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To dope 2D semiconductor channels, charge-transfer doping has generally been done by thermal deposition of inorganic or organic thin-film layers on top of the 2D channel in bottom-gate field-effect transistors (FETs). The doping effects are reproducible in most cases. However, such thermal deposition will damage the surface of 2D channels due to the kinetic energy of depositing atoms, causing hysteresis or certain degradation. Here, a more desirable charge-transfer doping process is suggested. A damage-free charge-transfer doping is conducted for 2D MoTe

The Plasmodium ovale curtisi (Poc) prevalence has increased substantially in sub-Saharan African countries as well as regions of Southeast Asia. Poc parasite biology has not been explored much to date; in particular, the invasion mechanism of this malaria parasite remains unclear. In this study, the binding domain of the Duffy binding protein of P. ovale curtisi (PocDBP) was characterized as an important ligand for reticulocyte invasion. The homologous region of the P. vivax Duffy binding protein in PocDBP, named PocDBP-RII herein, was selected, and the recombinant PocDBP-RII protein was expressed in an Escherichia coli system. This was used to analyze reticulocyte binding activity using fluorescence-activated cell sorting and immune serum production in rabbits. The binding specificity was proven by treating reticulocytes with trypsin, chymotrypsin and neuraminidase. The amino acid sequence homology in the N-terminal Cys-rich region was found to be ~ 44% between PvDBP and PocDBP. The reticulocyte binding activity of PocDBP-RII was significantly higher than the erythrocyte binding activity and was concentration dependent. Erythrocyte binding was reduced significantly by chymotrypsin treatment and inhibited by an anti-PocDBP-RII antibody. This finding suggests that PocDBP may be an important ligand in the reticulocyte invasion process of P. ovale curtisi.

Senescent cells accumulate in several tissues during ageing, including the skin, and contribute to the functional decline of the skin via the senescence-associated secretory phenotypes (SASPs) 1 . Due to the potential negative effects of SASPs during the ageing process, drugs that selectively target senescent cells or SASPs represent an important therapeutic strategy to delay skin ageing. The selective induction of cell death specifically to kill senescent cells using drugs, referred to as senolytics, is a main approach to achieve this strategy 2 .

A novel porcine circovirus 4 has been recently identified in China and Korea. A sensitive and specific diagnostic method is urgently required to detect the virus in field samples. We developed a loop-mediated isothermal amplification (LAMP) the assay for the visual detection of PCV4 and evaluated its sensitivity, specificity, and applicability in clinical samples. This assay's results can be directly visualized by the naked eye using hydroxynaphthol blue after incubation for 40 min at 64 °C. The assay specifically amplified PCV4 DNA and no other viral nucleic acids. The sensitivity of the assay was

Introduction: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. Materials and Methods: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). Results: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (Discussion/Conclusion: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

SUMMARY The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood. Here we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation, which is notable for its prevalence and prior molecular characterization. Consistent with its weak cancer penetrance in humans, homozygous p53178C/C mice show a modest increase in tumorigenesis but, surprisingly, are lean with decreased body fat content. They display evidence of increased lipolysis and upregulation of fatty acid metabolism in their inguinal white adipose tissue (iWAT). Gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses show that the mutant p53 bound and trans-activated Beta-3-Adrenergic Receptor (ADRB3), a gene that is known to promote lipolysis and is associated with obesity. This study reveals that a germline mutation of p53 can affect fat metabolism, which has been implicated in cancer development., Graphical Abstract, In Brief Knockin of the mouse homolog of a human TP53 germline mutation known to cause Li-Fraumeni syndrome, a cancer predisposition disorder, results in a mouse model characterized by lower body fat content. Kang et al. show that enhancing transactivation of the lipolytic gene ADRB3 by mutant p53 contributes to this phenotype.

