Blood Concentrations of Lead, Cadmium, and Mercury Are Associated With Alcohol-Related Liver Disease.

BACKGROUND: An association between environmental pollutants and alcohol-related liver disease (ALD) has not been determined until now. The objectives of this study were to examine the association of the pollutants with ALD, and whether the pollutants together increased the risk of ALD. METHODS: Data were extracted from the Korea National Health and Nutrition Examination Survey (2010-2013 and 2016-2017; n = 11,993). Blood levels of lead, cadmium, and mercury were measured. ALD was defined by a combination of excessive alcohol consumption and ALD/non-alcoholic fatty liver disease index > 0. The aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 score were used to evaluate ALD FIB. RESULTS: The odds ratios (ORs) of ALD for the highest versus the lowest quartiles of exposure were for lead, 7.39 (95% confidence interval [CI], 5.51-9.91); cadmium, 1.68 (95% CI, 1.32-2.14); and mercury, 5.03 (95% CI, 3.88-6.53). Adjusting for age, gender, smoking, occupation, education, and personal income attenuated the associations but indicated significant positive trends (all Ptrend < 0.001). A positive additive interaction between cadmium and lead was observed. The relative excess OR due to the interaction was 0.96 (95% CI, 0.41-1.51); synergy index = 2.92 (95% CI, 0.97-8.80). Among 951 subjects with ALD, advanced FIB was associated with lead and cadmium (OR, 3.46, 95% CI, 1.84-6.53; OR, 8.50, 95% CI, 2.54-28.42, respectively), but not with mercury. The effect estimates for lead and cadmium remained significant even after adjustment for daily alcohol intake. CONCLUSION: Blood levels of lead, cadmium, and mercury were significantly associated not only with the risk of ALD but also with ALD FIB. Cadmium and lead have synergistic effects that increase the risk of ALD.

Deep learning for rare disease: A scoping review.

Although individually rare, collectively more than 7,000 rare diseases affect about 10% of patients. Each of the rare diseases impacts the quality of life for patients and their families, and incurs significant societal costs. The low prevalence of each rare disease causes formidable challenges in accurately diagnosing and caring for these patients and engaging participants in research to advance treatments. Deep learning has advanced many scientific fields and has been applied to many healthcare tasks. This study reviewed the current uses of deep learning to advance rare disease research. Among the 332 reviewed articles, we found that deep learning has been actively used for rare neoplastic diseases (250/332), followed by rare genetic diseases (170/332) and rare neurological diseases (127/332). Convolutional neural networks (307/332) were the most frequently used deep learning architecture, presumably because image data were the most commonly available data type in rare disease research. Diagnosis is the main focus of rare disease research using deep learning (263/332). We summarized the challenges and future research directions for leveraging deep learning to advance rare disease research.

Improved gliotransmission by increasing intracellular Ca2+ via TRPV1 on multi-walled carbon nanotube platforms.

BACKGROUND: Astrocyte is a key regulator of neuronal activity and excitatory/inhibitory balance via gliotransmission. Recently, gliotransmission has been identified as a novel target for neurological diseases. However, using the properties of nanomaterials to modulate gliotransmission has not been uncovered. RESULTS: We prepared non-invasive CNT platforms for cells with different nanotopography and properties such as hydrophilicity and conductivity. Using CNT platforms, we investigated the effect of CNT on astrocyte functions participating in synaptic transmission by releasing gliotransmitters. Astrocytes on CNT platforms showed improved cell adhesion and proliferation with upregulated integrin and GFAP expression. In addition, intracellular GABA and glutamate in astrocytes were augmented on CNT platforms. We also demonstrated that gliotransmitters in brain slices were increased by ex vivo incubation with CNT. Additionally, intracellular resting Ca2+ level, which is important for gliotransmission, was also increased via TRPV1 on CNT platforms. CONCLUSION: CNT can improve astrocyte function including adhesion, proliferation and gliotransmission by increasing resting Ca2+ level. Therefore, our study suggests that CNT would be utilized as a new therapeutic platform for central nervous system diseases by modulating gliotransmission.

