Lymphotoxin regulates commensal responses to enable diet-induced obesity.

Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr(-/-) mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr(-/-) mice with their obese siblings rescued weight gain in Ltbr(-/-) mice, demonstrating the communicability of the obese phenotype. Ltbr(-/-) mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

Effectiveness of Interactive Digital Decision Aids in Prenatal Screening Decision-making: Systematic Review and Meta-analysis.

BACKGROUND: Increasing prenatal screening options and limited consultation time have made it difficult for pregnant women to participate in shared decision-making. Interactive digital decision aids (IDDAs) could integrate interactive technology into health care to a facilitate higher-quality decision-making process. OBJECTIVE: The objective of this study was to assess the effectiveness of IDDAs on pregnant women's decision-making regarding prenatal screening. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, Google Scholar, and reference lists of included studies until August 2021. We included the randomized controlled trials (RCTs) that compared the use of IDDAs (fulfilling basic criteria of International Patient Decision Aid Standards Collaboration and these were interactive and digital) as an adjunct to standard care with standard care alone and involved pregnant women themselves in prenatal screening decision-making. Data on primary outcomes, that is, knowledge and decisional conflict, and secondary outcomes were extracted, and meta-analyses were conducted based on standardized mean differences (SMDs). Subgroup analysis based on knowledge was performed. The Cochrane risk-of-bias tool was used for risk-of-bias assessment. RESULTS: Eight RCTs were identified from 10,283 references, of which 7 were included in quantitative synthesis. Analyses showed that IDDAs increased knowledge (SMD 0.58, 95% CI 0.26-0.90) and decreased decisional conflict (SMD -0.15, 95% CI -0.25 to -0.05). Substantial heterogeneity in knowledge was identified, which could not be completely resolved through subgroup analysis. CONCLUSIONS: IDDAs can improve certain aspects of decision-making in prenatal screening among pregnant women, but the results require cautious interpretation.

Vaccines targeting preS1 domain overcome immune tolerance in hepatitis B virus carrier mice.

Strong tolerance to hepatitis B virus (HBV) surface antigens limits the therapeutic effect of the conventional hepatitis B surface antigen (HBsAg) vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of the preS1 region could improve therapy gain, we explored vaccination with the long peptide of preS1 domain for HBV virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg vaccination induced robust immune responses in HBV carrier mice. The anti-preS1 rapidly cleared HBV virions in vivo and blocked HBV infection to hepatocytes in vitro. Intriguingly, vaccination of preS1-polypeptide even reduced the tolerized status of HBsAg, opening a therapeutic window for the host to respond to the HBsAg vaccine. A sequential administration of antigenically distinct preS1-polypeptide and HBsAg vaccines in HBV carrier mice could finally induce HBsAg/hepatitis B surface antibody serological conversion and clear chronic HBV infection in carrier mice. CONCLUSION: These results suggest that preS1 can function as a therapeutic vaccine for the control of CHB. (Hepatology 2017;66:1067-1082).

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination.

Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4(+) T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8(+) T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.

Temporal Changes in the Modes of Hepatitis C Virus Transmission in the USA and Northern China.

BACKGROUND: Predominant modes of hepatitis C virus (HCV) transmission vary between countries and over time. AIMS: To compare HCV transmission modes in the USA and northern China. METHODS: We conducted a prospective study enrolling two cohorts of chronic HCV patients in the USA, and in China at Beijing, and at Gu'an and Kuancheng counties in Hebei. Patients self-reported the most likely source and year of infection. RESULTS: A total of 1957 patients were studied (1000 USA; 957 China-428 Beijing, 387 Gu'an, 142 Kuancheng). The predominant infection sources were transfusion (23.0%) and injection drug use (IDU) (32.1%) in the USA and transfusion (64.5%) in northern China. Within China, transfusion was the most common source in Beijing (62.1%) and Gu'an (88.1%), and medical procedures (35.9%) and IDU (12.0%) in Kuancheng. Infection via transfusion decreased significantly in the USA (35.1-4.6%) and Beijing (84.2-14.3%) but remained frequent in Gu'an (90.5-72.5%) over time. Infection via IDU decreased from 32.4% in those ≥61 years to 25.0% in those 41-50 years but increased to 46.5% in those ≤40 years in US patients and decreased over time from 38.7 to 1.9% in Kuancheng. Infection via medical procedures increased over time in Beijing (7.0-33.3%) and remained frequent in Kuancheng (45.2-31.1%). CONCLUSIONS: There are major differences in presumed HCV infection source between the USA and northern China. Favorable as well as worrisome changes in the modes of HCV transmission in both countries were observed.

