A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Sleep quality according to chronotype in nurses working 8-hour shifts.

BACKGROUND: To date, studies have been focused on sleep disturbances of nurses working during night shifts. There is a lack of understanding regarding the sleep quality of nurses working in the rapid rotation system for each type of shift work. AIMS: To determine the relationship between chronotype and sleep quality according to shift type (i.e. day, evening and night shifts) in nurses working 8-hour rotating shifts. METHODS: A cross-sectional, descriptive study was conducted from two tertiary hospitals in South Korea from December 2021 to September 2022, including nurses working 8-hour rotating shifts (N = 74). They completed questionnaires to measure general, occupational and sleep-related characteristics, chronotype, insomnia severity and daytime sleepiness. Additionally, sleep parameters were collected from actigraphy and sleep diaries for 7 days. RESULTS: A total of 64% of nurses had an evening chronotype and 37% of nurses had an intermediate chronotype. Nurses had significantly less total sleep time and worsened sleep latency and efficiency during the day shift compared to other shift types. Compared to nurses with an intermediate chronotype, those with an evening chronotype had poorer sleep quality during day shift work. CONCLUSIONS: Strategies to enhance nurses' sleep quality during day shifts should consider a two-level approach: individual approaches, such as improving sleep hygiene, and administrative approaches, such as establishing a chronotype-based shift system for scheduling.

In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Observation of the frozen charge of a Kondo resonance.

The ability to control electronic states at the nanoscale has contributed to our modern understanding of condensed matter. In particular, quantum dot circuits represent model systems for the study of strong electronic correlations, epitomized by the Kondo effect. We use circuit quantum electrodynamics architectures to study the internal degrees of freedom of this many-body phenomenon. Specifically, we couple a quantum dot to a high-quality-factor microwave cavity to measure with exceptional sensitivity the dot's electronic compressibility, that is, its ability to accommodate charges. Because electronic compressibility corresponds solely to the charge response of the electronic system, it is not equivalent to the conductance, which generally involves other degrees of freedom such as spin. Here, by performing dual conductance and compressibility measurements in the Kondo regime, we uncover directly the charge dynamics of this peculiar mechanism of electron transfer. The Kondo resonance, visible in transport measurements, is found to be 'transparent' to microwave photons trapped in the high-quality cavity, thereby revealing that (in such a many-body resonance) finite conduction is achieved from a charge frozen by Coulomb interaction. This freezing of charge dynamics is in contrast to the physics of a free electron gas. We anticipate that the tools of cavity quantum electrodynamics could be used in other types of mesoscopic circuits with many-body correlations, providing a model system in which to perform quantum simulation of fermion-boson problems.

Telemedicine acceptance by older adults in Hong Kong during a hypothetical severe outbreak and after the COVID-19 pandemic: a cross-sectional cohort survey.

INTRODUCTION: Telemedicine services worldwide have experienced unprecedented growth since the early days of the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have shown that telemedicine is an effective alternative to conventional in-person patient care. This study explored the public perception of telemedicine in Hong Kong, specifically among older adults who are most vulnerable to COVID-19. METHODS: Medical students from The Chinese University of Hong Kong conducted in-person surveys of older adults aged ≥60 years. Each survey collected socio-demographic information, medical history, and concerns regarding telemedicine use. Univariate and multivariate logistic regression analyses were conducted to identify statistically significant associations. The primary outcomes were acceptance of telemedicine use during a hypothetical severe outbreak and after the COVID-19 pandemic. RESULTS: There were 109 survey respondents. Multivariate logistic regression analyses revealed that the expectation of government subsidies for telemedicine services was the strongest common driver and the only positive independent predictor of telemedicine use during a hypothetical severe outbreak (P=0.016) and after the COVID-19 pandemic (P=0.003). No negative independent predictors of telemedicine use during a hypothetical severe outbreak were identified. Negative independent predictors of telemedicine use after the COVID-19 pandemic included older age and residence in the New Territories (both P=0.001). CONCLUSION: Government support, such as telemedicine-specific subsidies, will be important for efforts to promote telemedicine use in Hong Kong during future severe outbreaks and after the COVID-19 pandemic. Robust dissemination of information regarding the advantages and disadvantages of telemedicine for the public, especially older adults, is needed.

Evaluation of Variant-Specific Peptides for Detection of SARS-CoV-2 Variants of Concern.

