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BackgroundThe safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients.MethodsThe data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression.ResultsInactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination.ConclusionCOVID-19 vaccination has no long-term impact on MG relapse.

Background We report a patient with a novel c.737 C > T variant (p.Ser246Leu) of the TPM3 gene presenting with adult-onset distal myopathy. Case presentation A 35-year-old Chinese male patient presented with a history of progressive finger weakness. Physical examination revealed differential finger extension weakness, together with predominant finger abduction, elbow flexion, ankle dorsiflexion and toe extension weakness. Muscle MRI showed disproportionate fatty infiltration of the glutei, sartorius and extensor digitorum longus muscles without significant wasting. Muscle biopsy and ultrastructural examination showed a non-specific myopathic pattern without nemaline or cap inclusions. Genetic sequencing revealed a novel heterozygous p.Ser246Leu variant (c.737C>T) of the TPM3 gene which is predicted to be pathogenic. This variant is located in the area of the TPM3 gene where the protein product interacts with actin at position Asp25 of actin. Mutations of TPM3 in these loci have been shown to alter the sensitivity of thin filaments to the influx of calcium ions. Conclusion This report further expands the phenotypic spectrum of myopathies associated with TPM3 mutations, as mutations in TPM3 had not previously been reported with adult-onset distal myopathy. We also discuss the interpretation of variants of unknown significance in patients with TPM3 mutations and summarise the typical muscle MRI findings of patients with TPM3 mutations.

B、C型肝炎病人需要定期追蹤及檢驗疾病發展狀況，以及早發現肝癌。彰化基督教醫院胃腸肝膽科於2010年開始實行衛生福利部中央健康保險署（下稱健保署）追蹤照護計畫，過程中因病人病識感低，以及門診收案及追蹤流程複雜，截至2016年收案率14.6%、年度完整追蹤率28.8%，皆未達健保署設定的3項品質獎勵監測指標。透過E化之B、C肝照護管理系統，改善並簡化門診收案流程，提升個案管理師收案追蹤效率及提高病人遵從醫囑率，大幅提升了B、C肝病人照護品質。於2017年開始執行E化追蹤管理，2019年收案率提升至58.91%(4542/7710)，年度完整追蹤率達74.45%(3107/4173)。健保署評比2018年度品質獎勵榮獲中區第一名，本院是中區唯一獲得品質獎勵之醫學中心。 Patients with hepatitis B and C require regular follow-up to monitor disease activity and screen for the presence of hepatocellular carcinoma. Since 2010, Changhua Christian Hospital has implemented a hepatitis B and C care plan guided by the National Health Insurance Administration (NHIA), Ministry of Health and Welfare (MOHW). The rates of patient enrollment and follow-up between 2010 and 2016 were unsatisfactory. The annual enrollment and follow-up rates were only 14.6% and 28.8%, respectively, in 2016, falling below the three quality indicator standards established by the NHIA. The absence of insight into patient disease and the complexity of patient enrollment and follow-up procedures were identified as the main problems. Therefore, in 2017, we developed a strategy for improving and simplifying the patient enrollment process, enhancing the efficiency of the case managers involved in patient enrollment and follow-up, and increasing the rate of medical compliance. An electronic follow-up reminder system was implemented to enhance our quality of care among patients with hepatitis B and C. Thus, in 2019, the annual enrollment and follow-up rates had dramatically increased to 58.91% (4542/7710) and 74.45% (3107/4173), respectively. Because of the improved care management system, our hospital was the only medical center in central Taiwan that won an NHI Quality Award in 2018. &nbsp

Supplemental material, sj-docx-1-ict-10.1177_15347354221150907 for Comparison of Quality of Life Between Breast Cancer Patients Treated With and Without Adjunctive Traditional Chinese Medicine in Taiwan by Yeong-Ruey Chu, Pei-Tseng Kung, Liang-Chih Liu, Chin-Yao Lin, Fu Ou-Yang, Chia-Herng Yue, Shan-Yu Su, Ying-Yu Chen, Wen-Ching Wang, Hui-Fen Kao, Wen-Yu Chou and Wen-Chen Tsai in Integrative Cancer Therapies

Supplemental material, sj-docx-1-ict-10.1177_15347354221150907 for Comparison of Quality of Life Between Breast Cancer Patients Treated With and Without Adjunctive Traditional Chinese Medicine in Taiwan by Yeong-Ruey Chu, Pei-Tseng Kung, Liang-Chih Liu, Chin-Yao Lin, Fu Ou-Yang, Chia-Herng Yue, Shan-Yu Su, Ying-Yu Chen, Wen-Ching Wang, Hui-Fen Kao, Wen-Yu Chou and Wen-Chen Tsai in Integrative Cancer Therapies

