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he first imported case of monkeypox in Taiwan was diagnosed in an Asian man with HIV-1 infection and asymptomatic COVID-19, returning from Germany. Atypical presentations included asynchronous skin lesions, anogenital lesions and prominent inguinal lymphadenopathy. Whole genomic sequence alignment indicate that the Taiwan strain clustered together with human monkeypox virus West African clade B.1, currently circulating in Europe. Prompt diagnosis and infection control measures are crucial to mitigate the spread of monkeypox.

The β-amyloid precursor protein (APP) is a crucial pathogenic gene linked to Alzheimer's disease (AD). A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) isolated from a female with APP gene mutation utilizing non-integrative Sendai virus. The iPSC line exhibits high expression of pluripotency markers, retains the APP mutation, displays a normal karyotype, and has the ability to differentiate into normal teratoma tissue. This iPSC line represents a valuable cell model for investigating the pathological mechanisms and therapeutic strategies of AD.

Abstract Background Liver ischemia reperfusion injury (LIRI) is not only a common injury during liver transplantation and major hepatic surgery, but also one of the primary factors that affect the outcome of postoperative diseases. However, there are still no reliable ways to tackle the problem. Our study aimed to find some characteristic genes associated with immune infiltration that affect LIRI, which can provide some insights for future research in the future. Therefore, it is essential for the treatment of LIRI, the elucidation of the mechanisms of LIRI, and exploring the potential biomarkers. Efficient microarray and bioinformatics analyses can promote the understanding of the molecular mechanisms of disease occurrence and development. Method Data from GSE151648 were downloaded from GEO data sets, and we performed a comprehensive analysis of the differential expression, biological functions and interactions of LIRI-associated genes. Then we performed Gene ontology (GO) analysis and Kyotoencydlopedia of genes and genomes (KEGG) enrichment analysis of DEGs. At last, we performed a protein-protein interaction network to screen out hub genes. Results A total of 161 differentially expressed genes (DEGs) were identified. GO analysis results revealed that the changes in the modules were mostly enriched in the neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil mediated immunity. KEGG enrichment analysis of DEGs demonstrated that LIRI mainly involved the cytokine-cytokine receptor interaction. Our data indicated that macrophages and neutrophils are closely related to LIRI. 9 hub genes were screened out in the protein-protein interaction network. Conclusions In summary, our data indicated that neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity and cytokine-cytokine receptor interaction may play a key role in LIRI, HRH1, LRP2, P2RY6, PKD1L1, SLC8A3 and TNFRSF8, which were identified as potential biomarkers in the occurrence and development of LIRI. However, further studies are needed to validate these findings and explore the molecular mechanism of these biomarkers in LIRI.

Abstract Objective Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population‐based level are necessary to broaden generalizability to community settings. Methods Circulating GFAP levels were assayed using a Simoa HD‐1 analyzer in 4338 adults without prevalent dementia from four longitudinal community‐based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, race, diabetes, systolic blood pressure, antihypertensive medication, body mass index, apolipoprotein E ε4 status, site, and time between GFAP blood draw and the outcome. Associations with incident all‐cause and Alzheimer's disease dementia were evaluated with adjusted Cox proportional hazard models. Meta‐analysis was performed on the estimates derived from each cohort using random‐effects models. Results Meta‐analyses indicated that higher circulating GFAP associated with lower general cognition (ß = −0.09, [95% confidence interval [CI]: −0.15 to −0.03], p = 0.005), but not with total brain or hippocampal volume (p > 0.05). However, each standard deviation unit increase in log‐transformed GFAP levels was significantly associated with a 2.5‐fold higher risk of incident all‐cause dementia (Hazard Ratio [HR]: 2.47 (95% CI: 1.52–4.01)) and Alzheimer's disease dementia (HR: 2.54 [95% CI: 1.42–4.53]) over up to 15‐years of follow‐up. Interpretation Results support the potential role of circulating GFAP levels for aiding dementia risk prediction and improving clinical trial stratification in community settings.

BackgroundAbnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD).MethodThe thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed.ResultsNo difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p

BackgroundHuman hypopharygeal squamous cell carcinoma (HSCC) is a common head and neck cancer with a poor prognosis in advanced stages. The occurrence and development of tumor is the result of mutual influence and co-evolution between tumor cells and tumor microenvironment (TME). Tumor immune microenvironment (TIME) refers to the immune microenvironment surrounding tumor cells. Studying TIME in HSCC could provide new targets and therapeutic strategies for HSCC.MethodsWe performed single-cell RNA sequencing (scRNA-seq) and analysis of hypopharyngeal carcinoma, paracancerous, and lymphoid tissues from five HSCC patients. Subdivide of B cells, T cells, macrophages cells, and monocytes and their distribution in three kinds of tissues as well as marker genes were analyzed. Different genes of IGHG1 plasma cells and SPP1+ macrophages between HSCC tissues, adjacent normal tissues and lymphatic tissues were analyzed. Additionally, we studied proliferating lymphocytes, T cells exhaustion, and T cell receptor (TCR) repertoire in three kinds of tissues.ResultsTranscriptome profiles of 132,869 single cells were obtained and grouped into seven cell clusters, including epithelial cells, lymphocytes, mononuclear phagocytics system (MPs), fibroblasts, endothelial cells (ECs), plasmacytoid dendritic cells (pDCs), and mast cells. Tumor metastasis occurred in three lymphoid tissues. Four distinct populations were identified from lymphocytes, including B cells, plasma cells, T cells and proliferating lymphocytes. We found IGHA1 and IGHG1 specific plasma cells significantly overexpressed in HSCC tissues compared with normal hypopharygeal tissues and lymphatic tissues. Five distinct populations from MPs were identified, including macrophages, monocytes, mature dendritic cells (DCs), Type 1 conventional dendritic cells (cDC1) and Type 2 conventional dendritic cells (cDC2). SPP1+ macrophages were significantly overexpressed in HSCC tissues and lymphatic tissues compared with normal hypopharygeal tissues, which are thought to be M2-type macrophages. Exhaustion of CD8+ Teff cells occurred in HSCC tissues. At last, we verified that IgA and IgG1 protein expression levels were significantly up-regulated in HSCC tissues compared to adjacent normal tissues.ConclusionOverall, this study revealed TIME in HSCC and lymphatic metastasis, and provided potential therapeutic targets for HSCC.

IntroductionClear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.MethodsClinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.ResultsA total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.ConclusionsThe NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.

Abstract Triple‐negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes due to lack of specific target sites and effective treatments. Herein, a transformable prodrug (DOX‐P18) based on neuropeptide Y analogue with tumor microenvironment responsiveness is developed for TNBC treatment. The prodrug DOX‐P18 can achieve reversible morphological transformation between monomers and nanoparticles through the manipulation of protonation degree in different environments. It can self‐assemble into nanoparticles to enhance the circulation stability and drug delivery efficiency in the physiological environment while transforming from nanoparticles to monomers and being endocytosed into the breast cancer cells in the acidic tumor microenvironment. Further, the DOX‐P18 can precisely be enriched in the mitochondria, and efficiently activated by matrix metalloproteinases. Then, the cytotoxic fragment (DOX‐P3) can subsequently be diffused into the nucleus, generating a sustained cell toxicity effect. In the meanwhile, the hydrolysate residue P15 can assemble into nanofibers to construct nest‐like barriers for the metastasis inhibition of cancer cells. After intravenous injection, the transformable prodrug DOX‐P18 demonstrated superior tumor growth and metastasis suppression with much better biocompatibility and improved biodistribution compared to free DOX. As a novel tumor microenvironment‐responsive transformable prodrug with diversified biological functions, DOX‐P18 shows great potential in smart chemotherapeutics discovery for TBNC.

