The role of YAP/TAZ on joint and arthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common forms of arthritis with undefined etiology and pathogenesis. Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ), which act as sensors for cellular mechanical and inflammatory cues, have been identified as crucial players in the regulation of joint homeostasis. Current studies also reveal a significant association between YAP/TAZ and the pathogenesis of OA and RA. The objective of this review is to elucidate the impact of YAP/TAZ on different joint tissues and to provide inspiration for further studying the potential therapeutic implications of YAP/TAZ on arthritis. Databases, such as PubMed, Cochran Library, and Embase, were searched for all available studies during the past two decades, with keywords "YAP," "TAZ," "OA," and "RA."

Care Quality for Patients with Chronic Obstructive Pulmonary Disease in the Readmission Penalty Era.

Rationale: Chronic obstructive pulmonary disease (COPD) is the fifth-leading cause of admissions and third-leading cause of readmissions among U.S. adults. Recent policies instituted financial penalties for excessive COPD readmissions. Objectives: To evaluate changes in the quality of care for patients hospitalized for COPD after implementation of the Hospital Readmissions Reduction Program (HRRP). Methods: We conducted a retrospective cohort study of patients older than 40 years of age hospitalized for COPD across 995 U.S. hospitals (Premier Healthcare Database). Measurements and Main Results: Quality of care before and after HRRP implementation was measured via adherence to recommended inpatient care treatments for acute exacerbations of COPD (recommended care, nonrecommended care, "ideal care" [all recommended and no nonrecommended care]). We included 662,842 pre-HRRP (January 2010-September 2014) and 285,508 post-HRRP (October 2014-December 2018) admissions. Recommended care increased at a rate of 0.16% per month pre-HRRP and 0.01% per month post-HRRP (P < 0.001). Nonrecommended care decreased at a rate of 0.15% per month pre-HRRP and 0.13% per month post-HRRP. Ideal care increased at a rate of 0.24% per month pre-HRRP and 0.11% per month post-HRRP (P < 0.001). Conclusions: The pre-HRRP trends toward improving care quality for inpatient COPD care slowed after HRRP implementation. This suggests that financial penalties for readmissions did not stimulate higher quality of care for patients hospitalized with COPD. It remains unclear what policies or approaches will be effective to ensure high care quality for patients hospitalized with COPD exacerbations.

Neighborhood-level factors associated with COVID-19 vaccination rates: a case study in Chicago.

INTRODUCTION: Chicago's deeply-rooted racial and socioeconomic residential segregation is a pattern mirrored in other major cities, making it a prototype for studying the uptake of public health interventions across the US. Residential segregation is related to availability of primary care, sense of community, and trust in the healthcare system, components which are essential in the response to crises like Covid-19 in which vaccine rollout was primarily community-based. We aimed to evaluate the association between rates of access to primary care and community-belonging with Covid-19 vaccination within Chicago's neighborhoods. METHODS: Data from Chicago Department of Public Health (12/2020-6/2022) on Covid-19 vaccination rates, race/ethnicity (% Black and % Hispanic/Latinx residents), age (% >65), gender (% female), socioeconomic status (% below the federal poverty line), access to needed care rate, and rate of self-reported sense of community-belonging on the neighborhood level were analyzed. Linear mixed models (LMMs) were used to study the impact of variables on vaccination; each neighborhood was added as a random effect to account for with-community association. RESULTS: The average Covid-19 vaccination rates across Chicago's neighborhoods was 79%, ranging from 37 to 100%, with median 81%. We found that Covid-19 vaccination rates were positively correlated with access to needed care (p < 0.001) and community-belonging (p < 0.001). Community areas that had lower vaccination rates had greater percentage of Black residents (p < 0.0001) and greater poverty rates (p < 0.0001). After adjusting for poverty, race, gender and age in the models, the association between vaccination rates and access to care or community-belonging were no longer significant, but % Black residents and poverty remained significant. CONCLUSIONS: Though access to needed primary care and community-belonging are correlated with vaccination rates, this association was not significant when controlling for demographic factors. The association between poverty, race and vaccination status remained significant, indicating that socioeconomic and racial disparities across Chicago drive Covid-19 vaccine recommendation adherence regardless of care access. Understanding how poverty, and its intersectional relation to race and primary care access, affects vaccination should be a priority for public health efforts broadly.