Background Malaria parasites form intracellular membranes that separate the parasite from the internal space of erythrocytes, and membrane proteins from the parasites are exported to the host via the membrane. In our previous study, Plasmodium vivax early transcribed membrane protein (PvETRAMP) 11.2, an intracellular membrane protein that is highly expressed in blood-stage parasites, was characterized as a highly immunogenic protein in P. vivax malaria patients. However, the other PvETRAMP family proteins have not yet been investigated. In this study, PvETRAMPs were expressed and evaluated to determine their immunological profiles. Methods The protein structure and amino acid alignment were carried out using bioinformatics analysis software. A total of six PvETRAMP family proteins were successfully expressed and purified using a wheat germ cell free protein expression system and the purified proteins were used for protein microarray and immunization of mice. The localization of the protein was determined with serum against PvETRAMP4. IgG subclasses were assessed from the immunized mice. Results In silico analysis showed that P. vivax exhibits nine genes encoding the ETRAMP family. The ETRAMP family proteins are relatively small molecules with conserved structural features. A total of 6 recombinant ETRAMP proteins were successfully expressed and purified. The serum positivity of P. vivax malaria patients and healthy individuals was evaluated using a protein microarray method. Among the PvETRAMPs, ETRAMP4 showed the highest positivity rate of 62%, comparable to that of PvETRAMP11.2, which served as the positive control, and a typical export pattern of PvETRAMP4 was observed in the P. vivax parasite. The assessment of IgG subclasses in mice immunized with PvETRAMP4 showed high levels of IgG1 and IgG2b. PvETRAMP family proteins were identified and characterized as serological markers. Conclusions The relatively high antibody responses to PvETRAMP4 as well as the specific IgG subclasses observed in immunized mice suggest that the ETRAMP family is immunogenic in pathogens and can be used as a protein marker and for vaccine development.

OBJECTIVE. The purpose of this study is to propose a sensitive CT criterion (the presence of any of 10 CT features) for complicated appendicitis that could be used in the nonoperative management of appendicitis and to compare the diagnostic performance of this sensitive CT criterion with that of gestalt assessment. MATERIALS AND METHODS. This retrospective study, which was conducted in a tertiary teaching hospital, included 100 patients with suspected appendicitis on CT. Complicated appendicitis, defined as gangrenous or perforated appendicitis, was pathologically or surgically confirmed in 32 patients. Six radiologists independently determined the presence of 10 previously reported CT features of complicated appendicitis (contrast enhancement defect of the appendiceal wall, abscess, extraluminal air, intraluminal air, extraluminal appendicolith, intraluminal appendicolith, moderate-to-severe periappendiceal fat stranding, periappendiceal fluid, ileus, and ascites) and rated the likelihood score for complicated appendicitis using gestalt assessment. The sensitivity and specificity of CT for complicated appendicitis were measured by the presence of any of 10 CT features (the any-of-10-features criterion) and by the radiologists' gestalt assessment. Pooled sensitivity and specificity were compared using a generalized linear mixed model. RESULTS. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment (92% vs 64%; difference, 28% [95% CI, 10-46%]; p < 0.001), although the pooled specificity was lower (43% vs 76%; difference, -33% [95% CI, -48% to -17%]; p < 0.001). CONCLUSION. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment, at the cost of lower specificity. For prudent selection of patients who should receive nonoperative treatment of appendicitis, the any-of-10-features criterion may be used to decrease treatment failure associated with a false-negative diagnosis of complication.

Doxorubicin is a widely used chemotherapeutic agent that causes dose-dependent cardiotoxicity in a subset of treated patients, but the genetic determinants of this susceptibility are poorly understood. Here, we report that a noncanonical tumor suppressor activity of p53 prevents cardiac dysfunction in a mouse model induced by doxorubicin administered in divided low doses as in the clinics. While relatively preserved in wild-type (p53(+/+)) state, mice deficient in p53 (p53(−/−)) developed left ventricular (LV) systolic dysfunction after doxorubicin treatment. This functional decline in p53(−/−) mice was associated with decreases in cardiac oxidative metabolism, mitochondrial mass, and mitochondrial genomic DNA (mtDNA) homeostasis. Notably, mice with homozygous knockin of the p53 R172H (p53(172H/H)) mutation, which like p53(−/−) state lacks the prototypical tumor suppressor activities of p53 such as apoptosis but retains its mitochondrial biogenesis capacity, showed preservation of LV function and mitochondria after doxorubicin treatment. In contrast to p53-null state, wild-type and mutant p53 displayed distinct mechanisms of transactivating mitochondrial transcription factor A (TFAM) and p53-inducible ribonucleotide reductase 2 (p53R2), which are involved in mtDNA transcription and maintenance. Importantly, supplementing mice with a precursor of NAD(+) prevented the mtDNA depletion and cardiac dysfunction. These findings suggest that loss of mtDNA contributes to cardiomyopathy pathogenesis induced by doxorubicin administered on a schedule simulating that in the clinics. Given a similar mtDNA protection role of p53 in doxorubicin-treated human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, the mitochondrial markers associated with cardiomyopathy development observed in blood and skeletal muscle cells may have prognostic utility.