The efficiency of immunotherapy for triple-negative breast cancer (TNBC) is relatively low due to the difficulty in accurately detecting immune checkpoints. The detection of TNBC-related programmed cell death ligand-1 (PD-L1) expression is important to guide immunotherapy and improve treatment efficiency. Surface-enhanced Raman spectroscopy (SERS) and magnetic resonance (MR) imaging exhibit great potential for early TNBC diagnosis. SERS, an optical imaging mode, has the advantages of high detection sensitivity, good spatial resolution, and “fingerprint” spectral characteristics; however, the shallow detection penetration of SERS bioprobes limits its application in vivo. MR has the advantages of allowing deep penetration with no radiation; however, its spatial resolution needs to be improved. SERS and MR have complementary imaging features for tumor marker detection. In this study, gold nanorod and ultrasmall iron oxide nanoparticle composites were developed as dual-modal bioprobes for SERS-MRI to detect PD-L1 expression. Anti-PD-L1 (aPD-L1) was utilized to improve the targeting ability and specificity of PD-L1 expression detection. TNBC cells expressing PD-L1 were accurately detected via the SERS imaging mode in vitro, which can image at the single-cell level. In addition, bioprobe accumulation in PD-L1 expression-related tumor-bearing mice was simply and dynamically monitored and analyzed in vivo using MR and SERS. To the best of our knowledge, this is the first time a SERS-MRI dual-modal bioprobe combined with a PD-L1 antibody has been successfully used to detect PD-L1 expression in TNBC. This work paves the way for the design of high-performance bioprobe-based contrast agents for the clinical immunotherapy of TNBC.

Abstract Objective Ischemic stroke is a leading cause of human mortality and long‐term disability worldwide. As one of the main forms of regulator of calcineurin 1 (RCAN1), the contribution of RCAN1.4 in diverse biological and pathological conditions has been implicated. But the role of RCAN1.4 in ischemic stroke progression remains elusive. This study is to explore the expression changes and roles of RCAN1.4 in ischemic stroke as well as the underlying mechanisms for these changes and effects of RCAN1.4 in ischemic stroke. Methods Middle cerebral artery occlusion model in C57BL/6J mice and oxygen–glucose deprivation (OGD) model in primary astrocytes were performed to induce the cerebral ischemic stroke. The expression pattern of RCAN1.4 was assessed using real‐time quantitative PCR and western blotting in vivo and in vitro. Mechanistically, the underlying mechanism for the elevation of RCAN1.4 in the upstream was investigated. Lentiviruses were administrated, and the effect of RCAN1.4 in postischemic inflammation was clearly clarified. Results Here we uncovered that RCAN1.4 was dramatically increased in mouse ischemic brains and OGD‐induced primary astrocytes. HIF1α, activated upon OGD, significantly upregulated RCAN1.4 gene expression through specifically binding to the RCAN1.4 promoter region and activating its promoter activity. The functional hypoxia‐responsive element (HRE) was located between −254 and −245 bp in the RCAN1.4 promoter region. Moreover, elevated RCAN1.4 alleviated the release of pro‐inflammatory cytokines TNFα, IL1β, IL6 and reduced expression of iNOS, COX2 in primary astrocytes upon OGD, whereas RCAN1.4 silencing has the opposite effect. Of note, RCAN1.4 overexpression inhibited OGD‐induced NF‐κB activation in primary astrocytes, leading to decreased degradation of IκBα and reduced nuclear translocation of NF‐κB/p65. Interpretation Our results reveal a novel mechanism underscoring the upregulation of RCAN1.4 by HIF1α and the protective effect of RCAN1.4 against postischemic inflammation, suggesting its significance as a promising therapeutic target for ischemic stroke treatment.

Abstract Background As the COVID-19 pandemic evolves, more information is needed on its long-term impacts on health-related quality of life (HRQoL) and social determinants of health (SDoH). The aim of the study was to assess HRQoL and SDoH among a predominantly Latino population of COVID-19 survivors and to compare effects in Latinos versus non-Latinos. Methods This cross-sectional study consisted of a survey (in English and Spanish) of COVID-19 survivors from December 2020 to July 2021. The study assessed sociodemographic data, clinical characteristics, and SDoH, consisting of 10 COVID-19—related concerns. The PROMIS-29 + 2 (PROPr) measure, which captures 8 HRQoL domains and a preference-based health utility, was used to assess HRQoL. Bivariate analyses included chi-square tests and t-tests. Generalized linear models were conducted for multivariable analyses. Results Of 230 respondents (6.3% response rate), the mean [SD] age was 43.1 [14.3] years; 83.0% were Latino; the mean [SD] time since diagnosis was 8.1 [3.2] months; and 12.6% had a history of hospitalization with COVID-19. HRQoL scores were slightly worse than population norms on all domains, especially anxiety; the mean [SD] PROPr health utility was 0.36 [0.25]. Domain scores were similar by ethnicity except for cognitive function—abilities, where scores were lower in Latinos. Multivariable analyses revealed that: (1) financial concerns were associated with worse health utility, as well as worse scores on all 8 PROMIS domains; (2) interpersonal conflict was associated with worse health utility and worse scores on 6 of the 8 PROMIS domains (anxiety, depression, fatigue, sleep disturbance, social function, and pain interference); and (3) Latino ethnicity was only associated with 1 PROMIS domain (cognitive function—abilities) after controlling for covariates. Conclusion COVID-19 infection is associated with HRQoL decrements long after the acute infection, and financial concerns and interpersonal conflict are particularly associated with worse HRQoL.

