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Western blots showing PEAk1 and YAP1 depletion in PDAC cells treated with two independent shRNAs

List of PEAK1 regulated proteins involved in cytoskeleton organization

In pancreatic ductal adenocarcinoma (PDAC), mutant KRAS stimulates the translation initiation factor eIF5A and upregulates the focal adhesion kinase PEAK1, which transmits integrin and growth factor signals mediated by the tumor microenvironment. Although eIF5A-PEAK1 signaling contributes to multiple aggressive cancer cell phenotypes, the downstream signaling processes that mediate these responses are uncharacterized. Through proteomics and informatic analyses of PEAK1-depleted PDAC cells, we defined protein translation, cytoskeleton organization, and cell-cycle regulatory pathways as major pathways controlled by PEAK1. Biochemical and functional studies revealed that the transcription factors YAP1 and TAZ are key targets of eIF5A-PEAK1 signaling. YAP1/TAZ coimmunoprecipitated with PEAK1. Interfering with eIF5A-PEAK1 signaling in PDAC cells inhibited YAP/TAZ protein expression, decreasing expression of stem cell–associated transcription factors (STF) including Oct4, Nanog, c-Myc, and TEAD, thereby decreasing three-dimensional (3D) tumor sphere growth. Conversely, amplified eIF5A-PEAK1 signaling increased YAP1/TAZ expression, increasing expression of STF and enhancing 3D tumor sphere growth. Informatic interrogation of mRNA sequence databases revealed upregulation of the eIF5A-PEAK1-YAP1-TEAD signaling module in PDAC patients. Taken together, our findings indicate that eIF5A-PEAK1-YAP signaling contributes to PDAC development by regulating an STF program associated with increased tumorigenicity. Cancer Res; 77(8); 1997–2007. ©2017 AACR.

Cofactor flavin adenine dinucleotide (FAD), a compound with flavin moiety and a derivative of riboflavin (vitamin B2), is shown to bind to Sox9 (a key transcription factor in early pancreatic development) and, subsequently, induce a large increase in markers of pancreatic development, including Ngn3 and PTF1a. Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, also binds to Sox9 and results in a similar increase in pancreatic development markers. Sox9 is known to be specifically important for pancreatic progenitors. Previously, there was no known link between FAD, PLP, or other co-factors and Sox9 for function. Thus, our findings show the mechanism by which FAD and PLP interact with Sox9 and result in the altered expression of pancreatic progenitor transcription factors involved in the pancreas development.

This letter presents a fully integrated wideband, ultralow average noise figure (NF), low power consumption, compact, and electrostatic discharge protected 6.7–15.3-GHz low-noise amplifier (LNA). A peak-gain distribution technique with a large transistor and two-stage broadband noise matching technique are proposed. For verification, a two-stage common source LNA is implemented in a 65-nm bulk complementary metal–oxide–semiconductor technology. The fabricated LNA achieved an average NF of 2.08 dB and an average gain of 19.1 dB with in-band gain ripple of ±0.75 dB in the frequency range of 7.6–14.7 GHz. It has a 3-dB fractional bandwidth of 78% and the third-order input intercept point is −9.0 dBm at 10 GHz. It consumes a 16 mA at a 0.8-V supply and has an area of 0.144 mm2.

In this letter, we propose an area-efficient series-connected resonant tunneling diode pair device (SCRTD) to utilize as a binary neuron device in cellular neural networks (CNNs). The proposed SCRTD (P-SCRTD) consists of two RTDs interconnected by a floating metal layer with a high-doped epitaxial layer. The P-SCRTD shows a 48 % reduction in area by eliminating the isolation area in the conventional SCRTD (C-SCRTD) owing to the symmetrical I-V characteristic of the RTD, without any performance penalty on the DC and RF characteristics by means of adopting the floating metal layer, compared to the C-SCRTD. CNN application of the P-SCRTD is investigated, showing inherent threshold operation and high-speed (12.5 Gbps) low-power (21 mW) performance, despite using the $2~\mu \text{m}$ technology node, for a unit cell for edge extraction.