Background: According to research, the neurotoxicity caused by the accumulation of the excitatory neurotransmitter glutamate is closely related to Alzheimer's disease. However, even after 50 years of research, little is known about the relationship between glutamate-related carriers and Alzheimer's disease, and it is unclear whether glutamate metabolism target genes are involved in the occurrence and development of AD.As a result, the goal of our investigations was to identify glutamate metabolism target genes involved in the onset and progression of AD, as well as to validate and mine the relationship between them. Results: In this paper, we analysed the Gene Expression Omnibus (GEO) data further and discovered that the expression of glutamate carrier SLC25A18 is correlated with Alzheimer's disease by screening the differential genes in different regions of the brain of Alzheimer's disease patients. To verify the expression of SLC25A18 during Alzheimer's disease development, we created animal models (5×FAD transgenic AD animal model, chemically induced AD animal model, natural ageing animal model), and the results showed that the expression of SLC25A18 increased when Alzheimer's disease occurred in various animal models. After that, we checked the expression of SLC25A18 in Aβ1-42-induced Neuro 2A cells, and the results revealed that neurons had higher SLC25A18 expression after Aβ1-42 induction. Conclusions: The results indicate that SLC25A18 is related to the onset and progression of Alzheimer's disease and that it could be a target for treatment.

HOX transcript antisense intergenic RNA (HOTAIR) is a lncRNA with a length of 2,158 nucleotides and its two terminal domains could combine with different complexes to function at the level of transcription and translation. It overexpresses in many cancers including gastric cancer. HOTAIR could play an oncogenic role in the initiation and progression of gastric cancer through interaction with microRNAs, such as miR-330/618/126 in the PI3K/Akt signaling pathways. HOTAIR single nucleotide polymorphisms (SNPs) may have genotype-function and allele-specific effect on gastric cancer by a mechanism that specific SNP could give rise to a variation of HOTAIR and alter the binding site of microRNAs. Both rs920778 T allele and rs4759314 G allele will enhance the susceptibility to gastric cancer in the Chinese populations. In a word, the suppression of HOTAIR and overexpression of downstream microRNAs may be potential therapeutic strategies of gastric cancer related to HOTAIR.

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex–midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

IntroductionPhospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson’s disease (namely, PARK14). Compared to idiopathic Parkinson’s disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14.DesignThis case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson’s disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation.MethodsThe diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson’s disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants’ serum using UHPLC-QTOF/MS analysis, a well-established technology.ResultsWe quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients’ serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models.ConclusionThe significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation.

Background There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. Methods Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. Results At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). Conclusion Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Bromodomain (BRD)-containing proteins are a class of epigenetic readers with unique recognition for N-acetyl-lysine in histones and functions of gene transcription and chromatin modification, known to be critical in various cancers. However, little is known about the roles of distinct BRD-containing protein genes in hepatocellular carcinoma (HCC). Most recently, we investigated the transcriptional and survival data of BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 in HCC patients through ONCOMINE, UALCAN, Human Protein Atlas, GEPIA, cBioPortal, STRING, TIMER databases. BRD1/2/3/4/7/8/9 were over-expressed in HCC and were significantly associated with clinical cancer stages and pathological tumor grades. High mRNA expressions of BRD4/8/9 were promising candidate biomarkers in HCC patients. The rate of sequence alternations in BRD1/2/3/4/7/8/9 was relatively high (52%) in HCC patients, and the genetic alternations were correlated with shorter overall survival and disease-free survival in HCC patients. Additionally, the mRNA expression levels of individual BRD genes were significantly positively associated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. And the associations between BRD1/2/3/4/7/8/9 and diverse immune marker sets showed a significance. Overall, these results indicated that BRD4/8/9 could be potential prognostic markers and druggable epigenetic targets in HCC patients.

Transit Timing Variation (TTV) of hot Jupiters provides direct observational evidence of planet tidal dissipation. Detecting tidal dissipation through TTV needs high precision transit timings and long timing baselines. In this work, we predict and discuss the potential scientific contribution of SiTian Survey in detecting and analyzing exoplanet TTV. We develop a tidal dissipation detection pipeline for SiTian Survey that aims at time-domain astronomy with 72 1-meter optical telescopes. The pipeline includes the modules of light curve deblending, transit timing obtaining, and TTV modeling. SiTian is capable to detect more than 25,000 exoplanets among which we expect $\sim$50 sources showing evidence of tidal dissipation. We present detection and analysis of tidal dissipating targets, based on simulated SiTian light curves of XO-3b and WASP-161b. The transit light curve modeling gives consistent results within 1$\sigma$ to input values of simulated light curves. Also, the parameter uncertainties predicted by Monte-Carlo Markov Chain are consistent with the distribution obtained from simulating and modeling the light curve 1000 times. The timing precision of SiTian observations is $\sim$ 0.5 minutes with one transit visit. We show that differences between TTV origins, e.g., tidal dissipation, apsidal precession, multiple planets, would be significant, considering the timing precision and baseline. The detection rate of tidal dissipating hot Jupiters would answer a crucial question of whether the planet migrates at an early formation stage or random stages due to perturbations, e.g., planet scattering, secular interaction. SiTian identified targets would be constructive given that the sample would extend tenfold., Comment: Accept for publication to RAA