Role of an FNIP Repeat Domain-Containing Protein Encoded by Megavirus Baoshan during Viral Infection.

FNIP repeat domain-containing protein (FNIP protein) is a little-studied atypical leucine-rich repeat domain-containing protein found in social amoebae and mimiviruses. Here, a recently reported mimivirus of lineage C, Megavirus baoshan, was analyzed for FNIP protein genes. A total of 82 FNIP protein genes were identified, each containing up to 26 copies of the FNIP repeat, and mostly having an F-box domain at the N terminus. Both nucleotide and amino acid sequences of FNIP repeat were highly conserved. Most of the FNIP protein genes clustered together tandemly in groups of two to 14 genes. Nearly all FNIP protein genes shared similar expression patterns and were expressed 4 to 9 h postinfection. A typical viral FNIP protein, Mb0983, was selected for functional analysis. Protein interactome analysis identified two small GTPases, Rap1B and Rab7A, that interacted with Mb0983 in cytoplasm. The overexpression of Mb0983 in Acanthamoeba castellanii accelerated the degradation of Rap1B and Rab7A during viral infection. Mb0983 also interacted with host SKP1 and cullin-1, which were conserved components of the SKP1-cullin-1-F-box protein (SCF)-type ubiquitin E3 ligase complex. Deletion of the F-box domain of Mb0983 not only abolished its interaction with SKP1 and cullin-1 but also returned the speed of Rap1B and Rab7A degradation to normal in infected A. castellanii. These results suggested that Mb0983 is a part of the SCF-type ubiquitin E3 ligase complex and plays a role in the degradation of Rap1B and Rab7A. They also implied that other viral F-box-containing FNIP proteins might have similar effects on various host proteins. IMPORTANCE Megavirus baoshan encodes 82 FNIP proteins, more than any other reported mimiviruses. Their genetic and transcriptional features suggest that they are important for virus infection and adaption. Since most mimiviral FNIP proteins have the F-box domain, they were predicted to be involved in protein ubiquitylation. FNIP protein Mb0983 interacted with host SKP1 and cullin-1 through the F-box domain, supporting the idea that it is a part of the SCF-type ubiquitin E3 ligase complex. The substrates of Mb0983 for degradation were identified as the host small GTPases Rap1B and Rab7A. Combining the facts of the presence of a large number of FNIP genes in megavirus genomes, the extremely high expression level of the viral ubiquitin gene, and the reported observation that 35% of megavirus-infected amoeba cells died without productive infection, it is likely that megavirus actively explores the host ubiquitin-proteasome pathway in infection and that viral FNIP proteins play roles in the process.

Improving Diabetes Care Through Population Health Innovations and Payments: Lessons from Western Maryland.

BACKGROUND: Global budgets might incentivize healthcare systems to develop population health programs to prevent costly hospitalizations. In response to Maryland's all-payer global budget financing system, University of Pittsburgh Medical Center (UPMC) Western Maryland developed an outpatient care management center called the Center for Clinical Resources (CCR) to support high-risk patients with chronic disease. OBJECTIVE: Evaluate the impact of the CCR on patient-reported, clinical, and resource utilization outcomes for high-risk rural patients with diabetes. DESIGN: Observational cohort study. PARTICIPANTS: One hundred forty-one adult patients with uncontrolled diabetes (HbA1c > 7%) and one or more social needs who were enrolled between 2018 and 2021. INTERVENTIONS: Team-based interventions that provided interdisciplinary care coordination (e.g., diabetes care coordinators), social needs support (e.g., food delivery, benefits assistance), and patient education (e.g., nutritional counseling, peer support). MAIN MEASURES: Patient-reported (e.g., quality of life, self-efficacy), clinical (e.g., HbA1c), and utilization outcomes (e.g., emergency department visits, hospitalizations). KEY RESULTS: Patient-reported outcomes improved significantly at 12 months, including confidence in self-management, quality of life, and patient experience (56% response rate). No significant demographic differences were detected between patients with or without the 12-month survey response. Baseline mean HbA1c was 10.0% and decreased on average by 1.2 percentage points at 6 months, 1.4 points at 12 months, 1.5 points at 18 months, and 0.9 points at 24 and 30 months (P<0.001 at all timepoints). No significant changes were observed in blood pressure, low-density lipoprotein cholesterol, or weight. The annual all-cause hospitalization rate decreased by 11 percentage points (34 to 23%, P=0.01) and diabetes-related emergency department visits also decreased by 11 percentage points (14 to 3%, P=0.002) at 12 months. CONCLUSIONS: CCR participation was associated with improved patient-reported outcomes, glycemic control, and hospital utilization for high-risk patients with diabetes. Payment arrangements like global budgets can support the development and sustainability of innovative diabetes care models.