Background/Aims: Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+-adenosine triphosphatase (H+, K+-ATPase) and stimulating interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+-ATPase and IL-1β after Hp eradication. Methods: Two hundred twentyone subjects were categorized as Hp-negative (n=84) or Hppositive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction. Results: The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hperadicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3-4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant. Conclusions: Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication. (Gut Liver 2020;14:735-745)

To predict the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) using data from breathing sounds recorded using a noncontact device during sleep.Prospective cohort study.Tertiary referral hospital.Audio recordings during sleep were performed using an air-conduction microphone during polysomnography. Breathing sounds recorded from all sleep stages were analyzed. After noise reduction preprocessing, the audio data were segmented into 5-second windows and sound features were extracted. Estimation of AHI by regression analysis was performed using a Gaussian process, support vector machine, random forest, and simple linear regression, along with 10-fold cross-validation.In total, 116 patients who underwent attended, in-laboratory, full-night polysomnography were included. Overall, random forest resulted in the highest performance with the highest correlation coefficient (0.83) and least mean absolute error (9.64 events/h) and root mean squared error (13.72 events/h). Other models resulted in somewhat lower but similar performances, with correlation coefficients ranging from 0.74 to 0.79. The estimated AHI tended to be underestimated as the severity of OSA increased. Regarding bias and precision, estimation performances in the severe OSA subgroup were the lowest, regardless of the model used. Among sound features, derivative of the area methods of moments of overall standard deviation demonstrated the highest correlation with AHI.AHI was fairly predictable by using data from breathing sounds generated during sleep. The prediction model may be useful not only for prescreening but also for follow-up after treatment in patients with OSA.

Background: Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study.Methods: CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400).Results: The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0).Conclusion: Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

This letter presents a fully integrated two-stage monolithic microwave integrated circuit (MMIC) power amplifier (PA) with a 1:1 transformer balun in Taiwan Semiconductor Manufacturing Company (TSMC) 180-nm CMOS process. To optimize the performance of PA, an on-chip 1:1 turn spiral transformer balun (STB) was used with a high supply power through the cascode topology. The proposed PA achieved a 40–43-dB gain and a saturation power ( $P_{\mathrm {sat}}$ ) of 29.9–30.3 dBm with a 40%–45% of power-added efficiency (PAE) in the frequency range of 820–1000 MHz. Using the antiphase biasing technique, the PA achieves a linear output power of 25 dBm with 29.5% PAE in 20-MHz spacing two-tone measurement, which satisfies IMD3 $3.3\times 0.86\,\,{\mathrm {mm}}^{2}$ .

This letter presents a 25-GHz power amplifier (PA) in bulk 65-nm CMOS technology. To ensure improved efficiency, the proposed PA was implemented using a three-stage antiphase linearization technique. The circuit of the three-stage antiphase linearization technique consisted of the predistortion drive stage, interstage, and the power stage. The positive-signed third-order intermodulation distortion (IMD3) is produced in the predistortion drive stage with subthreshold bias condition and is compensated with the negative-signed IMD3 divided by the interstage and power stage. Consequently, as the class burden of the power stage is reduced, the overall efficiency can be increased. The proposed CMOS PA was operated within a frequency range of 24–27 GHz. For a supply voltage of 1 V, the proposed PA achieved an average output power of 10.3 dBm, power-added efficiency (PAE) of 6.8%, and error vector magnitude (EVM) of 5.17% at 25 GHz for a 20-MHz bandwidth, 64 QAM, and 10.55-dB peak to average power ratio (PAPR) Long Term Evolution (LTE) signal. The proposed PA achieved a 32-dB peak gain, 33% peak PAE, 17.7-dBm saturated output power ( $P_{\text {sat}}$ ), and 16.3-dBm output 1-dB compression point.