Risk Assessment of Hepatocellular Carcinoma in Patients with Hepatitis C in China and the USA.

BACKGROUND: Hepatitis C (HCV) infection is an increasingly common cause of hepatocellular carcinoma (HCC) in China. AIMS: We aimed to determine differences in demographic and behavioral profiles associated with HCC in HCV+ patients in China and the USA. METHODS: Consecutive HCV+ patients were recruited from centers in China and the USA. Clinical data and lifestyle profiles were obtained through standardized questionnaires. Multivariable analysis was conducted to determine factors associated with HCC diagnosis within groups. RESULTS: We included 41 HCC patients from China and 71 from the USA, and 931 non-HCC patients in China and 859 in China. Chinese patients with HCC were significantly younger, less likely to be male and to be obese than US patients with HCC (all p < 0.001). Chinese patients with HCC had a significantly lower rate of cirrhosis diagnosis (36.6 vs. 78.9%, p < 0.001); however, they also had a higher rate of hepatitis B core antibody positivity (63.4 vs. 36.8%, p = 0.007). In a multivariable analysis of the entire Chinese cohort, age > 55, male sex, the presence of diabetes, and time from maximum weight were associated with HCC, while tea consumption was associated with a decreased HCC risk (OR 0.37, 95% CI 0.16-0.88). In the US cohort, age > 55, male sex, and cirrhosis were associated with HCC on multivariable analysis. CONCLUSIONS: With the aging Chinese population and increasing rates of diabetes, there will likely be continued increase in the incidence of HCV-related HCC in China. The protective effect of tea consumption on HCC development deserves further validation.

Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000.

BACKGROUND: The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally. AIMS: The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA. METHODS: A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28-98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14-27.8). CONCLUSIONS: Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results.

Targeting the dendritic cell-secreted immunoregulatory cytokine CCL22 alleviates radioresistance.

PURPOSE: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after radiation. EXPERIMENTAL DESIGN: Transcriptomics and high dimensional flow cytometry revealed changes in murine tumor cDC that not only mediate Treg infiltration after RT, but associate with worse survival in human cancer datasets. Antibodies perturbing a cDC-CCL22-Treg axis were tested in syngeneic murine tumors. A prototype interferon-anti-epidermal growth factor receptor fusion protein (αEGFR-IFNα) was examined to block Treg infiltration and promote a CD8+ T cell response after RT. RESULTS: Radiation expands a population of mature cDC1 enriched in immunoregulatory markers that mediates Treg infiltration via the Treg-recruiting chemokine CCL22. Blocking CCL22 or Treg depletion both enhanced RT efficacy. αEGFR-IFNα blocked cDC1 CCL22 production while simultaneously inducing an antitumor CD8+ T cell response to enhance RT efficacy in multiple EGFR-expressing murine tumor models, including following systemic administration. CONCLUSIONS: We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

Voice Outcomes of Straw Phonation Exercises for Telephone Customer Service Staff.

OBJECTIVE: This study aimed to investigate the effectiveness of a straw phonation exercise program in preventing voice problems in telephone customer service staff. STUDY DESIGN: Prospective study. METHODS: Twenty-eight participants with no obvious voice problems were placed into two groups: the experimental (n = 13) and control (n = 15) groups. The experimental group received voice hygiene instructions and participated in a 3-week straw phonation exercise program, while the control group only received voice hygiene instructions. The acoustic parameters and Mandarin Chinese version of the Vocal Fatigue Index (CVFI) scores were statistically analyzed before training, immediately after training, followed up one and 3 months after training. RESULTS: The results showed that speaking fundamental frequency (SF0), shimmer, and cepstral peak prominence (CPP) of the experimental group improved immediately after the straw phonation exercise program, and shimmer of the experimental group after training was also significantly lower than that of the control group. A higher SF0 and lower shimmer were noted in the experimental group during the follow-up phase, whereas factors 1 (voice load and fatigue) and 2 (physiological symptoms) of the CVFI did not differ significantly until the third month after training. CONCLUSION: The study results suggest that the straw phonation exercise program can help telephone service staff to establish an appropriate speaking pitch and prevent voice fatigue.

Effect of intensive water resistance phonation therapy for people with presbyphonia: A pilot study.

