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Introduction. The prompt and specific diagnosis of Listeria monocytogenes meningoencephalitis (LMM) is challenging. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) is an emerging technique for diagnosing infrequent causative pathogens. Hypothesis/Gap statement. We hypothesized that NGS of CSF is an effective approach for diagnosing LMM. Aim. To evaluate the effectiveness of NGS, we present five cases of LMM diagnosed using NGS of the CSF. Methodology. Between August 2017 and 30 September 2020, we used NGS of the CSF to detect pathogens in patients with clinically suspected central nervous system infections. The clinical characteristics, laboratory tests, imaging findings and NGS results are reviewed. Results. Five patients were diagnosed with LMM using NGS of the CSF within 2 to 4 days, although the clinical manifestations, medical history and imaging findings varied strikingly. NGS of CSF showed sequence reads corresponding to L. monocytogenes species ranging from 118 to 1997 bp, genomic coverage of 0.29–5.96 %, relative abundance of 14.83–32.16 % and sequencing depth of 1.12 to 1.35. The prompt diagnosis resulted in targeted and effective treatment with the appropriate antibiotics, although two patients with the most severe cerebral parenchymal lesions showed little improvement. Conclusion. Our results demonstrate the power of NGS of CSF for the prompt diagnosis of LMM. NGS of CSF is an important complementary tool for identifying L. monocytogenes .

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.

Background: Evidence for antioxidants, minerals and vitamins in relation to the risk of Crohn's disease (CD) and ulcerative colitis (UC) is limited and inconsistent. This mendelian randomization (MR) study aimed to examine the causal associations of circulating levels of antioxidants, minerals and vitamins with CD and UC. Methods: Single-nucleotide polymorphisms associated with antioxidants (beta-carotene, lycopene and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc and selenium), and vitamins (folate, vitamins A, B6, B12, C, D, E and K1) were employed as instrumental variables. Genetic associations with CD and UC were extracted from the UK Biobank, the FinnGen study and the International Inflammatory Bowel Disease Genetics Consortium. The inverse variance weighted method and sensitivity analyses were performed. Results: Genetically predicted higher lycopene (OR = 0.94, 95% CI: 0.91–0.97), vitamins D (OR = 0.65, 95% CI: 0.54–0.79) and K1 (OR = 0.93, 95% CI: 0.90–0.97) levels were inversely associated with CD risk, whereas genetically predicted higher magnesium (OR = 1.53, 95% CI: 1.23–1.90) levels were positively associated with CD risk. Higher levels of genetically predicted lycopene (OR = 0.91, 95% CI: 0.88–0.95), phosphorus (OR = 0.69, 95% CI: 0.58–0.82), selenium (OR = 0.91, 95% CI: 0.85–0.97), zinc (OR = 0.91, 95% CI: 0.89–0.94), folate (OR = 0.71, 95% CI: 0.56–0.92) and vitamin E (OR = 0.78, 95% CI: 0.69–0.88) were associated with reduced UC risk, whereas genetically predicted high levels of calcium (OR = 1.46, 95% CI: 1.22–1.76) and magnesium (OR = 1.24, 95% CI: 1.03–1.49) were associated with increased risk of UC. Conclusions: Our study provided evidence that circulating levels of antioxidants, minerals and vitamins might be causally linked to the development of IBD.

