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This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer.A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not.The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status.The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Sugar substitutes have been recommended to be used for weight and glycemic control. However, numerous studies indicate that consumption of artificial sweeteners exerts adverse effects on glycemic homeostasis. Although sucralose is among the most extensively utilized sweeteners in food products, the effects and detailed mechanisms of sucralose on insulin sensitivity remain ambiguous. In this study, we found that bolus administration of sucralose by oral gavage enhanced insulin secretion to decrease plasma glucose levels in mice. In addition, mice were randomly allocated into three groups, chow diet, high-fat diet (HFD), and HFD supplemented with sucralose (HFSUC), to investigate the effects of long-term consumption of sucralose on glucose homeostasis. In contrast to the effects of sucralose with bolus administration, the supplement of sucralose augmented HFD-induced insulin resistance and glucose intolerance, determined by glucose and insulin tolerance tests. In addition, we found that administration of extracellular signal-regulated kinase (ERK)-1/2 inhibitor reversed the effects of sucralose on glucose intolerance and insulin resistance in mice. Moreover, blockade of taste receptor type 1 member 3 (T1R3) by lactisole or pretreatment of endoplasmic reticulum stress inhibitors diminished sucralose-induced insulin resistance in HepG2 cells. Taken together, sucralose augmented HFD-induced insulin resistance in mice, and interrupted insulin signals through a T1R3-ERK1/2-dependent pathway in the liver.

Background: Since non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity, cardiovascular disease, and diabetes, biomarkers for the diagnosis of NAFLD have become an important issue. Although cardiotrophin-1 (CT-1) has a protective effect on the liver in NAFLD animal models, the serum levels of CT-1 in human subjects with NAFLD were still unknown. Objective: The present study aimed to investigate the relationship between the circulating concentration of CT-1 and the severity of hepatic steatosis graded by the value of the controlled attenuation parameter (CAP) in humans. Design and Methods: The study was designed as a cross-sectional study, and a total of 182 subjects were enrolled. Hepatic steatosis measurement was carried out with a Firoscan® device and recorded by CAP. The enrolled study subjects were categorized into CAP < 238 dB/m, 238 ≤ CAP ≤ 259 dB/m, 260 ≤ CAP ≤ 290 dB/m, and CAP > 290 dB/m. Serum CT-1 concentrations were determined by enzyme-linked immunosorbent assay. The association between the serum CT-1 concentration and NAFLD was examined by multivariate linear regression analysis. Results: Body mass index, percentage of body fat, systolic and diastolic blood pressure, alanine aminotransferase (ALT), cholesterol, triglyceride, hemoglobin A1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly increased in groups with higher CAP value, whereas high-density lipoprotein cholesterol was significantly decreased. In addition, serum CT-1 concentrations were significantly decreased in subjects with higher CAP values. In multivariate linear regression models, including age, sex, body fat percentage, CAP, high sensitivity- C reactive protein, uric acid, creatinine, ALT, total cholesterol, and HOMA-IR, only age, CAP and uric acid independently associated with CT-1 levels. Moreover, having NAFLD was independently associated with CT-1 after adjustment for sex, obesity and type 2 diabetes. Conclusions: Serum CT-1 concentrations are decreased in subjects with NAFLD and negatively associated with CAP.

Separating oil from water allows us to reuse both fluids for various applications, leading to a more economical process. Membrane separation has been evidenced as a cost-effective process for wastewater treatment. A hollow fiber membrane made of polyacrylonitrile (PAN) is an excellent choice for separating oil from water because of its superior chemical resistance. Its low antifouling ability, however, reduces the effectiveness of its separation. Hence, in this study, we used tannic acid (TA) and FeIII complex to modify the surface of the PAN hollow fiber membrane. To improve membrane performance, different reaction times were investigated. The results demonstrate that even when the TA-FeIII covered the pores of the PAN membrane, the water flux remained constant. However, when an emulsion was fed to the feed solution, the flux increased from 50 to 66 LMH, indicating low oil adhesion on the surface of the modified membrane. When compared to the pristine membrane, the modified membrane had superior antifouling and reusability. As a result, the hydrophilic TA-FeIII complex on PAN surface improves overall membrane performance.