Multitask Siamese Network for Remote Photoplethysmography and Respiration Estimation.

Heart and respiration rates represent important vital signs for the assessment of a person's health condition. To estimate these vital signs accurately, we propose a multitask Siamese network model (MTS) that combines the advantages of the Siamese network and the multitask learning architecture. The MTS model was trained by the images of the cheek including nose and mouth and forehead areas while sharing the same parameters between the Siamese networks, in order to extract the features about the heart and respiratory information. The proposed model was constructed with a small number of parameters and was able to yield a high vital-sign-prediction accuracy, comparable to that obtained from the single-task learning model; furthermore, the proposed model outperformed the conventional multitask learning model. As a result, we can simultaneously predict the heart and respiratory signals with the MTS model, while the number of parameters was reduced by 16 times with the mean average errors of heart and respiration rates being 2.84 and 4.21. Owing to its light weight, it would be advantageous to implement the vital-sign-monitoring model in an edge device such as a mobile phone or small-sized portable devices.

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide.

Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.

Columbia Open Health Data for COVID-19 Research: Database Analysis.

BACKGROUND: COVID-19 has threatened the health of tens of millions of people all over the world. Massive research efforts have been made in response to the COVID-19 pandemic. Utilization of clinical data can accelerate these research efforts to combat the pandemic since important characteristics of the patients are often found by examining the clinical data. Publicly accessible clinical data on COVID-19, however, remain limited despite the immediate need. OBJECTIVE: To provide shareable clinical data to catalyze COVID-19 research, we present Columbia Open Health Data for COVID-19 Research (COHD-COVID), a publicly accessible database providing clinical concept prevalence, clinical concept co-occurrence, and clinical symptom prevalence for hospitalized patients with COVID-19. COHD-COVID also provides data on hospitalized patients with influenza and general hospitalized patients as comparator cohorts. METHODS: The data used in COHD-COVID were obtained from NewYork-Presbyterian/Columbia University Irving Medical Center's electronic health records database. Condition, drug, and procedure concepts were obtained from the visits of identified patients from the cohorts. Rare concepts were excluded, and the true concept counts were perturbed using Poisson randomization to protect patient privacy. Concept prevalence, concept prevalence ratio, concept co-occurrence, and symptom prevalence were calculated using the obtained concepts. RESULTS: Concept prevalence and concept prevalence ratio analyses showed the clinical characteristics of the COVID-19 cohorts, confirming the well-known characteristics of COVID-19 (eg, acute lower respiratory tract infection and cough). The concepts related to the well-known characteristics of COVID-19 recorded high prevalence and high prevalence ratio in the COVID-19 cohort compared to the hospitalized influenza cohort and general hospitalized cohort. Concept co-occurrence analyses showed potential associations between specific concepts. In case of acute lower respiratory tract infection in the COVID-19 cohort, a high co-occurrence ratio was obtained with COVID-19-related concepts and commonly used drugs (eg, disease due to coronavirus and acetaminophen). Symptom prevalence analysis indicated symptom-level characteristics of the cohorts and confirmed that well-known symptoms of COVID-19 (eg, fever, cough, and dyspnea) showed higher prevalence than the hospitalized influenza cohort and the general hospitalized cohort. CONCLUSIONS: We present COHD-COVID, a publicly accessible database providing useful clinical data for hospitalized patients with COVID-19, hospitalized patients with influenza, and general hospitalized patients. We expect COHD-COVID to provide researchers and clinicians quantitative measures of COVID-19-related clinical features to better understand and combat the pandemic.

M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria.