Increased droughts are associated with climate change. Here, the authors reveal an association between long-term drought and an elevated risk of diarrhea in children under five in low- and middle income countries, and suggest that improving water quality, sanitation, and hygiene practices might reduce the risk.

Background: Patients with hypertrophic obstructive cardiomyopathy (HOCM) have few available nonsurgical treatment options. The feasibility of CARTOSound-guided catheter radiofrequency ablation (RFA) has been reported previously; however, relevant data are limited. The objective is to retrospectively evaluate the effectiveness and safety of CARTOSound-guided RFA for patients with HOCM. Methods: Thirty-seven patients with successive HOCM accompanied by severe left ventricular outflow tract (LVOT) obstruction underwent CARTOSound-guided RFA were reviewed. The intracardiac echocardiography (ICE) images obtained were merged with the CARTO system to create a shell of the left ventricle. The systolic anterior motion-septal contact area marked from the ICE images was considered the target area for the current delivery of RFA. Follow-up data of the LVOT gradient examined before, 1 month, 6 months, 1 year, and every year after catheter-mediated RFA were accessed. Results: The symptoms of 30 patients (81.1%) improved during the follow-up after RFA. The symptoms of all 30 patients were alleviated from the New York Heart Association (NYHA) class IV/III/II to the NYHA class II/I. A sustained and significant gradient reduction was observed in 28 patients (75.7%). The invasive pressure gradient of LVOT was 84.43 ± 27.55 mm Hg before RFA and 42.78 ± 36.38 mm Hg after RFA (P < .001), with a decrease of 41.65 ± 19.72 mm Hg. The median drop in pressure gradient was 36.0% (1.0-67.0%). Conclusions: Catheter-mediated RFA is an effective and safe treatment for patients with HOCM. However, its long-term efficacy and safety should be validated in the future by conducting multicenter clinical trials with large sample sizes. [ABSTRACT FROM AUTHOR]

Mist spraying is an active cooling technology used to alleviate heat stress during hot summers. However, there is limited experimental research on the relationship between ambient thermal parameters and spray cooling efficiency, as well as the transient and short-term thermal perceptions of local residents. In this study, an intermittent mist spraying system was set up, and environmental measurements, coupled with questionnaire surveys, were conducted under typical high temperature and still air conditions. The aim was to investigate the relationship among environmental factors, spray cooling effects, and dynamic improvements in human thermal perception. The results showed that higher ambient temperatures resulted in a more significant cooling effect, with a maximum value of 5.68 °C. Upon entering the spraying area, people experienced a large perceptual change, with the mean thermal sensation and thermal comfort change covering 73% and 62% of the total change ranges, respectively. This study indicated that the mist spray system can be activated if the ambient temperature exceeds 32.5 °C, helping local residents maintain a physiological state close to slightly hot and neutral comfort. These findings suggest that mist spraying can be applied in environmental design as an outdoor cooling spot to mitigate urban overheating, providing valuable insights for the application of mist spray systems in actual outdoor settings in hot-humid areas.

A Faradaic junction solar rechargeable device is one of the promising technologies to address the problem of solar energy storage but the working mechanism remains unclear. Here, the authors report a photovoltage memory effect in a portable Si/CoOx/KBi(aq)/MnOx Faradaic junction device.

Abstract Background New COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation. Methods We produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application. Results We reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD. Conclusions Here, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses.

Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.