The unique stacked morphology of the Golgi apparatus had been a topic of intense investigation among the cell biologists over the years. We had previously shown that the two Golgin tethers (GM130 and Golgin45) could, to a large degree, functionally substitute for GRASP-type Golgi stacking proteins to sustain normal Golgi morphology and function in GRASP65/55-double depleted HeLa cells. However, compared to well-studied GM130, the exact role of Golgin45 in Golgi structure remains poorly understood. In this study, we aimed to further characterize the functional role of Golgin45 in Golgi structure and identified Golgin45 as a novel Syntaxin5-binding protein. Based primarily on a sequence homology between Golgin45 and GM130, we found that a leucine zipper-like motif in the central coiled-coil region of Golgin45 appears to serve as a Syntaxin5 binding domain. Mutagenesis study of this conserved domain in Golgin45 showed that a point mutation (D171A) can abrogate the interaction between Golgin45 and Syntaxin5 in pull-down assays using recombinant proteins, whereas this mutant Golgin45 binding to Rab2-GTP was unaffected in vitro. Strikingly, exogenous expression of this Syntaxin5 binding deficient mutant (D171A) of Golgin45 in HeLa cells resulted in frequent intercisternal fusion among neighboring Golgi cisterna, as readily observed by EM and EM tomography. Further, double depletion of the two Syntaxin5-binding Golgin tethers also led to significant intercisternal fusion, while double depletion of GRASP65/55 didn’t lead to this phenotype. These results suggest that certain tether-SNARE interaction within Golgi stack may play a role in inhibiting intercisternal fusion among neighboring cisternae, thereby contributing to structural integrity of the Golgi stack.

This study describes the development of the optimal control strategies of eight parallel heat pumps in an existing building. The building consists of seven floors above ground and two floors underg...

To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception.Patients (18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019.A total of 859 enema reductions were performed during the past decade, more in males and in the age1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.

Background KDEL receptor helps establish cellular equilibrium in the early secretory pathway by recycling leaked ER-chaperones to the ER during secretion of newly synthesized proteins. Studies have also shown that KDEL receptor may function as a signaling protein that orchestrates membrane flux through the secretory pathway. We have recently shown that KDEL receptor is also a cell surface receptor, which undergoes highly complex itinerary between trans-Golgi network and the plasma membranes via clathrin-mediated transport carriers. Ironically, however, it is still largely unknown how KDEL receptor is distributed to the Golgi at steady state, since its initial discovery in late 1980s. Results We used a proximity-based in vivo tagging strategy to further dissect mechanisms of KDEL receptor trafficking. Our new results reveal that ACBD3 may be a key protein that regulates KDEL receptor trafficking via modulation of Arf1-dependent tubule formation. We demonstrate that ACBD3 directly interact with KDEL receptor and form a functionally distinct protein complex in ArfGAPs-independent manner. Depletion of ACBD3 results in re-localization of KDEL receptor to the ER by inducing accelerated retrograde trafficking of KDEL receptor. Importantly, this is caused by specifically altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, eventually leading to increased Arf1-GTP-dependent tubular carrier formation at the Golgi. Conclusions These results suggest that ACBD3 may function as a negative regulator of PKA activity on KDEL receptor, thereby restricting its retrograde trafficking in the absence of KDEL ligand binding. Since ACBD3 was originally identified as PAP7, a PBR/PKA-interacting protein at the Golgi/mitochondria, we propose that Golgi-localization of KDEL receptor is likely to be controlled by its interaction with ACBD3/PKA complex at steady state, providing a novel insight for establishment of cellular homeostasis in the early secretory pathway.

Summary: Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval [CI], −1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (−8•0 points; 95% CI, -14•1 to −1•8, p = 0•0108), male sexual problems (−19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (−5•4 points on a 35-point scale; 95% CI, −8•0 to −2•7, p

Metformin is a common and generally the first medication prescribed for treatment of type 2 diabetes. Its mechanism involves affecting pathways that regulate glucose and lipid metabolism in metabolic cells such as that of muscle and liver cells. In spite of various studies exploring its effects, the proteome changes in adipocytes in response to metformin remains poorly understood. In this study, we performed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic profiling to study the effects of metformin specifically on 3T3-L1 adipocytes. We define proteins that exhibited altered levels with metformin treatment, 400 of them showing statistically significant changes in our study. Our results suggest that metformin affects not only the PPAR signaling pathway, as well as glucose and lipid metabolism, but also protein folding, endoplasmic reticulum stress, negative regulation of appetite, and one-carbon folate metabolism in adipocytes. This proteomic investigation provides important insight into effects of metformin in adipocytes.

