Role and function of plakophilin 3 in cancer progression and skin disease.

Plakophilin 3 (PKP3), a component of desmosome, is aberrantly expressed in many kinds of human diseases, especially in cancers. Through direct interaction, PKP3 binds with a series of desmosomal proteins, such as desmoglein, desmocollin, plakoglobin, and desmoplakin, to initiate desmosome aggregation, then promotes its stability. As PKP3 is mostly expressed in the skin, loss of PKP3 promotes the development of several skin diseases, such as paraneoplastic pemphigus, pemphigus vulgaris, and hypertrophic scar. Moreover, accumulated clinical data indicate that PKP3 dysregulates in diverse cancers, including breast, ovarian, colon, and lung cancers. Numerous lines of evidence have shown that PKP3 plays important roles in multiple cellular processes during cancer progression, including metastasis, invasion, tumor formation, autophagy, and proliferation. This review examines the diverse functions of PKP3 in regulating tumor formation and development in various types of cancers and summarizes its detailed mechanisms in the occurrence of skin diseases.

An Injectable Puerarin Depot Can Potentiate Chimeric Antigen Receptor Natural Killer Cell Immunotherapy Against Targeted Solid Tumors by Reversing Tumor Immunosuppression.

Chimeric antigen receptor natural killer (CAR-NK) cell therapy represents a potent approach to suppressing tumor growth because it has simultaneously inherited the specificity of CAR and the intrinsic generality of NK cells in recognizing cancer cells. However, its therapeutic potency against solid tumors is still restricted by insufficient tumor infiltration, immunosuppressive tumor microenvironments, and many other biological barriers. Motivated by the high potency of puerarin, a traditional Chinese medicine extract, in dilating tumor blood vessels, an injectable puerarin depot based on a hydrogen peroxide-responsive hydrogel comprising poly(ethylene glycol) dimethacrylate and ferrous chloride is concisely developed. Upon intratumoral fixation, the as-prepared puerarin depot (abbreviated as puerarin@PEGel) can activate nitrogen oxide production inside endothelial cells and thus dilate tumor blood vessels to relieve tumor hypoxia and reverse tumor immunosuppression. Such treatment can thus promote tumor infiltration, survival, and effector functions of customized epidermal growth factor receptor (HER1)-targeted HER1-CAR-NK cells after intravenous administration. Consequently, such puerarin@PEGel-assisted HER1-CAR-NK cell treatment exhibits superior tumor suppression efficacy toward both HER1-overexpressing MDA-MB-468 and NCI-H23 human tumor xenografts in mice without inducing obvious side effects. This study highlights a potent strategy to activate CAR-NK cells for augmented treatment of targeted solid tumors through reprogramming tumor immunosuppression.

Hybrid-FHR: a multi-modal AI approach for automated fetal acidosis diagnosis.

BACKGROUND: In clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques. METHODS: In this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer's convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy. RESULTS: Our ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively. CONCLUSIONS: Our algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.

[An EHG-based Preterm Delivery Prediction Algorithm via Convolution Neural Network].

Premature delivery is one of the direct factors that affect the early development and safety of infants. Its direct clinical manifestation is the change of uterine contraction intensity and frequency. Uterine Electrohysterography(EHG) signal collected from the abdomen of pregnant women can accurately and effectively reflect the uterine contraction, which has higher clinical application value than invasive monitoring technology such as intrauterine pressure catheter. Therefore, the research of fetal preterm birth recognition algorithm based on EHG is particularly important for perinatal fetal monitoring. We proposed a convolution neural network(CNN) based on EHG fetal preterm birth recognition algorithm, and a deep CNN model was constructed by combining the Gramian angular difference field(GADF) with the transfer learning technology. The structure of the model was optimized using the clinical measured term-preterm EHG database. The classification accuracy of 94.38% and F1 value of 97.11% were achieved. The experimental results showed that the model constructed in this paper has a certain auxiliary diagnostic value for clinical prediction of premature delivery.

Squid Beak Inspired Cross-Linked Cellulose Nanocrystal Composites.

