An injectable hydrogel loaded with GMSCs-derived neural lineage cells promotes recovery after stroke.

Ischemic stroke is a devastating medical condition with poor prognosis due to the lack of effective treatment modalities. Transplantation of human neural stem cells or primary neural cells is a promising treatment approach, but this is hindered by limited suitable cell sources and low in vitro expansion capacity. This study aimed i) to use small molecules to reprogram gingival mesenchymal stem cells (GMSCs) commitment to the neural lineage cells in vitro, and ii) to use hyaluronic acid (HA) hydrogel scaffolds seeded with GMSCs-derived neural lineage cells to treat ischemic stroke invivo. Neural induction was carried out with a small molecule cocktail-based one-step culture protocol over a period of 24 hours. The induced cells were analyzed for expression of neural markers with immunocytochemistry and qRT-PCR. The SD rats (n=100) were subjected to the middle cerebral artery occlusion (MCAO) reperfusion ischemic stroke model. Then, after 8 days post-MCAO, the modelled rats were randomly assigned to six study groups (n=12 per group): (i) GMSCs, (ii) GMSCs-derived neural lineage cells, (iii) HA and GMSCs-derived neural lineage cells, (iv) HA, (v) PBS, and (vi) sham transplantation control, and received their respective transplantation. Evaluation of post-stroke recovery were performed by the behavioral tests and histological assessments. The morphologically altered nature of neural lineages has been observed of the GMSCs treated with small molecules compared to the untreated controls. As shown by the qRT-PCR and immunocytochemistry, small molecules further signifcantly enhanced the experession level of neural markers of GMSCs as compared with the untreated controls (all p<0.05). Intracerebral injection of self-assembling HA hydrogel carrying GMSCs-derived neural lineage cells promoted the recovery of neural function and reduced ischemic damage in rats with ischemic stroke, as demonstrated by histological examination and behavioral assessments (all p<0.05). In conclusion, the small molecule cocktail significantly enhanced the differentiation of GMSCs into neural lineage cells. The HA hydrogel was found to facilitate the proliferation and differentiation of GMSCs-derived neural lineage cells. Furthermore, HA hydrogel seeded with GMSCs-derived neural lineage cells could promote tissue repair and functional recovery in rats with ischemic stroke and may be a promising alternative treatment modality for stroke.

Polyp segmentation based on implicit edge-guided cross-layer fusion networks.

Polyps are abnormal tissue clumps growing primarily on the inner linings of the gastrointestinal tract. While such clumps are generally harmless, they can potentially evolve into pathological tumors, and thus require long-term observation and monitoring. Polyp segmentation in gastrointestinal endoscopy images is an important stage for polyp monitoring and subsequent treatment. However, this segmentation task faces multiple challenges: the low contrast of the polyp boundaries, the varied polyp appearance, and the co-occurrence of multiple polyps. So, in this paper, an implicit edge-guided cross-layer fusion network (IECFNet) is proposed for polyp segmentation. The codec pair is used to generate an initial saliency map, the implicit edge-enhanced context attention module aggregates the feature graph output from the encoding and decoding to generate the rough prediction, and the multi-scale feature reasoning module is used to generate final predictions. Polyp segmentation experiments have been conducted on five popular polyp image datasets (Kvasir, CVC-ClinicDB, ETIS, CVC-ColonDB, and CVC-300), and the experimental results show that the proposed method significantly outperforms a conventional method, especially with an accuracy margin of 7.9% on the ETIS dataset.

Pharmacodynamic and Toxicity Studies of 6-Isopropyldithio-2'-guanosine Analogs in Acute T-Lymphoblastic Leukemia.

(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010. (2) Results: YLS010 has exhibited potent anti-tumor effects by inducing cell apoptosis and ferroptosis. A dose gradient was designed for in vivo experiments based on tentative estimates of the toxicity dose using acute toxicity in mice and long-term toxicity in rats. The study found that YLS010 at a dose of 8 mg/kg prolonged the survival of late-stage acute T-lymphoblastic leukemia mice in the mouse model study. (3) Conclusions: YLS010 has demonstrated specific killing effects against acute T-lymphoblastic leukemia both in vivo and in vitro. Preclinical studies of YLS010 offer a new opportunity for the treatment of patients with acute T-lymphoblastic leukemia in clinical settings.