SummaryObjectiveThere are few prospective data exploring the combined effect of genetic and lifestyle factors on the incidence of inflammatory bowel disease (IBD), and whether genetic risk of IBD may be mitigated by lifestyle remains unclear.DesignWe conducted a prospective cohort study based on the UK Biobank to examine the associations across genetic risk, modifiable lifestyle factors, and risk of Crohn’s disease (CD) and ulcerative colitis (UC). Genetic susceptibility to CD and UC was estimated by polygenic risk scores using common genetic variants identified by genome-wide association studies and was further categorized into high, intermediate, and low genetic risk categories. Weighted unhealthy lifestyle scores were constructed based on disease-related lifestyle factors, including ever smoking, unhealthy diet, physical inactivity, obesity, and abnormal sleep duration, and were categorized into ‘favorable’, ‘intermediate’, and ‘unfavorable’ categories. The Cox proportional hazard regression model was used to estimate the HRs and 95% CIs for their associations and accumulative risk for developing CD and UC were estimated for each risk group.ResultsDuring a median follow-up of 12.0 years, 707 CD and 1576 UC cases were diagnosed. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk and there was no multiplicative interaction between them. Compared with participants with low genetic risk, the hazard ratios (HRs) of CD and UC were 2.24 (95% confidence interval [CI] 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with high genetic risk, respectively. The HRs of CD and UC for individuals in unfavorable lifestyle category were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively, compared with those in favorable category. When considering genetic risk and lifestyle jointly, the HRs of individuals with high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI, 1.58-2.66 for UC) were reduced nearly by half comparing to those with high genetic risk but an unfavorable lifestyle (4.40, 95% CI, 2.91-6.66 for CD and 4.44, 95% CI, 3.34-5.91 for UC).ConclusionGenetic and lifestyle factors were independently associated with susceptibility to CD and UC. Participants at high genetic risk could reduce nearly 50% risk of CD and UC by adherence to a favorable lifestyle.FundingXL: the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001). XYW: National Natural Science Foundation of China (81970494) and Key Project of Research and Development Plan of Hunan Province(2019SK2041); SCL: the Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden); ET: CRUK Career Development Fellowship (C31250/A22804); KFD: Project of the regional diagnosis and treatment center of the Health Planning Committee (No. JBZX-201903).What is already known on this topicPrevious studies have identified a number of genetic variants and several modifiable risk factors for IBD. However, there is a lack of studies on the combined effects of genetic and lifestyle factors on IBD risk.What this study addsIn this prospective cohort study, genetic risk and modifiable lifestyle factors were independently associated with the risk of incident Crohn’s disease and ulcerative colitis. Participants at high genetic risk could reduce nearly 50% of their genetic susceptibility to Crohn’s disease and ulcerative colitis by adherence to a favorable lifestyle.How this study might affect research, practice or policyPromoting a healthy lifestyle is an effective strategy to lower the incidence of these diseases, especially among those with high-risk genetic background.

Background: To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy. Methods: The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease outcomes in UK Biobank (N = 339,197). Identified associations were examined for replication in FinnGen (N = 260,405). We further performed tissue -specific gene expression MR, colocalization analyses, and MR with 247 blood biomarkers. A systematic review of randomized controlled trials (RCTs) on TYK2 inhibitor was performed to complement the genetic evidence. Findings: PheWAS-MR found that genetically-proxied TYK2 inhibition was associated with lower risk of a wide range of autoimmune diseases. The associations with hypothyroidism and psoriasis were confirmed in MR analysis of tissue-specific TYK2 gene expression and the associations with systemic lupus erythematosus, psoriasis, and rheumatoid arthritis were observed in colocalization analysis. There were nominal associations of genetically-proxied TYK2 inhibition with increased risk of prostate and breast cancer but not in tissue-specific expression MR or colocalization analyses. Thirty-seven blood biomarkers were associated with the TYK2 loss-of-function mutation. Evidence from RCTs confirmed the effectiveness of TYK2 inhibitors on plaque psoriasis and reported several adverse effects. Interpretation: This study supports TYK2 inhibitor as a potential treatment for psoriasis and several other autoim-mune diseases. Increased pharmacovigilance is warranted in relation to the potential adverse effects. De två första författarna delar förstaförfattarskapet.De tre sista författarna delar sistaförfattarskapet.

This study investigated how semantically relevant auditory information might affect the reading of subtitles, and if such effects might be modulated by the concurrent video content. Thirty-four native Chinese speakers with English as their second language watched video with English subtitles in six conditions defined by manipulating the nature of the audio (Chinese/L1 audio vs. English/L2 audio vs. no audio) and the presence versus absence of video content. Global eye-movement analyses showed that participants tended to rely less on subtitles with Chinese or English audio than without audio, and the effects of audio were more pronounced in the presence of video presentation. Lexical processing of subtitles was not modulated by the audio. However, Chinese audio, which presumably obviated the need to read the subtitles, resulted in more superficial post-lexical processing of the subtitles relative to either the English or no audio. On the contrary, English audio accentuated post-lexical processing of the subtitles compared with Chinese audio or no audio, indicating that participants might use English audio to support subtitle reading (or vice versa) and thus engaged in deeper processing of the subtitles. These findings suggest that, in multimodal reading situations, eye movements are not only controlled by processing difficulties associated with properties of words (e.g., their frequency and length) but also guided by metacognitive strategies involved in monitoring comprehension and its online modulation by different information sources.

A precipitation barycenter reflects the overall spatial distribution and long-term evolution of regional precipitation. Understanding the changes in precipitation barycenter has significant implications for drought management, flood control, and water resource management. This paper analyzed the distribution and transfer of monthly, interannual, and interdecadal precipitation barycenter on the Huang-Huai-Hai Plain (‘3H’ Plain). We also discussed the influence of the station network spatial distribution on the changes in precipitation barycenter. The results were as follows: (1) The trajectory of the monthly precipitation barycenter on the ‘3H’ Plain was generally ‘8’-shaped. The rainy and dry season precipitation barycenters were located in the upper and lower parts of the ‘8’-shaped, respectively. (2) In the past 60 years, the interannual precipitation barycenter had a trend of moving southwest, but the trend was not apparent. (3) Station network density and uniformity dominated the changes in precipitation barycenter, showing positive correlations. When the station network density was large and exceeded a certain range, the influence of station network density on the changes in precipitation barycenter decreased. HIGHLIGHTS Precipitation barycenters of the Huang-Huai-Hai Plain.; The monthly precipitation barycenter generally follows an ‘8’-shaped movement track.; The interannual precipitation barycenter tended to move southwest in the past 60 years.; Precipitation barycenter relationship with the spatial distribution of station network.