Pragmatic Clinical Trial of Population Health, Portal-Based Depression Screening: the PORTAL-Depression Study.

BACKGROUND: A population health approach to depression screening using patient portals may be a promising strategy to proactively engage and identify patients with depression. OBJECTIVE: To determine whether a population health approach to depression screening is more effective than screening during clinic appointments alone for identifying patients with depression. DESIGN: A pragmatic clinical trial at an adult outpatient internal medicine clinic at an urban, academic, tertiary care center. PATIENTS: Eligible patients (n = 2713) were adults due for depression screening with active portal accounts. Patients with documented depression or bipolar disorder and those who had been screened in the year prior to the study were excluded. INTERVENTION: Patients were randomly assigned to usual (n = 1372) or population healthcare (n = 1341). For usual care, patients were screened by medical assistants during clinic appointments. Population healthcare patients were sent letters through the portal inviting them to fill out an online screener regardless of whether they had a scheduled appointment. The same screening tool, the Computerized Adaptive Test for Mental Health (CAT-MH™), was used for clinic- and portal-based screening. MAIN MEASURES: The primary outcome was the depression screening rate. KEY RESULTS: The depression screening rate in the population healthcare arm was higher than that in the usual care arm (43% (n = 578) vs. 33% (n = 459), p < 0.0001). The rate of positive screens was also higher in the population healthcare arm compared to that in the usual care (10% (n = 58) vs. 4% (n = 17), p < 0.001). CONCLUSION: Findings suggest depression screening via a portal as part of a population health approach can increase screening and case identification, compared to usual care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03832283.

New Frontiers in Diabetes Care: Quality Improvement Study of a Population Health Team in Rural Critical Access Hospitals.

BACKGROUND: Rural populations are older, have higher diabetes prevalence, and have less improvement in diabetes-related mortality rates compared to urban counterparts. Rural communities have limited access to diabetes education and social support services. OBJECTIVE: Determine if an innovative population health program that integrates medical and social care models improves clinical outcomes for patients with type 2 diabetes in a resource-constrained, frontier area. DESIGN/PARTICIPANTS: Quality improvement cohort study of 1764 patients with diabetes (September 2017-December 2021) at St. Mary's Health and Clearwater Valley Health (SMHCVH), an integrated health care delivery system in frontier Idaho. The United States Department of Agriculture's Office of Rural Health defines frontier as sparsely populated areas that are geographically isolated from population centers and services. INTERVENTION: SMHCVH integrated medical and social care through a population health team (PHT), where staff assess medical, behavioral, and social needs with annual health risk assessments and provide core interventions including diabetes self-management education, chronic care management, integrated behavioral health, medical nutritional therapy, and community health worker navigation. We categorized patients with diabetes into three groups: patients with two or more PHT encounters during the study (PHT intervention), one PHT encounter (minimal PHT), and no PHT encounters (no PHT). MAIN MEASURES: HbA1c, blood pressure, and LDL over time for each study group. KEY RESULTS: Of the 1764 patients with diabetes, mean age was 68.3 years, 57% were male, 98% were white, 33% had three or more chronic conditions, and 9% had at least one unmet social need. PHT intervention patients had more chronic conditions and higher medical complexity. Mean HbA1c of PHT intervention patients significantly decreased from baseline to 12 months (7.9 to 7.6%, p < 0.01) and sustained reductions at 18 months, 24 months, 30 months, and 36 months. Minimal PHT patients decreased HbA1c from baseline to 12 months (7.7 to 7.3%, p < 0.05). CONCLUSION: The SMHCVH PHT model was associated with improved hemoglobin A1c among less well-controlled patients with diabetes.

Evaluating inhaler education interventions for hospitalized children with asthma: A randomized controlled trial.