Light-sheet fluorescent microscopy has become the leading technique for in vivo imaging in the fields of disease, medicine, and cell biology research. However, designing proper illumination for high image resolution and optical sectioning is challenging. Another issue is geometric constraints arising from the multiple bulky components for illumination and detection. Here, we demonstrate that those issues can be well addressed by integrating nanophotonic meta-lens as the illumination component for LSFM. The meta-lens is composed of 800-nm-thick GaN nanostructures and is designed for a light-sheet well-adapted to biological specimens such as the nematode Caenorhabditis elegans (C. elegans). With the meta-lens, the complexity of the LSFM system is significantly reduced, and it is capable of performing multicolor fluorescent imaging of live C. elegans with cellular resolution. Considering the miniature size and plane geometry of the meta-lens, our system enables a new design for LSFM to acquire in vivo images of biological specimens with high resolution.

Background/purpose Immediate placement in the esthetic zone has been a predictable treatment option. However, it requires the clinician to be experienced and knowledgeable about esthetic diagnosis, accurate 3-dimensional (3D) implant placement, and restoratively driven planning/placement. Therefore, this study aimed to investigate a novel workflow integrating dynamic navigation to immediate single-implant placement in the aesthetic zone. Materials and methods We included ten patients who required at least one implant in the esthetic area and were treated with post-extraction socket implant placement. Osteotomy and implant placement followed computer-assisted implant positioning and image-guided dynamic navigation. Treatment outcomes were implant success rates, surgical and prosthetic complications, marginal bone level (MBL), modified pink esthetic score, and white score. Results In the consecutive clinical cases, patients were satisfied with implant therapy's function and esthetic outcome in the esthetic zone. No other surgical or biological complications occurred, which accounts for the 100% cumulative success rate. The mean MBL was −0.76 ± 0.15 mm assessed using standardized intraoral digital periapical radiographs. Conclusion The novel application of a dynamic guided navigation system is a dependable clinical protocol to obtain optimal implant position/angulation and esthetics on immediate implant placement.

In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPARα) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1., Using a model of time-restricted feeding in mice, Levine et al. show that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.

Background This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. Methods Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. Results Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn’s disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non–reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. Conclusions The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Purpose: Immune checkpoint inhibitors are effective therapies for advanced hepatocellular carcinoma (HCC); however, comparisons of the clinical efficacy and safety profile for these drugs are still scarce. Thus, the aims of this study were to investigate the differences in efficacy and safety between nivolumab and pembrolizumab in unresectable HCC patients in a real-world setting. Patients and methods: A total of 115 patients who received treatment with nivolumab (n = 73) or pembrolizumab (n = 42) in combination with or without tyrosine kinase inhibitors was enrolled. Therapeutic response, survival outcomes, and safety profiles were compared among these groups. Multivariate analysis of survival response was performed using Cox proportional hazards regression. Results: Patients treated with pembrolizumab demonstrated a significantly higher objective response rate than those with nivolumab (38.1% vs. 15.1%; odds ratio 4.18, p = 0.005) regardless of the combination strategies. In addition, pembrolizumab performed a better overall survival (OS) than nivolumab, (34.9 vs. 9.5 months; hazard ratio (HR) = 0.39, p = 0.004). In subgroup analysis, pembrolizumab exhibited favorable OS than nivolumab for monotherapy (HR = 0.16, p = 0.001) or combination therapy (HR = 0.33, p = 0.006) as second-line or later-line (HR = 0.19, p = 0.001) therapy and those with (HR = 0.31, p = 0.006) or without (HR = 0.15, p = 0.004) well-compensated liver disease. The incidence of adverse events was comparable for both treatments. Conclusion: Both pembrolizumab and nivolumab had significant effects for HCC therapy, and pembrolizumab had a significant survival benefit as compared with nivolumab.