Oxygen enrichment mediated by calcium peroxide loaded gelatin methacrylate hydrogel eradicates periodontal biofilms.

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment.

Interactions of Neuronally Induced Stem Cells from Apical Papilla Spheres, Stems Cells from Apical Papilla, and Human Umbilical Vascular Endothelial Cells on Vasculogenesis and Neurogenesis.

INTRODUCTION: Stem cell-based dental pulp regeneration has been extensively studied, mainly focusing on exploiting dental stem cells' osteogenic and angiogenic potentials. Dental stem cells' neurogenic role is often overlooked. Stem cells from apical papilla (SCAPs), originating from the neural crest and capable of sphere formation, display potent neurogenic capacity. This study aimed to investigate the interactions of neuronally induced stem cells from apical papilla (iSCAP) spheres, SCAPs, and human umbilical vascular endothelial cells (HUVECs) on vasculogenesis and neurogenesis. METHODS: SCAPs were isolated and characterized using flow cytometry and multilineage differentiation assays. SCAP monolayer culture and spheres were neuronally induced by a small molecule neural induction medium, and the neural gene expression and neurite formation at days 0, 3, and 7 were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and using phase-contrast light and fluorescence microscopy. Direct coculture or pulp-on-chip was used to investigate iSCAP sphere interaction with SCAPs and HUVECs. RT-qPCR, fluorescence microscopy, and immunostaining with ß-tubulin III, alpha-smooth muscle actin, and CD31 were used to study neural gene expression, neurite formation, and neurovascular cell interactions. RESULTS: Neural induction medium with small molecules rapidly induced SCAP differentiation toward neural-like cells. Gene expression of Nestin, ß-tubulin III, microtubule-associated protein 2, neuron-specific enolase, and NeuN was higher in iSCAP spheres than in iSCAPs. iSCAP spheres formed more and longer neurites compared with iSCAPs. iSCAP sphere, HUVEC, and SCAP direct coculture significantly enhanced vessel formation along with up-regulated VEGF (P < .001) and multiple neural markers, such as Nestin (P < .01), microtubule-associated protein 2 (P < .001), S100 (P < .001), and NG2 (P < .001). iSCAP spheres, SCAPs, and HUVECs cultured in a pulp-on-chip system promoted endothelial and neural cell migration toward each other and alpha-smooth muscle actin-positive and CD31-positive cells assembling for the vascular constitution. CONCLUSIONS: iSCAP-formed spheres interact with SCAPs and HUVECs, promoting vasculogenesis and neurogenesis.

Impact of Bariatric Surgery on Cardiac Function and Structure in Chinese Patients with Obesity.

Introduction: Obesity contributes to cardiac dysfunction and has an impact on atherosclerotic cardiovascular disease. Bariatric surgery (BS) is being considered a therapeutic option for patients with obesity and also can improve cardiac function. Very few studies considered the Chinese population. This study aimed to examine the effect of BS on cardiac function and structure in Chinese subjects with obesity. Methods: A single-center retrospective analysis of 143 patients with obesity was included. To observe and analyze the short-term, midterm, and long-term effects of BS on cardiovascular function and structure, the study population was divided into three groups according to the time of review. Fifty-two patients in group T1 (re-examination within 12 months); 53 patients in group T2 (re-examination within 12 to 24 months); and 38 patients in group T3 (re-examination over 24 months). The effects of BS on the cardiac function and structure were evaluated by analyzing the echocardiographic parameters. Results: After BS, body mass index (BMI) decreased from 39.7 ± 8.0 to 28.4 ± 6.4 kg/m2 (P < 0.001). Blood pressure decreased significantly. Left ventricular mass index (LVMI) decreased (43.7 ± 16.4 to 37.8 ± 13.4 g/m2.7, P < 0.001). The change in LVMI was correlated with the change in BMI (R2 = 0.14, P < 0.001). In subgroup analyses at different follow-ups, echocardiographic parameters showed varying degrees of change compared with the baseline. Conclusions: Significant weight loss by BS was associated with improved left ventricular structure and function in Chinese patients with obesity, suggesting potential favorable effects of BS on the cardiac function and structure.

