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Background: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. Methods: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/−) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). Results: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03–5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). Conclusion: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.

Oxygen vacancies are a major factor that controls the electrical characteristics of the amorphous indium-gallium-zinc oxide transistor (a-IGZO TFT). Oxygen vacancies are affected by the composition ratio of the a-IGZO target and the injected oxygen flow rate. In this study, we fabricated three types of a-IGZO TFTs with different oxygen flow rates and then investigated changes in electrical characteristics. Atomic force microscopy (AFM) was performed to analyze the surface morphology of the a-IGZO films according to the oxygen gas rate. Furthermore, X-ray photoelectron spectroscopy (XPS) analysis was performed to confirm changes in oxygen vacancies of a-IGZO films. The optimized a-IGZO TFT has enhanced electrical characteristics such as carrier mobility (μ) of 12.3 cm2/V·s, on/off ratio of 1.25 × 1010 A/A, subthreshold swing (S.S.) of 3.7 V/dec, and turn-on voltage (Vto) of −3 V. As a result, the optimized a-IGZO TFT has improved electrical characteristics with oxygen vacancies having the highest conductivity.

Background: In emergency departments, rapid screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for arranging limited isolation resources and patient care during the coronavirus disease 2019 (COVID-19) pandemic. STANDARD M10 SARS-CoV-2 (SD Biosensor) is a recently developed cartridge-based RT-PCR that provides a turnaround time of 1 h, which is shorter than that for conventional RT-PCR. This study evaluated the clinical performance of STANDARD M10 in an emergency department. Methods: From March to June 2022, two pairs of nasopharyngeal and oropharyngeal swabs were collected from patients visiting an emergency department. Respective specimens underwent rapid RT-PCR using STANDARD M10 and conventional RT-PCR using Allplex SARS-CoV-2 (Seegene). When discordant results occurred, specimens undergoing the STANDARD M10 were retested with the Allplex to exclude specimen variations. Retest results replaced initial results of the Allplex. Clinical performance of STANDARD M10 was compared with Allplex. Results: The study enrolled 1,971 patients. COVID-19 prevalence was 6.2% based on the Allplex. Compared with the Allplex, overall agreement, positive percent agreement, and negative percent agreement of STANDARD M10 were 99.5% (95% CI: 99.1–99.8%), 95.9% (95% CI: 90.8–98.3%), and 99.8% (95% CI: 99.4–99.9%), respectively. Discordant results between STANDARD M10 and Allplex were observed only in specimens with Ct >33 using the Allplex. Conclusions: The STANDARD M10 showed reliable diagnostic performance for detecting SARS-CoV-2 in emergency departments and is a useful tool in emergency healthcare systems because of its easy-to-use cartridge-based assay and short resulting time for detecting SARS-CoV-2.

Background Despite widely use of femoral neck system system (FNS®), there is little evidence for mechanical property according to type of femoral neck fracture. This study is to assess the structural/mechanical stability of fixation constructs with a femur neck system by using the finite-element (FE) analysis after simulating the femur neck fractures and to introduce the clinical implications. Methods We simulated the fracture models of subcapital, transcervical, basicervical, and vertical types by using the right femur model (SAWBONES®) and imported the implant model of FNS® to ANSYS® to place the implant in the optimal position. The distal end of the femur model was completely fixed and was abducted 7°. The force vector was set laterally at an angle of 3° and posteriorly 15° in the vertical ground. We did the analysis using Ansys® software with the von Mises stress (VMS) in megapascal (MPa). Results The max VMS of the fracture site was 67.01 MPa for a subcapital fracture, 68.56 MPa for a transcervical fracture, 344.54 MPa for a basicervical fracture, and 130.59 MPa for a vertical fracture. The max VMS of FNS® was 840.34 MPa for a subcapital fracture, 637.37 MPa for a transcervical fracture, 464.07 MPa for a basicervical fracture, and 421.01 MPa for a vertical fracture. The max VMS of the implant corresponded to the value of the entire fixation construct and thus, FNS® mainly functions as a load-bearing implant. When we compared the basicervical and vertical fractures, the stress distribution between the implant and the fracture sites differed significantly, and the basicervical fracture had higher VMS in the bone, implant, and fracture sites. Conclusion Considering the stress distribution of the assembly model, FNS® fixation should consider the osseous anchorage between the proximal bolt and cancellous bone of femoral head and might be appropriate for vertical fractures. Regarding the VMS of fracture site, FNS® might be applied cautiously just in the basicervical fracture of anatomical reduction without gap and comminution.

