Ceph-Net: automatic detection of cephalometric landmarks on scanned lateral cephalograms from children and adolescents using an attention-based stacked regression network.

BACKGROUND: The success of cephalometric analysis depends on the accurate detection of cephalometric landmarks on scanned lateral cephalograms. However, manual cephalometric analysis is time-consuming and can cause inter- and intra-observer variability. The purpose of this study was to automatically detect cephalometric landmarks on scanned lateral cephalograms with low contrast and resolution using an attention-based stacked regression network (Ceph-Net). METHODS: The main body of Ceph-Net compromised stacked fully convolutional networks (FCN) which progressively refined the detection of cephalometric landmarks on each FCN. By embedding dual attention and multi-path convolution modules in Ceph-Net, the network learned local and global context and semantic relationships between cephalometric landmarks. Additionally, the intermediate deep supervision in each FCN further boosted the training stability and the detection performance of cephalometric landmarks. RESULTS: Ceph-Net showed a superior detection performance in mean radial error and successful detection rate, including accuracy improvements in cephalometric landmark detection located in low-contrast soft tissues compared with other detection networks. Moreover, Ceph-Net presented superior detection performance on the test dataset split by age from 8 to 16 years old. CONCLUSIONS: Ceph-Net demonstrated an automatic and superior detection of cephalometric landmarks by successfully learning local and global context and semantic relationships between cephalometric landmarks in scanned lateral cephalograms with low contrast and resolutions.

Outbreak of COVID-19 among children and young adults in a cancer centre daycare unit.

Nosocomial transmission of COVID-19 among immunocompromised hosts can have a serious impact on COVID-19 severity, underlying disease progression and SARS-CoV-2 transmission to other patients and healthcare workers within hospitals. We experienced a nosocomial outbreak of COVID-19 in the setting of a daycare unit for paediatric and young adult cancer patients. Between 9 and 18 November 2020, 473 individuals (181 patients, 247 caregivers/siblings and 45 staff members) were exposed to the index case, who was a nursing staff. Among them, three patients and four caregivers were infected. Two 5-year-old cancer patients with COVID-19 were not severely ill, but a 25-year-old cancer patient showed prolonged shedding of SARS-CoV-2 RNA for at least 12 weeks, which probably infected his mother at home approximately 7-8 weeks after the initial diagnosis. Except for this case, no secondary transmission was observed from the confirmed cases in either the hospital or the community. To conclude, in the day care setting of immunocompromised children and young adults, the rate of in-hospital transmission of SARS-CoV-2 was 1.6% when applying the stringent policy of infection prevention and control, including universal mask application and rapid and extensive contact investigation. Severely immunocompromised children/young adults with COVID-19 would have to be carefully managed after the mandatory isolation period while keeping the possibility of prolonged shedding of live virus in mind.

Efficacy of an interdental brush in cleaning artificial plaque on a 3D-printed model base.

BACKGROUND: Among interdental cleaning aids (ICAs), interdental brushes (IDBs) are in the spotlight because they can effectively remove plaque from interdental surfaces. Guidance on the correct use of ICAs, such as IDBs, is required to prevent dental plaque accumulation. Since it is impossible to confirm the interdental proximal surface unless extracted, it is difficult to conduct quantitative experiments. This study presented an efficient way to evaluate IDBs by realizing dental structures and embrasures using a Dental computer-aided design (CAD) software and a 3D printer. METHODS: Two different sizes of embrasure (0.7 and 1.2 mm) crown models were prepared with CAD software and a 3D printer. To evaluate the cleaning efficacy of IDBs of each size (0.6, 0.7, 0.8, 1.0, 1.2, and 1.5 mm diameters), the 9th cycle of brush move was performed where artificial plaque was spread and a digital camera was used to record the process. The pixels and percentage of cleaning from the recorded digital images were analyzed. RESULTS: The plateau was formed after the 5th brushing cycle under all conditions-after the 5th cycle, the cleaning efficacy of the two crown models was 69.3-86.4% and 49.8-75.4%. In these results, the optimal diameters for the IDB were 1.2 and 1.5 mm for embrasure sizes of 0.7 and 1.2 mm, respectively. Moreover, the cleaning efficacy was the highest at 86.4% and 75.4% after the 9th cycle. CONCLUSIONS: The 3D-printed model base for the human oral embrasure structure is an adequate model to test artificial plaque removal using IDB. The use of IDBs for more than five cycles does not support the conventional idea that a greater number of IDB brushing moves is more effective in a statistically substantial manner.

Optical edge effects create conjunctival indentation thickness artefacts.