The SARS-CoV-2 omicron variant presented significant challenges to the global effort to counter the pandemic. SARS-CoV-2 is predicted to remain prevalent for the foreseeable future, making the ability to identify SARS-CoV-2 variants imperative in understanding and controlling the pandemic. The predominant variant discovery method, genome sequencing, is time-consuming, insensitive, and expensive. Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) offers an exciting alternative detection modality provided that variant-containing peptide markers are sufficiently detectable from their tandem mass spectra (MS/MS). We have synthesized model tryptic peptides of SARS-CoV-2 variants alpha, beta, gamma, delta, and omicron and evaluated their signal intensity, HCD spectra, and reverse phase retention time. Detection limits of 781, 781, 65, and 65 amol are obtained for the molecular ions of the proteotypic peptides, beta (QIAPGQTGNIADYNYK), gamma (TQLPSAYTNSFTR), delta (VGGNYNYR), and omicron (TLVKQLSSK), from neat solutions. These detection limits are on par with the detection limits of a previously reported proteotypic peptide from the SARS-CoV-2 spike protein, HTPINLVR. This study demonstrates the potential to differentiate SARS-CoV-2 variants through their proteotypic peptides with an approach that is broadly applicable across a wide range of pathogens.

Development of a high-resolution typing method for SLA-3, swine MHC class I antigen 3.

We developed a high-resolution and comprehensive typing method for swine leukocyte antigen 3 (SLA-3), an MHC class I gene, employing locus-specific genomic PCR followed by subsequent direct sequencing. A total of 292 individuals from nine pure, one cross-breed and six cell lines were successfully typed. A total of 21 SLA-3 alleles were identified, of which four were found to be novel alleles. However, the allelic diversity of SLA-3 was lower than that of previously reported class I genes, SLA-1 and -2. More SLA-3 alleles were observed in the Landrace and Yorkshire breeds than the other breeds. SLA-3*04:01 was identified in seven out of nine breeds and was the most widely distributed allele across all breeds. Therefore, the typing method reported in this study completes our efforts to develop high-resolution typing methods for major SLA molecules, facilitating the combined analysis of major SLA genes from field samples, which is important to understand the relationship between the adaptive immune responses against pathogens and the immunogenetic makeup of an individual.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Optimizing the Integration of a Biopesticide (Bacillus subtilis QST 713) with a Single-Site Fungicide (Benzovindiflupyr) to Reduce Reliance on Synthetic Multisite Fungicides (Captan and Mancozeb) for Management of Apple Scab.

Apple scab is one of the most economically important diseases of apple in temperate production regions. In the absence of durable host resistance in commercially preferred cultivars, considerable applications of fungicides are needed to manage this disease. With the sequential development of resistance to nearly all classes of single-site fungicides in the apple scab pathogen Venturia inaequalis, synthetic multisite fungicides, such as mancozeb and captan, often comprise the core of chemical management programs for apple scab. Although these fungicides have demonstrable benefits for both disease and fungicide resistance management, the sustainability movement within agriculture aims to reduce reliance on such fungicides because of their broader environmental impacts. In this study, we establish a framework to enhance the feasibility of chemical management programs that do not rely on use of synthetic multisite protectant fungicides to manage apple scab. Specifically, we wish to evaluate chemical programs that integrate the biopesticide Bacillus subtilis QST 713 (Serenade Opti) in rotation with benzovindiflupyr (Aprovia), a single-site fungicide belonging to the class of succinate dehydrogenase inhibitors (SDHI), to circumvent the need for applications of synthetic multisite fungicides. During implementation of these programs, disease incidence data were taken at biweekly intervals. Regardless of the seasonal challenges presented in the 2 years of this study, when Bacillus subtilis QST 713 was used in place of captan and mancozeb mixtures, we did not observe any significant differences (P > 0.05) in development of apple scab symptoms between any of the management programs for the vertical axis or super spindle orchards in either year. This potential for substituting synthetic multisite fungicides with biopesticides is best realized when the programs are used with a decision support system in a super spindle planting system, where trees have reduced canopy densities. This 2-year study shows the potential to achieve adequate disease control using the integration of SDHI fungicides and biological controls without the use of synthetic multisite fungicides.

Spatiotemporal behaviors of the ridership of a public transportation system during an epidemic outbreak: case of MERS in Seoul.

During May and June 2015, an outbreak of the Middle East respiratory syndrome (MERS) occurred in Korea, which raised the fear of contagion throughout society and suppressed the use of public transportation systems. Exploring daily ridership data of the Seoul bus transportation system, along with the number of infected patients and search volume in web portals, we observe that ridership decreased abruptly while attention was heavily focused online. Then this temporal reduction recovered exponentially with a characteristic time of 3 weeks when newly confirmed cases began to decrease. We also find with the data of ranked keywords of web portals that areas with severely reduced ridership tended to cluster and spatiotemporal variations of such clusters were highly associated with general hospitals where MERS patients were treated. On the other hand, the spatial reduction in ridership relaxed algebraically with the distance from a general hospital while the outbreak was severe. We further probe the influence of the epidemic outbreak in the framework of linear response theory, which relates the responses to the epidemic outbreak ("perturbation") with correlations in the absence of the perturbation. Indeed, the spatial correlation function of the ridership changes is observed to follow a power law, sharing the same exponent as the spatial relaxation of the response function. This new theoretical approach offers a useful tool for understanding responses of public transportation system to epidemic or accidental disasters.