Self-powered and broadband CuSCN/Si heterojunction photodetector for multi-color imaging based on diffuse reflection mode.

Copper thiocyanate (CuSCN) has been widely used in photodetectors (PDs). However, the reported CuSCN-based PDs are suffered from narrow operating wavelength range and relatively low photodetection performance. Here, we fabricate an CuSCN/Si heterojunction PD by a simple low-temperature solution spin-coating method achieving excellent performance. Our designed CuSCN/Si PD exhibits a broadband response range covering ultraviolet-visible-infrared, a high detectivity of 2.26 × 1012Jones coming from an ultralow dark current of 23 pA, and a decent responsivity of 11 mA W-1, a high linear dynamic range of 122 dB, and short response time of 25/150µ(rise and decay time). Moreover, we demonstrate multi-color imaging across the wide wavelength range, indicating the CuSCN/Si PD has a promising potential in the imaging field. This work may pave the way for fabricating low-cost, nontoxicity, and high-performance CuSCN-based PD and broadening its applications.

Pneumococcal vaccination coverage among US adults enrolled in Medicaid and newly diagnosed with underlying medical conditions.

BACKGROUND: Adults with chronic or immunocompromising conditions have an elevated risk of invasive pneumococcal disease, yet their pneumococcal vaccination rates remain low. METHODS: This retrospective cohort study used the IBM MarketScan® Multi-State Medicaid database to examine pneumococcal vaccination uptake among adults 19-64 years of age with underlying conditions. Gompertz accelerated failure time model was used to examine factors associated with vaccination. RESULTS: In the study population of 108,159 adults, the vaccination rate was 4.1% after 1 year of follow-up and 19.4% after 10 years. The mean time from initial diagnosis to vaccination was 3.9 years. Adults aged 35-49 and 50-64 years (relative to 19-34) or those receiving an influenza vaccination were more likely to receive a pneumococcal vaccination. Adults with HIV/AIDS were more likely, while adults with chronic heart or lung disease, alcohol or tobacco dependence, or cancer were less likely to be vaccinated than adults with diabetes mellitus. Adults diagnosed by specialists were less likely to be vaccinated than those diagnosed by primary care providers. CONCLUSIONS: The rates of pneumococcal vaccination among adults with Medicaid plans and underlying conditions were well under Healthy People Initiative targets. Insights into factors associated with vaccination can inform efforts to improve vaccination rates among this population.

Direct contact with endothelial cells drives dental pulp stem cells toward smooth muscle cells differentiation via TGF-ß1 secretion.

AIM: Prevascularization is vital to accelerate functional blood circulation establishment in transplanted engineered tissue constructs. Mesenchymal stem cells (MSCs) or mural cells could promote the survival of implanted endothelial cells (ECs) and enhance the stabilization of newly formed blood vessels. However, the dynamic cell-cell interactions between MSCs, mural cells and ECs in the angiogenic processes remain unclear. This study aimed to explore the interactions of human umbilical vein ECs (HUVECs) and dental pulp stem cells (DPSCs) in an in vitro cell coculture model. METHODOLOGY: Human umbilical vascular ECs and DPSCs were directly cocultured or indirectly cocultured with transwell inserts in endothelial basal media-2 (EBM-2) supplemented with 5% FBS for 6 days. Expression of SMC-specific markers in DPSCs monoculture and HUVEC+DPSC cocultures was assessed by western blot and immunofluorescence. Activin A and transforming growth factor-beta 1 (TGF-ß1) in conditioned media (CM) of HUVECs monoculture (E-CM), DPSCs monoculture (D-CM) and HUVEC+DPSC cocultures (E+D-CM) were analysed by enzyme-linked immunosorbent assay. TGF-ß RI kinase inhibitor VI, SB431542, was used to block TGF-ß1/ALK5 signalling in DPSCs. RESULTS: The expression of SMC-specific markers, α-SMA, SM22α and Calponin, were markedly increased in HUVEC+DPSC direct cocultures compared to that in DPSCs monoculture, while no differences were demonstrated between HUVEC+DPSC indirect cocultures and DPSCs monoculture. E+D-CM significantly upregulated the expression of SMC-specific markers in DPSCs compared to E-CM and D-CM. Activin A and TGF-ß1 were considerably higher in E+D-CM than that in D-CM, with upregulated Smad2 phosphorylation in HUVEC+DPSC cocultures. Treatment with activin A did not change the expression of SMC-specific markers in DPSCs, while treatment with TGF-ß1 significantly enhanced these markers' expression in DPSCs. In addition, blocking TGF-ß1/ALK5 signalling inhibited the expression of α-SMA, SM22α and Calponin in DPSCs. CONCLUSIONS: TGF-ß1 was responsible for DPSC differentiation into SMCs in HUVEC+DPSC cocultures, and TGF-ß1/ALK5 signalling pathway played a vital role in this process.