BACKGROUND: Most children with asthma have poor inhaler technique, with detrimental morbidity effects. Guidelines recommend clinicians provide inhaler education at every opportunity, yet resources are limited. A low-cost, technology-based intervention-Virtual Teach-to-Goal (V-TTG)-was developed to deliver tailored inhaler technique education with high fidelity. OBJECTIVE: To evaluate whether V-TTG leads to less inhaler misuse among children with asthma who are hospitalized vs brief intervention (BI, reading steps aloud). METHODS: A single-center randomized controlled trial of V-TTG vs BI was conducted with 5-to-10-year-old children with asthma hospitalized between January 2019 and February 2020. Inhaler technique was assessed pre- and post-education using 12-step validated checklists (misuse: < 10 steps correct). RESULTS: Among 70 children enrolled, mean age was 7.8 years (SD = 1.6). Most (86%) were Black. Most had an emergency department visit (94%) or hospitalization (90%) in the previous year. At baseline, nearly all children misused inhalers (96%). The proportion of children with inhaler misuse decreased significantly in V-TTG (100%→74%, P = .002) and BI (92%→69%, P = .04) groups, with no difference between groups at both time points (P = .2 and .9). On average, children performed 1.5 more steps correctly (SD = 2.0), with greater improvement with V-TTG (mean [SD] = 1.7 [1.6]) vs BI (mean [SD] = 1.4 [2.3]), though not significant (P = .6). Concerning pre and post technique, older children were significantly more likely than younger children to show more correct steps (mean change = 1.9 vs 1.1, P = .002). CONCLUSION: A technology-based intervention for tailored inhaler education led to improved technique among children, similarly to reading steps aloud. Older children saw greater benefits. Future studies should evaluate the V-TTG intervention across diverse populations and disease severities to identify the greatest impact. CLINICAL TRIAL REGISTRATION: NCT04373499.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

Exchange between Interlayer and Intralayer Exciton in WSe2/WS2 Heterostructure by Interlayer Coupling Engineering.

Because of type-II band alignment, interlayer exciton (IX) is found in a van der Waals (vdW) heterostructure (HS) formed by two monolayers of transition-metal dichalcogenides. Manipulation of IXs is of great importance for excitonic integrated devices. Here, we demonstrate that high pressure and tensile strain can be applied to enhance and reduce interlayer coupling of WSe2/WS2 HS, respectively. High pressure induces the transform of intralayer excitons to IX, while tensile strain leads to the transform of IXs to intralayer excitons. In addition, there is a direct-to-indirect band gap transition of WSe2/WS2 HS. The interlayer distance of WSe2/WS2 HS is reduced under high pressure, but it increased under uniaxial tensile strain from first-principles calculations. The calculated band structures explain well the transformation between interlayer and intralayer excitons of WSe2/WS2 HS. This work demonstrates the exchange of interlayer and intralayer excitons and paves the way to manipulate excitons of HS for excitonic applications.

Pressure Tunable van Hove Singularities of Twisted Bilayer Graphene.

The giant light-matter interaction induced by van Hove singularities (vHSs) of twisted bilayer graphene (tBLG) is responsible for enhanced optical absorption and strong photoresponse. Here, we investigated the evolution of vHSs in tBLG under pressure by using Raman spectroscopy. Pressure not only induces a blue shift of the G/R band but also tunes the intensity of the G/R band. The blue shift of the G/R band is due to the reduction of the in-plane lattice constant, and the variation of the G/R band intensity is due to the vHSs' shift of tBLG. Moreover, the main band in the absorption spectrum of tBLG is attributed to multiple transitions from valence to conduction bands. Because the ratio of R to G band intensity increases under pressure and the origins of R and G bands are different, we claim that pressure enhances intervalley electron scattering. This study paves the way for pressure engineering of vHS and the corresponding photon-electron-phonon interaction in tBLG.

Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/ß-catenin pathway via stabilizing Dishevelled Segment Polarity Protein 3.