This article reports six experiments in which participants made speeded binary decisions about letter strings that were displayed for 100 vs. 300 ms at different retinal eccentricities in the left vs. right visual field to examine how these variables and task demands influence word-identification accuracy and latency. Across the experiments, lexical-processing performance decreased with eccentricity, but to a lesser degree for words displayed in the right visual field, replicating previous reports. However, the effect of eccentricity was attenuated for the two tasks that required “deep” semantic judgments (e.g., discriminating words that referenced animals vs. objects) relative to the tasks that required “shallow” letter and/or lexical processing (e.g., detecting words containing a pre-specified target letter, discriminating words from nonwords). These results suggest that lexical and supra-lexical knowledge play a significant role in supporting lexical processing, especially at greater eccentricities, thereby allowing readers to extend the visual span, or region of effective letter processing, into the perceptual span, or region of useful information extraction. The broader theoretical implications of these findings are discussed in relation to existing and future models of reading.

The potential of palm oil and derived wastewater pretreated by enzyme as co-substrates to accumulate polyhydroxyalkanoate (PHA) rich in short and medium-chain-length monomers under two feeding strategies was evaluated batchwise through mixed microbial cultures (MMCs) in activated sludge. A terpolymer with the maximum PHA content of 30.5 wt%, volumetric yield of 0.372 g COD/g COD and composition of ca. 84.7 ∼ 97.4/0.5 ∼ 1.6/2.1 ∼ 13.7 (3-hydroxybutyrate/ 3-hydroxyvalerate/ 3-hydroxyoctanoate, %) was achieved as a result of co-substrate incorporation. From the perspective of economic benefits, PHA accumulated via adopting strategy of supplementing carbon source to the same initial concentration per cycle saved 42.7 % of carbon consumption, along with a reduction in culture time (72 h). The above discoveries signify that the combination of palm oil and derived wastewater plus MMCs provides an alternative to the plastics industries for a more sustainable and efficient utilization of biological resources and an economic PHA accumulation approach.

Jianwei Wang,1,2,&ast; Lili Yu,1,3,&ast; Yulong Sun,4,&ast; Liangming Zhang,1,3 Mingshu Tu,1,3 Liqing Cai,1,3 Xiaoqing Yin,3,5 Xiaojie Pan,1,6 Tao Wang,4 Yi Huang1,3,7,8 1Provincial Clinical College, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, Fuzhou, 350008, People’s Republic of China; 3Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 4Shanghai Liangrun Biomedicine Technology Limited Company, Shanghai, 200000, People’s Republic of China; 5Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China; 6Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 7Central Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 8Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Huang; Tao Wang Email hyi8070@126.com; wangtao@microdiag.comPurpose: Our pilot study has shown that cystatin SN (CST1) protein is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. We intend to develop a chemiluminescent enzyme immunoassay (CLEIA) available for serum CST1 detection and define the diagnostic value of CST1 detection for early ESCC patients, and establish a panel of CST1 with traditional tumor markers to improve the diagnostic sensitivity for early ESCC.Methods: Detection performance of CLEIA for CST1 was evaluated by linearity, detection limit, accuracy, precision, anti-interference and stability. Diagnostic performance of CST1 for early ESCC was evaluated by detecting CST1 of 112 early ESCC, 107 esophageal benign lesions (EBL), and 151 healthy controls (HC). CEA, CYFRA21-1 and SCC-Ag were detected by chemiluminescence immunoassay (CLIA).Results: The linear range and detection limit of CLEIA for CST1 were 6.25– 400 pg/mL and 1.35 pg/mL, respectively; the average recovery rate was 102.65%; CVs of intra-batch precision and inter-batch precision were < 1/4 TEa and < 1/3 TEa, respectively; 8 interferents including 7 common interferents and CST4 had no interference on CST1 detection; stability evaluation showed good sample and reagent stability. The level and positive rate of CST1 in early ESCC group were significantly higher than those in EBL/HC groups (P< 0.05). The diagnostic sensitivity of CST1 for early ESCC was 31.25% (specificity 92.64%, AUC 0.654). The diagnostic sensitivity of traditional tumor markers ranged from 16.07% to 28.57%, at > 93.0% specificity, and SCC-Ag showed the highest AUC (0.709). Combination of CST1 and CEA, SCC-Ag exhibited the highest AUC up to 0.736 (sensitivity 49.11%, specificity 89.53%).Conclusion: CLEIA has excellent detection performance for CST1. CST1 might be a prospective serological biomarker for early diagnosis of ESCC, while combination of CST1 and CEA, SCC-Ag might improve the early diagnostic performance.Keywords: esophageal squamous cell carcinoma, cystatin SN, chemiluminescence enzyme immunoassay, methodological evaluation, early diagnosis