Regional factors associated with pneumococcal vaccination coverage among U.S. adults with underlying chronic or immunocompromising conditions.

The Centers for Disease Control recommends pneumococcal vaccination for U.S. adults aged 19-64 years with chronic or immunocompromising conditions, however, vaccination coverage is low and regional variations in coverage are rarely studied. This study examined pneumococcal vaccination coverage at the metropolitan statistical area (MSAs) level and identified regional factors associated with pneumococcal vaccination using the combined IBM® Watson Health MarketScan® Commercial and Medicare Supplemental databases. Pneumococcal vaccination coverage, clinical and socioeconomic factors were calculated for each MSA. Ordinary least square and spatial regression models were used to examine factors associated with vaccination. Results indicated that the national pneumococcal vaccination coverage was 13.4% with a large variation across MSAs (0-34%). The spatial error model, model with the best fit, showed that proportions of the population who were ≥50 years of age, received an influenza vaccine, or had health maintenance organization health plans were positively associated with pneumococcal vaccination coverage. In summary, we found that national pneumococcal vaccination coverage was low and there was substantial variation across MSAs. Regional factors identified may help inform interventions to improve pneumococcal vaccination coverage across geographies.

Effects of L-Chg10-Teixobactin on Viability, Proliferation, and Osteo/Odontogenic Differentiation of Stem Cells from Apical Papilla.

INTRODUCTION: Intracanal medicament is one of the essential steps for ensuring success in regenerative endodontic procedures. L-Chg10-teixobactin is a novel antimicrobial agent that exhibited potent antibacterial and antibiofilm effects against Enterococcusfaecalis at low concentrations compared with ampicillin. At the same time, its cytotoxicity on dental stem cells has not been studied. This study aimed to investigate the effects of L-Chg10-teixobactin on the viability, proliferation, migration, and osteo/odontogenic differentiation of stem cells from apical papilla (SCAPs). MATERIALS AND METHODS: SCAPs isolated from immature human third molars were treated with various concentrations of L-Chg10-teixobactin, calcium hydroxide, and dimethyl sulfoxide. The viability and proliferation of SCAPs were assessed using the LIVE/DEAD Viability/Cytotoxicity Kit and Cell Counting Kit-8. A scratch wound healing test was used to evaluate the lateral migration capacity of SCAPs. Alkaline phosphatase (ALP) activity, calcium mineralization ability tests -ie, ALP staining and alizarin red S staining, and quantitative real-time polymerase chain reaction were performed to assess the osteo /odontogenic differentiation of SCAPs. RESULTS: The tested concentrations of L-Chg10-teixobactin (0.01, 0.02, and 0.03 mg/mL), 1 mg/mL calcium hydroxide, and 0.03% dimethyl sulfoxide had no significant cytotoxic effect on SCAPs at any time point (P > .05). Besides, there were no significant differences between the control and experimental groups in SCAPs' viability, proliferation, and migration. L-Chg10-teixobactin upregulated the gene expression of osteo/odontogenic markers in SCAPs, while no significant difference was found in the ALP activity and alizarin red S staining. CONCLUSIONS: L-Chg10-teixobactin demonstrated excellent biocompatibility on SCAPs at concentrations from 0.01 to 0.03 mg/mL and potentially enhance the osteo/odontogenic differentiation of SCAPs; suggesting its promising role as root canal medicament for regenerative endodontic procedures.