PURPOSE: A variety of studies have connected circadian rhythm to the initiation and progression of hepatocellular carcinoma (HCC). The purpose of this study was to figure out about the circadian genes' profile characteristics, prognostic significance, and targeted values in HCC. METHODS: The expression profiles and prognostic significance of circadian genes in the cancer genome atlas liver hepatocellular carcinoma (TCGA-LIHC) database were investigated using bioinformatics analysis. The expression features of Casein Kinase 1 Delta (CSNK1D), a robust signature gene, was further detected by immunohistochemistry, western blotting and Real-time quantitative PCR (RT-qPCR) in a local HCC cohort. The effect of CSNK1D on corresponding phenotypes of HCC cells was evaluated using Cell Counting Kit-8 (CCK8), flowcytometry, clone assay, Transwell assay, and xenograft assay. In addition, the underlying mechanisms of CSNK1D in the Wnt/ß-catenin signaling were validated by multiple molecular experiments. RESULTS: Abnormal expression of the Circadian genome was associated with the malignant clinicopathological characteristics of HCC patients. A 10 circadian gene-based signature with substantial prognostic significance was developed using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. Of them, CSNK1D, significantly elevated in a local HCC cohort, was chosen for further investigation. Silencing or overexpression of CSNK1D significantly reduced or increased proliferation, invasion, sorafenib resistance, xenograft development, and epithelial-mesenchymal transformation (EMT) of HCC cells, respectively. Mechanically, CSNK1D exacerbated the aggressiveness of HCC cells by activating Wnt/ß-catenin signaling through interacting with Dishevelled Segment Polarity Protein 3 (DVL3). CONCLUSIONS: The Circadian gene CSNK1D was found to contribute to HCC progression by boosting the Wnt/ß-catenin pathway, hinting that it could be a prospective therapeutic target for HCC.

A Tandem Interfaced (Ni3 S2 -MoS2 )@TiO2 Composite Fabricated by Atomic Layer Deposition as Efficient HER Electrocatalyst.

Reported herein is a highly active and durable hydrogen evolution reaction (HER) electrocatalyst, which is constructed following a tandem interface strategy and functional in alkaline and even neutral medium (pH ≈ 7). The ternary composite material, consisting of conductive nickel foam (NF) substrate, Ni3 S2 -MoS2 heterostructure, and TiO2 coating, is synthesized by the hydrothermal method and atomic layer deposition (ALD) technique. Representative results include: (1) versatile characterizations confirm the proposed composite structure and strong electronic interactions among comprised sulfide and oxide species; (2) the material outperforms commercial Pt/C by recording an overpotential of 115 mV and a Tafel slope of 67 mV dec-1 under neutral conditions. A long-term stability in alkaline electrolytes up to 200 h and impressive overall water splitting behavior (1.56 V @ 10 mA cm-2 ) are documented; (3) implementation of ALD oxide tandem layer is crucial to realize the design concept with superior HER performance by modulating a variety of heterointerface and intermediates electronic structure.

Impact of the Early Phase of the COVID-19 Pandemic on Medical Student Well-Being: a Multisite Survey.

BACKGROUND: The COVID-19 pandemic drastically impacted medical student experiences. Little is known about the impact of the pandemic on student well-being and protective factors for burnout. OBJECTIVE: Assess US medical student burnout, stress, and loneliness during the initial phase of the pandemic, compare results to pre-pandemic data, and identify risk factors for distress and protective factors to inform support interventions. DESIGN: Cross-sectional survey of medical students conducted between May and July 2020. PARTICIPANTS: 3826 students from 22 medical schools. MAIN MEASURES: Burnout (MBI-HSS), stress (PSS-10), loneliness (UCLA scale), and student experiences. Compared burnout and stress to pre-pandemic studies (2010-2020). KEY RESULTS: Of 12,389 students, 3826 responded (31%). Compared to pre-pandemic studies, burnout was lower (50% vs. 52%, P = 0.03) while mean stress was higher (18.9 vs. 16.0, P < 0.001). Half (1609/3247) reported high (≥ 6/9) loneliness scores. Significant differences were found in burnout and stress by class year (P = 0.002 and P < 0.001) and race (P = 0.004 and P < 0.001), with the highest levels in second- and third-year students and Black, Asian, or other racial minority students. Students experiencing financial strain or racism had higher burnout and stress (P < 0.001 for all). Respondents with COVID-19 diagnoses in themselves or family members had higher stress (P < 0.001). Nearly half (1756/3569) volunteered during the pandemic, with volunteers reporting lower burnout [48% (782/1639) vs. 52% (853/1656), P = 0.03]. CONCLUSIONS: While stress was higher compared to pre-pandemic data, burnout was significantly lower. Higher burnout and stress among Black, Asian, and other racial minority students and those who experienced financial strain, racism, or COVID-19 diagnoses likely reflect underlying racial and socioeconomic inequalities exacerbated by the pandemic and concurrent national racial injustice events. Volunteer engagement may be protective against burnout. Schools should proactively support vulnerable students during periods of stress.