Fluorescence microscopy with optical sectioning capabilities is extensively utilized in biological research to obtain three-dimensional structural images of volumetric samples. Tunable lenses have been applied in microscopy for axial scanning to acquire multiplane images. However, images acquired by conventional tunable lenses suffer from spherical aberration and distortions. Here, we design, fabricate, and implement a dielectric Moiré metalens for fluorescence imaging. The Moiré metalens consists of two complementary phase metasurfaces, with variable focal length, ranging from ∼10 to ∼125 mm at 532 nm by tuning mutual angles. In addition, a telecentric configuration using the Moiré metalens is designed for high-contrast multiplane fluorescence imaging. The performance of our system is evaluated by optically sectioned images obtained from HiLo illumination of fluorescently labeled beads, as well as ex vivo mice intestine tissue samples. The compact design of the varifocal metalens may find important applications in fluorescence microscopy and endoscopy for clinical purposes.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2–12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child–Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-020-02845-9.

Background and study aims Early detection of upper gastrointestinal (UGI) rebleeding is not easy by observing clinical symptoms. We developed a novel UGI monitoring system and aimed to test its feasibility of continuous tracking of UGI bleeding. Patients and methods A prospective study was conducted on patients with moderate to high risk of rebleeding. The UGI monitoring system was installed to monitor their gastric contents. It would alarm if rebleeding was suspected and the physician could review the images to make a further decision. The patient’s comfort level was also evaluated. Results Sixteen patients were enrolled. Rebleeding occurred in one patient and was detected by this system more than 5 hours earlier than with clinical symptoms. The interobserver reliability for reviewing the images to define the blood clearance in the stomach was excellent (intraclass correlation coefficient 0.79–0.96). The comfort level assessed by patients was 1.90 ± 1.39 (on the scale of 0–5). Conclusions This pilot study demonstrated the potential of this UGI monitoring system for early detection of rebleeding.

Vacuum ultraviolet (VUV) light plays an essential role across science and technology, from molecular spectroscopy to nanolithography and biomedical procedures. Realizing nanoscale devices for VUV light generation and control is critical for next-generation VUV sources and systems, but the scarcity of low-loss VUV materials creates a substantial challenge. We demonstrate a metalens that both generates—by second-harmonic generation—and simultaneously focuses the generated VUV light. The metalens consists of 150-nm-thick zinc oxide (ZnO) nanoresonators that convert 394 nm (~3.15 eV) light into focused 197-nm (~6.29 eV) radiation, producing a spot 1.7 μm in diameter with a 21-fold power density enhancement as compared to the wavefront at the metalens surface. The reported metalens is ultracompact and phase-matching free, allowing substantial streamlining of VUV system design and facilitating more advanced applications. This work provides a useful platform for developing low-loss VUV components and increasing the accessibility of the VUV regime.

Electromagnetic anapole mode is a nonradiative state of light originating from the deconstructive interference of radiation of the oscillating electric and toroidal dipole moments. The high quality anapole-related resonances can be used in enhancing nonlinear electromagnetic properties of materials and in sensor applications. In this work, we experimentally demonstrate plasmonic anapole metamaterial sensor of environmental refractive index in the optical part of the spectrum. Our results show that the sensor exhibits high sensitivity to the ambient refractive index at the level of 330 nm/RIU and noise floor of 8.7 × 10-5 RIU. This work will pave the way for applications of anapole metamaterials in biosensing and spectroscopy. Ministry of Education (MOE) Published version This work is supported by the UK Engineering and Physical Science Research Council (grants EP/M009122/1 and EP/ T02643X/1), the Royal Society (grant IEC/R3/170092), the European Research Council (Advanced Grant No. FLEET786851), the Singapore Ministry of Education (N.I.Z.; grant MOE2016-T3-1-006), the University Grants Committee / Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. AoE/P-502/20 and GRF Project: 15303521), the Shenzhen Science and Technology Innovation Commission (Grant No. SGDX2019081623281169), the Department of Science and Technology of Guangdong Province (2020B1515120073), and the City University of Hong Kong (Grant No. 9380131).

We demonstrated a Moiré meta-lens to perform fluorescence bioimaging. The focal length can be varied by tuning mutual angles. The compact design plays an important role in fluorescence microscopy and endoscopy for clinical purposes.

Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it is strongly associated with obesity. To combat obesity, artificial sweeteners are often used to replace natural sugars, and sucralose is one of the most extensively used sweeteners. It was known that sucralose exerted effects on lipid metabolism dysregulation, and hepatic inflammation; however, the effects of sucralose on hepatic steatosis were still obscure. In this study, we found that supplements of sucralose enhanced high-fat-diet (HFD)-induced hepatic steatosis. In addition, treatment of sucralose increased reactive oxygen species (ROS) generation and induced endoplasmic reticulum (ER) stress in HepG2 cells. Pretreatment of ROS or ER stress inhibitors reversed the effects of sucralose on lipogenesis. Furthermore, pretreatment of taste receptor type 1 membrane 3 (T1R3) inhibitor or T1R3 knockdown reversed sucralose-induced lipogenesis in HepG2 cells. Taken together, sucralose might activate T1R3 to generate ROS and promote ER stress and lipogenesis, and further accelerate to the development of hepatic steatosis.

COVID-19 caused an unprecedented public health crisis and was declared a global pandemic on 11 March 2020, by the World Health Organization. The Taiwanese government’s early deployment mitigated the effect of the pandemic, yet the breakout in May 2021 brought a new challenge. This study focuses on examining Taiwanese newspaper articles regarding the government response before and after the soft lockdown, collecting 125,570 articles reported by three major news channels from 31 December 2019, to 30 June 2021, and splitting them into four stages. Latent Dirichlet Allocation topic modeling and sentiment analysis were used to depict the overall picture of Taiwan’s pandemic. While the news media focused on the impact and shock of the pandemic in the initial stage, prevention measures were more present in the last stage. Then, to focus on the government response indicators, we retrieved 31,089 related news from 125,570 news articles and categorized them into ten indicators, finding the news centered on the fundamental measures that were taken early and that were transformed into advanced measures in the latest and hardest period of the pandemic. Furthermore, this paper examines the temporal distribution of the news related to each indicator with the support of a sentiment analysis of the news’ titles and content, indicating the preparation of Taiwanese society to confront the pandemic.

Introduction: The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response. Objective: This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis. Results: We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS. Conclusions: PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders.

Tomography is an informative imaging modality that is usually implemented by mechanical scanning, owing to the limited depth-of-field (DOF) in conventional systems. However, recent imaging systems are working towards more compact and stable architectures; therefore, developing nonmotion tomography is highly desirable. Here, we propose a metalens-based spectral imaging system with an aplanatic GaN metalens (NA = 0.78), in which large chromatic dispersion is used to access spectral focus tuning and optical zooming in the visible spectrum. After the function of wavelength-switched tomography was confirmed on cascaded samples, this aplanatic metalens is utilized to image microscopic frog egg cells and shows excellent tomographic images with distinct DOF features of the cell membrane and nucleus. Our approach makes good use of the large diffractive dispersion of the metalens and develops a new imaging technique that advances recent informative optical devices., Bioimaging: metalenses make 3D analysis effortless An ultrathin “metalens” that uses semiconductor nanostructures to focus light can help microscopes resolve detailed images of live cells without complex mechanical components. In conventional tomographic imaging, a scanning instrument passes over the sample and takes multiple cross-sectional images, which are then reconstructed into a 3D picture. Tao Li from Nanjing University in China and colleagues have now simplified this technique by fabricating lenses patterned with concentric rings of gallium nitride nanopillars. The lens made of nanopillars has wavelength-dependent properties that enable focusing on different regions of a target simply by sweeping through the visible light spectrum. Experiments with frog egg cells demonstrated this approach could zoom in and obtain detailed, high quality images of the inner membrane and nucleus without harming the sample or moving the metalens.

Background/purpose: Immediate implant placement has been considered to be a successful treatment procedure. The bone plate perforation (BPP) may be one of severe complication and potentially life-threatening situation. The aim of this virtual study is to evaluate the influences of angled implant insertion on BPP during immediate implant installation in the posterior mandible. Materials and methods: Cone beam computed tomography images of 488 posterior teeth from 61 patients were selected. Virtual immediate implant placement (VIIP) was performed at each posterior tooth following the appropriate axis with the prosthetic-driven planning and different deviation angles of 3-, 6-, or 9-degree. BPP was then examined from cross-sectional images obtained. Furthermore, the relation of lingual bony morphology and BPP were also determined. Results: The incidence of buccal and lingual BPP increased as the deviation angle increased in posterior mandible area. Incidence of lingual BPP was significantly influenced by angular deviation and type of lingual bony morphology after adjusting for age, gender, tooth type, and right/left side. An increase in incidence odds of over 6-fold (OR = 6.583) was noted for placements angled by 9° compared with placements made without angulation, and an increase in incidence odds of over 3-fold (OR = 3.622) was noted for teeth with the undercut-type lingual morphology compared with the other types. Conclusion: The present Results indicate that accurate selection of the implant insertion angle and full awareness of the bony anatomy at the implant recipient site are essential to prevent BPP in the posterior mandible. Keywords: Complication, Dental implant, Mandible, Anatomy, Cone beam computed tomography