Background To review, analyze and characterize the pregnancy and lactation-related osteoporosis (PLO) with vertebral fractures based on the extraction data in the previous studies. Methods A comprehensive literature search of electronic databases including the PubMed, Embase and Web of Science was conducted from January 1st,1990 to December 1st, 2020. The enrolled data were pooled to analyze the baseline characteristics, clinical features, risk factors and treatment options. Results A total of 65 articles with 338 cases were enrolled for data extraction. The enrolled cases aged from 19 to 47 years, with a mean value of 35.7 years old. The average body mass index (BMI) was 22.2 kg/m2 ranged from 16.0 to 39.0 kg/m2. Of the 173 cases, 149 cases with vertebral fractures occurred in the first pregnancy, 19 cases in the second pregnancy, four cases in the third pregnancy and one case in the fourth pregnancy. Up to 91.5% of the back pain occurred within the last 3 months of pregnancy and the first 3 months after delivery. The most involved vertebral levels were L2, L1 and T12 accounting for 32.6% of all the fractures. The average fracture numbers were 4.4 levels per patient. The lumbar Z-scores were mostly recorded with a mean value of − 3.2 ranged from − 7.8 to 0. Conclusions PLO with vertebral fractures is a rare clinical entity, which is more likely to occur in older and thinner pregnant women. Back pain is the clinical complaint and mostly occurs in the late pregnancy and early lactation periods. Most vertebral fractures appear in the first pregnancy but it can occur in any time of pregnancy. Thoracolumbar region is the mostly involved region. As compared with postmenopausal osteoporotic fractures, PLO usually has multiple levels fractures. Bisphosphonates are the most widely used treatment so far, however, many factors need to be taken into account to decide which drug to choose in PLO and further studies are necessary for clear recommendation in the future.

Objective In order to create a comprehensive scoring system based on maternal characteristics and ultrasonographic features for predicting placenta accreta spectrum (PAS). Materials and methods This was a retrospective review of pregnant women who underwent routine ultrasound examination in the third trimester of pregnancy from January 2014 to November 2018 were used as a training set to establish the scoring system for PAS prediction while those who underwent examination from January 2019 to December 2019 served as a validation set.. Maternal characteristics including maternal age, parity, previous vaginal deliveries, previous curettage, previous cesarean section (CS), history of hypertension and diabetes mellitus, prenatal body mass index (BMI) were recorded. Ultrasonographic features including abnormal placental lacunae, subplacental hypervascularity, myometrial thinning, placental bulge, bladder wall interruption, location of placenta, placenta previa (yes or not) were recorded. Multivariate analysis was applied to analyze independent risk factors and assess the predictive power of selected parameters predicting PAS. Receiver operating characteristics (ROC) curve was used to evaluate the diagnosis power. Results Parity, previous curettage and CS were independent risk factors. The best comprehensive scoring system was established as follow: the number of abnormal lacunae ≥3, 2 points; lacuna maximum dimension ≥2 cm, 5 points; subplacental hypervascularity (rich), 1 point; subplacental hypervascularity (extremely rich and disordered), 3 points; bladder wall interruption, 9 points; placental bulge, 9 points; placenta previa, 8 points; anterior placenta, 1 point; previous CS ≥ 1, 1 point; parity ≥ 4, 3 point; previous abortions ≥ 2, 1 point. The area under the ROC curve of the scoring system diagnosing PAS was 0.925. Sensitivity and specificity were 83.3% and 85.7%, respectively. Cross-validation for our model showed that sensitivity, specificity, positive predictive value and negative predictive value of the model in diagnosis of PAS were 82.6%, 81.8%, 82.6% and 81.8%, respectively. Diagnosis of 37 cases were consistent with the “gold standard”, and the coincidence rate was 82.2% (37/45). Conclusion The comprehensive scoring system established in this study can effectively diagnose PAS.