Background: Mounting evidence supports an association between nonoptimal ambient temperatures (i.e., heat or cold) and risk of low birthweight (LBW) (

BackgroundIf lymph node metastasis occurs in breast cancer patients, the disease can progress rapidly. Based on the infiltrative immune cells of breast cancer patients with lymph node positivity, we constructed the LNPRS for selecting prognostic predictors.MethodsThe LNPRS was established and the predictive value of the LNPRS was verified by independent testing cohorts. A nomogram was also established to confirm the therapeutic guidance significance of the LNPRS. The correlation of the LNPRS with tumor mutation burden, immune microenvironment score, immune checkpoints, the proportion of tumor-infiltrating immune cells, and GSEA and GSVA enrichment pathways were also evaluated.ResultsIn the training cohort, the overall survival of breast cancer patients who had high LNPRS was shorter than that of patients who had low LNPRS (7.98 years versus 20.42 years, P-value< 8.16E-11). The AUC values for 5-, 10-, and 15-years were 0.787, 0.739, and 0.800, respectively. The ability to predict prognosis for the LNPRS was also tested in 3 independent testing cohorts. Furthermore, the predictive value of the LNPRS for chemotherapy and immunotherapy was also proven. The GSEA and GSVA showed that the LNPRS was closely related to the activation of T and B lymphocytes and IFN-γ secretion. Moreover, breast cancer patients with low LNPRS had higher TME scores than those with high LNPRS.ConclusionWe can conclude that the LNPRS is a robust prognostic biomarker in breast cancer patients with positive lymph nodes and may be helpful for patients to make a clinical decision.

Objective:. To assess the association of Private, Medicare (MC), and Medicaid/Uninsured (MU) insurance type with 30-day emergency department visits/observation stays (EDOS), readmissions, and costs in a safety-net hospital (SNH) serving diverse socioeconomic status patients. Background:. MC’s hospital readmission reduction program (HRRP) disproportionately penalizes SNHs. Methods:. This retrospective cohort study used inpatient National Surgical Quality Improvement Program (2013–2019) data merged with cost data. Frailty, expanded operative stress score, case status, and insurance type were used to predict odds of EDOS and readmissions, as well as index hospitalization costs. Results:. The cohort had 1477 Private; 1164 MC; and 3488 MU cases with a patient mean age 52.1 years [SD = 14.7] and 46.8% of the cases were performed on male patients. MU [adjusted odds ratio (aOR) = 2.69, 95% confidence interval (CI) = 2.38–3.05, P < 0.001] and MC (aOR = 1.32, 95% CI = 1.11–1.56, P = 0.001) had increased odds of urgent/emergent surgeries and complications versus Private patients. Despite having similar frailty distributions, MU compared to Private patients had higher odds of EDOS (aOR = 1.71, 95% CI = 1.39–2.11, P < 0.001), and readmissions (aOR = 1.35, 95% CI = 1.11–1.65, P = 0.004), after adjusting for frailty, OSS, and case status, whereas MC patients had similar odds of EDOS and readmissions versus Private. Hospitalization variable cost %change was increased for MC (12.5%) and MU (5.9%), but MU was similar to Private after adjusting for urgent/emergent cases. Conclusions:. Increased rates and odds of urgent/emergent cases in MU patients drive increased odds of complications and index hospitalization costs versus Private. SNHs care for higher cost populations while receiving lower reimbursements and are further penalized by the unintended consequences of HRRP. Increasing access to care, especially for MU patients, could reduce urgent/emergent surgeries resulting in fewer complications, EDOS/readmissions, and costs.