Background US has served as a standard surveillance tool for hepatocellular carcinoma (HCC); however, the detection rate and false referral rate with this modality are suboptimal. Purpose To evaluate the added value of perfluorobutane-enhanced US when combined with conventional B-mode US as an HCC surveillance tool in participants with liver cirrhosis. Materials and Methods This prospective multi-institution diagnostic trial (https://ClinicalTrials.gov, NCT02188901) used an intraindividual comparison design in a single arm of study participants and was conducted at five referral hospitals. Eligible participants who had liver cirrhosis related to viral hepatitis and were undergoing US for HCC surveillance were enrolled from October 2014 to August 2016. Immediately after completion of B-mode US but before performance of perfluorobutane-enhanced US, operating radiologists entered the results of B-mode US. After completion of subsequent perfluorobutane-enhanced US (Kupffer phase with or without vascular-phase US), the radiologists recorded the results. The presence of HCC was confirmed either with pathologic analysis or radiologically by using dynamic contrast material-enhanced CT or gadoxetic acid-enhanced MRI. The primary end points were the detection rate of early-stage HCC (Barcelona Clinic Liver Cancer staging system stage 0 or A) and false referral rate. The primary end points were compared in a per-participant manner by using the McNemar test. Results A total of 524 participants (mean age, 54 years ± 9 [standard deviation]) were included. Of these, 493 (94.1%) had liver cirrhosis related to the hepatitis B virus. Ten HCCs were confirmed in eight participants. The detection rate of early-stage HCC was not significantly improved by adding perfluorobutane-enhanced US to conventional B-mode US (difference, 0.4% [95% confidence interval: -0.3%, 1.1%]; P = .16). The false referral rate was significantly reduced (difference, -3.2% [95% confidence interval: -5.0%, -1.4%]; P < .001). Conclusion The addition of perfluorobutane-enhanced US to conventional B-mode US reduced the false referral rate without a significant improvement in the detection rate of early-stage hepatocellular carcinoma for surveillance in a population in which the hepatitis B virus predominated. © RSNA, 2019 Online supplemental material is available for this article.

BACKGROUND Intracranial pressure (ICP) is affected after epidural saline solution or local anesthetic injection. Both ICP and epidural pressures have been shown to reach peak pressure just after epidural injection and begin decline thereafter. Measuring the optic nerve sheath diameter (ONSD) through ultrasonography is one of the noninvasive methods used for ICP assessment. OBJECTIVES The purpose of this study was to investigate the effect of the speed of epidural saline injection on the ONSD under awake conditions. STUDY DESIGN Prospective randomized trial. SETTING An interventional pain management practice in South Korea. METHODS This study included 40 patients receiving thoracic epidural catheterization for pain management after upper abdominal or thoracic surgery. Following successful epidural space confirmation, patients were randomized to receive epidural saline infusion with a speed of either 1 mL/second (slow speed, A group) or 3 mL/second (rapid speed, B group), respectively. For the measurement of ONSD, transorbital sonography was performed and ONSD was measured at 3 mm posterior to the optic nerve head. RESULTS The A and B groups showed significant increases in ONSD according to time. Post hoc analysis of this result revealed that ONSD at T10 and T30 were significantly increased from baseline values (T0) (*P < 0.05 vs. T0; +P < 0.001 vs. T0). The mean values at any of the time points and degree of changes (T1-T0, T10-T0, and T30-T0) in ONSD between groups A and B did not show any significance. LIMITATIONS We could not confirm the time of normalization of ONSD after the end of epidural injection of normal saline. CONCLUSIONS Thoracic epidural injection of 10 mL of normal saline solution resulted in a significant increase of ONSD compared to baseline, however, the speed of injection did not affect the increase of ONSD. KEY WORDS Epidural, saline, optic nerve, diameter. Trial registry number: Clinical trial registry information service (NCT03362255).

This study examines what kinds of paradoxes emerge in social enterprises and how they cope with those paradoxes. I argue social enterprises experience conflict due to their logic multiplicity. This research employs an inductive multiple case study design to examine management practices of social enterprises by using the sample of social enterprises in the Republic of Korea. The results empirically confirm four types of paradoxes and reveal that social enterprises use various approaches to address paradoxes, thereby sustaining their organizational hybridity. This study theoretically contributes to research on social enterprises as hybrid organizations, logic multiplicity, and organizational paradoxes.