Background: The activation of alveolar macrophages (AMs) modulated via leucine-rich repeat (NLR) pyrin domain containing 3 (NLRP3) inflammasome activation is key to the progression of renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Sirtuin-1 (SIRT1) can attenuate NLRP3 inflammasome activation during I/R stress and may be an important mechanism underlying ALI pathogenesis. Penehyclidine hydrochloride (PHC), an anticholinergic drug, exerts protective effects against rI/R-mediated ALI. This study aimed to decipher the effects of PHC on SIRT1 activation and the underlying mechanism of the protective activity of PHC against rI/R-mediated ALI.Materials and methods: We used an ALI rat model and the rat AMs cell line NR8383 to assess the degree of lung injury in vivo and in vitro.Results: The results show that PHC attenuates rI/R-mediated lung injury indices, myeloperoxidase, and apoptosis in vivo. It decreases the rI/R-mediated release of prostaglandin E2 and nitric oxide, mitochondrial reactive oxygen species production, and the activity of NADPH oxidase-4 in vitro. PHC ameliorates the rI/R-induced activation of the thioredoxin-interacting protein, caspase 1 (P10 unit), and NLRP3 inflammasome, along with reduced activation of interleukin-1β and interleukin-18 in vitro. We show that PHC alleviates the rI/R-induced reduction of SIRT1 and the depletion of SIRT1 eliminates the ameliorating activity of PHC on the NLRP3 inflammasome activation in vitro. Conclusions: In summary, the findings suggest that PHC ameliorates the rI/R-mediated ALI through the SIRT1-mediated NLRP3 inflammasome activation.

Aluminum nitride (AlN) ceramic is a material with many excellent properties, such as high thermal conductivity and outstanding electrical insulation, but the required raw powders are easily hydrolyzed that affects the performance after sintering. Therefore, surface modification of AlN powder is essential. In this study, the raw AlN powders were treated in an ethanol with silicic acid (H2SiO3) by heating and stirring at 80 °C. The treated powders will not be hydrolyzed under high temperature and stirring, which was confirmed by pH measurement (pH), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Transmission Electron Microscope (TEM) etc. methods. The XRD spectra proves that the characteristic crystalline peaks of the treated AlN powders after impregnating warm aqueous solution over twenty days are still the same as those of the raw AlN powders. The pH value of the suspension with treated AlN powders remains constant at 7.0–8.0 in 80 °C/90 °C water for 72 h. FTIR and TEM analysis shows that a 3–18 nm protective layer of Si–O–Si wrapped on the surface of the AlN powders. These results directly indicate that the AlN powders treated with H2SiO3 have good hydrolysis resistance. Moreover, the relative density and thermal conductivity of the ceramics sintered by the treated AlN powders can reach 97.21% and 144.505 w/(m· K), respectively.

Problem definition : We investigate wholesale price discrimination in a global sourcing marketplace. Academic/practical relevance : Previous research has found price discrimination in business-to-consumer markets, in which buyers are end customers. There is limited research on suppliers’ price-quoting behaviors and price discrimination in business-to-business (B2B) markets. It is unclear whether certain characteristics of B2B buyers, who are often representatives of firms and not end customers, would influence suppliers’ pricing decisions. Methodology : We collaborate with a global trading company that runs a field experiment on a B2B platform. Results : We find that there is no significant difference in the wholesale prices quoted to buyers selling in U.S. and South African markets. We also find that suppliers quote significantly higher wholesale prices to white buyers than to Asian and black buyers regardless of country. However, price discrimination disappears when buyers present market information to suppliers, providing the lowest wholesale price offered by other suppliers in the market, whereas price discrimination remains when buyers present social information to suppliers, thereby indicating the buyer is referred by a previous customer. In addition, we show that market information can help buyers obtain a lower wholesale price because it signals a lower willingness to pay. Social information, however, can reduce price quotes for only black and white buyers but not for Asian (particularly Chinese) buyers. Managerial implications : Our work can provide guidance to suppliers’ pricing strategies, buyers’ inquiry strategies, and B2B platforms’ information strategies to attract and retain users.

Background: Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes. Methods: In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18–99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test. Findings: Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, pdiff=0·31) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0·96 [0·92–1·00] for p-tau217, AUC=0·91 [0·82–1·00] for p-tau181; p diff=0·22). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0·93 [0·91–0·96] for p-tau217, AUC=0·91 [0·88–0·94] for p-tau181; p diff=0·01). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0·91 [0·88–0·94]) than was p-tau181 (n=214, AUC=0·89 [0·86–0·93]; p diff=0·049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0·80 vs r=0·72; p diff

An elaborate composite of molecularly imprinted polymer (MIP)-modified gold nanoparticles (AuNPs)@silica dioxide (SiO

In this study, we examined the effects of word and character frequency across three commonly used word-identification tasks (lexical decision, naming, and sentence reading) using the same set of two-character target words (