Supplemental material, sj-docx-1-aop-10.1177_10600280211059040 for Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies by Na He, Yingying Yan, Shan Su, Qinggang Ge and Suodi Zhai in Annals of Pharmacotherapy

Single-line spectroscopic binaries recently contribute to the stellar-mass black hole discovery, independently of the X-ray transient method. We report the identification of a single-line binary system LTD064402+245919, with an orbital period of 14.50 days. The observed component is a subgiant with a mass of 2.77$\pm$0.68M$_{\odot}$, radius 15.5$\pm$2.5R$_{\odot}$, effective temperature $T_{\rm eff}$ 4500$\pm$200K, and surface gravity log\emph{g} 2.5$\pm$0.25dex. The discovery makes use of the LAMOST time-domain (LAMOST-TD) and ZTF survey. Our general-purpose software pipeline applies the Lomb-Scargle periodogram to determine the orbital period and uses machine-learning to classify the variable type from the folded light curves. We apply a combined model to estimate the orbital parameters from both the light and radial velocity curves, taking constraints on the primary star mass, mass function, and detection limit of secondary luminosity into consideration. We obtain a radial velocity semi-amplitude of 44.6$\pm$1.5 km s$^{-1}$, mass ratio of 0.73$\pm$0.07, and an undetected component mass of 2.02$\pm$0.49M$_{\odot}$ when the type of the undetected component is not set. We conclude that the inclination is not well constrained, and that the secondary mass is larger than 1M$_{\odot}$ when the undetected component is modelled as a compact object. According to our investigations using an MCMC simulation, increasing the spectra SNR by a factor of 3 would enable the secondary light to be distinguished (if present). The algorithm and software in this work are able to serve as general-purpose tools for the identification of compact objects quiescent in X-rays., Accepted by ApJ

The wavelength-dependent transit depth indicates the atmosphere composition of an exoplanet. We analyze the transit depth of HATS-5b using the data from the Transiting Exoplanet Survey Satellite (TESS) and compare the radius ratio of the planet to the star with the different band result in previous work. We generate a photometric pipeline to obtain the TESS light curve. The fitting of the HATS-5b light curve derives similar bandpass independent parameters compared to the reference work, e.g., the differences in the inclination and the semi-major axis within 1 $\sigma$ . We fix the bandpass-independent parameters to values from the previous work for comparison purposes. The wavelength-dependent $R_{p}/R_{\ast}$ obtained is 2.5% (1.9 $\sigma$ ) smaller compared to the joint band result from the referenced work. The difference of $R_{p}$ / $R_{\ast}$ suggests a haze-dominant model preferred by observation (with $\chi^{2}=1.68$ ) when fitting with different atmospheric models. The opaque featureless atmospheric model has a $\chi^{2}\sim4$ , while the other models are ruled out with $\chi^{2}> 7$ . We also predict an $R_{p}/R_{\ast}$ difference of ∼1 $\%$ , correlating the presence of water at $z$ -band observation. This difference is detectable at 3 $\sigma$ if the photometry precision reaches 500 ppm with 2 minute exposure for one-night observation.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91-411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54-151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13-9.78] pg/ml, median [IQR]) (p 0.05). The level of NfL in the remission phase group was higher than in HCs group (p 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

We present a novel, iterative method using an empirical Bayesian approach for modeling the limb darkened WASP-121b transit from the TESS light curve. Our method is motivated by the need to improve $R_{p}/R_{\ast}$ estimates for exoplanet atmosphere modeling, and is particularly effective with the limb darkening (LD) quadratic law requiring no prior central value from stellar atmospheric models. With the non-linear LD law, the method has all the advantages of not needing atmospheric models but does not converge. The iterative method gives a different $R_{p}/R_{\ast}$ for WASP-121b at a significance level of 1$\sigma$ when compared with existing non-iterative methods. To assess the origins and implications of this difference, we generate and analyze light curves with known values of the limb darkening coefficients (LDCs). We find that non-iterative modeling with LDC priors from stellar atmospheric models results in an inconsistent $R_{p}/R_{\ast}$ at 1.5$\sigma$ level when the known LDC values are as those previously found when modeling real data by the iterative method. In contrast, the LDC values from the iterative modeling yields the correct value of $R_{p}/R_{\ast}$ to within 0.25$\sigma$. For more general cases with different known inputs, Monte Carlo simulations show that the iterative method obtains unbiased LDCs and correct $R_{p}/R_{\ast}$ to within a significance level of 0.3$\sigma$. Biased LDC priors can cause biased LDC posteriors and lead to bias in the $R_{p}/R_{\ast}$ of up to 0.82$\%$, 2.5$\sigma$ for the quadratic law and 0.32$\%$, 1.0$\sigma$ for the non-linear law. Our improvement in $R_{p}/R_{\ast}$ estimation is important when analyzing exoplanet atmospheres., Comment: Accepted by AJ