Tumor suppressor p53 is not only affects immune responses but also contributes to antibacterial activity. However, its bactericidal function during mycobacterial infection remains unclear. In this study, we found that the p53-deficient macrophages failed to control Mycobacterium tuberculosis (Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels of p53 during Mtb infection were stronger in M1 macrophages than in M2 macrophages. The TLR2/JNK signaling pathway plays an essential role in the modulation of M1 macrophage polarization upon Mtb infection. It facilitates p53-mediated apoptosis through the production of reactive oxygen species, nitric oxide and inflammatory cytokines in Mtb-infected M1 macrophages. In addition, nutlin-3 effectively abrogated the intracellular survival of mycobacteria in both TB patients and healthy controls after H37Ra infection for 24 h, indicating that the enhancement of p53 production effectively suppressed the intracellular survival of Mtb in hosts. These results suggest that p53 can be a new therapeutic target for TB therapy.

Correction to: M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria.

The original version of this article unfortunately contains an error in the acknowledgement section. The text "Brain Korea 21 PLUS Project for Medical Science, Chungnam National University" was omitted by mistake. The correct and complete acknowledgment is given below: Acknowledgments This work was supported by the research fund of Chungnam National University and the Brain Korea 21 PLUS Project for Medical Science, Chungnam National University. The funders had no role in study design, data collection and analysis decision to publish, or preparation of the manuscript.

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis.

BACKGROUND: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies. METHODS: We used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints. RESULTS: A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group. CONCLUSION: In conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.

Reactive oxygen species-mediated endoplasmic reticulum stress response induces apoptosis of Mycobacterium avium-infected macrophages by activating regulated IRE1-dependent decay pathway.

Mycobacterium avium, a slow-growing nontuberculous mycobacterium, causes fever, diarrhoea, loss of appetite, and weight loss in immunocompromised people. We have proposed that endoplasmic reticulum (ER) stress-mediated apoptosis plays a critical role in removing intracellular mycobacteria. In the present study, we investigated the role of the regulated IRE1-dependent decay (RIDD) pathway in macrophages during M. avium infection based on its role in the regulation of gene expression. The inositol-requiring enzyme 1 (IRE1)/apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) signalling pathway was activated in macrophages after infection with M. avium. The expression of RIDD-associated genes, such as Bloc1s1 and St3gal5, was decreased in M. avium-infected macrophages. Interestingly, M. avium-induced apoptosis was significantly suppressed by pretreatment with irestatin (inhibitor of IRE1α) and 4µ8c (RIDD blocker). Macrophages pretreated with N-acetyl cysteine (NAC) showed decreased levels of reactive oxygen species (ROS), IRE1α, and apoptosis after M. avium infection. The expression of Bloc1s1 and St3gal5 was increased in NAC-pretreated macrophages following infection with M. avium. Growth of M. avium was significantly increased in irestatin-, 4µ8c-, and NAC-treated macrophages compared with the control. The data indicate that the ROS-mediated ER stress response induces apoptosis of M. avium-infected macrophages by activating IRE1α-RIDD. Thus, activation of IRE1α suppresses the intracellular survival of M. avium in macrophages.

Incidence and risk factors of Pneumocystis jirovecii pneumonia in Korean patients with inflammatory bowel disease.

BACKGROUND AND AIM: Little is known whether routine prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is needed in patients with inflammatory bowel disease (IBD) on immunosuppression, especially in Asian populations. We, therefore, sought to investigate the incidence and risk factors of PJP in patients with IBD in Korea. METHODS: We investigated the incidence of PJP in patients with IBD and compared the characteristics of IBD patients with PJP episodes (IBD-PJP group) with those of matched controls (IBD-only group) using a large, well-characterized referral center-based cohort. RESULTS: Among the 6803 IBD patients (3171 with Crohn's disease and 3632 with ulcerative colitis) enrolled in the Asan IBD Registry between June 1989 and December 2016, six patients (0.09%) were diagnosed with PJP. During the 57 776.0 patient-years of follow-up (median 7.2 years per patient), the incidence of PJP was 10.4 cases per 100 000 person-years, and none of these patients had received PJP prophylaxis. In case-control analysis, the IBD-PJP group (n = 6) showed significantly higher C-reactive protein level at diagnosis of IBD (P = 0.006), as well as higher exposure to corticosteroids (P = 0.017), than did controls (n = 24). In addition, the IBD-PJP group showed higher rates of double (50% vs 12.5%) or triple (33.3% vs 4.2%) immunosuppression than did controls, although these are not statistically significant. CONCLUSIONS: Although the incidence of PJP in Korean patients with IBD is low, careful monitoring is necessary for the early detection of PJP. In addition to the patients receiving double or triple immunosuppression, PJP prophylaxis should be considered especially in patients with severe disease activities requiring corticosteroids.

