Dental treatments in patients with special needs provided by university medical center in Southern Taiwan: a retrospective study.

OBJECTIVES: We perform special-need dental treatment at outpatient department (OPD), under general anesthesia (GA) when necessary, and provide domiciliary dental care. We aim to evaluate the profile and the characteristics of special needs patients (SNPs). MATERIALS AND METHODS: We consecutively enrolled 3117 SNPs from January 1, 2019 to December 31, 2022. Eighty patients with rare or genetic diseases were excluded. Demographic data were retrospectively collected. RESULTS: There were totally 3037 SNPs (mean age: 48.2 years; range, 1-100; male-to-female ratio, 1.5); 89.1% (n = 2705) SNPs received dental care at the OPD (OPD-SNPs), 7.9% (n = 239) received dental treatment under GA, and 3.0% (n = 93) received domiciliary dental care. Among those SNPs who received dental treatment under GA (n = 239), 91.2% (n = 218) were mental/intellectual disabled, and most underwent cavity filling (69.5%) and dental extractions (56.5%). OPD-SNPs with mental/intellectual disabilities (n = 1340) received significantly more items of dental treatment than those without (n = 1365). SNPs with more severe disabilities received more fluoride application and ultrasonic scaling (both p < 0.001, trend tests). Interestingly, among OPD-SNPs with mental/intellectual disabilities (n = 1340), more severe patients received more fluoride application (p < 0.001) and ultrasonic scaling (p < 0.001) but fewer root canal treatment (p = 0.007, trend test). CONCLUSIONS: GA benefited SNPs with more dental procedures, including invasive items. SNPs with mental/intellectual disabilities can tolerate more measures and SNPs with more severe mental/intellectual disabilities received more preventive measures but less invasive measures. Similarly, more severe SNPs with other disabilities received more preventive measures but not invasive measures. CLINICAL RELEVANCE: Our findings may provide useful information for special needs dentists and for doctor-patient communication.

The effect of the Litcubanine A on the treatment of murine experimental periodontitis by inhibiting monocyte-macrophage chemotaxis and osteoclast differentiation.

BACKGROUND: Periodontal disease is an inflammatory disease of periodontal tissues that is closely connected with systemic diseases. During periodontitis, the inappropriate recruitment and activation of monocytes-macrophages causes an increase in osteoclast activity and disrupts bone homeostasis. Therefore, it is a promising therapeutic strategy to treat periodontitis by regulating the functions of monocytes-macrophages. Litcubanine A (LA) is an isoquinoline alkaloid extracted from the traditional Chinese medicine Litsea cubeba, which was proven to have reproducible anti-inflammatory effects, but its regulatory role on bone homeostasis in periodontitis is still not clear. METHODS: In this study, zebrafish experiments and a mouse ligature-induced periodontitis model were performed, and histological analysis was used to investigate the effect of LA on macrophage chemotaxis under the inflammatory environment. Real-time PCR was used to detect the regulatory effect of LA (100 nM ~ 100 µM) on the chemotaxis function of macrophages induced by LPS. Apoptosis assay and flow cytometry were used to elucidate the influence of LA on macrophage apoptosis and proliferation. To further clarify the regulatory role of LA on macrophage osteoclast differentiation, real-time PCR, histological analysis, western blot, and micro-computed tomography (micro-CT) were performed in vivo and in vitro to verify the impact of LA on bone homeostasis. RESULTS: Compared with the control group, the chemotaxis function of macrophage was significantly attenuated by LA in vivo. LA could significantly inhibit the expression of genes encoding the chemokine receptors Ccr1 and Cxcr4, and its ligand chemokine Cxcl12 in macrophages, and suppresses the differentiation of osteoclastic precursors to osteoclasts through the MAPK signaling pathway. There were significantly lower osteoclast differentiation and bone loss in the LA group compared with the control in the ligature-induced periodontitis model. CONCLUSION: LA is a promising candidate for the treatment of periodontitis through its reproducible functions of inhibiting monocyte-macrophage chemotaxis and osteoclast differentiation.

Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well as abnormalities of the brain, skeletal system, movement/gait, and behavior were variable features. Phenotyping of knocked down wars-1 in a Caenorhabditis elegans model showed depletion is associated with defects in germ cell development. A wars1 knockout vertebrate model recapitulates the human clinical phenotypes, confirms variant pathogenicity, and uncovers evidence implicating the p.Met1? variant as potentially impacting an exon critical for normal hearing. Together, our findings provide consolidating evidence for biallelic disruption of WARS1 as causal for an autosomal recessive neurodevelopmental syndrome and present a vertebrate model that recapitulates key phenotypes observed in patients.

WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly.

Aminoacylation of transfer RNA (tRNA) is a key step in protein biosynthesis, carried out by highly specific aminoacyl-tRNA synthetases (ARSs). ARSs have been implicated in autosomal dominant and autosomal recessive human disorders. Autosomal dominant variants in tryptophanyl-tRNA synthetase 1 (WARS1) are known to cause distal hereditary motor neuropathy and Charcot-Marie-Tooth disease, but a recessively inherited phenotype is yet to be clearly defined. Seryl-tRNA synthetase 1 (SARS1) has rarely been implicated in an autosomal recessive developmental disorder. Here, we report five individuals with biallelic missense variants in WARS1 or SARS1, who presented with an overlapping phenotype of microcephaly, developmental delay, intellectual disability, and brain anomalies. Structural mapping showed that the SARS1 variant is located directly within the enzyme's active site, most likely diminishing activity, while the WARS1 variant is located in the N-terminal domain. We further characterize the identified WARS1 variant by showing that it negatively impacts protein abundance and is unable to rescue the phenotype of a CRISPR/Cas9 wars1 knockout zebrafish model. In summary, we describe two overlapping autosomal recessive syndromes caused by variants in WARS1 and SARS1, present functional insights into the pathogenesis of the WARS1-related syndrome and define an emerging disease spectrum: ARS-related developmental disorders with or without microcephaly.

Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts.

The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a potential therapeutic agent for bone repair. Herein, a strontium peroxide (SrO2)-loaded poly(lactic-co-glycolic acid) (PLGA)-gelatin scaffold system was developed as an implantable bone substitute. Gelatin sponges serve as porous osteoconductive scaffolds, while PLGA not only reinforces the mechanical strength of the gelatin but also controls the rate of water infiltration. The encapsulated SrO2 can release Sr2+ in a sustained manner upon exposure to water, thus effectively stimulating the proliferation of osteoblasts and suppressing the formation of osteoclasts. Moreover, SrO2 can generate hydrogen peroxide and subsequent oxygen molecules to increase local oxygen tension, an essential niche factor for osteogenesis. Collectively, the developed SrO2-loaded composite scaffold shows promise as a multifunctional bioactive bone graft for bone tissue engineering.

In Vitro Bioactivity and Antibacterial Effects of a Silver-Containing Mesoporous Bioactive Glass Film on the Surface of Titanium Implants.

Peri-implantitis is defined as a bacterial infection-induced inflammation and suppuration of soft and hard tissues surrounding a dental implant. If bacteria further invade the alveolar bone, they can easily cause bone loss and even lead to the early failure of a dental implant surgery. In the present study, an 80SiO2-15CaO-5P2O5 mesoporous bioactive glass film system containing 1, 5, and 10 mol% of silver was prepared on titanium implant discs (MBG-Ag-coated Ti) using sol-gel and spin coating methods. The wettability and adhesion strength of the films were evaluated using contact angle measurements and adhesion strength tests, respectively. The phase composition, chemical bonding, morphology, and oxidation states of the films were analyzed via X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). In vitro bioactivity analysis of the films was performed by immersion in a simulated body fluid (SBF) for 24 h. Disk diffusion tests were performed on the early colonizing bacteria Aggregatibacter actinomycetemcomitans and Streptococcus mutans to evaluate the antibacterial ability of the films. A silver-containing mesoporous bioactive glass film with excellent biocompatibility and antibacterial properties was successfully prepared.

The Antimicrobial Effects of Bacterial Cellulose Produced by Komagataeibacter intermedius in Promoting Wound Healing in Diabetic Mice.