Two new bibenzyls from Pleione grandiflora (Rolfe) Rolfe and their antioxidant activity.

Two new bibenzyls (1 and 2) were isolated from the pseudobulbs of Pleione grandiflora (Rolfe) Rolfe along with six known compounds, including isoarundinin I (3), isoarundinin II (4), bulbocodin D (5), batatasin III (6), 5,3'-dihydroxy- 4-(p-hydroxybenzyl)-3-methoxybibenzyl (7) and shancigusin F (8). Their structures were established on the basis of spectroscopic methods. These compounds showed potent DPPH free radical scavenging effects with IC50 values ranging from 49.72 ± 0.35 µM to 65.41 ± 0.49 µM.

Formation of Three-Dimensional Spheres Enhances the Neurogenic Potential of Stem Cells from Apical Papilla.

Cell-based neural regeneration is challenging due to the difficulty in obtaining sufficient neural stem cells with clinical applicability. Stem cells from apical papilla (SCAPs) originating from embryonic neural crests with high neurogenic potential could be a promising cell source for neural regeneration. This study aimed to investigate whether the formation of 3D spheres can promote SCAPs' neurogenic potential. MATERIAL AND METHODS: Three-dimensional SCAP spheres were first generated in a 256-well agarose microtissue mold. The spheres and single cells were individually cultured on collagen I-coated µ-slides. Cell morphological changes, neural marker expression, and neurite outgrowth were evaluated by confocal microscope, ELISA, and RT-qPCR. RESULTS: Pronounced morphological changes were noticed in a time-dependent manner. The migrating cells' morphology changed from fibroblast-like cells to neuron-like cells. Compared to the 2D culture, neurite length, number, and the expression of multiple progenitors, immature and mature neural markers were significantly higher in the 3D spheres. BDNF and NGF-ß may play a significant role in the neural differentiation of SCAP spheres. CONCLUSION: The formation of 3D spheres enhanced the neurogenic potential of SCAPs, suggesting the advantage of using the 3D spheres of SCAPs for treating neural diseases.

Prognostic effects of clinical parameters, genetic abnormalities, and subtypes in primary gastric diffuse large B-cell lymphoma: a cohort analysis of 146 patients.

This study included 146 primary gastric diffuse large B-cell lymphoma patients. Next-generation RNA sequencing and fluorescent in situ hybridization were performed on tumors from 27 and 38 patients, respectively. Five-year and 10-year overall survival (OS) rates were 77% and 57%, respectively. Lugano and TNM clinical stage were independent survival factors. Tier I mutation was found in 21 patients. The genetic subtypes were A53 (n = 3), MCD (n = 5), BN2 (n = 5), N1 (n = 5), EZB (n = 1), and NOS (n = 8). OS was significantly shorter in high-risk genetic subtypes (A53, MCD, and N1) than low-risk subtypes (BN2, EZB, and NOS). Frequencies of high-risk genetic subtypes were higher in patients with Lugano stage II/IV and TNM clinical stage III + IV than in those with Lugano stage I and TNM clinical stage I + II. Although genetic testing was performed in only a small number of cases, the results suggested that high-risk genetic subtypes were associated with advanced clinical stages and shorter survival.

Long-Term Treatment Outcomes of the Elder Patients with Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma with Definitive Chemoradiotherapy or Radiotherapy.