TNF-α-mediated ER stress causes elimination of Mycobacterium fortuitum reservoirs by macrophage apoptosis.

Mycobacterium fortuitum (MF), a rapidly growing nontuberculosis mycobacterium, is recognized as an important human pathogen. We investigated whether the endoplasmic reticulum (ER) stress response is associated with the apoptosis of MF-infected macrophages. The expression of ER molecular chaperones was significantly induced by MF infection. We found that MF-induced reactive oxygen species (ROS) generation plays a critical role in the induction of ER stress-mediated apoptosis. Excess TNF-α in the ER led to ER stress-mediated apoptosis during MF infection. The intracellular survival of MF was significantly increased by TNF-α knockdown compared with the control. This is the first report of MF-induced TNF-α as a cause of ER stress in macrophages. Furthermore, we found that TLR2-mediated ER stress response contributed to the elimination of intracellular MF in vivo. These results suggest that TNF-α-mediated ER stress during MF infection contributes to the suppression of intracellular survival of MF in macrophages. Our findings provide new insight into the importance of ER stress in mycobacterial infection.-Oh, S.-M., Lim, Y.-J., Choi, J.-A., Lee, J., Cho, S.-N., Go, D., Kim, S.-H., Song, C.-H. TNF-α-mediated ER stress causes elimination of Mycobacterium fortuitum reservoirs by macrophage apoptosis.

Ensembles of natural language processing systems for portable phenotyping solutions.

BACKGROUND: Manually curating standardized phenotypic concepts such as Human Phenotype Ontology (HPO) terms from narrative text in electronic health records (EHRs) is time consuming and error prone. Natural language processing (NLP) techniques can facilitate automated phenotype extraction and thus improve the efficiency of curating clinical phenotypes from clinical texts. While individual NLP systems can perform well for a single cohort, an ensemble-based method might shed light on increasing the portability of NLP pipelines across different cohorts. METHODS: We compared four NLP systems, MetaMapLite, MedLEE, ClinPhen and cTAKES, and four ensemble techniques, including intersection, union, majority-voting and machine learning, for extracting generic phenotypic concepts. We addressed two important research questions regarding automated phenotype recognition. First, we evaluated the performance of different approaches in identifying generic phenotypic concepts. Second, we compared the performance of different methods to identify patient-specific phenotypic concepts. To better quantify the effects caused by concept granularity differences on performance, we developed a novel evaluation metric that considered concept hierarchies and frequencies. Each of the approaches was evaluated on a gold standard set of clinical documents annotated by clinical experts. One dataset containing 1,609 concepts derived from 50 clinical notes from two different institutions was used in both evaluations, and an additional dataset of 608 concepts derived from 50 case report abstracts obtained from PubMed was used for evaluation of identifying generic phenotypic concepts only. RESULTS: For generic phenotypic concept recognition, the top three performers in the NYP/CUIMC dataset are union ensemble (F1, 0.634), training-based ensemble (F1, 0.632), and majority vote-based ensemble (F1, 0.622). In the Mayo dataset, the top three are majority vote-based ensemble (F1, 0.642), cTAKES (F1, 0.615), and MedLEE (F1, 0.559). In the PubMed dataset, the top three are majority vote-based ensemble (F1, 0.719), training-based (F1, 0.696) and MetaMapLite (F1, 0.694). For identifying patient specific phenotypes, the top three performers in the NYP/CUIMC dataset are majority vote-based ensemble (F1, 0.610), MedLEE (F1, 0.609), and training-based ensemble (F1, 0.585). In the Mayo dataset, the top three are majority vote-based ensemble (F1, 0.604), cTAKES (F1, 0.531) and MedLEE (F1, 0.527). CONCLUSIONS: Our study demonstrates that ensembles of natural language processing can improve both generic phenotypic concept recognition and patient specific phenotypic concept identification over individual systems. Among the individual NLP systems, each individual system performed best when they were applied in the dataset that they were primary designed for. However, combining multiple NLP systems to create an ensemble can generally improve the performance. Specifically, the ensemble can increase the results reproducibility across different cohorts and tasks, and thus provide a more portable phenotyping solution compared to individual NLP systems.

