study, we introduced an active shimming method that utilized iterative adjustment of shim coil currents to improve the magnetic field homogeneity based on the full width at half maximum (FWHM) of the spectrum. The proposed method can determine the optimal set of currents for shim coils, effectively enhancing spatial field homogeneity by converging the FWHM. Experimental validation on a 25 T NMR superconducting magnet demonstrated the efficacy of the proposed method. Specifically, the active shimming method improved the field homogeneity of a 10 mm DSV from 7.09 ppm to 2.27 ppm with only four shim coils, providing a superior magnetic field environment for solid NMR and further magnetic resonance imaging (MRI) experiment. Furthermore, the proposed method can be promoted to more customized micro-bore magnets that require high magnetic field homogeneity.

Modern therapy for severe alveolar ridge atrophy.

This clinical report illustrates a modern method for oral rehabilitation of severe edentulous atrophic ridge. Shallow vestibule and small denture-bearing area of the maxilla provide insufficient retention, and only the symphyseal region of the mandible has obvious alveolar ridge. The surgery of deepening vestibule of the maxilla ridge was done by using tentative miniscrew combined with old denture and soft liner. The osseointegrated dental implants were installed over symphyseal region of the mandible to act as retentive devices for prostheses. In addition, functional reline with rebase material to build buccal-tongue contact over the retromolar area after denture delivery obtained high satisfaction from the patient. Many clinical conditions cannot be managed solely with implants or preprosthetic surgery alone, whereas a combination of the 2 can achieve successful outcome.

Development and validation of a gene-based classification model for pN2 lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) with pathological ipsilateral mediastinal lymph node (LN) involvement (pN2) exhibits strong biological and clinical heterogeneity. Thus, it is necessary to classify the biomolecular characteristics that lead to the prognostic heterogeneity of pN2-LUAD. Methods: The clinical characteristics and bulk RNA sequencing (RNA-seq) data of 75 patients with pN2-LUAD obtained from The Cancer Genome Atlas (TCGA) database were collected as the training set. The disease-free survival (DFS) and overall survival (OS) of patients with different molecular classifications were evaluated. Next, differentially expressed genes (DEGs), biology, and immune cell infiltration in the microenvironment were analysed. Finally, DEGs in the pN2-A and pN2-B groups were included using a least absolute shrinkage and selection operator (LASSO) model, and gene signatures were selected for pN2-A/B type classification. The RNA-seq and single-nucleus RNA sequencing (snRNA-seq) data from our center (n=58) and the GSE68465 dataset (n=53) were used as the validation data sets. Results: Patients with pN2 LUAD were classified into two distinct molecular categories (pN2-A and pN2-B) based on transcriptome information, pN2-A and pN2-B represent low-risk and high-risk patients, respectively. The survival analysis showed that pN2-A patients had significantly better DFS (P=0.0162) and OS (P=0.0105) compared to pN2-B patients. Multivariate analysis confirmed that molecular classification was an independent factor affecting the prognosis of pN2 LUAD (P=0.0038, and P=0.0024). Next, we found that compared with pN2-A stage patients, pN2-B stage patients had a higher frequency of canonical oncogenic pathway mutations and enrichments. At the single-cell level, we also found that the increase of endothelial cells and the decrease of cytotoxic T/natural killer (NK) cells led to a worse prognosis for pN2-B patients compared to pN2-A patients. Moreover, we established a reasonable gene prediction model of 18 differentially expressed genes (DEGs) to classify the pN2-A and pN2-B patients. Finally, the key above-mentioned results were confirmed using our data and the GES68645 dataset. Conclusions: The molecular classification of pN2 LUAD is expected to be a powerful supplement to pN2 substaging. Driver gene status and the immune microenvironment mediate different molecular types of LUAD and provide evidence for individualized treatment strategies.