Bioinspired cross-linked polymer nanocomposites that mimic the water-enhanced mechanical gradient properties of the squid beak have been prepared by embedding either carboxylic acid- or allyl-functionalized cellulose nanocrystals (CNC) into an alkene-containing polymer matrix (poly(vinyl acetate-co-vinyl pentenoate), P(VAc-co-VP)). Cross-linking is achieved by imbibing the composite with a tetrathiol cross-linker and carrying out a photoinduced thiol-ene reaction. Central to this study was an investigation on how the placement of cross-links (i.e., within matrix only or between the matrix and filler) impacts the wet mechanical properties of these materials. Through cross-linking both the CNCs and matrix, it is possible to access larger wet mechanical contrasts (E'stiff/E'soft = ca. 20) than can be obtained by just cross-linking the matrix alone (where contrast E'stiff/E'soft of up 11 are observed). For example, in nanocomposites fabricated with 15 wt % of allyl-functionalized tunicate CNCs and P(VAc-co-VP) with about 30 mol % of the alkene-containing VP units, an increase in the modulus of the wet composite from about 14 MPa to about 289 MPa at physiological temperature (37 °C) can be observed after UV irradiation. The water swelling of the nanocomposites is greatly reduced in the cross-linked materials as a result of the thiol-ene cross-linking network, which also contributes to the wet modulus increase. Given the mechanical turnability and the relatively simple approach that also allows photopatterning the material properties, these water-activated bioinspired nanocomposites have potential uses in a broad range of biomedical applications, such as mechanically compliant intracortical microelectrodes.

Intent-to-treat analysis of cluster randomized trials when clusters report unidentifiable outcome proportions.

BACKGROUND: Cluster randomized trials are designed to evaluate interventions at the cluster or group level. When clusters are randomized but some clusters report no or non-analyzable data, intent-to-treat analysis, the gold standard for the analysis of randomized controlled trials, can be compromised. This article presents a very flexible statistical methodology for cluster randomized trials whose outcome is a cluster-level proportion (e.g. proportion from a cluster reporting an event) in the setting where clusters report non-analyzable data (which in general could be due to nonadherence, dropout, missingness, etc.). The approach is motivated by a previously published stratified randomized controlled trial called, "The Randomized Recruitment Intervention Trial (RECRUIT)," designed to examine the effectiveness of a trust-based continuous quality improvement intervention on increasing minority recruitment into clinical trials (ClinicalTrials.gov Identifier: NCT01911208). METHODS: The novel approach exploits the use of generalized estimating equations for cluster-level reports, such that all clusters randomized at baseline are able to be analyzed, and intervention effects are presented as risk ratios. Simulation studies under different outcome missingness scenarios and a variety of intra-cluster correlations are conducted. A comparative analysis of the method with imputation and per protocol approaches for RECRUIT is presented. RESULTS: Simulation results show the novel approach produces unbiased and efficient estimates of the intervention effect that maintain the nominal type I error rate. Application to RECRUIT shows similar effect sizes when compared to the imputation and per protocol approach. CONCLUSION: The article demonstrates that an innovative bivariate generalized estimating equations framework allows one to implement an intent-to-treat analysis to obtain risk ratios or odds ratios, for a variety of cluster randomized designs.

Comparison of Lymphocyte Count, Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting the Severity and the Clinical Outcomes of Acute Cerebral Infarction Patients.

BACKGROUND: To compare the prediction values of lymphocyte counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) for the severity and the clinical outcomes of acute cerebral infarction (ACI). METHODS: A total of 139 patients diagnosed with ACI were enrolled in this study. Data were gathered from medical records of patients who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS). The clinical outcomes of ACI patients were evaluated using the Glasgow Outcome Scale (GOS) at day 30. Patients were classified into two groups based on their GOS at day 30. The Student's t-test of independent samples was adopted for the com-parison of the mean between two groups. The lymphocyte counts, NLR and PLR were evaluated by comparing the areas under the receiver operating characteristic curve (AUC) in predicting the clinical outcomes of ACI. The lin-ear correlations were specifically evaluated to determine the relationship between lymphocyte counts, NLR, PLR and the NIHSS score and the clinical outcomes of ACI. Comparison of AUC was performed using the Z-test. RESULTS: The lymphocyte counts were significantly decreased in the poor outcomes group compared with the good outcomes group of ACI, while NLR and PLR were significantly increased (all p < 0.05); moreover, AUC in pre-dicting 30-day poor outcomes of ACI was 0.697 (95% confidence interval (CI), 0.614 to 0.772) for lymphocyte counts, 0.744 (95% CI, 0.663 to 0.814) for NLR, and 0.689 (95% CI, 0.605 to 0.764) for PLR, but there were no significant statistical differences (all p > 0.05). Finally, the lymphocyte counts were negatively correlated with the NIHSS score of ACI patients, while NLR and PLR were positively correlated (all p < 0.05); on the other hand, the lymphocyte counts were positively correlated with the GOS score of ACI patients, while NLR and PLR were nega-tively correlated (all p < 0.05). CONCLUSIONS: As an inflammatory and immune biomarker, lymphocyte counts demonstrate similar test perfor-mance as NLR and PLR for predicting the severity and 30-day poor outcomes of ACI.