Digital Measurements With Hallux Valgus Before and After Modified Long Oblique Osteotomy.

Radiographic measurements of the hallux valgus (HV) angle (HVA) and the first intermetatarsal angle (IMA1-2) are important for assessing the severity of HV. The purpose of the present study was to digitally investigate the intraobserver and interobserver reliability of various methods for measuring HVA and IMA1-2, as well as each axis composing them, such as axes of the first proximal phalanx (PP1), the first metatarsal (MT1), and the second metatarsal (MT2) in patients with a metatarsal shaft osteotomy-modified long oblique osteotomy. Three orthopedic surgeons measured the HVA, IMA1-2, and the angles between axes of PP1, MT1, and MT2, and the digitally-set reference line (α, ß, and γ, respectively) using 6 different methods for 39 patients with a minimum of 1 year of follow-up after operative treatment. The intraobserver and interobserver intraclass correlation coefficients (ICC) and agreements were calculated. Significant differences were observed within the methods with regard to preoperative HVA, IMA1-2, α, and ß, and postoperative IMA1-2 and ß. Intraobserver and interobserver ICC were high or very high in most methods. For HVA and IMA1-2, the method connecting the center of the head through the center of the base showed the highest agreement. For α, ß, and γ, this method showed the highest agreement, more than 80% intraobserver and interobserver agreement and a discrepancy of <2°. A digital method connecting the center of the head through the center of the base was regarded as the least variable for the HV evaluation and the assessment of the radiographic results in a metatarsal shaft osteotomy-modified long oblique osteotomy.

Cytotoxicity and proinflammatory cytokine expression induced by interim resin materials in primary cultured human dental pulp cells.

STATEMENT OF PROBLEM: Acrylic resin materials for interim restoration may adversely affect pulp tissue during the polymerization phase. PURPOSE: The purpose of this in vitro study was to determine the cytotoxic and proinflammatory cytokine production effects induced by interim resin materials in primary cultured human dental pulp cells (hDPCs). MATERIAL AND METHODS: Five interim resin materials were evaluated: 3 types of chemically activated products, 1 light-activated product, and 1 computer-aided design and computer-aided manufacturing (CAD-CAM) product. After obtaining eluates from interim resin materials that either were in the process of polymerizing or were already polymerized, these extracts were cocultured with hDPCs under serially diluted conditions (50%, 25%, 12.5%, 6.25%, and 3.125%) for 24 hours with positive (1% phenol) and negative (distilled water) controls. A cell viability assay with tetrazolium was used to evaluate toxic effects on the cells, and images of both live and dead cells were captured using confocal microscopy. Proinflammatory cytokine levels were measured using cytokine antibody arrays. All experiments were independently repeated 3 times, and data were analyzed using 1-way ANOVA and post hoc Tukey honest significant differences test (α=.05). RESULTS: Cell viabilities less than 70% were observed from the eluates of the 3 chemically activated products under the 50% conditions. Among the chemically activated products, the adverse effects were significantly greater with eluates derived from the polymerizing phase compared than those that had already polymerized, as shown by confocal microscopy images of live and dead cells. However, the light-activated and CAD-CAM-fabricated products did not adversely affect the hDPCs. Significantly increased levels of proinflammatory cytokines were not detected in 12.5% of extract from polymerizing compared with distilled water control. CONCLUSIONS: The 50% eluates derived from chemically activated interim resin during the polymerizing phase were cytotoxic to hDPCs and may adversely affect pulp tissue. Recommendations such as excess washing are necessary during fabrication.