Protein intake and osteosarcopenic adiposity in Korean adults aged 50 years and older.

Intake of plant-based protein and recommended protein intake are associated with a lower risk of osteosarcopenic adiposity (co-occurrence of osteopenia/osteoporosis, sarcopenia, and adiposity) in elderly Korean men. INTRODUCTION: Osteosarcopenic adiposity (OSA) syndrome is defined as the concurrent presence of osteopenia/osteoporosis, sarcopenia, and adiposity and leads to negative functional and metabolic outcomes in late adulthood. This study aimed to investigate the association between OSA and protein intake in adults aged 50 or older. METHODS: A population-based, cross-sectional survey was conducted using the Korea National Health and Nutrition Examination Survey 2008-2009 data and included 645 men and 706 women aged 50 or older. Subjects were classified into normal and OSA groups. Protein intake was analyzed using the 24-h recall method. RESULTS: There was no significant difference in the intake of total protein and animal-based protein between normal and OSA groups. However, in males, the intake of plant-based protein (p = 0.0031) was significantly lower in the OSA group than that in the normal group. Further, the protein intake in the OSA group was 0.96 g/kg/day, which was significantly lower than that in the normal group (1.06 g/kg/day; p = 0.0203). After adjusting for confounding factors, men over 65 years old who consumed less than the recommended nutrient intake (RNI) of 0.91 g/kg/day had 5.82 times higher risk of OSA compared with subjects consuming protein equal to or greater than the RNI amount (95% CI 1.81-18.66). CONCLUSION: In conclusion, a protein intake of RNI or more is associated with a lower risk of OSA in Korean elderly men.

Comparison of a 1064-nm neodymium-doped yttrium aluminum garnet picosecond laser using a diffractive optical element vs. a nonablative 1550-nm erbium-glass laser for the treatment of facial acne scarring in Asian patients: a 17-week prospective, randomized, split-face, controlled trial.

BACKGROUND: Novel picosecond lasers using a diffractive optical element (P-DOE) have been available for skin resurfacing with distinct mechanisms. However, there are limited data directly comparing P-DOE and conventional fractional lasers for the treatment of atrophic acne scarring. OBJECTIVES: We sought to compare the efficacy and safety of a 1064-nm neodymium-doped yttrium aluminium garnet P-DOE and a non-ablative fractional laser (NAFL) in the treatment of acne scarring. METHODS: A prospective, randomized, split-face, controlled trial was performed. One randomly assigned half-side of each patient's face (n = 25) was treated with four consecutive sessions of P-DOE at 3-week intervals and the other side with NAFL, with subsequent follow-up for 8 weeks after the final sessions. The efficacy and safety of the two lasers were determined by the Echelle d'Evaluation Clinique des Cicatrices d'acné (Scale of Clinical Evaluation of Acne Scars; ECCA) grading scale, Investigator's Global Assessment (IGA) score and patients' reports at the final visit. Histologic analysis was also performed. RESULTS: The P-DOE-treated side achieved a significantly better improvement in acne appearance (ECCA per cent reduction: 55% vs. 42%) with less severe pain (4.3 vs. 5.6) (P < 0.05). The IGA score and subjective satisfaction were consistent with ECCA score results. Occurrences of treatment-related side-effects were also lower in the group treated with P-DOE (P < 0.05). Histologic analysis revealed elongation and increased density of neocollagen fibres, elastic fibres and mucin throughout the dermis from both sides. CONCLUSIONS: Compared with NAFL, P-DOE afforded better clinical outcomes and fewer side-effects in the treatment of acne scarring in Asian patients.

Parkinson's disease and skin cancer risk: a nationwide population-based cohort study in Korea.

BACKGROUND: Previous studies have reported that patients with Parkinson's disease (PD) have a significantly lower risk of cancer. Studies reporting prevalence of skin cancers in Parkinson's disease mostly involve Caucasians. OBJECTIVE: A nationwide population-based study was conducted to determine the risk of skin cancer in patients diagnosed with PD in Korea. METHODS: Data obtained from National Health Insurance Claims records were used to retrieve information about 70 780 patients with newly diagnosed PD between January 2010 and December 2015. The control group included 353 900 sex- and age-matched patients without PD. In this nationwide population-based cohort study, we investigated the association between PD and skin cancer. RESULTS: The overall hazard ratio (HR) of skin cancers in patients with PD was 1.169 (95% CI, 1.005-1.359) compared with non-PD group. Among patients with PD, males aged above 65 had a 2.8-fold increase in the risk for melanoma development than the non-PD group (HR, 2.825; 95% CI, 1.395-5.721). In addition, female PD patients aged above 65 years showed a 1.3-fold increase in non-melanoma skin cancer risk than the non-PD group (HR, 1.305; 95% 1.073-1.589). CONCLUSION: Compared with the general population, Korean patients diagnosed with PD had a greater risk of skin cancer. Especially, male patients aged 65 years and above, and diagnosed with PD had a significant risk of melanoma development compared with control.