Adipocyte differentiation is a general physiological process that is also critical for metabolic syndrome. In spite of extensive study in the past two decades, adipogenesis is a still complex cellular process that is accompanied by complicated molecular mechanisms. Here, we performed SILAC-based quantitative global proteomic profiling of 3T3-L1 adipocyte differentiation. We report protein changes to the proteome profiles, with 354 proteins exhibiting significant increase and 56 proteins showing decrease in our statistical analysis. Our results show that adipocyte differentiation is involved not only in metabolic processes by increasing TCA cycle, fatty acid synthesis, lipolysis, acetyl-CoA production, antioxidants, and electron transport, but also in nicotinamide metabolism, cristae formation, mitochondrial protein import, and Ca2+ transport into mitochondria and ER. A search for Chromosome-Centric Human Proteome Project (C-HPP) using neXtprot highlighted one protein with a protein existence uncertain (PE5) and 17 proteins as functionally uncharacterized protein existence 1 (uPE1). This study provides quantitative information on proteome changes in adipogenic differentiation, which is helpful in improving our understanding of the processes of adipogenesis.

This paper presents a two-stage 24–32 GHz low-noise amplifier (LNA) with excellent gain flatness for wide bandwidth communication applications. A new band-pass type 2-stage common-source (CS) LNA configuration using the pole-tuning technique that actively exploits the parasitic capacitance of a CMOS device is proposed for bandwidth extension with low in-band gain variation. To demonstrate the feasibility of the proposed circuit configuration, a wideband LNA is implemented using a 65-nm CMOS process. The LNA shows a gain variation of ±0.19 dB in frequency band of 24 to 32 GHz with a peak gain of 18.64 dB and a noise figure of 2.27 dB while consuming 10.0 rnA from a 1V supply. The core circuit occupies an area of 0.23 × 0.43 mm2.

Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to compare the quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer. Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were EORTC QLQ-C30 and CR38 quality-of-life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78·4%) underwent sphincter preservation surgery and 74 (21·6%) underwent abdominoperineal resection. After 3 years, abdominoperineal resection was associated with a worse body image (adjusted mean difference, 9·8 points on a 100-point scale; 95% CI, 2·9 to 16·6, p=0·0052), micturition symptoms (-8·0 points; 95% CI, -14·1 to -1·8, p=0·0108), male sexual problems (-19·9 points; 95% CI, -33·1 to -6·7, p=0·0032), less confidence in getting and maintaining an erection in males (0·5 points on a 5-point scale; 95% CI, 0·1 to 0·8, p=0·0155), and worse urinary symptoms (-5·4 points on a 35-point scale; 95% CI, -8·0 to -2·7, p

This article compares two modeling approaches for optimal operation of a turbo chiller installed in an office building: (1) a machine learning model developed with artificial neural network (ANN) a...

To evaluate prevalence, incidence, morbidity, and mortality rates of cervical ossification of posterior longitudinal ligament (OPLL) using data from a 12-year national cohort of 1,025,340 Korean people.A nested case-control cohort study was performed from 2002 to 2013 using the insurance claims database provided by the National Health Insurance Service. We examined prevalence and incidence of cervical OPLL. Age- and sex-matched control subjects were randomly extracted, with 10 times the number of OPLL cases. Differences in sex, comorbidity, and relative survival rate compared with control subjects were assessed.Cumulative prevalence was 20,960 per 1,025,340 people for 12 years. Annual incidence was approximately 199-371 per 1 million people. Overall crude mortality rate was 7.64%. Relative survival rate of OPLL cases was not significantly different from control cases. Diabetes, hypertension, cardiovascular disease, and cerebrovascular disease, except renal disease, correlated significantly with OPLL compared with control cases (P0.001). Additionally, between dead and surviving patients among OPLL cases, all comorbidities correlated more significantly with death (P 0.001). Furthermore, between surgery and nonsurgery cases of OPLL, diabetes, hypertension, and renal disease (P 0.05) were significantly associated with surgery.Annual incidence of OPLL was 199-371 per 1,025,340 people for 10 years. Diabetes, hypertension, cardiovascular disease, and cerebrovascular disease, except renal disease, correlated significantly with OPLL compared with control cases. Especially, diabetes, hypertension, and renal disease were associated with patients with OPLL who underwent surgery.