Chinese is a visually complex logographic script that consists of square-shaped characters, with each character composed of strokes. Previous masked priming studies using single-character Chinese stroke neighbors (i.e., visually similar characters differing in only one or two strokes, e.g., 大/犬) have shown facilitatory or inhibitory priming effects. We tested whether the mixed pattern of stroke neighbor priming might be an instance of asymmetry in priming that has been observed previously with Japanese kana and Latin alphabets. Specifically, a prime lacking a stroke (or line segment) that is present in the target speeds up the recognition of its stroke neighbor almost as much as the identity prime (e.g., 刀-刃 = 刃-刃), but not the converse (e.g., 刃-刀 >> 刀-刀). Two experiments, one using a character match task and the second using lexical decision, showed a robust asymmetry in priming by stroke neighbors. The results suggest that the early letter identification process is similar across script types, as anticipated by the Noisy Channel model, which regards the first stage of visual word recognition as a language-universal perceptual process.

Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat lung cancer. Several natural and synthetic products exhibit the pro-anoikis potential in lung cancer cells and in vivo models. These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis.

Background: Nutritional status affects the health of the public and is one of the key factors influencing social-economic development. To date, little research on the nutritional status of the Macao university student population has been conducted. Objectives: To identify and evaluate the dietary pattern and the nutritional intake among Macao university students. Methods: The Macao students were selected by the stratified cluster random sampling method. A semi-quantitative food frequency questionnaire was used to investigate food consumption. Data were analyzed through a t-test and factor analysis by using SPSS Version 24.0. Results: A total of 1230 questionnaires were distributed. From the respondents, 1067 (86.7%) were valid. In general, we identified three major dietary patterns in this population: (1) fruit and vegetable dietary pattern, characterized by abundant consumption of fruits and vegetables; (2) grain and high fat dietary pattern, characterized as high intakes of grains and animal foods; (3) high sugar dietary pattern, characterized by a large quantity of daily sugary drinks. The average daily intake of vitamin A, thiamine, calcium, and iodine were significantly lower than the Chinese Recommended Nutrient Intake (RNI) in the subjects. Conclusions: The dietary pattern of Macao students is similar to that of other Asians. Surprisingly, the daily intake of vitamin A, thiamine, calcium, and iodine by Macao university students is significantly lower than the Chinese RNI.

Tower cranes are well-known underactuated systems, where the design of controllers for them with time-varying rope length was weak in the past because of their complex dynamic characteristic. The payload oscillation will become worse when the jib slew angle, the trolley position and the rope length are changed simultaneously. The proposed method is designed based on robust adaptive sliding mode control via tracking non-zero initial reference trajectories, in which, frictions and lumped disturbances in the crane system are eliminated, as well as unknown payload mass is effectively estimated online. Lyapunov technique is combined with LaSalle's invariance theorem to design controller and analyze stability. Various and strict simulations are applied, which validate the effectiveness and extreme robustness of the proposed method.

The Xin'anjiang model and the Sacramento model are two widely used short-term watershed rainfall-runoff forecasting models, each with their own unique model structure, strengths, weaknesses and applicability. This paper introduces a weight factor to integrate the two models into a combined model, and uses the cyclic coordinate method to calibrate the weight factor and the parameters of the two models to explore the possibility of the complementarity between the two models. With application to the Yuxiakou watershed in Qingjiang River, it is verified that the cyclic coordinate method, although simple, can converge rapidly to a satisfactory calibration accuracy, mostly after two iterations. Also, the results in case studies show that the forecast accuracy of the new combined rainfall-runoff model can improve the forecast precision by 4.3% in a testing period, better in runoff process fitting than the Xin'anjiang model that performs better than the Sacramento model. HIGHLIGHT This paper introduces a weight factor to integrate the two models into a combined model, and uses the cyclic coordinate method to calibrate the weight factor.; It is verified that the cyclic coordinate method can converge fast to a satisfactory calibration accuracy.; The results show that the forecast accuracy of the new combined rainfall-runoff model can improve the forecast precision.

Background The risk of locoregional recurrence (LRR) after mastectomy for breast invasive micropapillary carcinoma (IMPC) remains poorly defined. We aimed to construct an effective prognostic nomogram to estimate the individualized risk of LRR for providing accurate information for long-term follow-up. Patients and Methods A total of 388 patients with breast IMPC were included in the current study. Based on the Cox regression and clinical significance, a nomogram with an online prediction version was created. This model was evaluated and internally validated by concordance index and calibration plot. Receiver operating characteristic curve and decision curve analysis were used to assess the discrimination and clinical utility, and Kaplan-Meier curves estimated the probability of LRR. Results The variables (age, lymph node metastasis, hormone receptor status, lymphovascular invasion, histologic grade, and adjuvant radiotherapy) were included in the nomogram. This model was well-calibrated to predict the possibility of LRR and displayed favorable clinical utility; the concordance index was 0.86 (95% confidence interval, 0.81-0.91), which was higher than any single predictor. The area under the curve of the nomogram was 0.89, whereas that of the conventional staging system was 0.72. An online prognostic nomogram was built for convenient use. Kaplan-Meier curves showed that the nomogram had a better risk stratification than the conventional staging system. Conclusions The nomogram could accurately predict the individualized risk of LRR after mastectomy for breast IMPC. By identifying the risk stratification, this model is expected to assist clinicians and patients in improving long-term follow-up strategies.