Mental health states and influencing factors of risky and problem drinking in South Korean female adolescents.

OBJECTIVES: Alcohol is one of the most used and abused psychoactive substances by adolescents. We investigated influencing factors of risky and problem drinking in Korean female adolescents. STUDY DESIGN: The study design used is a cross-sectional modeling. METHODS: We used data from the 13th Korean Youth Risk Behavior Web-based Survey (KYRBS) conducted in 2017. KYRBS data were obtained from a stratified, multistage, clustered sample. Risky drinking was binge drinking and problem drinking was drinking with several conflicts association with alcohol consumption. RESULTS: Among 62,276 participants, the rates of current, risky, and problem drinking among all participants were 16.1%, 8.3%, and 6.1%, respectively. Although all of these rates were higher in males, risky and problem drinking rates among current female drinkers were higher than those of males (55.4 vs 48.5%, 38.9 vs 37.2%, respectively). Problem drinking was most strongly associated with risky drinking (adjusted odds ratio: 17.53 [95% confidence interval: 14.63-21.00]), similarly, risky drinking was most strongly associated with problem drinking in female current drinkers (17.76 [14.84-21.27]). Current smoking was the second strongest risk factor for risky and problem drinking in females (5.22 [3.92-6.95] and 2.93 [2.21-3.89], respectively). CONCLUSION: Many female adolescents in Korea drink alcohol in an unhealthy manner. The female risky and problem drinking rates among current drinkers were higher than those of males. Risky drinking and problem drinking was most significant influencing factor among females, reciprocally. Public education on abstinence in female adolescents is warranted.

MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.

Autoantibodies in SLE: prediction and the p value matrix.

Autoantibodies (AA) and antinuclear antibodies (ANA) serve as key diagnostic and classification criteria for systemic lupus erythematosus (SLE). More than 200 different AA have been reported in SLE, although only a handful (<20) are considered "mainstream" because they are widely and routinely used in diagnostic, research and clinical medicine. Although the vast majority of AA have been relegated to the diminished status of "orphan" AA, some serve as predictors of SLE because they first appear in very early or subclinical SLE. Some AA are pathogenic, whereas others are thought to protect against or ameliorate disease progression and, hence, taken together can be used as predictive biomarkers of prognosis. Although studies have shown that specific AA are detected in the preclinical phase of SLE and are biomarkers of increased risk of developing the disease, AA are currently not widely used to predict very early SLE in individuals who have low pretest probability of disease. With the advent of multianalyte arrays with analytic algorithms, emerging evidence indicates that when certain combinations of biomarkers, such as the interferon signature and stem cell factor accompany AA and ANA, the predictive power for SLE is markedly increased.

Prostate cancer detection rate according to lesion visibility using ultrasound and MRI.

AIM: To evaluate the difference in prostate cancer detection rates according to lesion visibility using transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) before biopsy. MATERIALS AND METHODS: Patients who underwent TRUS-guided prostate biopsy in 2016 and 2017 (n=1,022) were divided into three groups: (1) patients who did not undergo a prebiopsy MRI (group 1, n=622); (2) patients without visible lesions on the prebiopsy MRI (group 2, n=77); and (3) patients with visible lesions on the prebiopsy MRI (group 3, n=323). Biopsy results were compared using chi-square tests or independent t-tests between patients with and without TRUS-visible lesions in each group. A logistic regression test was used to determine the variables independently associated with the detection of clinically significant cancer. RESULTS: Focal lesions were visible on TRUS in 710 patients. Clinically significant cancers were detected in 39.4% and 13.1% of patients with and without TRUS-visible lesions, respectively (p<0.001). The cancer detection rate was significantly higher in patients with TRUS-visible lesions in groups 1 and 3 (p<0.001). Within group 1, the Gleason scores, number of positive cores, and the cancer involvement ratios were significantly greater in patients with TRUS-visible lesions than in patients without TRUS-visible lesions. MRI- and TRUS visibility were positively associated with the detection of clinically significant prostate cancer (p=0.002 and p<0.001, respectively). CONCLUSION: TRUS- and MRI-visible focal lesions in the prostate were significantly associated with the detection of clinically significant cancer.

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Prebiopsy biparametric MRI: differences of PI-RADS version 2 in patients with different PSA levels.

AIM: To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10 ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis. RESULTS: csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively. CONCLUSION: Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group.