Two main job stress models-the Demand-Control-Support (DC) model and the Effort-Reward Imbalance (ERI) model have been used to assess the impact of psychosocial work-related factors for cardiovascular disease (CVD). Limited evidence elaborates the independent and combined effects on CVD events, especially for professional drivers. This study assesses the independent and combined effects of DC and ERI models on an 8-year risk of CVD among professional drivers.The Taiwan Bus Driver Cohort Study recruited 1650 professional drivers from a large bus company in 2005. The subjects were interviewed in person and completed the two job stress questionnaires. Researchers found 94 new cases of CVD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 390-459) from 2006 to 2012. A Cox proportional hazards model was performed to estimate the hazard ratio (HR) for CVD events.Occupational drivers with high overcommitment scores (thresholds of 15) had an elevated risk for CVD (HR = 1.71; 95% CI = 1.04, 2.82). Regarding target disease, overcommitment had an increased risk for CVD (not including hypertensive disease) (HR = 1.27; 95% CI = 1.05, 1.54) and ischemic heart disease (HR = 1.32; 95% CI = 1.05-1.65).Overcommitment, which is associated with job stress, appears to be associated with CVD risk in professional drivers.

Most common ovarian cancers are epithelial carcinoma in which the etiology for carcinogenesis remains elusive. ANO1/TMEM16A, a member of Ca2+ -activated Cl- channels (CaCCs), has been demonstrated to promote epithelium-originated cancers and whether it plays a role in the pathogenesis of ovarian cancer is unknown. In our study we found that ANO1 proteins were overexpressed in human epithelial ovarian cancer cells and tissue samples. ANO1 protein upregulation was correlated with the clinical FIGO (International Federation of Gynecology and Obstetrics) staging and poor grade in ovarian cancer tissues. Interestingly, the upregulation of ANO1 gene expression was also detected in the peripheral blood mononuclear cells (PBMCs) from preoperative patients with ovarian tumors, and the down-regulation of ANO1 in the PBMCs from postoperative patients. Silencing of ANO1 inhibited proliferation and invasion of ovarian cancer cells. Mechanistically, ANO1 knockdown attenuated phosphorylation of PI3K/Akt, and inhibition of PI3K/Akt signaling by specific inhibitor LY294002 resulted in suppression of ovarian cancer cells growth promoted by ANO1 expression. Furthermore, intratumoral injection of ANO1 siRNA suppressed subcutaneous xenograft tumor growth in nude mice implanted with ovarian cancer SKOV3 cells. Taken together, our findings demonstrate that ANO1 overexpression is involved in the pathogenesis of human epithelial ovarian cancer. Inhibition of ANO1 upregulation or inactivating PI3K/Akt signaling may have therapeutic potential for epithelial ovarian cancer, and the detection of ANO1 expression level in PBMCs from patients may also serve as a biomarker for diagnosis and prognosis of epithelial ovarian cancers.

High-efficiency video coding (HEVC), which is the latest video coding standard, is expected to have a dominant position in the market in the near future. However, most video resources are now encoded using the H.264/AVC standard. Consequently, there is a growing need for fast H.264/AVC to HEVC transcoders to facilitate the migration to the updated standard. This paper proposes a fast H.264/AVC to HEVC transcoding scheme, which constructs a three-level classifier using an optimised tree-augmented Naive Bayesian approach to predict the HEVC coding unit depth. A feature selection method is then proposed to improve prediction accuracy. A motion vector (MV) calculation method is also proposed to reduce the complexity of MV prediction in HEVC by reusing MVs from H.264/AVC. Experimental results show that, compared with other state-of-the-art transcoding algorithms, the proposed algorithm considerably reduces coding complexity while causing only negligible rate-distortion degradation.

BACKGROUND: Accurate staging plays a pivotal role in cancer care. The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been suggested as alternatives to the N staging since the TNM system has the risk of stage migration. The prognostic significance of LNR and LODDS in young patients with gastric cancer (GC) has not been reported. This study aims to investigate the correlations between LNR and LODDS and survival of young patients with GC, and compare the predictive performance of these LN staging methods. METHODS: GC patients before the age of 40 from 2004 to 2016 in the Surveillance, Epidemiology and End Results database were enrolled. The prognostic evaluation of the N factor, LNR and LODDS was compared using the time-dependent receiver operating characteristic (ROC) analysis, area under the curve (AUC), C-index and Akaike information criterion (AIC). RESULTS: Multivariate survival analysis identified that the LNR and LODDS were significantly independent prognostic indicators for overall survival (OS) in young patients with GC and in the subgroups comprised of patients with ≤15 LNs examined. The time-dependent ROC curves of the LNR and LODDS were continuously superior to that of the N factor in predicting OS during the observation period. And the AUCs revealed that the predictive accuracy of the LNR and LODDS was remarkably superior to the N factor at 1 and 3 years (P

Additional file 1: Table S1. Efficacy of anti-TB treatment when combined with anti-PD(L)-1 therapy.