Diagnostic Values of Neutrophil and Neutrophil to Lymphocyte Ratio in Distinguishing between Acute Cerebral Infarction and Vertigo.

BACKGROUND: Vertigo and acute cerebral infarction (ACI) patients show similar symptoms such as dizziness and imbalance. This study was to investigate the diagnostic values of neutrophil counts and neutrophil to lymphocyte ratio (NLR) in distinguishing patients with ACI from those with vertigo. METHODS: This retrospective study was performed and data were gathered from medical records of patients with vertigo symptoms from the Department of Emergency and Neurology Clinics who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2017 and January 2019. Of the 173 patients with vertigo symptoms, 111 non-ACI vertigo patients (vertigo group) and 62 cases diagnosed with ACI (ACI group) were enrolled in this study. The neutrophil counts, lymphocyte counts, platelet counts, NLR, and PLT to lymphocyte ratio (PLR) within 24 hours after admission were compared between the two groups. Student's t-test of independent samples was adopted for the comparison of the mean between two groups. The neutrophil counts and NLR were evaluated by comparing the areas under the receiver operating characteristic curve (AUC) in distinguishing patients with ACI from those with vertigo. Comparison of AUC was performed using the Z-test. RESULTS: The neutrophil counts and NLR were significantly increased in the ACI group compared with the vertigo group (all p < 0.05), while there were no significant statistical differences of the lymphocyte counts, platelet counts, and PLR (all p > 0.05); moreover, AUC in distinguishing patients with ACI from those with vertigo was 0.647 (95% confidence interval (CI), 0.570 to 0.718) for neutrophil counts and 0.639 (95% CI, 0.562 to 0.710) for NLR, but there was no significant statistical difference (p > 0.05); finally, the cutoff values were 3.1 x 109/L in distinguishing patients with ACI from those with vertigo (specificity 41.44% and sensitivity 83.87%) for neutrophil counts and 2 (specificity 55.86% and sensitivity 67.74%) for NLR. CONCLUSIONS: As easy-to-obtain inflammatory biomarkers, both neutrophil counts and NLR could demonstrate diagnostic values in distinguishing between ACI and vertigo.

DeepFHR: intelligent prediction of fetal Acidemia using fetal heart rate signals based on convolutional neural network.

BACKGROUND: Fetal heart rate (FHR) monitoring is a screening tool used by obstetricians to evaluate the fetal state. Because of the complexity and non-linearity, a visual interpretation of FHR signals using common guidelines usually results in significant subjective inter-observer and intra-observer variability. OBJECTIVE: Therefore, computer aided diagnosis (CAD) systems based on advanced artificial intelligence (AI) technology have recently been developed to assist obstetricians in making objective medical decisions. METHODS: In this work, we present an 8-layer deep convolutional neural network (CNN) framework to automatically predict fetal acidemia. After signal preprocessing, the input 2-dimensional (2D) images are obtained using the continuous wavelet transform (CWT), which provides a better way to observe and capture the hidden characteristic information of the FHR signals in both the time and frequency domains. Unlike the conventional machine learning (ML) approaches, this work does not require the execution of complex feature engineering, i.e., feature extraction and selection. In fact, 2D CNN model can self-learn useful features from the input data with the prerequisite of not losing informative features, representing the tremendous advantage of deep learning (DL) over ML. RESULTS: Based on the test open-access database (CTU-UHB), after comprehensive experimentation, we achieved better classification performance using the optimal CNN configuration compared to other state-of-the-art methods: the averaged ten-fold cross-validation of the accuracy, sensitivity, specificity, quality index defined as the geometric mean of the sensitivity and specificity, and the area under the curve yielded results of 98.34, 98.22, 94.87, 96.53 and 97.82%, respectively CONCLUSIONS: Once the proposed CNN model is successfully trained, the corresponding CAD system can be served as an effective tool to predict fetal asphyxia objectively and accurately.

Chiral DMAP-N-oxides as Acyl Transfer Catalysts: Design, Synthesis, and Application in Asymmetric Steglich Rearrangement.

A DMAP-N-oxide, featuring an α-amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O-acylated azlactones afforded C-acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP-N-oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP-N-oxides for asymmetric acyl transfer reactions.

Inhibition of 5-lipoxygenase represses neutrophils activation and activates apoptosis in pancreatic tissues during acute necrotizing pancreatitis.