Acrylic acid and its ester derivatives are important chemicals utilized to synthesize numerous end products. Acrylic acid is industrially produced via propylene oxidation. We report in this study a nickel oxide-silica core-shell catalyst (NiO@SiO2) for acetylene hydroxycarbonylation as an alternative way to synthesize acrylic acid. NiO@SiO2 catalyst provided the higher turnover frequency and yield than commercial nickel oxide catalyst on acetylene hydroxycarbonylation. The carbon monoxide/acetylene ratio influenced more significantly to initial reaction rate than final acrylic acid yield. The silica shell protected the nickel oxide from sintering during reaction, however, the catalyst was deactivated by coke formation, attributed to acetylene decomposition.

First, to measure inter-observer agreement regarding tumor resectability and response, and second, to measure diagnostic performance in predicting negative resection margin, on re-staging CTs of patients who received neoadjuvant therapy for pancreatic cancer.This retrospective study included patients who received neoadjuvant therapy for borderline resectable pancreatic cancer from 2017 to 2020. Six readers independently evaluated initial staging and re-staging CT images. They categorized the resectability on re-staging CT based on the NCCN guideline, and evaluated tumor response to neoadjuvant therapy according to our proposed criteria on a 5-grade scale. For inter-observer agreement, Gwet's agreement coefficients were used. A crossed random effect model was used to pool the sensitivity and specificity of six readers in predicting negative resection margin.Seventy-seven patients with the median age of 66 (59-70) were included. The pooled agreement for tumor resectability was 0.64 (95% CI, 0.56-0.71) for differentiating the three categories, and 0.84 (0.77-0.91) for differentiating resectable or borderline resectable cancer vs. unresectable cancer. Agreement for tumor response grade was 0.89 (0.85-0.92). The pooled sensitivity and specificity for predicting negative resection margin were 48% (43-52%) and 61% (57-64%), respectively, when only "resectable" on re-staging CT was considered as index test positive. When either "resectable"' or "borderline resectable" was considered as positive, the pooled sensitivity and specificity were 91% (89-94%) and 5% (4-6%), respectively.CT can be used reliably with a high inter-observer agreement in selecting candidates for surgery after neoadjuvant therapy of pancreatic cancer.• On CT following neoadjuvant therapy of pancreatic cancer, six readers showed high agreement in differentiating resectable or borderline resectable vs. unresectable cancer (Gwet's coefficient, 0.84). • Inter-observer agreement was also high for our proposed tumor response grade (Gwet's coefficient, 0.89). • Specificity was very low (5%) while sensitivity was high (91%) when either resectable or borderline resectable cancer on re-staging CT was considered as predictive of negative resection margin status.

Background Imaging techniques are commonly used for understanding disease mechanisms and their biological features in such a microenvironment of the cell. In recent work, the understanding of parasite biology of malaria Plasmodium knowlesi was compiled from functional in vitro and imaging analysis using serial block-face scanning electron microscopy (SEM). Sample fixation during SEM analysis possibly makes the parasite membrane destruction. Methods In this study, we used a non-invasive optical technique, tomography, to explore the biological changes during the development of infected red blood cells (RBCs) by P. knowlesi. The commercial common-path diffraction optical tomography was used to measure individual infected RBCs' three-dimensional refractive index tomogram without an additional dyeing agent. Results We simultaneously examined structural, chemical, and physical modification by a parasite inside of host RBCs. The results had similar patterns with previous studies using SEM and other parasites such as P. falciparum and Babesia. Interestingly we found that P. knowlesi did not use hemoglobin as much as P. falciparum as a source of nutrition. Conclusions This tomography technique opens new ways to study the pathophysiology of malaria parasites more efficiently and is considered a promising tool for studying each Plasmodium species more in-depth.