HMGA1 promotes hepatocellular carcinoma proliferation, migration, and regulates cell cycle via miR-195-5p.

HMGA1 has been reported to be aberrantly expressed and correlate with the poor prognosis of many carcinomas. This study aimed to investigate the clinical significance and molecular mechanism of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). Analysis of TCGA dataset by TANRIC website and R2 platform, we found that HMGA1 expression was significantly higher in HCC tissues compared to that in normal liver tissues and was associated with Edmondson grade. Patients with highly expressed HMGA1 had worse overall survival. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis showed the potential relationships between HMGA1 and other genes in HCC. We also demonstrated that the downregulation of HMGA1 dramatically suppressed the proliferation and migration of HCC cells. Furthermore, ectopic expression of HMGA1 blocked G0/G1 to S transition. Subsequent investigation characterized HMGA1 as a direct target of miR-195-5p, and miR-195-5p downregulation abrogated the effect of HMGA1 on HCC proliferation, migration, and cell cycle arrest. In addition, we also demonstrated that miR-195-5p downregulation abrogated the effect of HMGA1 on HCC growth in vivo. Taken together, our data provide strong evidence that HMGA1 promotes HCC and is negatively regulated by the tumor-suppressor, miR-195-5p.

Bi3TeBO9: A Promising Mid-Infrared Nonlinear Optical Crystal with a Large Laser Damage Threshold.

Mid-infrared (mid-IR) nonlinear optical (NLO) crystals are key materials in the field of laser technology. Nevertheless, the applications of these significant optical materials are always limited by their low laser damage threshold (LDT). Here, an oxide mid-IR NLO crystal, Bi3TeBO9, with a large LDT was discovered. The centimeter-sized Bi3TeBO9 single crystal was successfully grown by the top-seeded solution growth (TSSG) method. The Bi3TeBO9 features a high LDT of 450 MW/cm2 (∼15 × AgGaS2) and the widest transparent range (0.35-7.10 µm) among known borate crystals. The second-harmonic generation (SHG) effect is about 1.6 times that of KDP. First-principles calculations and structural analysis show that the optical characteristics of Bi3TeBO9 are mainly affected by distorted [BiO6] groups. Furthermore, its thermal characteristics including specific heat, thermal diffusivity, thermal conductivity, and thermal expansion were also measured.

Standup comedy principles and the personal monologue to explore interpersonal bias: experiential learning in a health disparities course.

BACKGROUND: Interpersonal biases between clinicians and patients contribute to disparities in health care and outcomes by race, ethnicity, and socioeconomic status. We used standup comedy principles and exercises to help medical students recognize how others perceive them and how they perceive others, and engage in difficult discussions around implicit biases and interpersonal racism. METHODS: 90 min Zoom workshop with 40 first-year medical students in urban medical school. Intervention consisted of three exercises: Naming icebreaker, Rant and Rave (communicate strong perspective clearly), and Personal Monologue about how others perceive you and how you perceive yourself. Discussion debriefed the personal monologue exercise. Likert scale questions on post-session survey evaluated workshop overall, whether workshop increased skills, and safety of learning environment. Open-ended questions included what trainees liked about the module, what could be improved, and what impact the module had on them? RESULTS: Seventeen (42.5%) students responded to survey. Six respondents identified as white, 4 as Asian, 1 as Black, 1 as multiracial, and 5 did not identify. Seventy-six percent rated the module as "very good" or "excellent", and 94% would recommend the module to others. Most respondents reported the workshop helped them become better listeners (75%) and more observant (82%). Eighty-three percent reported the training could help them take better care of patients with lived experiences different than their own. All respondents believed the learning environment was safe, and 94% reported that instructors created an atmosphere in which they could take risks. Thirty-six percent felt stressed. Students reported the workshop helped them recognize their own identities, others' perceptions, and bidirectional biases, and inspired them to strive for more accurate, authentic interactions with patients. CONCLUSIONS: Standup comedy principles show promise for engaging students in meaningful, safe discussions about perceptions and interpersonal biases rooted in their own personal experiences and those of their classmates.

More change in task repetition, less cost in task switching: Behavioral and event-related potential evidence.