Purpose: The aim of this pilot study was to explore the efficacy of an intensive 3 week water resistance phonation (WRP) therapy program for people with presbyphonia.Method: Participants included 13 people with presbyphonia who received intensive WRP therapy. All participants completed eight sessions of therapy over 3 weeks. Auditory perceptual ratings, and acoustic and aerodynamic assessments were performed before and after treatment. Participants also completed the voice-related quality of life questionnaire before and after the treatment.Result: After 3 weeks of intensive voice therapy, significant improvements were demonstrated in acoustic, aerodynamic, and auditory perceptual parameters, as well as patient perceptions of voice-related quality of life. Acoustically, it was found there were significant decreases in shimmer (p = 0.019), noise-to-harmonic ratio (p = 0.016), and smoothed cepstral peak prominence (p = 0.001). Perceptually, the clients with presbyphonia showed significant reductions in the ratings of the overall grade, roughness, asthenia, and strain. Moreover, there was a significant increase in the total score of the Mandarin version of the Voice-Related Quality of Life measure post-therapy.Conclusion: The investigation provides preliminary evidence that people with presbyphonia can improve their vocal function and voice-related quality of life through intensive WRP therapy within a short period of time.

Bi-Weekly Voice Therapy Versus Weekly Voice Therapy for Muscle Tension Dysphonia.

OBJECTIVES: To compare the outcomes of bi-weekly voice therapy (BWVT) with weekly voice therapy on perception, acoustics, and quality of life for individuals with muscle tension dysphonia (MTD). METHODS: Thirty participants with MTD were enrolled either BWVT (40 min/session, two sessions per week for 4 weeks) or weekly voice therapy (40 min/session, once a week for 8 weeks). Auditory perceptual ratings, acoustic parameters, and the Mandarin version of the voice-related quality of life questionnaire (MV-RQOL) scores were statistically analyzed before and after treatment. RESULTS: There were significant improvements in the voice qualities such as overall grade, roughness, asthenia, and strain in both groups after treatment. Acoustics analyses showed that fundamental frequency, speaking fundamental frequency, jitter, shimmer, and cepstral peak prominence significantly improved in both groups after treatment. For the MV-RQOL questionnaire scores, the result also demonstrated that both groups felt significant improvements in voice-related quality of life after treatment. However, there were no significant differences between the two groups of treatment effects. CONCLUSIONS: Patients with MTD can restore voice qualities and quality of life if they are able to complete a full course of voice therapy, regardless of the intensity of voice therapy. However, if they can receive the BWVT, they would be able to regain their voice faster. The results of this study can be provided as a reference for clinicians when treating patients with MTD.

Voice Outcomes of Intensive Voice Feminization Therapy for Transgender Women Delivered via Telepractice: Pilot Study.

OBJECTIVES: The aim of this pilot study is to investigate the efficacy of an intensive voice feminization therapy program provided via telepractice. METHODS: A total of 10 transgender women participated, with nine completing the therapy program. All participants received 12 sessions of resonant voice therapy in combination with Vocal Function Exercises and voice hygiene, which were completed within 4weeks. Acoustic and aerodynamic measures, auditory-perceptual ratings, Trans Woman Voice Questionnaire (TWVQ) and self-rated voice femininity were conducted before and after treatment. RESULTS: Statistical analysis showed significant improvements in acoustic measures such as fundamental frequency and semitones, TWVQ scores, auditory-perceptual ratings and self-perception of voice femininity after intensive voice therapy. CONCLUSIONS: This study provides preliminary evidence to suggest that transgender women can benefit from intensive voice therapy when provided via telepractice, with a more feminine voice and better self-perceived voice-related quality of life. The limitations of this study were that the single-group study design lacked a control group for comparison, and the small sample size. Therefore, a randomize controlled and follow-up study with a larger sample size, exploring the effects of different treatment modalities on transgender women's voices is warranted.

Consistent and low is the only way to go: A polynomial regression approach to the effect of abusive supervision inconsistency.