Purpose The purpose of this paper is to explore two types of Net-generation practitioners – writers and makers born in the 1980s – and how they describe their professions and their information practices. Design/methodology/approach The authors distinguished the information practices of Net-generation writers and makers from those of their older counterparts and then examined the contextual factors associated with the shared meanings in each community of practice, by interviewing a total of 14 participants, 7 writers and 7 makers, and qualitatively analyzed the resulting data. Findings First, the professional boundaries perceived by Net-generation practitioners are more blurred than those of their older counterparts. Second, they rely on life experience, online platforms and print for their sources of information and inspiration. Third, Facebooking and the use of filter bubbles are among the most popular information practices. Fourth, diversity, uniqueness, multimodal, participatory and self-media are keywords in their content creation and information produced. Fifth, connectivity (connecting people and resources) and collective intelligence (emphasizing how expertise is collected and distributed) are key themes associated with these digital natives. Sixth, the authors also identified and compared differences between these two groups. Research limitations/implications The study limitations include the small sample size of each practitioner group and the fact that the methods are dependent on the participants’ abilities to describe their information practices. Originality/value This study is among the first to focus on the characteristics of digital natives and their information practices. It provides a tentative framework for further exploration and contributes to our initial understanding of this topic.

Background The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. Methods Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th–14th day and 4th–28th day after the first bleeding episode. Results The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores

To explore how an online platform provides opportunities for new literacy practices to members of a learning community to connect and collaborate with one another within a participatory culture in supporting the learning experience in the physical space of a dormitory, we used the six-year Facebook (FB) public group data of a university residential program as an open laboratory. A total of 7396 postings by 764 authors were retrieved using a computational approach (a total of 1572 members participated in these posts). For the purposes of this study, the “Likes” received by each posting were considered an indication of the level of approval of others' viewpoints or appreciation for the information shared by other participants. The 311 posts (4%) that received more than 41 Likes represented 19,451 Likes (21.6%) expressed by the group members. We selected and examined them in depth using qualitative content analysis and discourse analysis. Finally, the 122 authors of the 311 entries were clustered into three profiles and analyzed to determine the patterns of “magnet” participants or opinion leaders. Overall, this study provided a vehicle to determine the ways by which the characteristics of new literacy practices, especially “collective intelligence,” “appropriation,” and “fun,” are applied in the context of a FB group, which functions as an informal learning environment in a formal learning setting. The study also identified the content, format, peer interactions, and student-teacher interactions of a student-managed and residential teacher-facilitated, technology-enhanced learning environment in support of the mission of the residential program. The study's findings demonstrate how an online platform played a significant role in supporting the learning experience occurring in a dormitory and the face-to-face activities of the participants. Such a platform has the advantages of involving more people and supplementing the college students' process of striving for social and intellectual development by allowing them to state opinions, negotiate meanings, address confrontation, articulate reasoning, and consider options. The platform also facilitates the equally important process of emotional development, as it provides the students with a sense of belonging, allows them to enjoy shared moments, and enhances their perceptions of being able to contribute to a common goal.

