Staged urethroplasty with groin full-thickness skin graft for managing complex anterior urethral strictures: surgical outcomes and predictive factors.

PURPOSE: To describe outcomes of staged-urethroplasty in complex anterior urethral strictures using full-thickness-skin-graft (FTSG) harvested from the hairless groin area, and to identify factors influencing successful outcomes. METHODS: Through retrospective chart review, we identified a total of 67 men who underwent the first-stage operation (grafting) using groin-FTSG for staged-urethroplasty to treat complex anterior urethral strictures unsuitable for one-stage urethroplasty. Among these, 59 underwent the second-stage operation (tubularization) at a median duration of 5.1-months after grafting. Patients were assessed for outcomes as scheduled after tubularization outcomes were analyzed only for 48 patients for whom ≥ 1-year follow-up data after tubularization were available. Their mean follow-up duration was 27.1 months. Success was defined as achieving physiologic voiding without requiring further procedures. RESULTS: Median stricture-length was 5.5 cm in all 67 patients. After grafting, neourethral-opening-narrowing occurred in 18. Partial graft-loss occurred in 8, of whom only 3 underwent re-grafting. The percentage of patients who achieved successful outcomes was 81.3%. Improvements in maximum-urine-flow-rate and post-void-residual-urine-volume were maintained until the last follow-up visit. A urethrocutaneous-fistula occurred in one patient, while meatal-stenosis occurred in two. On multivariate-regression-analysis, the presence of neourethral-opening-narrowing was the only predictor of non-success after tubularization. Furthermore, the presence of hypertension, longer stricture-length, and a history of prior direct-vision-internal-urethrotomy were predictors of the occurrence of neourethral-opening-narrowing. CONCLUSION: Staged-urethroplasty using groin-FTSG is well worth considering as a useful therapeutic option for complex anterior urethral strictures, with an acceptable success rate and low morbidity. The absence of neourethral-opening-narrowing after the first-stage operation leads to success.

Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma.

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.

Predictive Value of KLASS-02-QC Assessment Score on KLASS-02 Surgical Outcomes: Validation of Surgeon Quality Control and Standardization for D2 Lymphadenectomy.

OBJECTIVE: The aim of this study was to audit the 22 items and assessed each item's predictive value on surgical outcomes. BACKGROUND: The KLASS-02 trial revealed that the oncologic outcomes of laparoscopic distal gastrectomy are not inferior to open distal gastrectomy in patients with advanced gastric cancer. The surgeons participating in this trial were chosen based on the assessment scores from the KLASS-02-QC trial, which used 22 items for standardization of D2 lymphadenectomy and quality control. METHODS: We reviewed proficiency scores (PSs) for 22 items for 20 surgeons who participated in KLASS-02. The surgeons were divided into 2 groups according to PS, and the perioperative outcomes of 924 patients enrolled in KLASS-02 were compared between groups. Each item's predictive value for perioperative outcome was then assessed using multivariable regression models. RESULTS: Of the total 924 patients, 529 were operated on by high-score surgeons (high PS) and 395 were operated on by low-score surgeons (low-PS). High-PS group had less intraoperative blood loss, longer operation times, and fewer complications, major complications, reoperations, and shorter first flatus and hospital stay than low-PS group ( P =0.006, P <0.001, P <0.001, P <0.001, P =0.042, P =0.013, and P <0.001, respectively). Some items used in KLASS-02-QC predicted perioperative outcomes, such as intraoperative blood loss, major complications, reoperation, and hospital stay. CONCLUSIONS: Although this study only analyzed data associated with qualified surgeons, the 22 items effectively assessed the surgeons based on PS. A high score was associated with longer operation times, but better perioperative outcomes.

Standard follow-up after curative surgery for advanced gastric cancer: secondary analysis of a multicentre randomized clinical trial (KLASS-02).