The literature on abusive supervision largely presumes that employees respond to abuse in a relatively straightforward way: When abuse is present, outcomes are unfavorable, and when abuse is absent, outcomes are favorable (or, at least less unfavorable). Yet despite the recognition that abusive supervision can vary over time, little consideration has been given to how past experiences of abuse may impact the ways employees react to it (or, its absence) in the present. This is a notable oversight, as it is widely acknowledged that past experiences create a context against which experiences in the present are compared. By applying a temporal lens to the experience of abusive supervision, we identify abusive supervision inconsistency as a phenomenon that may have different outcomes than would otherwise be predicted by the current consensus in this literature. We draw from theories on time and stress appraisal to develop a model that explains when, why, and for which employees, inconsistent abusive supervision may have negative outcomes (specifically, identifying anxiety as a proximal outcome of abusive supervision inconsistency that has downstream effects on turnover intentions). Moreover, the aforementioned theoretical perspectives dovetail in identifying employee workplace status as a moderator that may buffer employees from the stressful consequences of inconsistent abusive supervision. We test our model using two experience sampling studies with polynomial regression and response surface analyses. Our research makes important theoretical and practical contributions to the abusive supervision literature, as well as the literature on time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Elevated serum IL-8 is associated with the presence of hepatocellular carcinoma and independently predicts survival.

Tumor immune responses have prognostic importance to hepatocellular carcinoma (HCC). Serum cytokines may differentiate HCC patients from cirrhotic patients or have prognostic significance. Serum IL-8 was elevated in 90 HCC patients compared to 180 cirrhotic controls, whereas IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-10, IL-12, IL-13, IL-15, IL-17, IL-21, and VEGF were similar. IL-8 predicted HCC presence with an area under the receiver-operator curve (ROC) of 0.68. HCC patients with highest IL-8 had worse survival. Multivariate analysis showed that high IL-8 (HR 2.15; 95%CI:1.21-3.74) and stage (HR 1.92; 95%CI:1.22-3.97) independently predicted mortality; while viral etiology was protective (HR 0.69; 95%CI:0.41-0.98). Therefore, HCC IL-8 mediated events may be worthy of future investigation.

Reliability and Validity of the Mandarin Version of Singing Voice Handicap Index - 10 (MSVHI-10).

OBJECTIVES: The present study aims to evaluate the reliability and validity of the Mandarin version of the Singing Voice Handicap Index-10 (MSVHI-10). METHODS: One hundred and fifteen singers, aged from 21 to 65, participated in this study. All the subjects completed the Mandarin version of the SVHI-10 and the Voice Handicap Index-10 (VHI-10). Other gathered information include sex, age, type of singing performance, and the accumulated years of singing. We also asked the participants to self-report the presence of singing voice complaint. Statistical analyses were performed to evaluate the validity, reliability, and the Receiver Operating Characteristic (ROC) curve of MSVHI-10. RESULTS: The results showed high internal consistency (Cronbach's α =0.96), with the scores of each question ranged from 0.57 to 0.90. Forty-three singers re-filled the MSVHI-10 with an interval of 12.7 ± 9.3 days (mean ± standard deviation), and the results showed a high test-retest reliability (r = 0.98, P < 0.01). The SVHI-10 scores were significantly correlated with the VHI-10 (r = 0.54-0.72, P < 0.01). ROC analysis revealed a high differentiating accuracy for distinguishing between the subjects with or without singing voice complaints, with an area under the curve (AUC) of 0.97. At the cut-off score of 21.5, the sensitivity and specificity were 85.7% and 95.9%, respectively. CONCLUSIONS: The Mandarin version of the SVHI-10 has been shown to be a reliable and valid instrument for evaluating the self-perception of singing voice complaints.

Dealing with new members: Team members' reactions to newcomer's attractiveness and sex.

We examine how team members respond to the inclusion of new members' physical attractiveness and sex. Drawing on Social Exchange Theory, we argue and show that incumbent team members engage in three behaviors (mimicry, ingratiation, and challenging) in response to the inclusion of more or less attractive male or female members in their team. Using a multilevel experimental design, we show that existing team members mimic newcomers who are higher on physical attractiveness and that the effect is more pronounced when there is a sex match (i.e., existing males mimic new males more). Furthermore, they ingratiate toward the physically attractive newcomers who are also committed to the task. In addition, we find that existing team members challenge physically attractive females who are committed to the task. Our findings suggest that the basic combinations of primary cues of newcomers' characteristics affect intrateam behaviors and produce different outcomes across sexes for attractiveness. By shifting the attention to the effect that newcomers have on team behaviors, the study provides novel insights for scholars that help move the discussion of team membership changes beyond the traditional accounts of new member socialization and team effectiveness. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Patient involvement in healthcare is associated with higher rates of surveillance for hepatocellular carcinoma.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis, but earlier studies suggest that it is used less than one-third of the time. Patient factors associated with surveillance rates are incompletely understood. GOALS: The aims of our study were to determine HCC surveillance rates in a tertiary-care center and to identify patient predictors of receiving surveillance. STUDY: Patients with Child A or B cirrhosis seen in the University of Michigan liver clinics between October 2008 and March 2009 were enrolled to complete a self-administered survey. Surveillance rates and clinical data were extracted from the patient electronic medical record. RESULTS: Of the 160 patients enrolled, 74.4% had HCC surveillance performed in the past year. On multivariate analysis, predictors of receiving surveillance included male sex (odds ratio 7.1, 95% confidence interval, 1.2-43.2) and patient involvement in their care (odds ratio 3.4, 95% confidence interval, 1.5-7.9). Patients expressed high levels of concern regarding HCC, desired more information from their physicians, and wanted to be more involved in their care. CONCLUSIONS: HCC surveillance rates in a tertiary-care center were significantly higher than earlier reported rates. Direct patient involvement in decisions regarding HCC surveillance may help to improve surveillance rates.