Pancreatic glandular necrosis is rapid inflammation of the pancreas and contributes to severe acute pancreatitis in humans. The pathogenesis of pancreatic tissue inflammation during acute pancreatitis is still largely unknown. Recent studies suggest that 5-lipoxygenase (5-LOX) is an essential mediator in modulating cell death pathways in human diseases. In this study, we aimed to evaluate the effects of a 5-LOX inhibitor, zileuton, on tissue apoptosis and neutrophils activation in pancreatic tissues during acute necrotizing pancreatitis (ANP) in a rat model. In this present study, both mRNA and protein levels of 5-LOX are upregulated during ANP and zileuton treatment is shown to repress ANP-induced upregulation of 5-LOX levels. In addition, zileuton treatment is found to repress blood biomarkers of neutrophils activation such as soluble intercellular adhesive molecular 1 (ICAM-1), soluble E-selectin (E-selectin), soluble P-selectin (P-selectin), leukotriene B4 (LTB4), and myeloperoxidase (MPO). Also, zileuton treatment attenuates pancreatic tissue pathology, upregulates caspase-3, downregulates B-cell lymphoma 2 (Bcl-2), and activates tissue apoptosis evaluated by TUNEL staining. Our results show that 5-LOX plays an important role in activating apoptosis and repressing neutrophils activation during ANP. The current study suggests that 5-LOX can be used as a potential target for the treatment of ANP.

The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry.

INTRODUCTION: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. RESEARCH QUESTION: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. DESIGN: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. RESULTS: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. CONCLUSION: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

The Impact of the Share 35 Policy on Racial and Ethnic Disparities in Access to Liver Transplantation for Patients with End Stage Liver Disease in the United States: An Analysis from UNOS Database.

BACKGROUND: The Share 35 policy was instituted in June 2013 by the United Network for Organ Sharing (UNOS) in order to reduce death on liver transplant waiting list. The effect of this policy on racial and ethnic disparities in access to liver transplantation has not been examined. METHODS: A total of 14,585 adult patients registered for liver transplantation between 2012 and 2015 were identified from UNOS database. Logistic and proportional hazards models were used to model the effects of race and ethnicity on access to liver transplantation. Stratification on pre- and post-Share 35 periods was performed to compare the first 18 months of Share 35 policy to an equivalent time period before. RESULTS: Comparison of the pre- and post-Share 35 periods showed significantly decreased time on waiting list and increased numbers of minorities having access to liver transplantation. Hispanic recipients still experienced significantly longer waiting time (HR: 0.69, 95% CI: 0.53-0.88) before they received liver transplantation after Share 35 policy took effect. CONCLUSION: The Share 35 policy did not lead to improved access to liver transplantation among minorities but eliminated the previously observed racial and ethnic disparities in transplant rates as well as shortened the waiting time.

Design of a cluster-randomized minority recruitment trial: RECRUIT.

BACKGROUND: Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. METHODS: We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RESULTS: RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). CONCLUSION: RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

Impact of Donor Recipient Gender and Race Mismatch on Graft Outcomes in Patients With End-Stage Liver Disease Undergoing Liver Transplantation.

CONTEXT: The discrepancy between donor supply and organ demand increased the possibility of gender and race mismatch between the donors and recipients. However, the findings of their impact on graft and patient survival are outdated and mixed. OBJECTIVE: To estimate the effects of gender and race mismatch on graft survival and patient survival among adult patients (18 years and older) with end-stage liver disease. DESIGN: A total of 38 768 patients undergoing liver transplant between 2002 and 2011 were identified from United Network for Organ Sharing database. Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regressions with backward elimination adopting a marginal approach with a working independence assumption and stratification on recipient hepatitis C virus status were used. MAIN OUTCOME MEASURES: Posttransplantation graft survival and patient survival. RESULTS: Both gender mismatch (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.09-1.12) and race mismatch (HR 1.08, 95%C: 1.04-1.12) had significantly adverse effects on graft survival and patient survival after controlling for other factors, especially among hepatitis C-positive female recipients with male donors (HR 1.13, 95%CI 1.03-1.24), black recipients with white donors (1.39, 1.29-1.49) or Hispanic donors (HR 1.48, 95%CI 1.27-1.72), and these effects were even worse among hepatitis C-positive recipients. CONCLUSION: Gender and race mismatch between donors and recipients adversely affected graft survival and patient survival among adult patients with end-stage liver disease, both independently and after the adjustment for other factors. Future research is recommended to explore other factors such as new model for end-stage liver disease sharing policy change and disparities in access to waiting-list or transplantation.

Single-Lead Fetal ECG Extraction Based on a Parallel Marginalized Particle Filter.