Objective Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism. Methods Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 μg/kg), a selective antagonist of α7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1β, were detected by Nissl staining, immunofluorescence, and Western blot assays. Results EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1β 35 days after AS, while α-BGT partially reversed these changes. Conclusion EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1–NF-κB via an α7-nAChR signal in the microglia., Graphical Abstract

Chinese words consist of a variable number of characters that are normally written in continuous lines, without the blank spaces that are used to separate words in most alphabetic writing systems. These conventions raise questions about the relative roles of character versus whole-word processing in word identification, and how words are segmented from strings of characters for the purpose of their identification and saccade targeting. The present article attempts to address these questions by reporting an eye-movement experiment in which 60 participants read a corpus of sentences containing two-character target words that varied in terms of their overall frequency and the frequency of their initial characters. We examine participants' eye movements using both corpus-based statistical models and more standard analyses of our target words. In addition to documenting how key lexical variables influence eye movements and highlighting a few discrepancies between the results obtained using our two statistical approaches, our experiment shows that high-frequency initial characters can actually slow word identification. We discuss the theoretical significance of this finding and others for current models of Chinese reading, and then describe a new computational model of eye-movement control during the reading of Chinese. Finally, we report simulations showing that this model can account for our findings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In this study, hydrothermal treatments (duration: 2 h, 5 h, 8 h; temperature: 60°C, 80°C, 100°C), ultrasonic treatments (duration: 60 min, 90 min, 120 min; temperature: 40°C, 50°C, 60°C; ultrasonic power: 400 W, 600 W, 800 W) and freeze-drying treatments (vacuum degree: 0.05 mbar, 0.1 mbar, 0.5 mbar, 1.0 mbar, 1.7 mbar) were performed respectively to improve the permeability of glue-laminated bamboo. The effects of different pre-treatments on the permeability were compared according to the water absorption test and the mercury intrusion porosimetry test. The microstructure change of the samples was observed by scanning electron microscope (SEM). The results showed that freeze-drying treatment was an effective way to increase the permeability of the samples, in which the water absorption rate can be increased by 47%, and the porosity can be increased by 10% at 0.5 mbar vacuum. From SEM analysis, some small holes appeared in the cell wall of the freeze-dried samples, because he free water inside the samples was changed into ice, and the volume became larger, and the pore diameter of the bamboo was enlarged.

Forest fires are important natural disturbances that influence accurate estimations of forest carbon budgets, largely owing to the uncertainty of carbon emissions from forest fires. Fuel burning efficiency is an important factor affecting accurate estimations of carbon emissions and is difficult to quantify. Here, we quantified burning efficiencies of fuel strata by fire severity and forest types and investigated influencing factors. Burning efficiencies of fuel strata increased with increasing fire severity. The tree stratum had low values of burning efficiency of 0.76, 0.83, 6.84% under low-, moderate-, high-severity fires respectively. The burning efficiency of the herb stratum was the highest, over 95%, followed by the litter stratum between 49 and 85%. Although the tree stratum accounted for the largest carbon storage of aboveground fuels, most carbon consumed during fires came from the shrub and herb strata. Among forest types, the burning efficiency of aboveground fuels in Pinus pumila–Larix gmelinii forest was much higher than the other two studied. Fire Weather Index (FWI) and temperature exerted a positive effect on the burning efficiency of understorey fuels. Precipitation mainly had a negative influence on the burning efficiency of shrub and duff.