Reliability and Validity of the Mandarin Version of the Voice-Related Quality of Life (MV-RQOL) Measure.

OBJECTIVES: The reliability and validity of the Voice-Related Quality of Life (V-RQOL) measure has been conducted in languages other than Mandarin. Therefore, this study aims to analyze the reliability and validity of the Mandarin version of the V-RQOL (MV-RQOL) questionnaire. METHODS: The MV-RQOL was completed by a total of 57 participants, including 27 individuals with voice disorders (VD) and 30 individuals without voice disorders (NVD). Statistical analyses were carried out to evaluate the validity, reliability, reproducibility, and the Receiver Operating Characteristic (ROC) curve was also derived. RESULTS: Statistical analyses demonstrated the MV-RQOL has strong internal consistency. The test-retest reliability was found to be high as well. There was a significant difference between the groups with and without voice disorders. The NVD group had higher scores compared with the VD group for the overall MV-RQOL score and for the 2 domains. In addition, the scores between males and females showed no significant differences. A significant difference was found between the MV-RQOL scores of individuals who defined their voices as good and very good, and those who defined their voices as poor and fair. Area under the curve value from ROC curve was found to be 0.994. The optimal cutoff value was found to be 85.00, with sensitivity of 96.7% and specificity of 96.3%. CONCLUSIONS: Based on the results, it can be suggested that the MV-RQOL measure is a reliable and valid self-assessment tool, that discriminates well between patients with and without voice disorders, in the Taiwanese population.

Anxiety responses to the unfolding COVID-19 crisis: Patterns of change in the experience of prolonged exposure to stressors.

An immense amount of work has investigated how adverse situations affect anxiety using chronic (i.e., average) or episodic conceptualizations. However, less attention has been paid to circumstances that unfold continuously over time, inhibiting theoretical testing and leading to possible erroneous conclusions about how stressors are dynamically appraised across time. Because stressor novelty, predictability, and patterns are central components of appraisal theories, we use the COVID-19 crisis as a context to illustrate how variation in the phenomenon's patterns of change (specifically, total cases [average level] but also the rate of linear [velocity] and nonlinear growth [acceleration] in cases) influence anxiety. We also show the implications of anxiety for next-day functioning at work. These effects are tested in data drawn from a sample of employed adults in a daily diary study conducted in four overlapping waves. The data span the emergence, exponential rise, and initial tapering of the virus in the United States (February 10, 2020 to April 28, 2020). Our results show that although the impact of level of COVID-19 cases on anxiety decreases over time, the effect of change in cases (velocity and acceleration) increases over time. Anxiety is then associated with next-day work functioning (engagement, performance, and emotional exhaustion). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. However, accurate diagnosis can be difficult as most of the patients who develop this tumor have symptoms similar to those caused by longstanding liver disease. Herein we developed an integrated platform to discover the glycoprotein biomarkers in early HCC. At first, lectin arrays were applied to investigate the differences in glycan structures on serum glycoproteins from HCC and cirrhosis patients. The intensity for AAL and LCA was significantly higher in HCC, indicating an elevation of fucosylation level. Then serum from 10 HCC samples and 10 cirrhosis samples were used to screen the altered fucosylated proteins by a combination of Exactag labeling, lectin extraction and LC-MS/MS. Finally, 27 HCC and 27 cirrhosis serum samples were used for lectin-antibody arrays to confirm the change of these fucosylated proteins. C3, CE, HRG, CD14 and HGF were found to be biomarker candidates for distinguishing early HCC from cirrhosis, with a sensitivity of 72% and specificity of 79%. Our work gives insight to the detection of early HCC, and the application of this comprehensive strategy has the potential to facilitate biomarker discovery on a large scale.