As a conventional medical dressing, medical gauze does not adequately protect complex and hard-to-heal diabetic wounds and is likely to permit bacterial entry and infections. Therefore, it is necessary to develop novel dressings to promote wound healing in diabetic patients. Komagataeibacter intermedius was used to produce unmodified bacterial cellulose, which is rarely applied directly to diabetic wounds. The produced cellulose was evaluated for wound recovery rate, level of inflammation, epidermal histopathology, and antimicrobial activities in treated wounds. Diabetic mices' wounds treated with bacterial cellulose healed 1.63 times faster than those treated with gauze; the values for the skin indicators in bacterial cellulose treated wounds were more significant than those treated with gauze. Bacterial cellulose was more effective than gauze in promoting tissue proliferation with more complete epidermal layers and the formation of compact collagen in the histological examination. Moreover, wounds treated with bacterial cellulose alone had less water and glucose content than those treated with gauze; this led to an increase of 6.82 times in antimicrobial protection, lower levels of TNF-α and IL-6 (39.6% and 83.2%), and higher levels of IL-10 (2.07 times) than in mice wounds treated with gauze. The results show that bacterial cellulose produced using K. intermedius beneficially affects diabetic wound healing and creates a hygienic microenvironment by preventing inflammation. We suggest that bacterial cellulose can replace medical gauze as a wound dressing for diabetic patients.

A study on facial features of children with Williams syndrome in China based on three-dimensional anthropometric measurement technology.

To describe special facial features of children with Williams syndrome in China by using method of three-dimensional craniofacial anthropometry. Using three-dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height-breadth index, nasal breadth-depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3-5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three-dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.

The efficacy of addition of Tenofovir Disoproxil Fumarate to Peg-IFNα-2b is superior to the addition of Entecavir in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone.

Background: There are limited data regarding the efficacy of addition of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to Peg-IFNα-2b in HBeAg positive chronic hepatitis B (CHB) patients without early response to Peg-IFNα-2b. In this study, we aimed to evaluate the efficacy of ETV and TDF in HBeAg positive CHB patients who had a poor response to Peg-INFα-2b at the end of 12 weeks of monotherapy. Methods: A total of 40 HBeAg-positive CHB patients who were naive to antiviral therapy were recruited. The patients received a subcutaneous injection of Peg-IFNα-2b (180 µg) once a week for 12 weeks. However, the patients had a poor response to Peg-INFα-2b at the end of the 12-week-period monotherapy. The patients were then divided into two therapeutic protocol groups: (1) Group A: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and ETV (0.5 mg) orally once daily for 48 weeks; (2) Group B: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and TDF (300 mg) orally once daily for 48 weeks. The therapeutic efficacy was evaluated. Blood samples were collected at baseline and every 12 weeks. Routine biochemical tests including ALT, AST, etc. were measured by automated biochemical technique. HBV DNA was quantified using the TaqMan PCR assay. The levels of HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were measured using a commercial chemiluminescent microparticle immunoassay. Results: The HBsAg level declined rapidly in both two treatment groups during the first 12 weeks and declined gradually in the next 36 weeks. At week 48, the mean ΔHBsAg level in Peg-IFNα-2b+TDF group was significantly higher than that in Peg-IFNα-2b +ETV group (-1.799 ± 0.3063 vs. -1.078 ± 0.2028, P=0.0491). The HBeAg loss rate was significantly higher in TDF add-on group than that in ETV add-on group at week 48 (40% vs. 10%, P=0.028). At week 48, the proportions of patients with undetectable HBV DNA (<500 IU/mL) were 80% (16 out of 20) and 95% (19 out of 20) in Peg-IFNα-2b+ETV group and Peg-IFNα-2b+TDF group, respectively. Conclusions: This real world study demonstrated that the efficacy of addition of TDF to Peg-IFNα-2b is superior to the efficacy of addition of ETV to Peg-IFNα-2b in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone. However, this present study also requires a larger sample size study to verify in the future.

Simple procedure to evaluate mid-face sagging: A pilot study from Taiwan.

An easy and objective way to evaluate mid-face sagging is marking straight lines between the nasal alar and the mandibular angle, one in the supine and the other in an upright position. The maximal distance between the two lines drawn is measured. Statistic analyses shows that this maximum distance demonstrates positive correlation with age and body mass index that reflects the level of mid-face sagging. This simple method may be utilised to evaluate the effect of anti-ageing treatment on the face in the context of mid-face sagging.

The association between denture self-satisfaction rates and OHRQoL - a follow-up study.