Background This study was performed to investigate clinical features of patients with severe SARS-CoV-2 pneumonia and identify risk factors for converting to severe cases in those who had mild to moderate diseases at the start of the pandemic in China. Methods In this retrospective, multicenter cohort study, patients with mild to moderate SARS-CoV-2 pneumonia were included. Demographic data, symptoms, laboratory values, and clinical outcomes were collected. Data were compared between non-severe and severe patients. Results 58 patients were included in the final analysis. Compared with non-severe cases, severe patients with SARS-CoV-2 pneumonia had a longer: time to clinical recovery (12·9 ± 4·4 vs 8·3 ± 4·7; P = 0·0011), duration of viral shedding (15·7 ± 6·7 vs 11·8 ± 5·0; P = 0·0183), and hospital stay (20·7 ± 1·2 vs 14·4 ± 4·3; P = 0·0211). Multivariate logistic regression indicated that lymphocyte count was significantly associated with the rate of converting to severe cases (odds ratio 1·28, 95%CI 1·06–1·54, per 0·1 × 109/L reduced; P = 0·007), while using of low-to-moderate doses of systematic corticosteroids was associated with reduced likelihood of converting to a severe case (odds ratio 0·14, 95%CI 0·02–0·80; P = 0·0275). Conclusions The low peripheral blood lymphocyte count was an independent risk factor for SARS-CoV-2 pneumonia patients converting to severe cases. However, this study was carried out right after the start of the pandemic with small sample size. Further prospective studies are warranted to confirm these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029839. Registered 15 February 2020 - Retrospectively registered.

Achieving both jib and trolley positioning and swing reduction become more difficult when tower cranes appear double-pendulum characteristic in dynamic. Moreover, in actual applications, the initial output value of actuators is usually physically constrained and the model uncertainties and external disturbances always exist. To solve these problems, a partial enhanced-coupling nonlinear controller with initial saturation is designed and analyzed by Lyapunov technique and LaSalle's invariance theorem. The control performance and strong robustness are severally verified by lots of simulations.

Propofol (Pro) confers protection against renal ischemia/reperfusion (rI/R) injury through incompletely characterized mechanisms. Since Pro has shown net anti-inflammatory properties as part of its beneficial effects, we examined the potential role of Pro in the modulation of macrophage polarization status during both rI/R injury in vivo and exposure of cultured peritoneal macrophages (PMs) to hypoxia/reoxygenation (H/R). Rats were subjected to 45-min r/IR surgery or a sham procedure and administered PBS (vehicle) or Pro during the ischemia stage. Pro administration attenuated rI/R-induced kidney damage and renal TNF-α, IL-6, and CXCL-10 expression. Enhanced macrophage M2 polarization, evidenced by reduced iNOS and increased Arg1 and Mrc1 mRNA levels, was further detected after Pro treatment both in the kidney, after rI/R in vivo, and in H/R-treated PMs. Pro administration also repressed phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and increased p-STAT3, p-STAT6, and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA levels in H/R-exposed PMs. Importantly, siRNA-mediated PPARγ silencing repressed Pro-mediated STAT3 activation in PMs and restored proinflammatory cytokine levels and prevented macrophage M2 marker expression in both rI/R-treated rats and cultured PMs. These findings suggest that Pro confers renoprotection against rI/R by stimulating PPARγ/STAT3-dependent macrophage conversion to the M2 phenotype.

microRNAs (miRNAs) and N6-methyladenosine (mTo screen mA total of 126 miRNAs were identified as mmiR-30c-5p inhibits OvCa progression and reduces the m

Purpose: Recent research on the potential of using eye-tracking to measure reading comprehension ability suggests that the relationship between standard eye-tracking measures and reading comprehension is influenced by differences in task demands between comprehension assessments. We compared standard eye-tracking measures and scanpath regularity as predictors of reading comprehension scores. Method: We used a dataset in which participants were administered three widely-used reading comprehension assessments with varying task demands while their eye movements were monitored: the York Assessment of Reading for Comprehension (YARC), the Gray Oral Reading Test (GORT-5), and the sentence comprehension subtest of the Wide Range Achievement Test (WRAT-4). Results: Results showed that scanpath regularity measures, similarly to standard eye-tracking measures, were influenced by differences in task demands between the three tests. Nevertheless, both types of eye-tracking measures made unique contributions as predictors of comprehension and the best set of predictors included both standard eye-tracking measures and at least one scanpath measure across tests. Conclusion: The results provide evidence that scanpaths capture differences in eye-movement patterns missed by standard eye-tracking measures. Overall, the results highlight the effect of task demands on eye-movement behavior and suggest that reading goals and task demands need to be considered when interpreting eye-tracking data.

Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal and widespread malignancies in China. Exosomes, a subset of tiny extracellular vesicles manufactured by all cells and present in all body fluids, contribute to intercellular communication and have become a focus of the search for new therapeutic strategies for cancer. A number of global analyses of exosome-mediated functions and regulatory mechanism in malignant diseases have recently been reported. There is extensive evidence that exosomes can be used as diagnostic and prognostic markers for cancer. However, our understanding of their clinical value and mechanisms of action in ESCC is still limited and has not been systematically reviewed. Here, we review current research specifically focused on the functions and mechanisms of action of ESCC tumor-derived exosomes and non-ESCC-derived exosomes in ESCC progression and describe opportunities and challenges in the clinical translation of exosomes.