In this study, we investigate the influence of Sc microalloying on the microstructure of the Al5083 alloy. Trace amounts of Sc addition drastically improve the mechanical properties of the Al5083 alloy from 216 MPa to 233 MPa. Macroscopically, the addition of Sc significantly reduces the grain size of Al by approximately 50%. Additionally, a microstructural investigation reveals that the Sc microalloying element induces fine Al3Sc nanoprecipitates in the Al matrix. The formation of Al3Sc nanoprecipitates results in a pinning effect on the dislocations, leading to accumulated dislocations. Compared to a Sc-free Al5083 alloy specimen, the number density of dislocations in the Sc-added Al5083 alloy significantly increases after hot rolling, enhancing the tensile properties. We reveal that the improved mechanical properties of Al5083 with Sc microalloying originate from the grain refinement and the formation of fine Al3Sc nanoprecipitates.

Shikimate is a key intermediate in high demand for synthesizing valuable antiviral drugs, such as the anti-influenza drug and oseltamivir (Tamiflu®). Microbial-based shikimate production strategies have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. Although shikimate biosynthesis has been reported in several engineered bacterial species, the shikimate production yield is still unsatisfactory. This study designed an Escherichia coli cell factory and optimized the fed-batch culture process to achieve a high titer of shikimate production. Using the previously constructed dehydroshikimate (DHS)-overproducing E. coli strain, two genes (aroK and aroL) responsible for converting shikimate to the next step were disrupted to facilitate shikimate accumulation. The genes with negative effects on shikimate biosynthesis, including tyrR, ptsG, and pykA, were disrupted. In contrast, several shikimate biosynthetic pathway genes, including aroB, aroD, aroF, aroG, and aroE, were overexpressed to maximize the glucose uptake and intermediate flux. The shiA involved in shikimate transport was disrupted, and the tktA involved in the accumulation of both PEP and E4P was overexpressed. The rationally designed shikimate-overproducing E. coli strain grown in an optimized medium produced approximately 101 g/l of shikimate in 7-l fed-batch fermentation, which is the highest level of shikimate production reported thus far. Overall, rational cell factory design and culture process optimization for microbial-based shikimate production will play a key role in complementing traditional plant-derived shikimate production processes.

We compared appendiceal visualization on 2-mSv CT vs. conventional-dose CT (median 7 mSv) in adolescents and young adults and analyzed the undesirable clinical and diagnostic outcomes that followed appendiceal nonvisualization.A total of 3074 patients aged 15-44 years (mean ± standard deviation, 28 ± 9 years; 1672 female) from 20 hospitals were randomized to the 2-mSv CT or conventional-dose CT group (1535 vs. 1539) from December 2013 through August 2016. A total of 161 radiologists from 20 institutions prospectively rated appendiceal visualization (grade 0, not identified; grade 1, unsure or partly visualized; and grade 2, clearly and entirely visualized) and the presence of appendicitis in these patients. The final diagnosis was based on CT imaging and surgical, pathologic, and clinical findings. We analyzed undesirable clinical or diagnostic outcomes, such as negative appendectomy, perforated appendicitis, more extensive than simple appendectomy, delay in patient management, or incorrect CT diagnosis, which followed appendiceal nonvisualization (defined as grade 0 or 1) and compared the outcomes between the two groups.In the 2-mSv CT and conventional-dose CT groups, appendiceal visualization was rated as grade 0 in 41 (2.7%) and 18 (1.2%) patients, respectively; grade 1 in 181 (11.8%) and 81 (5.3%) patients, respectively; and grade 2 in 1304 (85.0%) and 1421 (92.3%) patients, respectively (The use of 2-mSv CT instead of conventional-dose CT impairs appendiceal visualization in more patients. However, appendiceal nonvisualization on 2-mSv CT rarely leads to undesirable clinical or diagnostic outcomes.

Molybdenum disulfide (MoS

The assembly of single-walled carbon nanotubes (CNTs) into high-density horizontal arrays is strongly desired for practical applications, but challenges remain despite myriads of research efforts. Herein, we developed a non-destructive soft-lock drawing method to achieve ultraclean single-walled CNT arrays with a very high degree of alignment (angle standard deviation of ~0.03°). These arrays contained a large portion of nanometre-sized CNT bundles, yielding a high packing density (~400 µm

Although ethanol dry reforming is an attractive carbon utilization technology, problems of severe coke formation and low catalytic activity should be solved for realization of the technology. We demonstrate the effects of alkali metal additives (lithium, sodium, and potassium) on nickel catalyzed ethanol dry reforming. Potassium doped nickel catalyst (Ni/K2O-Al2O3) showed enhanced catalytic activity and durability in ethanol dry reforming. Thermogravimetric analysis (TGA) showed that Ni/K2O-Al2O3 had a high resistance to coke formation. The amounts of coke formed on Ni/K2O-Al2O3 were 1/3 lower than the amounts of coke formed on Ni/Al2O3. The total coke quantities were closely correlated to the number of basic sites of the nickel catalysts. Raman spectroscopy and transmission electron microscopy analyses revealed that the alkali metals control the coke formation on the catalysts.