BACKGROUD: The objectives of this study were to try to identify the key dimension in satisfaction from the combination of satisfaction clusters, and its effect on the change of OHRQoL(Oral Health-related Quality of Life) of elderly denture users. METHODS: This follow-up study was conducted in subjects aged 65 years and over. All participants (n = 2128) completed questionnaires before and approximately 6 months after receiving complete denture. Information obtained by questionnaire included demographic characteristics, patients' self-satisfaction rate and OHRQoL. The 6 satisfaction dimensions (including speaking, stability, esthetic, chewing, doctor and general dimensions) were classified as 5 cluster groups, which is the group of not at all satisfied in all dimensions (NAS); only satisfied with doctor and general dimensions(SDG); moderate satisfaction group(MS); quite satisfied group(QS); the highly satisfied group(HS) by an analysis of PCA (Principle component analysis) and CA (cluster analysis). Multiple linear regression was adapted to estimate the association between satisfaction and the responsiveness of OHIP-7T (Oral Health Impact Profile). RESULTS: When compared to the cluster "NAS", the greatest improvement of OHRQoL after treatment was found in the group "HS" (ß = 7.31(6.26-8.36), followed by group "QS" (ß = 4.71(3.54-5.87)), group "MS" (ß = 4.33(2.92-5.74)) and group "SDG" (ß = 3.25(2.10-4.41)). An increasing trend was detected in patient-rating satisfaction and OHRQoL. The satisfaction cluster group is an important factor of OHRQoL after adjusting for other confounders. CONCLUSION: Psychological-related aspects is the greatest impacting dimension on OHRQoL among denture wearers in Taiwan elderly. Better communication from the dental professional team with denture patients would improve their OHRQoL.

Factors contributing to surgical site infection in patients with oral cancer undergoing microvascular free flap reconstruction.

PURPOSE: Surgical site infections (SSIs) are associated with considerable medical expenditure. While head and neck free flap reconstruction has gradually become routine management following an ablative oncologic resection, reports on factors contributing to the SSIs are lacking. METHODS: We retrospectively analyzed 173 new patients with oral cancer without any antecedent treatment at a tertiary medical center from 2010 to 2015. We determined incidence rates of SSIs within 30 days postoperatively and identified independent risk factors using multivariate logistic regression analysis. RESULTS: Of 173 patients, 67 (38.7%) had SSIs. Multivariate analysis demonstrated operative time [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.036-1.389], mandibulectomy (OR = 2.759; 95% CI = 1.245-6.111), and oro-neck communication (OR = 5.358; 95% CI = 2.150-13.355) as independent predictors for SSIs. CONCLUSIONS: For patients with oral cancer undergoing free tissue reconstruction, mandibulectomy, oro-neck communication, and prolonged operative time were associated with increased incidence of SSIs.

Influences of Schneiderian membrane conditions on the early outcomes of osteotome sinus floor elevation technique: a prospective cohort study in the healing period.

OBJECTIVES: To radiographically investigate early outcomes of osteotome sinus floor elevation in the healing phase utilizing cone beam computed tomography and evaluate influences of Schneiderian membrane conditions. MATERIAL AND METHODS: One hundred patients were consecutively recruited for osteotome sinus floor elevation (OSFE) surgery using deproteinized bone mineral. CBCT was taken prior to (T0), immediately post-operatively (T1), and after the healing period (T2). Linear and volumetric measurements of the elevated region from T0 to T1 were performed for evaluation on computed tomography (CT). RESULTS: Osteotome sinus floor elevation were performed in 100 patients. One implant of each patient was selected. Mean residual bone height (RH) was 7.21 ± 1.12 mm. Mean sinus floor elevation height (SE) was 4.81 ± 0.75 mm. The mean endo-sinus bone gain after the healing period was 3.25 ± 0.83 mm. Pre-opterative CBCT scans revealed that 72 patients had a normal sinus membrane in osteotome region, 13 patients presented with flat thickened mucosa and 15 patients with antral pseudocysts. There is no significant difference in sinus mucosa elevation height, bone graft volume and new bone formation in group of Thickening membrane and Antral pseudocysts compared with normal. CONCLUSIONS: The radiographical results show that OSFE is a safe and predictable surgical procedure in residual bone height of 7.21 ± 1.12 mm. Mild flat thickening (>2 and <5 mm) and antral pseudocysts in a small size without clinical symptoms may not be contraindications to OSFE surgery.