Background: Few randomized trials are available to guide clinical management of elderly patients with esophageal cancer. Therefore, treatment approaches for the elderly are challenging. Objective: We believe that chemotherapy and radiotherapy are more effective than radiotherapy alone. We envision that chemotherapy is more effective than radiotherapy alone in elderly patients with esophageal cancer. Methods: Retrospective data of patients aged 70 years and older from 2008 to 2015 at our institution were analyzed. Of 61 eligible patients, 32 received definitive CTR and 29 received RT alone. Progression-free survival (PFS) was 16 months (range, 1-67 months), and the median overall survival was 19 months. Median PFS and OS in the chemoradiotherapy group were 17 months (95% confidence interval (CI), 15.1-24.8 months) and 22 months (95% confidence interval (CI), 20.4-32.7 months), respectively. Results: The median PFS and OS in the radiotherapy group were 16 months and 16 months, respectively. The OS rates at 1, 2, 3, and 5 years were 82%, 42.6%, 19.7%, and 6.6%, respectively. There was no difference in PFS between CRT and RT, but there was an advantage in OS for CRT. Positive nodules had an effect on PFS and OS. Conclusions: CRT is effective in elderly patients with nodal invasion of esophageal cancer. Higher radiation doses had an effect on PFS and OS, but there was no difference in PFS and OS between CRT and RT. Therefore, treatment approaches for the elderly are challenging.

Three-dimensional electroconductive carbon nanotube-based hydrogel scaffolds enhance neural differentiation of stem cells from apical papilla.

The radical treatment of neurological impairments remains a major clinical challenge. Stem cells with high neural differentiation ability delivered by electroconductive hydrogel scaffolds have demonstrated promising applications in neural tissue regeneration. However, there are still challenges in designing bioactive scaffolds with good biocompatibility, appropriate electrical conductivity, and neurogenic niche. Herein, a three-dimensional (3D) electroconductive gelatin methacryloyl-multi-walled carbon nanotube/cobalt (GelMA-MWCNTs/Co) hydrogel scaffold was fabricated by incorporating MWCNTs/Co composites into a GelMA hydrogel matrix. The surface morphology, pore size, elastic modulus, swelling ratio, and conductivity of the hydrogels were measured. GelMA-MWCNTs/Co exhibited higher electrical conductivity than GelMA-MWCNTs. Live/dead and CCK8 assays demonstrated the good biocompatibility of the hydrogel for stem cells from apical papilla (SCAP) growth and differentiation. The cells encapsulated in the GelMA-MWCNTs and GelMA-MWCNTs/Co hydrogel scaffolds exhibited significant neuronal cell-like changes and a notable level of neuronal-specific marker expression after the electrical stimulation (ES) for 7 days, compared to that in the hydrogels without ES. Notably, the neurite spreading and Tuj1 fluorescent intensity of the SCAP in the electrically conductive GelMA-MWCNTs/Co hydrogel were more prominent compared to those of the other two groups. In addition, the 3D conductive hydrogel scaffolds advanced the neural differentiation of SCAP to an earlier time point. Considering these aspects, the novel electroconductive GelMA-MWCNTs/Co hydrogel synergized with ES greatly promotes SCAP neuronal differentiation.

Pneumococcal vaccination coverage among adults newly diagnosed with underlying medical conditions and regional variation in the U.S.

BACKGROUND: The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends pneumococcal vaccination for adults with chronic or immunocompromising conditions to prevent pneumococcal disease, yet vaccination rates are low and have limited information on regional variation. This study examines factors associated with pneumococcal vaccination in adults with underlying conditions and describes regional variation in vaccination across the U.S. METHODS: Using IBM MarketScan Commercial Database and Medicare Supplemental Database, this retrospective cohort study included adults ages 19-64 newly diagnosed with chronic (i.e. diabetes, chronic heart, lung, or liver disease, alcohol or tobacco dependence) or immunocompromising (i.e. cancer, chronic renal disease, organ transplant, HIV/AIDS, and asplenia) conditions in 2013. Adults were followed up until the time of pneumococcal vaccination, death, or December 31, 2019, whichever came first. Cox proportional hazards model was used to examine factors associated with vaccination. Vaccination rate was calculated by metropolitan statistical area (MSA) and visually represented on a U.S. map. RESULTS: 255,330 adults were included. Vaccination rate increased from 6.0% to 21.1% among adults with one year and five years of follow-up, respectively. It took 2.4 years on average for adults to receive vaccination after initial diagnosis. Adults ages 50-64, 35-49 (relative to 19-34) or receiving influenza vaccination were more likely to receive pneumococcal vaccinations. Adults with HIV/AIDS were more likely and those with other conditions were less likely to be vaccinated than those with diabetes. Adults being diagnosed by other providers were less likely to be vaccinated than those diagnosed by primary care providers. Vaccination rate varied largely across MSAs, ranging from 0.0% (Ames, IA; Cheyenne, WY) to 34.0% (Ann Arbor, MI). CONCLUSION: Pneumococcal vaccination remains low and most adults with underlying conditions are unvaccinated. Insights into factors associated with vaccination, including regional variability, can help to increase pneumococcal vaccination.