ObjectiveGeneral anaesthesia with tracheal intubation results in sore throat. We evaluated the influence of the two-handed jaw thrust on postoperative sore throat in patients who require tracheal intubation.MethodsIn this prospective, double-blind, single-centre, parallel-arm, and randomised trial, 92 patients who were scheduled for general anaesthesia for total hip arthroplasty were allocated to one of two groups. In the jaw thrust group (n = 46), the two-handed jaw thrust manoeuvre was applied at intubation. In the control group (n = 46), conventional intubation with sham jaw thrust was performed. Incidences of airway morbidities including sore throat, hoarseness, and cough at 2, 4, and 24 hours postoperatively were compared.ResultsDuring the postoperative 24 hours, the incidence of sore throat (8 [17%] vs. 20 [44%]) and hoarseness were lower in the jaw thrust group (8 [17%] vs. 18 [39%]) compared with the control group. The incidence of cough during the postoperative 24 hours was similar between the groups.ConclusionsThe jaw thrust manoeuvre significantly reduced sore throat and hoarseness in patients after general anaesthesia using tracheal intubation. Clinical trial registration: NCT 03568279.

Implementing binary neural networks (BNNs) on computing-in-memory (CIM) hardware has several attractive features such as small memory requirement and minimal overhead in peripheral circuits such as analog-to-digital converters (ADCs). On the other hand, one of the downsides of using BNNs is that it degrades the classification accuracy. Recently, ResNet-style BNNs are gaining popularity with higher accuracy than conventional BNNs. The accuracy improvement comes from the high-resolution skip connection which binary ResNets use to compensate the information loss caused by binarization. However, the high-resolution skip connection forces the CIM hardware to use high-bit ADCs again so that area and energy overhead becomes larger. In this paper, we demonstrate that binary ResNets can be also mapped on CIM with low-bit ADCs via aggressive partial sum quantization and input-splitting combined with retraining. As a result, the key advantages of BNN CIM such as small area and energy consumption can be preserved with higher accuracy.

Background: Robot-assisted laparoscopic radical prostatectomy is an advanced and popular surgical technique. However, increased intracranial pressure which is caused by CO2 pneumoperitoneum and Trendelenburg position is the main cerebrovascular effect. Measurement of optic nerve sheath diameter using ocular ultrasound is a noninvasive and reliable method for the assessment of intracranial pressure. The primary endpoint of this study was to identify whether low blood pressure regulation has any benefit in attenuating an increase of optic nerve sheath diameter during robot-assisted laparoscopic radical prostatectomy.Methods: Optic nerve sheath diameter and cerebral oxygen saturation were measured at baseline (supine position), one and two hours after pneumoperitoneum and Trendelenburg position respectively, and after return to supine position in normal (n = 27) and low blood pressure groups (n = 24).Results: Mean optic nerve sheath diameter values measured at one and two hours after pneumoperitoneum and Trendelenburg position were significantly increased compared to the baseline value (P < 0.001 in normal blood pressure group; P = 0.003 in low blood pressure group). However, the mean optic nerve sheath diameter and cerebral oxygen saturation measured at any of the time points as well as degrees of change between the two groups did not show any significant changes. The peak values of optic nerve sheath diameter in normal and low blood pressure groups demonstrated 14.9% and 9.2% increases, respectively.Conclusions: Low blood pressure group demonstrated an effect in maintaining an increase of optic nerve sheath diameter less than 10% during CO2 pneumoperitoneum and Trendelenburg position.