BACKGROUND: The benefit of regular follow-up after curative resection for gastric cancer is controversial as there is no evidence that it will improve survival. This study assessed whether regular follow-up leads to improved survival in patients after surgery for gastric cancer. METHODS: A secondary analysis was undertaken of patients who participated in an RCT of laparoscopic versus open distal gastrectomy for advanced gastric cancer between November 2011 and April 2015. Depending on whether patients were compliant with the initial trial follow-up protocol or not, they were analysed as having had either regular or irregular follow-up. Clinicopathological characteristics, recurrence patterns, detection, treatments, and survival were compared between the groups. RESULTS: The regular and irregular follow-up groups comprised 712 and 263 patients respectively. Disease recurrence within 36 months was more common in the regular group than in the irregular group (17.0 versus 11.4 per cent; P = 0.041). Recurrence patterns did not differ between the groups. The 3-year recurrence-free survival rate was worse in the regular than in the irregular group (81.2 versus 86.5 per cent; P = 0.031). However, the 5-year overall survival rate was comparable (84.5 versus 87.5 per cent respectively; P = 0.160). Multivariable analysis revealed that type of follow-up was not an independent factor affecting 5-year overall survival. CONCLUSION: Regular follow-up after radical gastrectomy was not associated with improved overall survival.

Lowering the percent body fat in the obese population might reduce male lower urinary tract symptoms.

PURPOSE: This study aimed to investigate the practicality of percent body fat (PBF), calculated using bioelectrical impedance analysis (BIA), in predicting benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). METHODS: This study included 844 men who underwent medical checkups at our institution between 2014 and 2022. Demographic characteristics, serum PSA levels, and prostate volume were collected using TRUS. BPH was defined as a prostate volume ≥ 30 cc. Subjects were divided into two groups according to their quartiles of PBF: the normal PBF group (first to third quartile; PBF < 27.9%) and the high PBF group (fourth quartile; PBF ≥ 27.9%). Characteristics between the groups were compared using the chi-square test and Student's t-test. Multivariate logistic regression analysis was performed to evaluate risk factors for BPH and severe LUTS. RESULTS: The prostate volume (25.21 ± 8.4 vs 27.30 ± 9.0, p = 0.005) and percentage of BPH (22.9% vs. 32.1%, p = 0.007) were greater in the high PBF group. After multivariate analysis, old age (OR = 1.066, p < 0.001), higher appendicular skeletal muscle mass index (ASMI) (OR = 1.544, p = 0.001), and PBF ≥ 27.9% (OR = 1.455, p = 0.037) were risk factors for BPH. Larger prostate volume (OR = 1.035, p = 0.002) and PBF ≥ 27.9% (OR = 1.715, p = 0.025) were risk factors for severe LUTS. However, a greater ASMI had a protective effect against severe LUTS (OR = 0.654, p = 0.011). CONCLUSIONS: This study shows that PBF and ASMI are useful for predicting BPH/LUTS. We suggest that lowering PBF to the normal range in a population with high PBF might prevent BPH, while lowering PBF and maintaining adequate ASMI could lower LUTS.

Achromatic doublet electrowetting prism array for beam steering device in foveated display.

A foveated display is a technology that can solve the problem of insufficient angular resolution (relative to the human eye) for near-eye display. In a high-resolution foveated display, a beam steering element is required to track the human gaze. An electrowetting prism array is a transmissive non-mechanical beam steering device, that allows a light and compact optical system to be configured and a large aperture possible. However, the view is obstructed by the sidewall of the prism array. When the size of the cell prism is 7mm, the prism array has an 87% fill-factor. To push the fill-factor to 100%, the cell prisms were magnified using a lens array. Image processing was performed such that the image produced by the lens array was identical to the original. Beam steering by refraction is accompanied by chromatic dispersion, which causes chromatic aberration, making colors appear blurry. The refractive index condition to reduce chromatic dispersion was obtained using the doublet structure of the electrowetting prism. The chromatic dispersion was reduced by 70% on average.