BACKGROUND Spinal cord glioma grade IV is a rare, diffuse midline glioma. H3 K27M-mutant was classified in a different entity in the 2016 World Health Organization (WHO) classification recently. No reports about prognosis of spinal cord glioma grade IV are available yet. OBJECTIVE To analyze the prognostic factors for spinal cord glioma grade IV. METHODS Twenty-five patients with spinal cord glioma of grade IV who underwent surgery in a single institute were selected. All grade IV spinal cord glioma histologically confirmed as glioblastoma or "diffuse midline glioma with H3 K27M-mutant" by the 2016 WHO classification of the central nervous system were included. Basic demographics, treatment modalities, and pathological tumor molecular profiles were investigated for prognosis. RESULTS Mean age was 39.1 yr; male to female ratio was 18 : 7. Tumor was located in thoracic cord (53.3%), cervical cord (40%), and lumbar area (6.7%). Median overall survival was 37.1 mo; median disease-free survival was 18.5 mo. Treatment modality showed no statistical difference. Only K27M profile showed significant prognostic value, 20 patients (80%) showed K27M mutation positive, K27M mutation patients showed longer overall survival (40.07 mo) than K27M negative patients (11.63 mo, P

Objective This retrospective case control study aimed to evaluate the feasibility of using Estimation of Physiological Ability and Surgical Stress (E-PASS) and Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) systems in patients undergoing spinal surgical procedures. Degenerative spine disease has increased in incidence in aging societies, as has the number of older adult patients undergoing spinal surgery. Many older adults are at a high surgical risk because of comorbidity and poor general health. Methods We retrospectively reviewed 217 patients who had undergone spinal surgery at a single tertiary care. We investigated complications within 1 month after surgery. Criteria for both skin incision in E-PASS and operation magnitude in the POSSUM system were modified to fit spine surgery. We calculated the E-PASS and POSSUM scores for enrolled patients, and investigated the relationship between postoperative complications and both surgical risk scoring systems. To reinforce the predictive ability of the E-PASS system, we adjusted equations and developed modified E-PASS systems. Results The overall complication rate for spinal surgery was 22.6%. Forty-nine patients experienced 58 postoperative complications. Nineteen major complications, including hematoma, deep infection, pleural effusion, progression of weakness, pulmonary edema, esophageal injury, myocardial infarction, pneumonia, reoperation, renal failure, sepsis, and death, occurred in 17 patients. The area under the receiver operating characteristic curve (AUC) for predicted postoperative complications after spine surgery was 0.588 for E-PASS and 0.721 for POSSUM. For predicted major postoperative complications, the AUC increased to 0.619 for E-PASS and 0.842 for POSSUM. The AUC of the E-PASS system increased from 0.588 to 0.694 with the Modified E-PASS equation. Conclusions The POSSUM system may be more useful than the E-PASS system for estimating postoperative surgical risk in patients undergoing spine surgery. The preoperative risk scores of E-PASS and POSSUM can be useful for predicting postoperative major complications. To enhance the predictability of the scoring systems, using of modified equations based on spine surgery-specific factors may help ensure surgical outcomes and patient safety.

This letter presents a novel asymmetric single-pole double-throw (SPDT) triple-well CMOS TRx switch for 5G applications at millimeter-wave (mm-wave) frequencies of 25–30 GHz. In 5G applications, low losses in both TRx modes and high power-handling capability in the transmit mode are required. Hence, we proposed a novel structure in which the transmitter and receiver sides are designed asymmetrically to improve the power-handling capability by using all the transistors in the ON-state when in the transmit mode. The proposed TRx SPDT switch is fabricated using the 65-nm triple-well CMOS process and operates in the frequency range of 25–30 GHz with less than 1.16-dB insertion loss in both TRx modes. When in the transmit mode, the measurement result of IP1 dB is 31.8 dBm at 28 GHz. The measurement result of input third-order intercept point is 36 dBm at an input power of 5 dBm in the transmit mode, and the core area is 0.14 mm $\times0.31$ mm.