To compare 2-mSv CT and conventional-dose CT (CDCT, typically 7-8 mSv) regarding final diagnosis and patient disposition following equivocal CT results in adolescents and young adults with suspected appendicitis.In total, 3074 patients of 15-44 years (28 ± 9 years, 1672 women) from 20 hospitals were randomized to undergo contrast-enhanced 2-mSv CT (n = 1535) or CDCT (n = 1539) from December 2013 through August 2016. One hundred sixty-one radiologists prospectively rated the likelihood of appendicitis in a Likert scale (i.e., grades 1-5). The final diagnosis was based on CT image, surgical, pathologic, and clinical findings. Post hoc analysis was performed for final diagnosis, surgical procedure, and delay in patient management following equivocal results (i.e., grade 3).The 2-mSv CT and CDCT groups were comparable for final diagnosis following equivocal results, including confirmed appendicitis (1.2% [18 patients] vs. 1.2% [19], p0.99), negative appendectomy (0.1% [2] vs. 0.3% [4], p = 0.53), and perforated appendicitis (0.1% [1] vs. 0.2% [3], p = 0.53). More patients were confirmed as not having appendicitis following equivocal results in the CDCT group than in the 2-mSv CT group (2.2% [34] vs. 1.0% [16], p = 0.016). The two groups were comparable for the need of appendectomy (1.4% [22] vs. 1.5% [23], p0.99), need of additional imaging tests (0.7% [11] vs. 1.1% [17], p = 0.35), and delay in patient management following equivocal results.2-mSv CT is comparable to CDCT regarding final diagnosis and patient disposition following equivocal CT results.• Our results strengthen evidence justifying the use of low-dose CT instead of conventional-dose CT (CDCT) in adolescents and young adults with suspected appendicitis. • The 2-mSv CT and CDCT groups were comparable for final diagnosis following equivocal CT results, including confirmed appendicitis (1.2% vs. 1.2%, p0.99), negative appendectomy (0.1% vs. 0.3%, p = 0.53), and perforated appendicitis (0.1% vs. 0.2%, p = 0.53). • The two groups were comparable for the need for appendectomy (1.4% vs. 1.5%, p0.99), need for additional imaging tests (0.7% vs. 1.1%, p = 0.35), and delay in patient management, following equivocal CT results.

BACKGROUND Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg-1 ibuprofen, group P was treated with 30 mg·kg-1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face-legs-activity-crying-consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg-1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.

Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs.From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P 0.001) and Advanced gastric cancer (P 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039).p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.

OBJECTIVE. The objective of our study was to compare diagnostic performance of 2-mSv CT and standard-dose CT (SDCT) for the diagnosis of perforated appendicitis in adolescents and young adults. MATERIALS AND METHODS. We used the intention-to-treat analysis set of a pragmatic randomized controlled trial involving 3074 patients (age range, 15-44 years) with suspected appendicitis and 161 radiologists from 20 hospitals. The patients were randomized to undergo either 2-mSv CT or SDCT. Predefined endpoints were sensitivity and specificity. Considering potential verification bias caused by the difference in diagnostic interventions (2-mSv CT vs SDCT), we added endpoints of detection rate (DR) and false-referral rate. The reference standards were surgical or pathologic findings. We used Fisher exact tests. Sensitivity analyses included the following: first, a per-protocol analysis; second, an analysis of a surgical reference standard but not a pathologic reference standard; and, third, an analysis to adjust for site clustering. We tested for heterogeneity in DR and false-referral rate across various patient and hospital characteristics. RESULTS. The 2-mSv CT and SDCT groups were comparable regarding DR (5.1% [78/1535] vs 4.9% [76/1539]; 95% CI for the difference, -1.4 to 1.7 percentage points; p = 0.87), false-referral rate (3.1% [48/1535] vs 3.1% [47/1539]; 95% CI for the difference, -1.2 to 1.3 percentage points; p = 0.92), sensitivity (42.9% [78/182] vs 43.2% [76/176]; 95% CI for the difference, -10.6 to 9.9 percentage points; p > 0.99), and specificity (89.2% [305/342] vs 91.2% [354/388]; 95% CI for the difference, -6.4 to 2.3 percentage points; p = 0.38). Sensitivity analyses showed similar results. We found no significant subgroup heterogeneity. CONCLUSION. The performance of 2-mSv CT, with limited sensitivity but high specificity, is comparable to that of SDCT for the diagnosis of appendiceal perforation.