[Analysis of clinical features of traditional Chinese medicine symptoms and syndromes of 220 patients with chronic aplastic anemia].

OBJECTIVE: To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders. METHODS: From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed. RESULTS: (1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females). CONCLUSIONS: Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.

Mouth-controlled mouse for quadriplegic disabled people: System design and validation.

Disabled people with a high cervical cord injury or quadriplegia face difficulties when controlling a computer. This study presents a digital mouth-controlled mouse-control aid called the bite-press mouth-controlled mouse (BPMCM) to replace the traditional computer mouse. The BPMCM is equipped with a joystick and micro switch, and the disabled person uses neck and head movements to push the joystick and control the cursor position while the three mouse functions (i.e., left-click, right-click, and drag) are activated by bite-pressing for different time intervals. The proposed design eliminates the sip-and-puff technique and the need to recite orders for reduced adaptation time and increased convenience. Furthermore, this design supports plug-and-play and hot plugging in modern mainstream operating systems that can often be directly operated via mouse functions. Experimental results demonstrated that disabled people using a BPMCM were as capable as healthy participants in operating a computer, with both experiments completed within 5 min, and voluntary disabled people immediately adapted to the BPMCM. The proposed design is expected to allow disabled people to operate computers at the same level as healthy participants. The BPMCM also required only half the physical exertion of other mouth-controlled mouse-control aids that require orders to be recited.

Machine learning for prediction of schizophrenia based on identifying the primary and interaction effects of minor physical anomalies.

In the neurodevelopmental model of schizophrenia, minor physical anomalies (MPAs) are considered neurodevelopmental markers of schizophrenia. To date, there has been no research to evaluate the interaction between MPAs. Our study built and used a machine learning model to predict the risk of schizophrenia based on measurements of MPA items and to investigate the potential primary and interaction effects of MPAs. The study included 470 patients with schizophrenia and 354 healthy controls. The models used are classical statistical model, Logistic Regression (LR), and machine leaning models, Decision Tree (DT) and Random Forest (RF). We also plotted two-dimensional scatter diagrams and three-dimensional linear/quadratic discriminant analysis (LDA/QDA) graphs for comparison with the DT dendritic structure. We found that RF had the highest predictive power for schizophrenia (Full-training AUC = 0.97 and 5-fold cross-validation AUC = 0.75). We identified several primary MPAs, such as the mouth region, high palate, furrowed tongue, skull height and mouth width. Quantitative MPA analysis indicated that the higher skull height and the narrower mouth width, the higher the risk of schizophrenia. In the interaction, we further identified that skull height and mouth width, furrowed tongue and skull height, high palate and skull height, and high palate and furrowed tongue, showed significant two-item interactions with schizophrenia. A weak three-item interaction was found between high palate, skull height, and mouth width. In conclusion, we found that the two machine learning methods showed good predictive ability in assessing the risk of schizophrenia using the primary and interaction effects of MPAs.

Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14.

TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the ß-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara -/-;tspearb -/- double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

[Chemical constituents from roots of Machilus yaoshansis].

To study chemical constituents contained in ethanol extracts from roots of Machilus yaoshansis. Fifteen compounds were separated from the roots of M. yaoshansis by using various chromatographic techniques. Their structures were identified on the basis of their physicochemical properties and spectral data as twelve lignans(+)-guaiacin (1), kadsuralignan C (2), (+)-isolariciresinol (3), 5'-methoxy-(+)-isolariciresinol (4), (7'S, 8R, 8'R)-lyoniresinol (5), meso-secoisolariciresinol (6), isolariciresinol-9'-O-beta-D-xylopyranoside (7), 5'-methoxy-isolariciresinol-9'-O-beta-D-xylopyranoside (8), lyoniresinol-9'-O-beta-D-xylopyranoside (9), (2R, 3R) -2, 3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-3-methyl-5-(E)-propenylbenzofuran (10), 3, 5'-dimethoxy-4', 7-epoxy-8, 3'-neolignan-4, 9, 9'-triol (11), nectandrin B (12), and three flavanes(+)-catechin (13), (-)-epicatechin (14), and bis-8, 8'-catechinylmethane (15). All of the compounds 1-15 were separated from M. yaoshansis for the first time.