A precise transit ephemeris serves as the premise for follow-up exoplanet observations. We compare TESS Objects of Interest (TOI) transit timings of 262 hot Jupiters with the archival ephemeris and find 31 of them having TOI timing offsets, among which WASP-161b shows the most significant offset of -203.7$\pm$4.1 minutes. The median value of these offsets is 17.8 minutes, equivalent to 3.6 $\sigma$. We generate TESS timings in each sector for these 31 hot Jupiters, using a self-generated pipeline. The pipeline performs photometric measurements to TESS images and produces transit timings by fitting the light curves. We refine and update the previous ephemeris, based on these TESS timings (uncertainty $\sim$ 1 minute) and a long timing baseline ($\sim 10$ years). Our refined ephemeris gives the transit timing at a median precision of 0.82 minutes until 2025 and 1.21 minutes until 2030. We regard the timing offsets mainly originating from the underestimated ephemeris uncertainty. All the targets with timing offset larger than 10$\sigma$ present earlier timings than the prediction, which cannot be due to underestimated ephemeris uncertainty, apsidal precision, or R$\o$mer effect as those effects should be unsigned. For some particular targets, timing offsets are likely due to tidal dissipation. Our sample leads to the detection of period decaying candidates of WASP-161b and XO-3b reported previously., Comment: Submitted to ApJS; 24 pages

Binaries play key roles in determining stellar parameters and exploring stellar evolution models. We build a catalog of 88 eclipsing binaries with spectroscopic information, taking advantage of observations from both the Large Sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) and the Palomar Transient Factory (PTF) surveys. A software pipeline is constructed to identify binary candidates by examining their light curves. The orbital periods of binaries are derived from the Lomb-Scargle method. The key distinguishing features of eclipsing binaries are recognized by a new filter \textit{Flat Test}. We classify the eclipsing binaries by applying Fourier analysis on the light curves. Among all the binary stars, 13 binaries are identified as eclipsing binaries for the first time. The catalog contains information: position, primary eclipsing magnitude and time, eclipsing depth, the number of photometry and radial velocity observations, largest radial velocity difference, binary type, the effective temperature of observable star $T_{\rm eff}$, and surface gravity of observable star log \emph{g}. The false-positive probability is calculated by using both a Monte Carlo simulation and real data from the SDSS Stripe 82 Standard Catalog. The binaries in the catalog are mostly with a period of less than one day. The period distribution shows a 0.22-day cut-off which is consistent with the low probability of an eclipsing binary rotating with such a period., Comment: 31 pages, 10 figures, In Press (accepted by ApJS)

Systemic inflammation and interactions with host-tumor are currently identified as a hallmark of cancer. The purpose of this study was to assess the prognostic value of preoperative modified Glasgow Prognostic Score (mGPS), systemic inflammation score (SIS) and "lymphocyte C-reactive protein score" (LCS) in gastric cancer (GC) patients.358 GC patients were enrolled in this retrospective study. Kaplan-Meier method, multivariate Cox regression analysis, time-dependent receiver operating characteristics analysis (ROC), concordance index (C-index), and Akaike information criterion (AIC) were applied for assessments of the prognostic values.Preoperative increased mGPS, SIS and LCS were all significantly linked with unfavorable overall survival using the Kaplan-Meier method (P 0.001). Multivariate analysis proved that SIS was the only independent indicator among these three scoring systems. At the 4th-month point postoperatively, the time-dependent ROC curves of SIS and LCS crossed the curve of mGPS and were consistently superior to that of mGPS thereafter. The model incorporating SIS had higher C-index and smaller AIC than did the model without SIS or the models with mGPS or LCS.Preoperative SIS exceeded both the mGPS and LCS and was the most clinically promising and feasible prognostic scoring system for GC patients.

We investigate the relationship between the optical variability of galaxies and their distances from the centre of the Virgo Cluster using Palomar Transient Factory data. We define the ratio between the standard deviation of the galaxy brightness and the mean value of the standard deviation as a measure of a galaxy's optical variability. A sample of 814 Virgo galaxies with 230263 observations shows a monotonically decreasing trend of optical variability with increasing clustercentric distance. The variability level inside the cluster is 3.2$\sigma$ higher than the level outside. We fit the variability with a linear function and find that the data reject a distance-independent model. We examine 217 background galaxies for comparison and find no significant trend in galaxy variability. We assess the relation with Monte Carlo simulation by rebuilding the brightness of each galaxy. The simulation shows a monotonically decreasing relation for member galaxy variability and a distance-independent relation for background galaxies. Our result is consistent with the theory that the cold gas flowing inwards the cluster centre fuels AGN activity. This work is a new implementation of the method using optical variability to investigate the relation between galaxies evolution and their environment., Comment: 5 pages, 4 figures, in Press (accepted by MNRAS Letters)