Epidemic obesity and diabetes have led to increased use of low-calorie sweeteners. Although several studies have suggested that consumption of artificial sweeteners, such as aspartame and saccharin, might have negative effects, the potential impacts of natural sweeteners on human health remain largely unknown.The deferential effects of short term and long term consumption of sorbitol on glucose homeostasis in mice by oral gavage. The glucose homeostasis and utility were evaluated by both oral or intraperitoneal glucose tolerance tests. Insulin levels were determined using enzyme-linked immunosorbent assay. Changes of gut microbiome were evaluated by 16S rRNA gene sequencing, and analyzed by principal components analysis.Bolus feeding of sorbitol by gavage significantly increased plasma insulin concentrations and decreased fasting blood glucose levels. Intriguingly, long-term sorbitol gavage for four weeks showed no significant effects on intraperitoneal glucose tolerance test outcomes, but it induced glucose intolerance according to the oral glucose tolerance test. Thus, we tested whether long-term sorbitol gavage might alter the relative abundances of gut microbiome constituents in mice. Principal components analysis indicated that long-term sorbitol intake indeed caused significant changes to the gut microbiome. In particular, we found that long-term sorbitol intake significantly decreased the relative abundances of Bifidobacterium, Lachnospiraceae UCG 001, Lachnospiraceae NK4A136, Eubacterium ventriosum, Candidatus Arthromitus, and Ruminococcus torques. We also found that long-term sorbitol increased the relative abundances of Helicobacter, Tyzzerella, Alistipes, and Prevotella 9.Long-term sorbitol consumption may change the composition of the gut microbiome and potentially induce glucose intolerance.

The optical sectioning images of volumetric biological sample was obtained by varifocal metalens with Moire effect in fluorescence microscopy system in conjunction with telecentricity and HiLo image processing method. The varifocal metalens is capable of changing the focal depth ranging from 10 mm to 125 mm by tuning the relative angle between its paired metasurfaces. The standard resolution target and fluorescent mircrosphere are imaged and analyzed; its lateral resolution and optical sectioning capability are 2.46 μm and 7.5 μm, respectively. Our study offers a demonstration, a solid foundation, for developing more compact optical microscopy systems based on metasurface optics.

The optical tweezer is one of the important techniques for contactless manipulation in biological research to control the motion of tiny objects. For three-dimensional (3D) optical manipulation, shaped light beams have been widely used. Typically, spatial light modulators are used for shaping light fields. However, they suffer from bulky size, narrow operational bandwidth, and limitations of incident polarization states. Here, a cubic-phase dielectric metasurface, composed of GaN circular nanopillars, is designed and fabricated to generate a polarization-independent vertically accelerated two-dimensional (2D) Airy beam in the visible region. The distinctive propagation characteristics of a vertically accelerated 2D Airy beam, including non-diffraction, self-acceleration, and self-healing, are experimentally demonstrated. An optical manipulation system equipped with a cubic-phase metasurface is designed to perform 3D manipulation of microscale particles. Due to the high-intensity gradients and the reciprocal propagation trajectory of Airy beams, particles can be laterally shifted and guided along the axial direction. In addition, the performance of optical trapping is quantitatively evaluated by experimentally measured trapping stiffness. Our metasurface has great potential to shape light for compact systems in the field of physics and biological applications.

Optical meta-devices using meta-surfaces which composed of artificial nanostructures are able to manipulate the electromagnetic phase and amplitude at will. The great advantages of meta-devices are their new properties, lighter weight, small size, high efficiency, better performance, broadband operation, lower energy consumption, and CMOS compatibility for mass production. Given the demand for photonics, many optical meta-devices for the application and control of incident light are being quickly developed for beam deflection and reflection, polarization control and analysis, holography, second-harmonic generation, laser, tunability, imaging, absorption, focusing of light, multiplex color routing and light-field sensing. The design, fabrication and application of the novel optical meta-devices are reported in this talk.

We propose a Light-sheet fluorescent microscopy (LSFM) system with a flat metalens, which is used to replace the bulky illuminating components. The metalens is a diffractive optics elements (DOEs) composed of various gallium nitride (GaN) nanopillar for light-sheet generation, and it can be readily integrated in existing LSFM systems. In contrast to the traditional LSFM system, the metalens-based system is more compact and flexible, and its sectioning capability is comparable to the conventional illumination arm in LSFMs. The live fluorescent-labeled transgenic Caenorhabditis elegans (C. elegans) are exploited to verify the performance of this system. The intensity profile of oocytes in C. elegans with cellular resolution level was obtained.