Supplementary Figures 1-3 from Mutation Accumulation in the Intestine and Colon of Mice Deficient in Two Intracellular Glutathione Peroxidases

Mice deficient in two glutathione peroxidases (GPX), Gpx1 and Gpx2, [Gpx1/2-double knockout (DKO) mice] are prone to ileocolitis on a mixed C57BL/6 and 129S1/SvJ (B6.129) genetic background. We reported previously that ∼25% of B6.129 Gpx1/2-DKO mice develop ileocolonic tumors by 6 to 9 months of age, when their non-DKO littermates [having at least one wild-type (WT) Gpx1 or Gpx2 allele] rarely have inflammation and none have tumors. Because genetic background affects tumor susceptibility, we have generated a B6 Gpx1/2-DKO colony and discovered that these mice have fewer inflammatory cells, milder ileocolitis, and low mortality, and only 2.5% of B6 mice developed tumors. The mutant frequency of a cII reporter gene was about 2- to 3-fold higher in 28-day-old Gpx1/2-DKO and 4-fold higher in 8-month-old Gpx1/2-DKO ileal mucosa than in controls in both genetic backgrounds. In contrast, mutant frequencies in the unaffected B6 liver were not significantly different between WT and Gpx1/2-DKO mice. The mutant frequency of 8-month-old B6.129 Gpx1/2-DKO ileum was 38.94 ± 15.5−5, which was not significantly higher than the age-matched B6 ileum, 25.54 ± 10.33−5. The mutation spectra analysis has shown that B6 Gpx1/2-DKO ileum had a 3-fold increase in small nucleotide deletions at mononucleotide repeats over control B6, which are a signature mutation associated with oxidative stress. Unexpectedly, B6 Gpx1/2-DKO mice had fewer C to T transitions at CpG dinucleotides than the WT B6 (18.0% versus 40.1%; P < 0.001). Our results suggest that inflammation drives gene mutations, which leads to neoplastic transformation of intestinal epithelium in the B6.129 Gpx1/2-DKO mice but rarely in the B6 Gpx1/2-DKO mice. (Cancer Res 2006; 66(20): 9845-51)

Supplementary Information from Methylation of Polycomb Target Genes in Intestinal Cancer Is Mediated by Inflammation

Purpose: To report a case of metastatic breast cancer to the optic nerve with a favorable response to an increased dose of intravitreal bevacizumab injection.Case summary: A 60-year-old female presented to our clinic with blurred vision in her left eye for 3 weeks. The patient had a history of intraductal breast cancer carcinoma, metastasized to the mediastinum lymph nodes, liver, and bone and had received palliative chemotherapy and radiotherapy for 16 months. At her first presentation, best-corrected visual acuity of the left eye was 20/50 and the intraocular pressure was 11 mmHg. A yellowish elevated mass with hemorrhage at the optic disc with peripapillary swelling was observed in the left eye. Fluid at the subperipapillary and subfoveal areas and choroidal thickening with folds were observed with optic coherence tomography. The patient was diagnosed as having breast cancer metastasis to the optic nerve head. Three monthly intravitreal bevacizumab injections (0.05 mL, 1.25 mg) were administered, but showed limited effect. Two more intravitreal bevacizumab injections having twice the concentration of the previous dose (0.1 mL, 2.50 mg) were given. Tumor infiltration of the optic nerve head decreased, and serous retinal detachment subsided. No malignant cancer cells were detected in the anterior chamber.Conclusions: We report a rare case of breast cancer metastasis to the optic nerve. Administering intravitreal bevacizumab injections with twice the dosage concentration could be an alternative treatment option, to alleviate exudative retinal detachment associated with metastatic tumor progression to the optic nerve head.