Background Professional drivers' work under conditions predisposes them for development of sleep-disordered breathing (SDB) and cardiovascular disease (CVD). However, the effect of SDB on CVD risk among professional drivers has never been investigated. A cohort study was used to evaluate the effectiveness of overnight pulse oximeter as a sleep apnea screening tool to assess the 8-year risk of CVD events. Methods The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1014 professional drivers in Taiwan since 2005. The subjects completed questionnaire interview and overnight pulse oximeter survey. This cohort was linked to the National Health Insurance Research Dataset (NHIRD). Researchers found 192 CVD cases from 2005 to 2012. Cox proportional hazards model was performed to estimate the hazard ratio for CVD. The statistical analysis was performed using SAS software in 2015. Results ODI4 and ODI3 levels increased the 8-year CVD risk, even adjusting for CVD risk factors (HR: 1.36, 95% CI: 1.05 to 1.78; p=0.022, and HR: 1.40, 95% CI: 1.03 to 1.90; p=0.033). ODI4 and ODI3 thresholds of 6.5 and 10events/h revealed differences of CVD risks (HR: 1.72, 95% CI: 1.00 to 2.95; p=0.048, and HR: 1.76, 95% CI: 1.03 to 3.03; p=0.041). Moreover, the ODI levels had an increased risk for hypertensive disease (not including essential hypertension). Conclusions This study concludes that ODI for a sign of SDB is an independent predictor of elevated risk of CVD. Further research should be conducted regarding measures to prevent against SDB in order to reduce CVD risk in professional drivers.

Shan-Shan Su,1,* Sheng-Nan Zhang,1,* Jun-Ru Ye,1 Ling-Na Xu,1 Peng-Cheng Lin,1 Han-Yan Xu,1 Qing Wu,2 Yu-Ping Li1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, People’s Republic of China; 2The Center of Laboratory and Diagnosis, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Ping LiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, Zhejiang Province 325015, People’s Republic of ChinaTel/fax +86 577 5557 9273Email wzliyp@163.comBackground: Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet’s syndrome.Case presentation: A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet’s syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained.Conclusions: Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet’s syndrome is a common skin manifestation of the syndrome.Keywords: Talaromyces marneffei, Mycobacterium avium, Sweet’s syndrome, autoantibodies, interferon-gamma

We take advantage of the red clump stars to build the relation of the optical extinction (AV) and distance in each direction of supernova remnants (SNRs) with known extinction in the fourth Galactic quadrant. The distances of 9 SNRs are well determined by this method. Their uncertainties range from 10% to 30%, which is significantly improved for 8 SNRs, G279.0+1.1, G284.3-1.8, G296.1-0.5, G299.2-2.9, G308.4-1.4, G309.2-0.6, G309.8- 2.6, G332.4-0.4. In addition, SNR G284.3-1.8 with the new distance of 5.5 kpc is not likely associated with the PSR J1016-5857 at 3 kpc., 11 pages, 4figures, accepted by RAA

Predicting an agent's future trajectory is a challenging task given the complicated stimuli (environmental/inertial/social) of motion. Prior works learn individual stimulus from different modules and fuse the representations in an end-to-end manner, which makes it hard to understand what are actually captured and how they are fused. In this work, we borrow the notion of potential field from physics as an interpretable and unified representation to model all stimuli. This allows us to not only supervise the intermediate learning process, but also have a coherent method to fuse the information of different sources. From the generated potential fields, we further estimate future motion direction and speed, which are modeled as Gaussian distributions to account for the multi-modal nature of the problem. The final prediction results are generated by recurrently moving past location based on the estimated motion direction and speed. We show state-of-the-art results on the ETH, UCY, and Stanford Drone datasets.

The macro-bending induced optical fiber cladding modes frustrated total internal reflection effect is used to realize the liquid level probe with a simple structure of single macro-bend polymer optical fiber loop. The test results show that the extinction ratio reaches 1.06 dB. “First bath” phenomenon is not obvious (about 0.8%). The robustness of the sensor is better, and the ability of anti-pollution is stronger compared with the conventional sensors. The process of making this sensing probe is extremely easy, and the cost is very low.

Itch is an aversive sensation that evokes a desire to scratch. Paradoxically, scratching the itch also produces a hedonic experience. The specific brain circuits processing these different aspects of itch, however, remain elusive. Here, we report that GABAergic (GABA) and dopaminergic (DA) neurons in the ventral tegmental area (VTA) are activated with different temporal patterns during acute and chronic itch. DA neuron activation lags behind GABA neurons and is dependent on scratching of the itchy site. Optogenetic manipulations of VTA GABA neurons rapidly modulated scratching behaviors through encoding itch-associated aversion. In contrast, optogenetic manipulations of VTA DA neurons revealed their roles in sustaining recurrent scratching episodes through signaling scratching-induced reward. A similar dichotomy exists for the role of VTA in chronic itch. These findings advance understanding of circuit mechanisms of the unstoppable itch-scratch cycles and shed important insights into chronic itch therapy.