We design and fabricate a 60 × 60 GaN based achromatic meta-lens array to capture multidimensional optical information of the scene. The working wavelength is from 400 nm to 660 nm which covers the entire visible light range. The highest efficiency of single metalens can be up to 74% at a wavelength of 420 nm, while the average efficiency is approximately 39% over the whole working bandwidth. The light field images and the depth information of objects can be determined by reorganizing the patches of sub-images and calculating the disparity of neighboring sub-images, respectively. The depth information can be used to optimize the patch sizes to render the all-in-focus image without artifacts. Our work provides several advantages associated with light field imaging: elimination of chromatic aberration, polarization selectivity and compatibility of the semiconductor process.

A light-field camera captures both the intensity and the direction of incoming light1–5. This enables a user to refocus pictures and afterwards reconstruct information on the depth of field. Research on light-field imaging can be divided into two components: acquisition and rendering. Microlens arrays have been used for acquisition, but obtaining broadband achromatic images with no spherical aberration remains challenging. Here, we describe a metalens array made of gallium nitride (GaN) nanoantennas6 that can be used to capture light-field information and demonstrate a full-colour light-field camera devoid of chromatic aberration. The metalens array contains an array of 60 × 60 metalenses with diameters of 21.65 μm. The camera has a diffraction-limited resolution of 1.95 μm under white light illumination. The depth of every object in the scene can be reconstructed slice by slice from a series of rendered images with different depths of focus. Full-colour, achromatic light-field cameras could find applications in a variety of fields such as robotic vision, self-driving vehicles and virtual and augmented reality. A metalens array of GaN nanoantennas is used to make a full-colour achromatic light-field camera.

This is a rare case of a wild squirrel that was diagnosed with angiostrongyliasis characterized by the presence of larvae-induced eosinophilic meningoencephalomyelitis. A wild, intact, male Pallas’s squirrel (Callosciurus erythraeus) of unknown age was presented with a history of progressive paralysis in both forelimbs and hindlimbs. Gradually, the squirrel showed signs of deterioration, found dead and submitted for a complete pathological diagnosis. Necropsy revealed the presence of severe and diffuse congestion in the subarachnoid space of the brain and mild congestion in the spinal cord. Microscopically, severe meningoencephalomyelitis and interstitial pneumonia were consistent with lesions induced by Angiostrongylus cantonensis (A. cantonensis). Although A. cantonensis has been widely studied in rabbits, mice and humans, infection in squirrels has not been documented. This may be the first reported case of angiostrongyliasis in the Pallas’s squirrel.

Manipulation and precise delivery of optical energies in the regions of interest within specimens require different strategies. Hence, proper control of input beam parameters is a prerequisite. One of the prominent methods is metasurface optics, capable of crafting properties of light at nanoscales. Here, the generation of an abrupt autofocusing (AAF) beam by a nanophotonic metasurface for biomedical applications is demonstrated. Fluorescence guided laser microprofiling of mouse cardiac samples is experimentally investigated, using the AAF beam to deliver optical energy selectively to specific locations. In addition, photocoagulation of ex vivo swine skin tissue is performed and observed through optical coherence tomography. The results show great potentials for integrating metasurface optics to realize miniature laser surgery instruments for wide applications in biomedicine.

Statement of problem Restoring the edentulous maxilla with an implant-retained overdenture (IRO) can present a challenge because of increased implant divergence and the added wear of the implant abutments and attachments. However, knowledge pertaining to the degree of implant divergence and its effects on the wear pattern of the implant attachments is lacking. Purpose The purpose of this in vitro study was to investigate the change in the retention and wear characteristics of unsplinted abutments and attachments when used to retain a maxillary 4-implant palateless complete removable overdenture with different implant angulations. Material and methods Three groups of specimens of 0-, 15-, and 30-degree implant angulations were evaluated, each with 7 specimens. The retention of specimens was recorded after aging cycles equivalent to 1, 2.5, and 6 years of use. The surface of the attachments was examined with light and scanning electron microscope (SEM). Results Increasing the interimplant divergence improved the initial retention. After 1 year of use, retention of the 15- and 30-degree groups was significantly higher than that of the 0-degree group (P .05). After 2.5 and 6 years of use, no significant difference in retention was noted between groups (P>.05). Under light and SEM examination, the wear of the abutments and attachments was related to the interimplant divergence. Conclusions The initial retention of single attachments increased significantly as the implant divergence increased. The retention of the 15- and 30-degree groups was significantly higher than that of the 0-degree group after 1 year of use. No significant difference in retention was found after 2.5 and 6 years, regardless of implant angulation.