This paper presents a novel method for extracting the fetal ECG (FECG) from a single-lead abdominal signal. A dynamical model for a modified abdominal signal is proposed, in which both the maternal ECG (MECG) and the FECG are modeled, and then a parallel marginalized particle filter (par-MPF) is used for tracking the abdominal signal. Finally, the FECG and MECG are simultaneously separated. Several experiments are conducted using both simulated and clinical signals. The results indicate that the method proposed in this paper effectively extracts the FECG and outperforms other Bayesian filtering algorithms.

One-step hydrothermal synthesis of CTAB-modified SiO2 for removal of bisphenol A.

A stable SiO2 material marked as CTAB-Ms(x) was synthesized by a novel sol-gel method. It was modified with hexadecyl trimethyl ammonium bromide (CTAB), which resulted in high adsorption capacity. Its microstructure and surface functional groups were characterized by scanning electron microscope, transmission electron microscope and Fourier transform infrared. The results showed that CTAB-Ms(x) had a core/shell structure in which the core was a CTAB micelle and the shell was SiO2. The prepared material was applied to adsorb bisphenol A (BPA). Pseudo-first-order kinetics equation, pseudo-second-order kinetics equation, Langmuir adsorption isotherm model, Temkin adsorption isotherm model, and thermodynamic equations were used to fit and analyze the experiment results. The theoretical maximum adsorption capacities calculated according to linear and non-linear forms of the Langmuir isotherm were 370.37 mg·g-1 and 198.80 mg·g-1, and the adsorption equilibrium time was 120 min. A mechanism study showed that the high adsorption capacity was attributed to the solubilization effect of the CTAB micelle.

Associations between hematopoietic growth factors and risks of venous thromboembolism, stroke, ischemic heart disease and myelodysplastic syndrome: findings from a large population-based cohort of women with breast cancer.

PURPOSE: To determine the risk of venous thromboembolism (VTE), stroke, ischemic heart disease, and myelodysplastic syndrome (MDS) in association with the receipt of colony-stimulating factors (CSFs) and/or erythropoiesis-stimulating agents (ESAs) in women with breast cancer. METHODS: We studied 77,233 women with breast cancer aged ≥65 in 1992-2009 from the Surveillance, Epidemiology, and End Results-Medicare linked data with up to 19 years of follow-up. RESULTS: Incidence of VTE increased from 9 cases in women receiving no chemotherapy and no CSFs/ESAs to 22.79 cases per 1,000 person-years in those receiving chemotherapy with CSFs and ESAs. Women with chemotherapy who received both CSFs and ESAs (adjusted hazard ratio and 95 % confidence interval 2.01, 1.80-2.25) or received ESAs without CSFs (2.03, 1.74-2.36) were twice as likely to develop VTE than those receiving no chemotherapy and no CSFs/ESAs, whereas those receiving CSF alone without ESA were 64 % more likely to have VTE (1.64, 1.45-1.85). Risk of MDS was significantly increased by fivefold in patients receiving ESA following chemotherapy. CONCLUSIONS: Receipts of CSFs and ESAs were significantly associated with an increased risk of VTE in women with breast cancer. Use of ESAs was significantly associated with substantially increased risks of MDS. These findings support those of previous studies.

Temporal and Geographic Variations in the Receipt of Colony-Stimulating Factors and Erythropoiesis-Stimulating Agents in a Large Retrospective Cohort of Older Women With Breast Cancer From 2000 to 2009.

The purpose of this study was to use the most recent national data for a large cohort of patients diagnosed with breast cancer to evaluate temporal trend of receiving hematopoietic growth factors from 2000 to 2009 and to examine significant factors associated with increasing trends and geographic variations. We identified 26,130 women aged 65-89 years who were diagnosed with breast cancer and received chemotherapy in 2000-2009 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Colony-stimulating factors (CSFs) were identified if there was a claim from the following procedure codes: filgrastim, pegfilgrastim, or sargramostim. Erythropoiesis-stimulating agents (ESAs) were identified if there was a claim from the following procedure codes: epoetin or darbepoetin. Overall, 51.7% of patients with breast cancer received CSFs, which increased from 21.7% in 2000 to 63.2% in 2009. The percentage of patients receiving pegfilgrastim increased from 2.7% in 2000 to 19.5% in 2003 and then continuously to 49.7% in 2009. The overall percentage of patients receiving ESAs was 39.3%, which increased from 26.4% in 2000 to 60.8% in 2006, and then decreased significantly from 40.7% in 2007 to 12.9% in 2009. The receipt of both CSFs and ESAs differed significantly across different geographic areas. The receipt of CSFs continued to increase from 2000 to 2009, and pegfilgrastim started to replace filgrastim since 2003. The receipt of ESAs increased until 2006 and then declined substantially due to the black box warning. There were substantial geographic variations in the use of these hematopoietic growth factors.

Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids.

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.