We carry out a project to independently measure the distances of supernova remnants (SNRs) in the first quadrant of the Galaxy. In this project, red clump (RC) stars are used as standard candles and extinction probes to build the optical extinction (A$_V$) - distance(D) relation in each direction of extinction-known SNRs. 15 SNRs' distances are well determined. Among them, the distances of G65.8-0.5, G66.0-0.0 and G67.6+0.9 are given for the first time. We also obtain 32 upper/lower limits of distances, and the distances to G5.7-0.1, G15.1-1.6, G28.8+1.5 and G78.2+2.1 are constrained. Most of the distances measured by the RC method are consistent with previous results. The RC method provides an independent access to the distances of SNRs., Comment: 18 pages, 7 figures, published by APJS

The aim of this study was to identify the optimal cut-off value of T cell enzyme-linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic performance alone (in the peripheral blood) or in combination with the adenosine deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in patients with tuberculous pleurisy. Adult patients presenting with pleural effusion were included in this prospective cohort study. Tuberculous pleurisy was diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA activity test in pleural fluid and peripheral blood. Receiver operating characteristic (ROC) curve in combination with multivariate logistic regression was used to evaluate the diagnostic performance of the assays. Among a total of 189 patients with suspected tuberculous pleurisy who were prospectively enrolled in this study, 177 patients were validated for inclusion in the final analysis. ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming cells (SFCs)/2.5 × 105 cells were determined as the optimal cut-off value for T-SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%), whereas serial combination showed increased specificity (97.5%). The combination of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964. T-SPOT.TB in pleural fluid performed better than that in peripheral blood and the ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 × 105 cells. Combination of 3 assays might be a promising approach for tuberculous pleurisy diagnosis.

It is unclear whether obstructive sleep apnea (OSA) is independently associated with increased levels of the acute-phase reactant C-reactive protein (CRP). The purpose of this study was to evaluate the relationship between OSA and high-sensitivity CRP (hs-CRP) levels according to the presence or absence of metabolic syndrome (MetS). This study recruited 245 male bus drivers from one transportation company in Taiwan. Each participant was evaluated by a polysomnography (PSG) test, blood lipids examination, and hs-CRP. Severity of OSA was categorized according to the apnea-hypopnea index (AHI). Subjects were categorized into severe OSA group (n = 44; 17.9 %), moderate and mild OSA group (n = 117; 47.8 %), and non-OSA group (n = 84; 34.3 %). AHI had a significant association with hs-CRP (β = 0.125, p = 0.009) adjusting for age, smoking, drinking, and MetS status. Hs-CRP was elevated with severe OSA (β = 0.533, p = 0.005) even adjusting for BMI and MetS. Moreover, there was an independent effect for adjusted odds ratios (AORs) between the stratification of the severity for OSA and MetS. Elevated hs-CRP level is associated with severe OSA, independent of known confounders. The effect of OSA in CRP is independent of MetS was identified.

While highly active antiretroviral therapy has been successful in delaying progression into AIDS, late HIV diagnosis remains a major contributor to the mortality and morbidity of AIDS. An epidemiological study was conducted to evaluate the prevalence and factors of late diagnosis and the characteristics of those individuals with late diagnosis in Liuzhou city. Patients with late diagnosis were defined as either those who were diagnosed with AIDS at the time of HIV diagnosis or as those who developed AIDS no more than 1 year after HIV diagnosis. Of 899 participants, 72.6% had a late diagnosis. Common characteristics of those who experienced late diagnosis included older participants, those who were unexpectedly diagnosed while seeking other medical attention, participants who believed they could not acquire HIV from their regular heterosexual partners, those who never considered getting tested for HIV, and patients with unexplained weight loss, angular cheilitis, or prolonged fever prior to HIV diagnosis. On the other hand, those participants who were diagnosed via testing at compulsory rehabilitation centers and those whose annual household income was greater than 30,000 Yuan were less likely to be diagnosed late. These results suggested that late HIV diagnosis is common in Liuzhou city, and it is essential to promote appropriate strategies to detect HIV infections earlier. Strategies that require HIV/AIDS patients to notify their spouse/sexual-partners about their HIV-positive results within one month and start provider-initiated HIV testing and counseling in medical facilities are beneficial to earlier HIV diagnosis.

Acupuncture therapy had established in China and it distributed among Asian countries and developed in each country as traditional medicine. In this project we compared the procedures and effects of traditional acupuncture therapies in China, Korea and Japan by using 10 healthy young male volunteers with written informed consent. Total white cell counts, leukocyte subsets and noradrenalin contents were used as outcomes. Three well trained traditional acupuncture therapists were chosen and they treated the same subjects at random order with intervals of at least two months. Each acupuncturist made his diagnosis and points selection for potentiate vital conditions. Clearly different procedures and point selections were used among three traditional acupuncture therapies on the same subject and the obtained changes of outcome measures also differed. Although variations of data were quite large, these results clearly demonstrated that acupuncture therapies have developed among three countries in unique manner.