PURPOSE: Conjunctival compression observed in ultrahigh resolution optical coherence tomography (UHR-OCT) images of contact lens edges could be actual tissue alteration, may be an optical artefact arising from the difference between the refractive indexes of the lens material and the conjunctival tissue, or could be a combination of the two. The purpose of this study is to image the artefact with contact lenses on a non-biological (non-indentable) medium and to determine the origins of the observed conjunctival compression. METHODS: Two-dimensional cross-sectional images of the edges of a selection of marketed silicone hydrogel and hydrogel lenses (refractive index ranging from 1.40 to 1.43) were acquired with a research grade UHR-OCT system. The lenses were placed on three continuous surfaces, a glass sphere (refractive index n = 1.52), a rigid contact lens (n = 1.376) and the cornea of a healthy human subject (average n = 1.376). The displacement observed was analysed using ImageJ. RESULTS: The observed optical displacement ranged between 5.39(0.06) µm with Acuvue Advance and 11.99(0.18) µm with Air Optix Night & Day when the lens was imaged on the glass reference sphere. Similarly, on a rigid contact lens displacement ranged between 5.51(0.03) and 9.72(0.12) µm. Displacement was also observed when the lenses were imaged on the human conjunctiva and ranged from 6.49(0.80) µm for the 1-day Acuvue Moist to 17.4(0.22) µm for the Pure Vision contact lens. CONCLUSIONS: An optical displacement artefact was observed when imaging a contact lens on two rigid continuous surfaces with UHR-OCT where compression or indentation of the surface could not have been a factor. Contact lenses imaged in situ also exhibited displacement at the intersection of the contact lens edge and the conjunctiva, likely a manifestation of both the artefact and compression of the conjunctiva.

Coordinated wound responses in a regenerative animal-algal holobiont.

Animal regeneration involves coordinated responses across cell types throughout the animal body. In endosymbiotic animals, whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, we study the acoel Convolutriloba longifissura, which hosts symbiotic Tetraselmis sp. green algae and can regenerate entire bodies from tissue fragments. We show that animal injury causes a decline in the photosynthetic efficiency of the symbiotic algae, alongside two distinct, sequential waves of transcriptional responses in acoel and algal cells. The initial algal response is characterized by the upregulation of a cohort of photosynthesis-related genes, though photosynthesis is not necessary for regeneration. A conserved animal transcription factor, runt, is induced after injury and required for acoel regeneration. Knockdown of Cl-runt dampens transcriptional responses in both species and further reduces algal photosynthetic efficiency post-injury. Our results suggest that the holobiont functions as an integrated unit of biological organization by coordinating molecular networks across species through the runt-dependent animal regeneration program.

Correlation of circulating full-length visfatin (PBEF/NAMPT) with metabolic parameters in subjects with and without diabetes: a cross-sectional study.

OBJECTIVE: Here we use a novel ELISA that is specific for full-length visfatin (PBEF/NAMPT), compare it with the existing C-terminal based assay and use it to investigate associations of visfatin with metabolic parameters. DESIGN, PATIENTS AND MEASUREMENTS: We established the specificity and effectiveness of the new ELISA and evaluated the associations of full-length visfatin with clinical, anthropometric and metabolic parameters in a cross-sectional study of 129 Thai subjects, consisting of 50 outpatients with type 2 diabetes and 79 healthy volunteers. RESULTS: The new ELISA accurately recovered full-length recombinant visfatin and detected visfatin secreted by primary human and rat adipocytes. We found serum full-length visfatin was significantly higher in subjects with diabetes compared to their nondiabetic peers (median 2.75 vs. 2.22 ng/ml, P = 0.0142). After adjustment for age, gender and traditional metabolic risk factors, adjusted mean visfatin remained significantly higher in the diabetes group (3.80 vs. 2.10 ng/ml, P = 0.0021). On Spearman univariate correlation analysis, visfatin was significantly associated with resistin (r = 0.30, P = 0.0011), but not with any other anthropometric or metabolic variables, including adiponectin multimers. On multiple linear regression analysis, the only covariates independently associated with visfatin were diabetes (t = 3.11, P = 0.0024) and log resistin (t = 2.68, P = 0.0086). CONCLUSIONS: Circulating visfatin is independently associated with diabetes and resistin concentration, but is not related to adiponectin multimers or other metabolic covariates. These data are suggestive of a potential role of visfatin in subclinical inflammatory states.

Adjuvant effect of CIA07, a combination of Escherichia coli DNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen.