An inverse association between coffee consumption and the risk of diabetes mellitus (DM) has been observed. However, little is known about this association in Koreans, although they are now among the top global consumers of coffee. Therefore, the aim of this study was to evaluate the association between the prevalence of DM and the amount of coffee consumption using a unit of exact measurement, regardless of the type of coffee consumed. This study was based on data acquired from the Korea National Health and Nutrition Examination Survey 2012&ndash, 2016. The participants who completed the survey were included in the statistical analysis (n = 14,578). Subjects were stratified by age (19&ndash, 39 years old: young adult, 40&ndash, 64 years old: middle-aged adult) and gender (men, women). The amount of coffee was measured using a teaspoon (tsp) unit corresponding to 5 mL of powdered coffee and was analyzed as a continuous variable. The mean powdered coffee intake per day was 1.97 tsp in women groups, 2.24 tsp in young adult men, and 2.72 tsp in middle-aged men. The frequency of coffee consumption showed an inverse relationship with the amount of coffee intake at a time. With each 1-tsp increment in daily coffee intake, the odds of DM were 0.89 (95% confidence interval (CI): 0.86&ndash, 0.92, p &lt, 0.001) and 0.93 (95% CI: 0.90&ndash, 0.95, p = 0.003) in middle-aged women and men, respectively. Coffee consumption was inversely correlated with the prevalence of DM even with adjustment for covariates in middle-aged adults. We delineated that the prevalence for DM decreased as coffee intake increased in Korean middle-aged adults. Therefore, our data represented an inverse association between coffee consumption and the prevalence of DM, although Koreans have a unique coffee-drinking habit.

This paper proposes a wideband reflection-type phase shifter (RTPS) suitable for 5G applications at mm-wave. In this phase shifter, a quadrature hybrid coupler was used as a transformer-based quadrature hybrid for broadband operation. In addition, the reflection term is composed of a varactor, an inductor, and a transmission line. The RTPS is cascaded to satisfy the phase shift range of 180°. The RTPS was fabricated in 1V 1-poly 9-metal 65-nm CMOS technology. The experimental results show that the constructed RTPS has a phase-shifting range of 184.9°, an insertion loss of 9.1 dB, a return loss of 8 dB, and an insertion loss variation of ±2.5 dB at an operating frequency of 25–43 GHz.

PurposeTo evaluate the relationship between comorbidities, medical cost, and surgical outcome in patients with lumbar spinal stenosis (LSS) and diabetes mellitus (DM).MethodsData on patients with LSS (n = 14,298) were collected from the Korean National Health Insurance Service database from 2005 to 2007. After 8 years of follow-up, a "DM group" (n = 3,478) and a "non-DM group" (n = 10,820) were compared according to outcome measures. Cox proportional hazard regressions were performed to examine the relationship between DM, hypertension (HTN), cardiovascular disease (CVD), chronic kidney disease (CKD), cerebrovascular disease (CbVD), and surgery for LSS. The admission rate and medical cost as well asthe overall survival rate for those who underwent lumbar surgery were also assessed among patients with DM and LSS.ResultsMortality was about 1.35 times higher in the DM group than in the non-DM group. Patients with DM and comorbidities including HTN (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.25-1.56; pConclusionsIn patients with LSS, DM was associated both with poor prognosis (most significantly in those with CKD), and increased medical cost in those who underwent surgery. Nevertheless, surgical treatment for LSS in patients with DM was related to favorable prognosis compared with conservative treatment.

The effect of prior statin exposure in critically ill patients remains controversial and has not been established in previous cohort studies. We performed a systematic review of previous cohort studies to evaluate the association of prior statin therapy with mortality in critically ill patients and conducted a meta-analysis. The MEDLINE, EMBASE, and Cochrane CENTRAL databases, from their inception to January 7, 2020, were used for this study. Statin users were defined as patients prescribed statin regularly before intensive care unit admission or diagnosis of a specific disease, such as sepsis. The Cochran chi-square test and I statistics were used to determine heterogeneity between studies. In total, 199,985 critically ill patients from nine studies (44,582 statin users and 155,403 non-statin users) were included in the meta-analysis. According to the random effect model, the 30-day mortality of statin users was 31% lower than that of non-statin users (hazard ratio: 0.69, 95% confidence interval: 0.56 to 0.85). This association was similar in atorvastatin users and simvastatin users. However, hospital mortality in statin users was not significantly associated with that in non-statin users [odds ratios (ORs): 0.71, 95% CI: 0.42 to 1.21]. This study showed that there was a beneficial association of prior statin therapy with 30-day mortality in critically ill patients. However, there was no significant association with hospital mortality. Additional prospective cohort studies with a large sample size should be performed to confirm these findings.