Objective:. Assess associations of social determinants of health (SDoH) using area deprivation index (ADI), race/ethnicity and insurance type with textbook outcomes (TO). Background:. Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included. Methods:. Three healthcare system cohort study using National Surgical Quality Improvement Program (2013–2019) linked with ADI risk-adjusted for frailty, case status, and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, emergency department/observation stays, and readmissions). Results:. Cohort (34,251 cases) mean age 58.3 [SD = 16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI >85, and 81.8% TO. Racial and ethnic minorities, non-private insurance, and ADI >85 patients had increased odds of urgent/emergent surgeries (adjusted odds ratios [aORs] range: 1.17–2.83, all P < 0.001). Non-Hispanic Black patients, ADI >85 and non-Private insurances had lower TO odds (aORs range: 0.55–0.93, all P < 0.04), but ADI >85 lost significance after including case status. Urgent/emergent versus elective had lower TO odds (aOR = 0.51, P < 0.001). ADI >85 patients had higher complication and mortality odds. Estimated reduction in TO probability was 9.9% (95% confidence interval [CI] = 7.2%–12.6%) for urgent/emergent cases, 7.0% (95% CI = 4.6%–9.3%) for Medicaid, and 1.6% (95% CI = 0.2%–3.0%) for non-Hispanic Black patients. TO probability difference for lowest-risk (White-Private-ADI 85-urgent/emergent) was 29.8% for very frail patients. Conclusion:. Multilevel SDoH had independent effects on TO, predominately affecting outcomes through increased rates/odds of urgent/emergent surgeries driving complications and worse outcomes. Lowest-risk versus highest-risk scenarios demonstrated the magnitude of intersecting SDoH variables. Combination of insurance type and ADI should be used to identify high-risk patients to redesign care pathways to improve outcomes. Risk adjustment including contextual neighborhood deprivation and patient-level SDoH could reduce unintended consequences of value-based programs.

Abstract Different functional connectivities in the brain, specifically in the frontoparietal and motor cortex–sensorimotor circuits, have been associated with superior performance in athletes. However, previous electroencephalogram (EEG) studies have only focused on the frontoparietal circuit and have not provided a comprehensive understanding of the cognitive–motor processes underlying superior performance. We used EEG coherence analysis to examine the motor cortex–sensorimotor circuit in golfers of different skill levels. Twenty experts, 18 amateurs, and 21 novices performed 60 putts at individual putting distances (40–60% success rate). The imaginary inter-site phase coherence (imISPC) was used to compute 8–13 Hz coherence that can be used to distinguish expert-novice and expert-amateur differences during motor preparation. We assessed the 8–13 Hz imISPC between the Cz and F3, F4, C3, C4, T3, T4, P3, P4, O1, and O2 regions. (1) Amateurs had lower 8–13 Hz imISPC in the central regions (Cz–C3 and C4) than novices and experts, but experts had lower 8–13 Hz imISPC than novices. (2) Skilled golfers (experts and amateurs) had lower 8–13 Hz imISPC in the central–parietal regions (Cz–P3 and P4) than novices. (3) Experts had lower 8–13 Hz imISPC in the central–left temporal regions (Cz–T7) than amateurs and novices. Our study revealed that refinement of the motor cortex–sensorimotor circuit follows a U-shaped coherence pattern based on the stage of learning. The early learning stage (i.e., novice to amateur) is characterized by lower connectivity between the regions associated with motor control and visuospatial processes, whereas the late learning stage (i.e., amateur to expert) is characterized by lower connectivity in the regions associated with verbal-analytic and motor control processes.

We aimed to explore the mechanism for hydrogen in the treatment of neuropathic pain in diabetic rats. Eight-week-old male SD rats were randomly divided into control, model and hydrogen treatment groups. Th e hydrogen treatment group was intraperitoneally injected with hydrogen-rich saline daily in 7th and 8th weeks aft er modeling. Before and 2, 4, 6 and 8 weeks aft er modeling, the neurological function, behavioral changes and levels of infl ammatory factors TNF-α and IL-6 in the sciatic nerve were detected, and MCP1 and CCR2 protein expressions were measured by Western blotting. Compared with the model group, the hydrogen treatment group had signifi cantly increased motor nerve conduction velocity, thermal withdrawal latency and mechanical withdrawal threshold (P

Polyetheretherketone (PEEK) is a potential implant material for dental application due to its excellent mechanical properties. However, its biological inertness and poor osteoinductive ability limited its clinical application. Based on a lay-by-layer self-assembly technique, here we incorporated casein phosphopeptide (CPP) onto PEEK surface by a simple two-step strategy to address the poor osteoinductive ability of PEEK implants. In this study, the PEEK specimens were positively charged by 3-ammoniumpropyltriethoxysilane (APTES) modification, then the CPP was adsorbed onto the positively charged PEEK surface electrostatically to obtain CPP-modified PEEK (PEEK-CPP) specimens. The surface characterization, layer degradation, biocompatibility and osteoinductive ability of the PEEK-CPP specimens were studied in vitro. After CPP modification, the PEEK-CPP specimens had a porous and hydrophilic surface and presented enhanced cell adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. These findings indicated that CPP modification could significantly improve the biocompatibility and osteoinductive ability of PEEK-CPP implants in vitro. In a word, CPP modification is a promising strategy for the PEEK implants to achieve osseointegration.