Titanium-Silver Alloy Miniplates for Mandibular Fixation: In Vitro and In Vivo Study.

PURPOSE: Titanium (Ti) alloys have received considerable attention as materials for oral and maxillofacial surgery, which require high mechanical strength, osteosynthesis, and biocompatibility. The objective was to implant miniplates fabricated from commercially pure Ti (CP Ti) and newly developed Ti-silver (Ag) alloy in fractured mandibles of adult dogs after preliminary mechanical and biological characterization. MATERIALS AND METHODS: The surface characteristics, biocompatibility, and pre-osteoblast adhesion and proliferation of CP Ti (grade 3) and Ti-Ag (2 at% Ag) alloys were evaluated. Next, the bending strength of 6- and 8-hole miniplates fabricated from CP Ti and Ti-Ag was compared according to ISO (International Organization for Standardization) 9585. Six-hole miniplates were implanted for 12 weeks in fractured mandibles of adult dogs. The Ag ion concentration in each alloy and implanted bone block with soft tissue was measured by inductively coupled plasma mass spectroscopy after euthanasia according to ISO 10993-12. RESULTS: Precipitated Ag was detected in Ti-Ag by alpha- and beta-phase Ti in x-ray powder diffraction. The biocompatibility with pre-osteoblasts of Ti-Ag and CP Ti was comparable in terms of cytotoxicity, cell adhesion, and proliferation (P > .05). Ti-Ag miniplates had up to 3-fold greater bending strength than CP Ti miniplates (P < .05). An in vivo study showed that CP Ti and Ti-Ag miniplates had comparable soft and hard tissue regeneration ability (P > .05). Ag ions were detected in Ti-Ag alloys and applied mandible blocks. CONCLUSIONS: The results of this study suggest that Ti-Ag alloys can be used to produce miniplates with high mechanical properties, as well as considerable biocompatibility, osteosynthesis ability, and Ag ion-release properties. Further studies, including preclinical investigations, are required to enable clinical use of Ti-Ag bone plates.

Air atmospheric-pressure plasma-jet treatment enhances the attachment of human gingival fibroblasts for early peri-implant soft tissue seals on titanium dental implant abutments.

OBJECTIVE: Although dental implants are commonly used for tooth restoration, there is a lack of studies of treatment regimens for preventing extra-oral infection and decreasing osseointegration failures by establishing early peri-implant soft tissue seals on titanium dental implant abutments. In this study, air atmospheric-pressure plasma-jet (AAPPJ) treatment was applied to titanium disks to assay the potential for early peri-implant soft tissue seals on titanium dental implant abutment. MATERIALS AND METHODS: After titanium disks were treated with AAPPJ for 10 s at 250, 500, 1000 and 1500 sccm, surface analysis was performed; the control group received air only or no treatment. Human gingival fibroblasts (HGF) were seeded onto the specimens for evaluating cell attachment and proliferation and adherent-cell morphology was visualized via confocal microscopy. RESULTS: In AAPPJ-treated specimens, the water contact angle decreased according to increased flow rate. Oxygen composition increased in XPS, but no topographical changes were detected. The effect of AAPPJ treatment at 1000 sccm was apparent 2 mm from the treated spot, with a 20% increase in early cell attachment and proliferation. Adherent HGF on AAPPJ-treated specimens displayed a stretched phenotype with more vinculin formation than the control group. CONCLUSIONS: Within the limitations of this study, the results indicate that AAPPJ treatment may enhance the early attachment and proliferation of HGF for establishing early peri-implant soft tissue seals on titanium dental implant abutments with possible favorable effects of osseointegration of dental implant.