A hybrid cutting using both plasma and end mill was developed for safe and efficient dismantling of nuclear facilities. In this cutting method, a moving arc plasma heats up the workpiece before milling. Thermally softened part of the workpiece is then removed quickly and deeply with an end mill. For the cutting experiments, a three-axis numerical control (NC) milling machine was combined with a commercialized arc plasma torch and used to cut 25 mm thick stainless steel plates. Experimental results revealed that pre-heating by arc plasmas can improve the cutting volume per unit time higher than 40% by reducing the cutting load and increasing the cuttable depth when using an end mill without cutting fluids. These advantages of a hybrid cutting process are expected to contribute to quick and safe segmentations of metal structures with radioactively contaminated inner surfaces.

Background: Percutaneous dilatational tracheostomy (PDT) is a common procedure in intensive care units (ICUs). Although it is thought to be safe and easily performed at the bedside, PDT usually requires endotracheal guidance, such as bronchoscopy. Here, we assessed the clinical outcomes and safety of PDT conducted without endotracheal guidance.Methods: In the ICU and coronary ICU at a tertiary hospital, PDT was routinely performed without endotracheal guidance by a single medical intensivist using the Griggs technique PDT kit (Portex Percutaneous Tracheostomy Kit). We retrospectively reviewed the electronic medical records of patients who underwent PDT without endotracheal guidance.Results: From January 1 to December 31, 2018, 78 patients underwent PDT without endotracheal guidance in the ICU and coronary ICU. The mean age of these subjects was 71.9±11.5 years, and 29 (37.2%) were female. The mean Acute Physiology And Chronic Health Evaluation (APACHE) II score at 24 hours after admission was 25.9±5.8. Fifty patients (64.1%) were on mechanical ventilation during PDT. Failure of the initial PDT attempt occurred in 4 patients (5.1%). In two of them, PDT was aborted and converted to surgical tracheostomy; in the other two patients, PDT was reattempted after endotracheal reintubation, with success. Minor bleeding at the tracheostomy site requiring gauze changes was observed in five patients (6.4%). There were no airway problems requiring therapeutic interventions or procedure-related sequelae.Conclusions: PDT without endotracheal guidance can be considered safe and feasible.

Photodynamic therapy (PDT) has been applied in clinical treatment of tumors for a long time. However, insufficient supply of pivotal factors including photosensitizer (PS), light, and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT. Nanoparticles have received an influx of attention as drug carriers, and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue. Physicochemical optimization for passive targeting, ligand modification for active targeting, and stimuli-responsive release achieved efficient delivery of PS to tumor tissue. Various trials using upconversion NPs, two-photon lasers, X-rays, and bioluminescence have provided clues for efficient methods of light delivery to deep tissue. Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation, Fenton reaction, and combination with other chemical drugs. In this review, we introduce these creative approaches to addressing the hurdles facing PDT in tumors. In particular, the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells., Highlights • Successful photodynamic therapy in tumors has been inhibited by obstacles including insufficient amount of photosensitizer, light attenuation, and unfavorable tumor microenvironmrnt. • Until now, various nanoparticles have been developed and used for tumor-targeted photodynamic therapy. • The nanpparticles showed potential to overcome the obstacles by efficient supply of photosensitizers, light, and oxygen.

The optimal architecture of three-dimensional (3D) interface between a polymer electrolyte membrane (PEM) and catalyst layer (CL) is one of the most important issues to improve PEM fuel cells' (PEMFCs) performance. Here, we report the fabrication of hierarchical wrinkled PEM/CL interface over a large area. We fabricated the hierarchical wrinkles on a multiscale from nanometers to micrometers by bottom-up-based facile, scalable, and simple method. Notably, it allows one to go beyond the limit of the catalyst utilization by extremely enlarged interfacial area. The resulting hierarchical wrinkled PEM/CL displays a dramatically increased electrochemically active surface area (ECSA) and power performance by the enhancement factors of 89% and 67% compared with those of flat interface, which is one of the best enhancements compared to previous PEMFCs. We believe the scalability of hierarchical wrinkled interface can be exploited to design advanced 3D interfaces for high-performance PEMFCs even with ultralow Pt-loading.

Transparent ZnO–PTFE composite thin films deposited via RF co-sputtering are demonstrated as antireflective and antimicrobial display coatings and high-sensitivity antimicrobial touch sensor for a wide range of applications in interactive devices for a safer experience.

Cerium oxide-containing interlocking interfacial layer improved mechanical adhesion and chemical stability of the interface. For the first time as a hydrocarbon-based membrane, it operated stably for more than 500 hours.