Bioengineered artificial blood vessels have been a major area of interest over the last decade. Of particular interest are small diameter vessels, as surgical options are currently limited. This study aimed to fabricate a small diameter, heterogeneous bilayer blood vessel-like construct in a single step with gelatin methacryloyl (GelMA) bioink using a 3D micro-extrusion bioprinter on a solid platform. GelMA was supplemented with Hyaluronic acid (HA), glycerol and gelatin to form a GelMA bioink with good printability, mechanical strength, and biocompatibility. Two separate concentrations of GelMA bioink with unique pore sizes were selected to fabricate a heterogeneous bilayer. A higher concentration of GelMA bioink (6% w/v GelMA, 2% gelatin, 0.3% w/v HA, 10% v/v glycerol) was used to load human umbilical vein endothelial cells (HUVECs) and form an inner, endothelial tissue layer. A lower concentration of GelMA bioink (4% w/v GelMA, 4% gelatin, 0.3% w/v HA, 10% v/v glycerol) was used to load smooth muscle cells (SMCs) and form an outer, muscular tissue layer. Bioprinted blood vessel-like grafts were then assessed for mechanical properties with Instron mechanical testing, and suture-ability, and for biological properties including viability, proliferation, and histological analysis. The resulting 20 mm long, 4.0 mm diameter lumen heterogeneous bilayer blood vessel-like construct closely mimics a native blood vessel and maintains high cell viability and proliferation. Our results represent a novel strategy for small diameter blood vessel biofabrication.

In this study, we developed injectable intratympanic hyaluronic acid (HA) depots for the treatment of hearing loss. We prepared an injectable click-crosslinking formulation by modifying HA with tetrazine (HA-TET) and trans-cyclooctene (HA-TCO), which crosslinked to form an HA depot (Cx-HA). Preparation of the click-crosslinking HA formulation was facile, and Cx-HA depot formation was reproducible. Additionally, the Cx-HA hydrogel was significantly stiffer than HA hydrogel. To monitor the degradation pattern of hydrogels, we mixed a zwitterionic near-infrared (NIR) fluorophore (e.g., ZW800-1C) in the click-crosslinking HA formulation. Then, HA-TET and HA-TCO solutions containing ZW800-1C were loaded separately into the compartments of a dual-barrel syringe for intratympanic injection. The Cx-HA depots formed quickly, and an extended residence time in the tympanic cavity was confirmed by performing NIR fluorescence imaging. We have successfully prepared an injectable click-crosslinking HA formulation that has promise as an intratympanic drug depot.

Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered

The field of tissue engineering and regenerative medicine has made numerous advances in recent years in the arena of fabricating multifunctional, three-dimensional (3D) tissue constructs. This can be attributed to novel approaches in the bioprinting of stem cells. There are expansive options in bioprinting technology that have become more refined and specialized over the years, and stem cells address many limitations in cell source, expansion, and development of bioengineered tissue constructs. While bioprinted stem cells present an opportunity to replicate physiological microenvironments with precision, the future of this practice relies heavily on the optimization of the cellular microenvironment. In order to fabricate tissue constructs that are useful in replicating physiological conditions in laboratory settings, or in preparation for transplantation to a living host, the microenvironment must mimic conditions that allow bioprinted stem cells to proliferate, differentiate, and migrate. The advances of bioprinting stem cells and directing cell fate have the potential to provide feasible and translatable approach to creating complex tissues and organs. This review will examine the methods through which bioprinted stem cells are differentiated into desired cell lineages through biochemical, biological, and biomechanical techniques.

Plasmodium vivax reemerged in 1993. It has been sustained for more than 25 years and become one of the important indigenous parasitic diseases in northern and western parts of the Republic of Korea near the demilitarized zone. In particular, relapse is a significant concern for the control of malaria, as short- and long-term incubation periods vary among those infected in Korea. In this study, the prevalence of asymptomatic carriers was examined among residents of high endemic areas of vivax malaria during nonseasonal transmission of mosquitoes. Blood samples from 3 endemic regions in northwestern Korea were evaluated by microscopic examination, rapid diagnostic testing, and nested PCR to identify asymptomatic patients carrying malaria parasites in the community. However, no positive malaria case among residents of endemic areas was detected. Additionally, serological analysis was carried out to measure antibodies against 3 antigenic recombinant proteins of P. vivax, merozoite surface protein 1-19, circumsporozoite surface protein-VK210, and liver-stage antigen (PvLSA-N), by the protein array method. Interestingly, seropositivity of sera between previous exposure and samples without exposure to malaria was significantly higher using the PvLSA-N antigen than the other antigens, suggesting that PvLSA-N can be used as a serological marker to analyze the degree of exposure for malaria transmission in endemic areas. This indicates a very low asymptomatic carrier prevalence during the nonmalaria season in the endemic areas of Korea.