Digital government transformation in turbulent times: Responses, challenges, and future direction.

We are living in turbulent times, with the threats of COVID-19 and related social conflicts. Digital transformation is not an option but a necessity for governments to respond to these crises. It has become imperative for governments worldwide to enhance their capacity to strategically use emerging digital technologies and develop innovative digital public services to confront and overcome the pandemic. With the rapid development of digital technologies, digital government transformation (DGT) has been legitimated in response to the pandemic, contributing to innovative efficacy, but it also has created a set of challenges, dilemmas, paradoxes, and ambiguities. This special issue's primary motive is to comprehensively discuss the promises and challenges DGT presents. It focuses on the nature of the problems and the dilemmatic situation in which to use the technologies. Furthermore, it covers government capacity and policy implications for managerial and institutional reforms to respond to the threats and the uncertainty caused by disruptive digitalization in many countries. To stimulate discussion of the theme of this special issue, this editorial note provides an overview of previous literature on DGT as a controlling measure of the pandemic and the future direction of research and practice on DGT.

Image stitching using an electrowetting-based liquid prism with a fabrication method.

In this paper, we propose a new method for image stitching using an electrowetting-based liquid prism. Several images were obtained by adjusting the voltages applied to four sidewalls of the liquid prism, and a panoramic image was achieved through an image stitching algorithm. The relationship between the tilting angle of the liquid prism and the normal vector of the liquid-liquid interface was presented. Novel fabrication method has been proposed to improve the performance of the liquid prism, including the addition of a new structure to prevent oil isolation, plastic chamber material, plastic laser cutting, and oil selection. The fabricated liquid prism has a size of 5 × 5 × 8 mm, a maximum beam steering angle of ±10.5 °, a response time of 19.1 ms, and a resolution of 14.25 lp/mm. The required number of images according to the overlapping area was presented through the simulation, and the image stitching using two or three images was demonstrated.

Attenuation of the human skull at broadband frequencies by using a carbon nanotube composite photoacoustic transducer.

The shockwave generated from a focused carbon nanotube (CNT) composite photoacoustic transducer has a wide frequency band that reaches several MHz in a single pulse. The objective of this study was to measure the transmission characteristics of a shockwave generated by a CNT composite photoacoustic transducer through Asian skulls and compare the results with numerical simulation ones. Three Korean cadaver skulls were used, and five sites were measured for each skull. The average densities and sound speeds of the three skulls were calculated from computed tomography images. The sound pressure after skull penetration was about 11% of the one before skull penetration. High-frequency energy was mostly attenuated. The average attenuation coefficients measured at the five sites of the three skulls were 3.59 ± 0.29, 5.99 ± 1.07, and 3.90 ± 0.86 np/cm/MHz. These values were higher than those previously measured at 270, 836, and 1402 kHz from other groups. The attenuation coefficients simulated by Sim4life were slightly smaller than the experimental values, with similar trends at most sites. The attenuation coefficients varied with measurement sites, skull shape, and thickness. These results may provide important data for future applications of shockwaves in noninvasive neurological treatments.

Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT).

OBJECTIVE: The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with open distal gastrectomy (ODG). SUMMARY BACKGROUND DATA: Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. METHODS: Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups. RESULTS: A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients' reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days' mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682). CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.

Nonmechanical three-dimensional beam steering using electrowetting-based liquid lens and liquid prism.