Aim A cohort study was used to follow up the outcomes of DM and treatments to assess for the 6 year risk of RTC event. Methods Taiwan Bus Driver Cohort Study (TBDCS) recruited 1650 professional drivers in Taiwan since 2005. The subjects were interviewed in person, completed the basic and working patterns questionnaires. Moreover, this cohort of drivers was linked to the National Traffic Accident Database (NTAD), and researchers found 152 new RTC events from 2005 to 2010. History of DM and DM treatments were found from National Health Insurance Research Dataset (NHIRD). Cox proportional hazards model were performed to estimate the hazard ratio (HR) for RTC. Results The RTC drivers had high frequency of DM (13.8% vs. 7.3%; p=0.007), type 2 DM (13.2% vs. 7.0%; p=0.009), and DM treatment (11.2% vs. 5.8%; p=0.014) in comparison to non-RTC drivers. DM and type 2 DM increased the 6 year RTC risks among professional drivers (HR: 2.31, 95% CI: 1.33 to 4.01; p=0.003, and HR: 2.31, 95% CI: 1.31 to 4.06; p=0.004), even after adjusting for education, caffeine drinks used, sleeping pills used, time since first employment, hypertension, and overnight oxygen desaturation index. Moreover, DM treatment with insulin secretagogue (Sulfonylurea and Meglitinde) and insulin sensitizer (Biguanide) had an increased risk for RTC (HR: 2.22, 95% CI: 1.01 to 4.93; p=0.049, and HR: 2.07, 95% CI: 1.06 to 4.05; p=0.033). Conclusion This study have proposed recommendations to labour or health care professionals for managing professional drivers with diabetes.

Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is not optimal and requires further improvement. Capsaicin, the major active component of chili peppers from the genus Capsicum, is not only the agonist of TRPV1 channel, but also displays antitumor activity and enhances the sensitivity of cancer cells to cytotoxic drugs. In this study, we investigated the antitumor effects of combined sorafenib and capsaicin on HCC cells in vitro and xenograft tumors. Treatment with capsaicin alone dose-dependently inhibited the proliferation of the HCC cell lines PLC/PRF/7, HuH7 and HepG2 with IC(50) values of 137, 108 and 140.7 μmol/L, respectively. No obvious expression of TRPV1 channel was detected in the 3 HCC cell lines and TRPV1 channel blockers did not alleviate the cytotoxicity of capsaicin. By contrast, combining capsaicin and sorafenib significantly enhanced the suppression on cell proliferation, achieving a high-level synergistic effect (inhibition rates over 50%) and promoting HCC cell apoptosis. In nude mice with PLC/PRF/5 xenografts, combined administration of capsaicin and sorafenib significantly enhanced the suppression on tumor growth without apparent gross toxicity compared to either agent alone. Mechanistically, capsaicin (10–200 μmol/L) dose-dependently increased the levels of phosphorylated ERK (p-ERK) in PLC/PRF/5 cells, thus leading to enhanced sorafenib sensitivity and a synergistic suppression on the tumor cells. Taken together, our results suggest that capsaicin-increased phosphorylation of ERK contributes to the enhanced antitumor activity of sorafenib, and capsaicin may be useful in improving the efficacy of sorafenib for the treatment of HCC.

Network latencies have become increasingly important for the performance of web servers and cloud computing platforms. Identifying network-related tail latencies and reasoning about their potential causes is especially important to gauge application run-time in online data-intensive applications, where the 99th percentile latency of individual operations can significantly affect the the overall latency of requests. This paper deconstructs the "tail at scale" effect across TCP-IP, UDP-IP, and RDMA network protocols. Prior scholarly works have analyzed tail latencies caused by extrinsic network parameters like network congestion and flow fairness. Contrary to existing literature, we identify surprising rare tails in TCP-IP round-trip measurements that are as enormous as 110x higher than the median latency. Our experimental design eliminates network congestion as a tail-inducing factor. Moreover, we observe similar extreme tails in UDP-IP packet exchanges, ruling out additional TCP-IP protocol operations as the root cause of tail latency. However, we are unable to reproduce similar tail latencies in RDMA packet exchanges, which leads us to conclude that the TCP/UDP protocol stack within the operating system kernel is likely the primary source of extreme latency tails., 10 pages, 12 figures, 1 table, Workshop on Duplicating, Deconstructing, and Debunking (WDDD) held in association with the International Symposium on Computer Architecture (ISCA) 2016

Background Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown. Objective To assess olfaction function among PD patients with Parkin mutations in Chinese population. Materials and Methods A total of 226 PD patients with a positive family history or an early‐onset age (

This paper studies a problem of inverse visual path planning: creating a visual scene from a first person action. Our conjecture is that the spatial arrangement of a first person visual scene is deployed to afford an action, and therefore, the action can be inversely used to synthesize a new scene such that the action is feasible. As a proof-of-concept, we focus on linking visual experiences induced by walking. A key innovation of this paper is a concept of ActionTunnel---a 3D virtual tunnel along the future trajectory encoding what the wearer will visually experience as moving into the scene. This connects two distinctive first person images through similar walking paths. Our method takes a first person image with a user defined future trajectory and outputs a new image that can afford the future motion. The image is created by combining present and future ActionTunnels in 3D where the missing pixels in adjoining area are computed by a generative adversarial network. Our work can provide a travel across different first person experiences in diverse real world scenes.

The special-shaped silencing sheet and its derivatives of folded plate and expansion muffler structure, improve the acoustic attenuation performance in low frequency. The technical difficulties how dissipative silencer can effectively control the low frequency noise, is solved, the noise band of dissipative silencer is broadened, transmission loss increases, aerodynamic performance is optimized.