Objective:. Association of insurance type with colorectal surgical complications, textbook outcomes (TO), and cost in a safety-net hospital (SNH). Background:. SNHs have higher surgical complications and costs compared to low-burden hospitals. How does presentation acuity and insurance type influence colorectal surgical outcomes? Methods:. Retrospective cohort study using single-site National Surgical Quality Improvement Program (2013–2019) with cost data and risk-adjusted by frailty, preoperative serious acute conditions (PASC), case status and open versus laparoscopic to evaluate 30-day reoperations, any complication, Clavien-Dindo IV (CDIV) complications, TO, and hospitalization variable costs. Results:. Cases (Private 252; Medicare 207; Medicaid/Uninsured 619) with patient mean age 55.2 years (SD = 13.4) and 53.1% male. Adjusting for frailty, open abdomen, and urgent/emergent cases, Medicaid/Uninsured patients had higher odds of presenting with PASC (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI] = 1.22–3.52, P = 0.009) versus Private. Medicaid/Uninsured (aOR = 1.80, 95% CI = 1.28–2.55, P < 0.001) patients were more likely to undergo urgent/emergent surgeries compared to Private. Medicare patients had increased odds of any and CDIV complications while Medicaid/Uninsured had increased odds of any complication, emergency department or observations stays, and readmissions versus Private. Medicare (aOR = 0.51, 95% CI = 0.33–0.88, P = 0.003) and Medicaid/Uninsured (aOR = 0.43, 95% CI = 0.30–0.60, P < 0.001) patients had lower odds of achieving TO versus Private. Variable cost %change increased in Medicaid/Uninsured patients to 13.94% (P = 0.005) versus Private but was similar after adjusting for case status. Urgent/emergent cases (43.23%, P < 0.001) and any complication (78.34%, P < 0.001) increased %change hospitalization costs. Conclusions:. Decreasing the incidence of urgent/emergent colorectal surgeries, possibly by improving access to care, could have a greater impact on improving clinical outcomes and decreasing costs, especially in Medicaid/Uninsured insurance type patients.

Fucosylated glycosaminoglycans (FGs) derived from sea cucumbers exhibit potent intrinsic Xase (iXase) inhibition, anticoagulation, and antithrombosis. Plasma activated partial thromboplastin time (APTT), a widely used screening test worldwide, is crucial for evaluating anticoagulant efficacy. However, the applicability of these commercially available APTT reagents for assessing anticoagulation of FGs remains unreported. In this study, we investigated the disparity between ellagic acid and colloidal silica APTT reagents in evaluating anticoagulation of dHG-5 and dHLFG-4, two depolymerized FGs, and elucidated the underlying rationale. The results demonstrated that dHG-5 and dHLFG-4 exhibited heightened sensitivity to the ellagic acid APTT reagent both in vitro and in vivo, and did not significantly affect the activation of APTT reagents for plasma. In addition, both ellagic acid and colloidal silica APTT reagents inhibited the anti-iXase of dHG-5 and dHLFG-4, and the inhibition of the ellagic acid APTT reagent was less pronounced compared to the colloidal silica APTT reagent. These findings suggest that the reduced impact of the ellagic acid APTT reagent on the anti-iXase activity of dHG-5 and dHLFG-4 is responsible for the increased sensitivity in plasma APTT analysis. This study offers valuable insights into the characteristics of two APTT reagents applied for assessing the anticoagulant activity of FG-related compounds.

Energy band alignment theory is used to understand interface charge transfer in semiconductor/semiconductor junctions but many abnormal results cannot be well explained. Here, the authors demonstrate a Faradaic junction theory with isoenergetic charge transfer at semiconductor/semiconductor interfaces to explain these abnormal results.