In this paper, we present a system for nonmechanical three-dimensional beam steering using an electrowetting based liquid lens and liquid prism. The optical design of the presented system was modeled with Zemax and three-dimensional beam steering was simulated by changing the ROC of the lens and the apex angle of the prism. The liquid lens from Corning-Varioptic was used and the liquid prism was fabricated and these were combined. The liquid lens and liquid prism were filled with two immiscible liquids whose densities are the same. The liquid lens provides variable focal lengths as the applied voltage is changed. The diopter range of the liquid lens is from -3.9 D to 14.5 D. Beam steering on the x-axis, y-axis, and xy-axis was achieved by applying different voltages to four sidewalls of the liquid prism. The liquid prism has a beam steering angle of up to 11.6 °, 12 °, and 11.8 ° on x-axis, y-axis, and xy-axis, respectively. By combining the electrowetting actuated liquid lens and liquid prism, three-dimensional beam steering control including the z-axis direction was demonstrated.

Method to reduce the aberration of a polygonal aperture focus-tunable lens array for high fill factor.

Focus-tunable liquid lens arrays have been used to improve depth in glass-free three-dimensional devices where high fill factor is required. For high fill factors, polygonal apertures should be used, but due to the difficulty of controlling aberrations during focus tuning, polygonal aperture focus-tunable lenses have rarely been studied. This Letter proposes a new structure with walls at the lens boundaries using a square parabolic lens model to control the quadrafoil aberration induced by the square aperture. ANSYS simulation confirmed that the lens surface was closest to the parabolic lens model when the wall thickness was 1.4 mm. A fabricated lens array demonstrated the quadrafoil inhibitory effect and confirmed the utility of the new structure.

Bioconversion of Corticosterone into Corticosterone-Glucoside by Glucosyltransferase.

Glucosylation of the 21-hydroxyl group of glucocorticoid changes its solubility into hydrophilicity from hydrophobicity and, as with glucocorticoid glucuronides as a moving object in vivo, it is conceivable that it exhibits the same behavior. Therefore, glucosylation to the 21-hydroxyl group while maintaining the 11ß-hydroxyl group is particularly important, and glucosylation of corticosterone was confirmed by high-resolution mass spectrometry and 1D (¹H and 13C) and 2D (COSY, ROESY, HSQC-DEPT and HMBC) NMR. Moreover, the difference in bioactivity between corticosterone and corticosterone 21-glucoside was investigated in vitro. Corticosterone 21-glucoside showed greater neuroprotective effects against H2O2-induced cell death and reactive oxygen species (ROS) compared with corticosterone. These results for the first time demonstrate that bioconversion of corticosterone through the region-selective glucosylation of a novel compound can present structural potential for developing new neuroprotective agents.

Self-Aligned Multichannel Graphene Nanoribbon Transistor Arrays Fabricated at Wafer Scale.

We present a novel method for fabricating large-area field-effect transistors (FETs) based on densely packed multichannel graphene nanoribbon (GNR) arrays using advanced direct self-assembly (DSA) nanolithography. The design of our strategy focused on the efficient integration of the FET channel and using fab-compatible processes such as thermal annealing and chemical vapor deposition. We achieved linearly stacked DSA nanopattern arrays with sub-10 nm half-pitch critical dimensions (CD) by controlling the thickness of topographic Au confinement patterns. Excellent roughness values (∼10% of CD) were obtained, demonstrating the feasibility of integrating sub-10 nm GNRs into commercial semiconductor processes. Based on this facile process, FETs with such densely packed multichannel GNR arrays were successfully fabricated on 6 in. silicon wafers. With these high-quality GNR arrays, we achieved FETs showing the highest performance reported to date (an on-to-off ratio larger than 10(2)) for similar devices produced using conventional photolithography and block-copolymer lithography.

Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01).

OBJECTIVE: To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. BACKGROUND: There is still a lack of large-scale, multicenter randomized trials regarding the safety of LADG. METHODS: A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS: : A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis. CONCLUSIONS: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.

Significance of calcium-sensing receptor expression in gastric cancer.

OBJECTIVE: The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors. MATERIALS AND METHODS: Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non-tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues. RESULTS: Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012). CONCLUSION: We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth.

Tension assisted metal transfer of graphene for Schottky diodes onto wafer scale substrates.