Previous studies have shown that the probability of task switching can vary the level of cognitive control and modulate the size of switch costs. However, it is unclear whether switch costs would be affected by a task-repetition context formed by varying the degree of response (and task-relevant stimulus property) change within the task repetition sequences while the probability of task switching remains constant. In the present study, participants were presented with a string of digits (e.g., ②②②). Basing on stimulus color, they were required to indicate either the presented digit, or the number of presented digits. Before task switching, stimulus and response in consecutive task-repeat trials varied more or less frequently. Behavioral results showed that the frequent-change context elicited smaller switch costs than the rare-change context. Event-related potential (ERP) results indicated that: (1) the frequent-change context evoked greater fronto-central N2 amplitudes for both task-repeat and task-switch trials, implying that cognitive control increased due to the variation of stimulus and response associations; (2) for the task switch trials, smaller P300 amplitudes were evoked in the frequent-change context than the rare-change context, reflecting the promoted task-set reconfiguration. These findings suggest that, the more change in stimulus and response during task repetition, the higher the overall level of cognitive control and the higher efficiency of task-switching.

Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection is associated with functionally impaired virus-specific T cell responses. Although the myeloid-derived suppressor cells (MDSCs) are known to play a critical role in impairing antiviral T cell responses, viral factors responsible for the expansion of MDSCs in chronic hepatitis B (CHB) remain obscure. In order to elucidate the mechanism of monocytic MDSCs (mMDSCs) expansion and T cell function suppression during persistent HBV infection, we analyzed the circulation frequency of mMDSCs in 164 CHB patients and 70 healthy donors, and found that the proportion of mMDSCs in HBeAg (+) CHB patients was significantly increased compared to that in HBeAg (-) patients, which positively correlated with the level of HBeAg. Furthermore, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy donors to HBeAg led to mMDSCs expansion and significant upregulation of IL-1ß, IL-6 and indoleamine-2, 3-dioxygenase (IDO), and depletion of the cytokines abrogated HBeAg-induced mMDSCs expansion. Moreover, HBeAg-induced mMDSCs suppressed the autologous T-cell proliferation in vitro, and the purified mMDSCs from HBeAg (+) subjects markedly reduced the proliferation of CD4+ and CD8+ T cells and IFN-γ production, which could be efficiently restored by inhibiting IDO. In summary, HBeAg-induced mMDSCs expansion impairs T cell function through IDO pathway and favors the establishment of a persistent HBV infection, suggesting a mechanism behind the development of HBeAg-induced immune tolerance.

Lower level of complement component C3 and C3a in the plasma means poor outcome in the patients with hepatitis B virus related acute-on-chronic liver failure.

BACKGROUND: The purpose of this study is to investigate whether or not the complement system is systemically activated and to specify the clinical and prognostic implications of its components during hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). METHODS: Blood samples were taken from twenty-seven patients diagnosed with HBV-ACLF, twenty-five patients diagnosed with chronic hepatitis B but without liver failure (CHB), and nine healthy volunteers (the control group). Plasma complement components were measured with Enzyme-linked immunosorbent assay. Correlative analysis were assessed between the levels of complement components and the liver failure related index. RESULTS: The concentrations of C3 was 6568 µg/ml in the HBV-ACLF group, 8916 µg/ml in the CHB group and 15,653 µg/ml in the control group, respectively (P <  0.05). The concentrations of C3a was 852 ng/ml in the HBV-ACLF group, 1008 ng/ml in the CHB group and 1755 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q was 50,509 ng/ml in the HBV-ACLF group, 114,640 ng/ml in the CHB group and 177,001 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q, C3, C3a, C4, C4a and sC5b-9 were significantly higher in the control group than those in the HBV-ACLF group (3.5, 2.4, 2.1, 1.4, 1.3 and 6.0 fold, respectively). However, there was no statistical significance of the differences in the plasma concentrations of mannose binding lectin and factor B between the HBV-ACLF group and control group. The levels of C3 and C3a were inversely correlated with MELDs or CLIF-C OFs (P <  0.05). CONCLUSIONS: Our analysis demonstrated that the activation of the classical pathway mediated by C1q may play an important role in the pathogenesis of HBV-ACLF. Furthermore, the plasma levels of C3 and C3a may be potential novel biomarkers in predicting the outcome of HBV-ACLF.