CIA07 is an immunostimulatory agent composed of bacterial DNA fragments and modified lipopolysaccharide, which has antitumor activity against bladder cancer in mice. In this study, the adjuvant activity of CIA07 was evaluated using hepatitis B virus surface antigen (HBsAg) as the immunogen. Mice were immunized intramuscularly three times at 1-week intervals with HBsAg alone or in combination with alum, bacterial DNA fragments, modified lipopolysaccharide, CIA07 or CpG1826, and immune responses were assessed. At 1 week after the final injection, the HBsAg-specific total serum IgG antibody titer in CIA07-treated mice was 14 times higher than that in animals administered antigen alone, six times higher than in mice given alum or bacterial DNA fragments and twice as high as those treated with modified lipopolysaccharide or CpG1826, and remained maximal until 8 weeks postimmunization. Animals receiving antigen alone or plus alum displayed barely detectable HBsAg-specific serum IgG2a antibody responses. However, coadministration of CIA07 with antigen led to markedly enhanced serum IgG2a antibody titer and IFN-gamma(+) production in splenocytes, indicating that CIA07 effectively induces Th1-type immune responses. In addition, the number of HBsAg-specific CD8(+) T cells in peripheral blood mononuclear cells was elevated in CIA07-treated mice. These data clearly demonstrate that CIA07 is able to induce both cellular and humoral immune responses to HBsAg, and confirm its potential as an adjuvant in therapeutic vaccines for hepatitis B virus infections.

Successful empirical antifungal therapy of intravenous itraconazole with pharmacokinetic evidence in pediatric cancer patients undergoing hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Empirical antifungal therapy prevents invasive fungal infections in patients with cancer. This study assessed the empirical efficacy of intravenous itraconazole in pediatric patients undergoing hematopoietic stem cell transplantation, and investigated the pharmacokinetics and clinical implications. METHODS: Oral itraconazole syrup was started (2.5 mg/kg twice daily) for prophylaxis, and patients with persistent neutropenic fever for more than 2 days were switched to intravenous itraconazole (5 mg/kg twice daily for 2 days for induction and 5 mg/kg daily for maintenance) as empirical treatment. Empirical antifungal efficacy was assessed retrospectively in 159 transplantations, and a full pharmacokinetic study was prospectively conducted in six of these patients. Successful antifungal efficacy was defined as the fulfillment of all components of a five-part composite end point. RESULTS: The overall empirical antifungal success rate fulfilling all criteria was 42.1 %. No death or drug-related serious adverse events occurred during the study. Mean trough plasma concentration of itraconazole after oral prophylaxis and intravenous induction were 577.2 and 1659.7 µg/L, respectively. Mean area under the concentration-time curve of itraconazole and its metabolite at steady state were 42,837 ± 24,746 µg·h/L and 63,094 ± 19,255 µg·h/L. CONCLUSIONS: Intravenous itraconazole was effective and safe as an empirical antifungal agent in pediatric patients; this was due to the fast and satisfactory increase in drug concentration by switching from oral to intravenous therapy.

Tensor total variation approach to optical coherence tomography reconstruction for improved visualization of retinal microvasculature.

A novel optical coherence tomography (OCT) reconstruction approach is introduced for improved visualization of inner-retina capillaries in retinal OCT tomograms. The proposed method utilizes a minimization framework based on a tensor total variation (TTV) energy functional, to enforce capillary structural characteristics in the spatial domain. By accounting for structure tensor characteristics, the TTV reconstruction method allows for contrast enhancement of capillary structural characteristics. The novel TTV method was tested on high resolution OCT images acquired in-vivo from the foveal region of the retina of a healthy human subject. Experimental results demonstrate significant contrast and visibility enhancement of the inner retina capillaries in the retinal OCT tomograms, achieved by use of the TTV reconstruction method. Therefore, the TTV method has a strong potential for improved disease progression analysis based on the study of disease-induced changes in the inner retina vasculature.

In vivo volumetric imaging of chicken retina with ultrahigh-resolution spectral domain optical coherence tomography.

The chicken retina is an established animal model for myopia and light-associated growth studies. It has a unique morphology: it is afoveate and avascular; oxygen and nutrition to the inner retina is delivered by a vascular tissue (pecten) that protrudes into the vitreous. Here we present, to the best of our knowledge, the first in vivo, volumetric high-resolution images of the chicken retina. Images were acquired with an ultrahigh-resolution optical coherence tomography (UHROCT) system with 3.5 µm axial resolution in the retina, at the rate of 47,000 A-scans/s. Spatial variations in the thickness of the nerve fiber and ganglion cell layers were mapped by segmenting and measuring the layer thickness with a semi-automatic segmentation algorithm. Volumetric visualization of the morphology and morphometric analysis of the chicken retina could aid significantly studies with chicken retinal models of ophthalmic diseases.

Serum vaspin concentrations in human obesity and type 2 diabetes.