We developed an effective graphene transfer method for graphene/silicon Schottky diodes on a wafer as large as 6 inches. Graphene grown on a large scale substrate was passivated and sealed with a gold layer, protecting graphene from any possible contaminant and keeping good electrical contact. The Au/graphene was transferred by the tension-assisted transfer process without polymer residues. The gold film itself was used directly as the electrodes of a Schottky diode. We demonstrated wafer-scale integration of graphene/silicon Schottky diode using the proposed transfer process. The transmission electron microscopy analysis and relatively low ideality factor of the diodes indicated fewer defects on the interface than those obtained using the conventional poly(methyl methacrylate)-assisted transfer method. We further demonstrated gas sensors as an application of graphene Schottky diodes.

Skull-Embedded Earring due to a Fall: A Complication and Therapeutic Considerations.

Although earring-related injuries are well described, an earring becoming forcefully embedded in the skull is unusual and has not previously been reported in the literature. We present the case of an 11-year-old child who posed interesting therapeutic considerations given this presentation.

Crystal Structure of Cytochrome P450 (CYP105P2) from Streptomyces peucetius and Its Conformational Changes in Response to Substrate Binding.

Cytochrome P450 monooxygenases (CYP, EC 1.14.14.1) belong to a large family of enzymes that catalyze the hydroxylation of various substrates. Here, we present the crystal structure of CYP105P2 isolated from Streptomyces peucetius ATCC27952 at a 2.1 Å resolution. The structure shows the presence of a pseudo-ligand molecule in the active site, which was co-purified fortuitously and is presumed to be a biphenyl derivative. Comparison with previously determined substrate-bound CYP structures showed that binding of the ligand produces large and distinctive conformational changes in α2-α3, α7-α9, and the C-terminal loop regions. This structural flexibility confirms our previous observation that CYP105P2 can accommodate a broad range of ligands. The structure complexed with a pseudo-ligand provides the first molecular view of CYP105P2-ligand interactions, and it indicates the involvement of hydrophobic residues (Pro82, Ala181, Met187, Leu189, Leu193, and Ile236) in the interactions between hydrophobic ligands and CYP105P2. These results provide useful insights into the structural changes involved in the recognition of different ligands by CYP105P2.

Crystal Structure of a Putative Cytochrome P450 Alkane Hydroxylase (CYP153D17) from Sphingomonas sp. PAMC 26605 and Its Conformational Substrate Binding.

Enzymatic alkane hydroxylation reactions are useful for producing pharmaceutical and agricultural chemical intermediates from hydrocarbons. Several cytochrome P450 enzymes catalyze the regio- and stereo-specific hydroxylation of alkanes. We evaluated the substrate binding of a putative CYP alkane hydroxylase (CYP153D17) from the bacterium Sphingomonas sp. PAMC 26605. Substrate affinities to C10-C12 n-alkanes and C10-C14 fatty acids with Kd values varied from 0.42 to 0.59 µM. A longer alkane (C12) bound more strongly than a shorter alkane (C10), while shorter fatty acids (C10, capric acid; C12, lauric acid) bound more strongly than a longer fatty acid (C14, myristic acid). These data displayed a broad substrate specificity of CYP153D17, hence it was named as a putative CYP alkane hydroxylase. Moreover, the crystal structure of CYP153D17 was determined at 3.1 Å resolution. This is the first study to provide structural information for the CYP153D family. Structural analysis showed that a co-purified alkane-like compound bound near the active-site heme group. The alkane-like substrate is in the hydrophobic pocket containing Thr74, Met90, Ala175, Ile240, Leu241, Val244, Leu292, Met295, and Phe393. Comparison with other CYP structures suggested that conformational changes in the ß1-ß2, α3-α4, and α6-α7 connecting loop are important for incorporating the long hydrophobic alkane-like substrate. These results improve the understanding of the catalytic mechanism of CYP153D17 and provide valuable information for future protein engineering studies.