Vanishing Point Detection Method Based on Constrained Classification for Checkpoints on Urban Roads.

To solve the problems of computational complexity and inaccuracy in classical vanishing point detection algorithms, such as the cascaded Hough transform, a vanishing point detection method based on constrained classification is proposed. First, the short line data are filtered to avoid interference in straight line detection, and then, the line segment is screened and classified by hierarchical clustering according to the image characteristics of the line segment and the variation pattern of angle similarity. Subsequently, Three types of straight line segments with the most significant angle differences are acquired. To prevent the optimization algorithm from getting stuck in the "wrong" local optimum neighborhood or failing to locate the global optimum, a set of constraints are set to further restrict the search. Afterward, the classified line segments are projected into a finite rhombic space, which are then quantified. The point with the maximum vote is eventually identified as the vanishing point. Experimental results show that the proposed method not only greatly reduces the computational complexity of vanishing points but also largely improves the accuracy of vanishing point detection.

Intelligent wireless theranostic contact lens for electrical sensing and regulation of intraocular pressure.

Engineering wearable devices that can wirelessly track intraocular pressure and offer feedback-medicine administrations are highly desirable for glaucoma treatments, yet remain challenging due to issues of limited sizes, wireless operations, and wireless cross-coupling. Here, we present an integrated wireless theranostic contact lens for in situ electrical sensing of intraocular pressure and on-demand anti-glaucoma drug delivery. The wireless theranostic contact lens utilizes a highly compact structural design, which enables high-degreed integration and frequency separation on the curved and limited surface of contact lens. The wireless intraocular pressure sensing modulus could ultra-sensitively detect intraocular pressure fluctuations, due to the unique cantilever configuration design of capacitive sensing circuit. The drug delivery modulus employs an efficient wireless power transfer circuit, to trigger delivery of anti-glaucoma drug into aqueous chamber via iontophoresis. The minimally invasive, smart, wireless and theranostic features endow the wireless theranostic contact lens as a highly promising system for glaucoma treatments.

Determination of Transdermal Rate of Metallic Microneedle Array through an Impedance Measurements-Based Numerical Check Screening Algorithm.

Microneedle systems have been widely used in health monitoring, painless drug delivery, and medical cosmetology. Although many studies on microneedle materials, structures, and applications have been conducted, the applications of microneedles often suffered from issues of inconsistent penetration rates due to the complication of skin-microneedle interface. In this study, we demonstrated a methodology of determination of transdermal rate of metallic microneedle array through impedance measurements-based numerical check screening algorithm. Metallic sheet microneedle array sensors with different sizes were fabricated to evaluate different transdermal rates. In vitro sensing of hydrogen peroxide confirmed the effect of transdermal rate on the sensing outcomes. An FEM simulation model of a microneedle array revealed the monotonous relation between the transdermal state and test current. Accordingly, two methods were primely derived to calculate the transdermal rate from the test current. First, an exact logic method provided the number of unpenetrated tips per sheet, but it required more rigorous testing results. Second, a fuzzy logic method provided an approximate transdermal rate on adjacent areas, being more applicable and robust to errors. Real-time transdermal rate estimation may be essential for improving the performance of microneedle systems, and this study provides various fundaments toward that goal.