OBJECTIVE: Vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: For the measurement of vaspin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating vaspin in a cross-sectional study of 187 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes before and after a 4-week physical training program. RESULTS: Vaspin serum concentrations were significantly higher in female compared with male subjects. There was no difference in circulating vaspin between individuals with NGT and type 2 diabetes. In the normal glucose-tolerant group, circulating vaspin significantly correlated with BMI and insulin sensitivity. Moreover, physical training for 4 weeks resulted in significantly increased circulating vaspin levels. CONCLUSIONS: We found a sexual dimorphism in circulating vaspin. Elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity, whereas type 2 diabetes seems to abrogate the correlation between increased circulating vaspin, higher body weight, and decreased insulin sensitivity. Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations.

Bacterial DNA containing methylated CpG motifs retains immunostimulatory activity in synergy with modified lipopolysaccharides.

We previously described the immunostimulatory activity of CIA07, a combination of bacterial DNA fragments and modified LPS, and demonstrated that CIA07 has antitumor activity in a mouse bladder cancer model. In this study, we investigated whether methylation of the CpG motifs on the bacterial DNA fragments affects the immunostimulatory potential of CIA07. E. coli DNA fragments were methylated with CpG methylase, and then combined with modified LPS for experiments. Our results revealed that methylated CIA07 (mCIA07) and unmethylated CIA07 were equally active in inducing cytokine secretion from human whole blood cells. In addition, both methylated DNA fragments and mCIA07 retained the ability to activate expression and nuclear translocation of NF-kappaB in RAW 264.7 cells. Finally, methylated DNA fragments and mCIA07 exhibited an antitumor activity comparable to those of their unmethylated counterparts in our mouse bladder cancer model. These data demonstrate that CpG methylation of E. coli DNA does not abrogate the immunostimulatory activity of DNA fragments or CIA07, suggesting that the synergistic activity by bacterial DNA in combination with LPS may be independent of the methylation status of CpG motifs.

Immune responses of mice to influenza subunit vaccine in combination with CIA07 as an adjuvant.

CIA07 is an immunostimulatory agent composed of E. coli DNA fragments and modified LPS lacking the lipid A moiety. In this study, we investigated whether CIA07 promotes immune responses as an adjuvant to the influenza subunit vaccine. Balb/c mice were immunized intramuscularly once or twice at a 4-week interval with the trivalent influenza subunit vaccine antigen alone or in combination with CIA07 as adjuvant. Antigen-specific serum antibody titers and hemagglutination-inhibition (HI) antibody titers were assessed. At 4 weeks after each immunization, the antigen-specific total serum IgG antibody titer in mice receiving CIA07 was 2 to 3 times higher than that in animals administered antigen alone (P<0.05). The CIA07-treated group additionally displayed higher HI antibody titers against each of the 3 vaccine strains, compared to the antigen group. Animals receiving antigen alone displayed barely detectable antigen-specific serum IgG2a antibody titers. In contrast, coadministration of CIA07 with antigen led to significantly enhanced IgG2a antibody responses, suggesting that CIA07 stimulates a Th1-type immune response. Moreover, the CIA07-treated group displayed a marked increase in the number of interferon gamma-producing CD8(+) T cells in splenocytes. These data collectively demonstrate that CIA07 has the ability to induce both Th1-type cellular and Th2-type humoral immune responses to the influenza subunit vaccine, and support its potential as an effective adjuvant to the influenza vaccine.

Identification of an anti-aldolase autoantibody as a diagnostic marker for diabetic retinopathy by immunoproteomic analysis.

Circulating autoantibodies specific for retinal proteins are associated with retinal destruction in patients with diabetic retinopathy (DR). In this study, we screened diabetic sera for the presence of anti-retinal autoantibodies with an aim of developing diagnostic markers for DR. Immunoblot analysis of DR patients' sera with human retinal cytosolic proteins revealed a higher incidence of anti-retinal autoantibodies, compared to normal blood donors or diabetic patients without DR. Anti-retinal protein autoantibody profiles of DR patient sera were obtained by 2-DE immunoblot analysis. Specifically, 20 protein spots reactive with DR patient sera were identified by ESI-MS/MS. Of these spots, 14 were specific for DR patients, and 4 reacted with both non-proliferative DR (non-PDR) and PDR sera. The anti-aldolase autoantibody was selected as a DR marker candidate, and specific reactivity of DR patient sera was confirmed by immunoblot analysis with rabbit aldolase. The serum anti-aldolase autoantibody level was measured by ELISA. DR patients showed significantly higher autoantibody levels than normal donors or diabetic patients without retinopathy. However, no significant differences were observed between non-PDR and PDR patients, suggesting that the level of anti-aldolase autoantibody is not determined by the severity of retinopathy in diabetic patients. Our data collectively demonstrate that the anti-aldolase autoantibody serves as a useful marker for DR diagnosis.