Air atmospheric pressure plasma jet pretreatment for drop-wise loading of dexamethasone on hydroxyapatite scaffold for increase of osteoblast attachment.

Periodontal disease affects alveolar bone resorption around the involved teeth. To gain bone height, bone graft materials have been widely used with drug carriers. Application of an atmospheric pressure plasma jet (APPJ) treatment is widely studied due to its ability to change surface characteristics without topographical change. The aim of this study is to identify whether the air APPJ (AAPPJ) treatment before drop-wise loading performance could change loaded amount of dexamethasone, and induce increase of cell attachment and proliferation. The results suggested that AAPPJ treatment decreased the contact angle down to about 13 degrees, which increased gradually but significantly lowered at least 4 days compared to no-treated group. After AAPPJ treatment, hydrocarbon was removed with change of zeta potential into positive charge. However, the AAPPJ treatment did not change the quantity or releasing profile of dexamethasone (p > 0.05). Confocal analysis combined with DNA proliferation analysis showed increase of osteoblast attachment and proliferation. Hence, AAPPJ could be a useful pretreatment method before drop-wise loading on HA scaffold with dexamethasone for increase of osteoblast attachment.

Utilization of systematic error-assessment software to improve phylogenetic accuracy.

Unlike classical systems based on the use of morphological data, modern phylogenetic analyses use genetic information to construct phylogenetic trees. Ongoing research in the field of phylogenetics is evaluating the accuracy of phylogenetic estimation results and the reliability of phylogenetic trees to explain evolutionary relationships. Recently, the probability of stochastic errors in large-scale phylogenetic datasets has decreased, while the probability of systematic errors has increased. Therefore, before constructing a phylogenetic tree, it is necessary to assess the causes of systematic bias to improve the accuracy of phylogenetic estimates. We performed analyses of three datasets (Terebelliformia, Daphniid, and Glires clades) using bioinformatics software to assess systematic error and improve phylogenetic tree accuracy. Then, we proposed a combination of systematic biases capable of discerning the most suitable gene markers within a series of taxa and generating conflicting phylogenetic topologies. Our findings will help improve the reliability of phylogenetic software to estimate phylogenies more accurately by exploiting systematic bias.

Multifunctional Molybdenum-Based Nanoclusters Engineered Gelatin Methacryloyl as In Situ Photo-Cross-Linkable Hybrid Hydrogel Dressings for Enhanced Wound Healing.

Skin injuries and wounds present significant clinical challenges, necessitating the development of advanced wound dressings for efficient wound healing and tissue regeneration. In this context, the advancement of hydrogels capable of counteracting the adverse effects arising from undesirable reactive oxygen species (ROS) is of significant importance. This study introduces a hybrid hydrogel with rapid photocuring and excellent conformability, tailored to ameliorate the hostile microenvironment of damaged skin tissues. The hybrid hydrogel, composed of photoresponsive Gelatin Methacryloyl (GelMA) and Molybdenum-based nanoclusters (MNC), exhibits physicochemical characteristics conductive to skin regeneration. In vitro studies demonstrated the cytocompatibility and ROS-responsive behavior of the MNC/GelMA hybrid hydrogels, confirming their ability to promote human dermal fibroblasts (HDF) functions. The incorporation of MNC into GelMA not only enhances HDF adhesion, proliferation, and migration but also shields against oxidative damage induced by hydrogen peroxide (H2O2). Notably, in vivo evaluation in murine full-thickness skin defects revealed that the application of hybrid hydrogel dressings led to reduced inflammation, accelerated wound closure, and enhanced collagen deposition in comparison to control groups. Significantly, this study introduced a convenient approach to develop in situ ROS-scavenging hydrogel dressings to accelerate the wound healing process without the need for exogenous cytokines or medications. We consider that the nanoengineering approach proposed herein offers potential possibilities for the development of therapeutic hydrogel dressings addressing various skin-related conditions.