We report electrostatically conjugated core- silica (SiO2) shell upconversion nanoparticle (UCNPs@SiO2), and gold nanorod (AuNR) nanocomposite (NC) combined with graphene to demonstrate > 200-fold UC fluorescence enhancement. Plasmonic AuNR and graphene, resulted in enhanced fluorescence in UCNP with a maximum for the SiO2 shell thickness of 7 nm supported by finite difference time domain simulation of electric field distribution. In addition to the conventionally reported spectroscopic evidence, the plasmon aided UC fluorescence enhancement was demonstrated by direct confocal fluorescence imaging also, which was corroborated by a ~40% decrease in fluorescence lifetime. Finally, we have fabricated a NC/graphene hybrid photodetector (PD) that showed broadband (455–980 nm) photoresponse, with photoresponsivity of ~5000 AW−1, and response times of 80–200 ms under 980 nm illumination. The multiphoton infrared (IR, ~980 nm) absorbing UCNPs also show interesting high energy (blue (B), green (G), and red (R)) photoresponse which is now conclusively attributed to one-photon absorption in the UCNPs. We report, probably for the first time, the performance of the hybrid PD under monochromatic and polychromatic illumination of B, G, R, B + G, B + R, G + R, and B + G + R, among others. The photocurrent under polychromatic conditions is dominated by the strongest monochromatic response, and does not scale with net power of the illumination. The loss in photocurrent is attributed to saturation in absorption, and photothermal heating. The fast response of the PD device has been demonstrated while detecting high frequency modulated AC remote controller signals, and attributed to the fast charge sweeping by the AuNRs.

This review identifies the important approaches to peptide arrays and discusses the various technical options that must be considered. Of the five important approaches that are now practiced and commercially available, it is clear that no single approach offers advantages for all applications. Instead, the variations of peptide arrays enable the study of a wide range of applications. For example, the approaches based on in situ synthesis can prepare the highest density arrays and do so at relatively low reagent costs (though with varying expense in the synthesis hardware). The approaches that prepare arrays by immobilizing presynthesized peptides have the primary benefits of compatibility with a broader range of surface chemistries (that may not be sufficiently stable toward the conditions for in situ synthesis). The use of self-assembled monolayers, for example, brings the important benefits of chemistries that prevent the nonspecific adsorption of protein, give excellent control over the densities of peptides in the array, and are uniquely compatible with the use of SAMDI mass spectrometry to perform a broad range of label-free assays.

Metalens-array–based quantum source Spontaneous down-conversion is an exotic optical process in a nonlinear crystal in which a high-energy photon splits into two lower-energy photons that are quantum mechanically entangled. These entangled pairs are valuable commodities for quantum information processing and quantum communications. Because the experimental setup is usually performed with bulk optical components, there is a need to decrease the size scale for application. Li et al. combined an array of specialized metalenses with a nonlinear crystal and show that the scale of the process can be shrunk substantially. The approach should prove useful for developing miniaturized integrated quantum optical technologies. Science , this issue p. 1487

H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7–14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p

Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD.

This study explores the overall picture of how people perceive the importance level and urgency level regarding issues associated with automated vehicles, by sorting out ten issues, developing a questionnaire with 66 measurement items, and investigating how Artificial Intelligence (AI) experts and Computer Science (CS)/Electrical Engineering (EE) majors assessed these issues. The findings suggest that AI experts in Taiwan believed that the top five issues for preparing a society for autonomous vehicles (AVs) should include (1) data privacy and cybersecurity, (2) regulation considerations, (3) infrastructure, (4) governance, and (5) public acceptance. On the other hand, for their student counterparts, the results (1) demonstrate a somewhat different order from the third to the fifth place, (2) show an attention-focused profile on the issue of cybersecurity and data privacy, and (3) indicate that gender and a few wider-impact variables (technology innovation, infrastructure) are significant predictors for the assessment on the importance level of AVs, while some wider-impact variables (technology innovation, governance, economic benefits, infrastructure), which are positively associated, as well as concerns variables (cybersecurity and data privacy, regulations), which are negatively associated, could be predictors for the urgency level of AVs. Suggestions for future research and policymakers are provided.

Background H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P