Purpose A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status. Materials and methods The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases. Results A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis. Conclusion This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.

Traditional 2D cell cultures with cells grown as monolayers on solid surface still represent the standard method in cancer research for drug testing. Cells grown in 2D cultures, however, lack relevant cell-matrix and cell-cell interactions and ignore the true three-dimensional anatomy of solid tumors. Cells cultured in 2D can also undergo cytoskeletal rearrangements and acquire artificial polarity associated with aberrant gene expression ( Edmondson et al., 2014 ). 3D culture systems that better mimic the in vivo situation have been developed recently. 3D in vitro cancer models (tumorspheres) for studying cancer stem cells have gained increased popularity in the field ( Weiswald et al., 2015 ). Systems that use matrix-embedded or encapsulated spheroids, spheroids cultured in hanging drops, magnetic levitation systems or 3D printing methods are already being widely used in research and for novel drug screening. In this article, we describe a detailed protocol for testing the effect of shRNA-mediated gene silencing on tumorsphere formation and growth. This approach allows researchers to test the impact of gene knockdown on the growth of tumor initiating cells. As verified by our lab, the protocol can be also used for isolation of 3D cancer cell lines directly from tumor tissues.

// Sangjeong Ahn 1, 6, * , Soomin Ahn 1, 2, * , Michael Van Vrancken 1, * , Minju Lee 1 , Sang Yun Ha 1 , Hyuk Lee 3 , Byung-Hoon Min 3 , Jun Haeng Lee 3 , Jae J. Kim 3 , Sunkyu Choi 4 , Sin-Ho Jung 4 , Min Gew Choi 5 , Jun-Ho Lee 5 , Tae Sung Sohn 5 , Jae Moon Bae 5 , Sung Kim 5 , Kyoung-Mee Kim 1, 2 1 Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea 3 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Present address: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine and BioMedical Research Institute, Pusan National University Hospital, Busan, Korea * These authors have contributed equally to this work Correspondence to: Kyoung-Mee Kim, e-mail: kkmkys@skku.edu Keywords: stomach, biopsy, operation, HER2, immunohistochemistry Received: June 29, 2015 Accepted: September 29, 2015 Published: October 09, 2015 ABSTRACT Intratumoral heterogeneity of HER2 expression is common in gastric cancers and pose a challenge for identifying patients who would benefit from anti-HER2 therapy. The aim of this study is to compare HER2 expression in biopsy and resection specimens of gastric carcinoma by immunohistochemistry (IHC) and to find the ideal number of biopsy tumor fragments that can accurately predict HER2 overexpression in the corresponding surgically resected specimen. The HER2 IHC results of 702 paired biopsy and resection specimens of gastric cancer were compared. The mean number of biopsy fragments among all cases was 4.3 (range 1–11). HER2 was positive in 130 (18.5%) endoscopic biopsies and in 102 (14.5%) gastrectomy specimens. Intratumoral heterogeneity of HER2 was found in 80 (61.5%) biopsies and 70 (68.6%) resection specimens. Out of the 70 surgical specimens with intratumoral heterogeneity, 24 (34.3%) of the corresponding biopsies were categorized as negative (positive conversion). In the 86 (12.3%) discrepant cases, negative conversion was observed in 57 (66.3%) cases and positive conversion in 29 (33.7%). The fragment numbers were significantly correlated with the discrepancy of results and positive predictability ( P = 0.0315 and P = 0.0052). ROC curve analysis and positive predictability showed that 4 fragments should be obtained to minimize the differences in HER2 scores between biopsy and resection specimen. In gastric carcinomas with discrepant HER2 results between biopsy and surgical resection specimens, intratumoral heterogeneity is common with most of them showing positive conversion. To predict HER2 status precisely, at least 4 biopsy fragments containing tumor cells are required.