Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88mut /CD79Bmut diffuse large B-cell lymphoma.

BACKGROUND: MCD (MYD88L265P /CD79Bmut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. AIMS: This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut . MATERIALS AND METHODS: Twenty-three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R2 ). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups. RESULTS: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R2 . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. DISCUSSION: The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88mut and/or CD79Bmut . In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. CONCLUSION: This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data.

Characteristics, treatment patterns and burden of illness in US patients with asthma newly initiating multiple-inhaler triple therapy.

INTRODUCTION: For patients with asthma who remain symptomatic on medium-dose inhaled corticosteroid/long-acting ß2-agonist, add-on long-acting muscarinic antagonist is a treatment option, which can be administered as multiple-inhaler triple therapy (MITT). A high proportion of patients (61.5%-88.2%) discontinue MITT use within 1 year postinitiation; however, which patients discontinue and their treatment patterns at initiation are unknown. This study aimed to understand the demographic, clinical and treatment-related characteristics of patients with asthma who newly initiated MITT, by discontinuation status. METHODS: This retrospective cohort study used administrative data from IBM Truven MarketScan Commercial Claims and Encounters Database with Medicare supplement between 1 January 2016 and 31 December 2019. Adult patients with asthma who initiated MITT between 1 January 2017 and 31 March 2019 were included and were classified based on their discontinuation status. 'Continuous users' had continuous use of MITT and 'discontinuers' discontinued treatment within the 6-month period postinitiation. Demographics and clinical characteristics, asthma treatment use prior to MITT initiation (12-month baseline period), mode of MITT initiation and complexity of regimen were described. RESULTS: Of 4132 patients (mean age: 49.0 years, 67.9% female), 78.0% (n=3224) were discontinuers; 22.0% (n=908) were continuous users. Demographic and other clinical and treatment-related characteristics during baseline were broadly similar between cohorts. A significantly higher proportion of continuous users versus discontinuers had ≥6 dispensed claims for short-acting ß2-agonist canisters (16.0% vs 12.5%; p=0.006) during baseline and initiated a once-daily MITT regimen (35.2% vs 26.2%; p<0.001). Fewer continuous MITT users used a mix of once-daily and twice-daily regimens than those who discontinued MITT (64.3% vs 72.3%; p<0.001). CONCLUSIONS: Most patients with asthma discontinued MITT within 6 months. Results indicate that patients with a history of uncontrolled, symptomatic asthma and those using less complex triple therapy regimens at initiation are less likely to discontinue MITT than patients with controlled asthma and those using a complex MITT regimen.

EBV-associated lymphoproliferative disease post-CAR-T cell therapy.

Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.

The chronic rhinosinusitis with nasal polyp patient journey in the United States and Europe.

In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate-severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.

Bright and Stable Red Perovskite LEDs under High Current Densities.

Perovskite LEDs (PeLEDs) have emerged as a next-generation light-emitting technology. Recent breakthroughs were made in achieving highly stable near-infrared and green PeLEDs. However, the operational lifetimes (T50) of visible PeLEDs under high current densities (>10 mA cm-2) remain unsatisfactory (normally <100 h), limiting the possibilities in solid-state lighting and AR/VR applications. This problem becomes more pronounced for mixed-halide (e.g., red and blue) perovskite emitters in which critical challenges such as halide segregation and spectral instability are present. Here, we demonstrate bright and stable red PeLEDs based on mixed-halide perovskites, showing measured T50 lifetimes of up to ∼357 h at currents of ≥25 mA cm-2, a record for the operational stability of visible PeLEDs under high current densities. The devices produce intense and stable emission with a maximum luminance of 28,870 cd m-2 (radiance: 1584 W sr-1 m-2), which is record-high for red PeLEDs. Key to this demonstration is the introduction of sulfonamide, a dipolar molecular stabilizer that effectively interacts with the ionic species in the perovskite emitters. It suppresses halide segregation and migration into the charge-transport layers, resulting in enhanced stability and brightness of the mixed-halide PeLEDs. These results represent a substantial step toward bright and stable PeLEDs for emerging applications.

The segregation of physician networks providing care to black and white patients with heart disease: Concepts, measures, and empirical evaluation.

Black-White disparities in cardiac care may be related to physician referral network segregation. We developed and tested new geographic physician network segregation measures. We used Medicare claims to identify Black and White Medicare heart disease patients and map physician networks for 169 hospital referral regions (HRRs) with over 1000 Black patients. We constructed two network segregation indexes ranging from 0 (integration) to 100 (total segregation): Dissimilarity (the unevenness of Black and White patient distribution across physicians [Dn]) and Absolute Clustering (the propensity of Black patients' physicians to have closer ties with each other than with other physicians [ACLn]). We employed conditional logit models to estimate the probability of using the best (lowest mortality) geographically available hospital for Black and White patients undergoing coronary artery bypass grafting (CABG) surgery in 126 markets with sufficient sample size at increasing levels of network segregation and for low vs. high HRR Black patient population. Physician network segregation was lower than residential segregation (Dissimilarity 21.9 vs. 48.7, and Absolute Clustering 4.8 vs. 32.4) and positively correlated with residential segregation (p < .001). Network segregation effects differed by race and HRR Black patient population. For White patients, higher network segregation was associated with a higher probability of using the best available hospitals in HRRs with few black patients but unchanged (ACLn) or lower (Dn) probability of best hospital use in HRRs with many Black patients. For Black patients, higher network segregation was not associated with a substantial change in the probability of best hospital use regardless of the HRR Black patient population size. Measuring physician network segregation is feasible and associated with nuanced effects on Black-White differences in high-quality hospital use for heart disease. Further work is needed to understand underlying mechanisms and potential uses in health equity policy.

Assessing runners' exposure to natural and built environments in the Netherlands: A descriptive assessment based on GPS tracking.

Running is a convenient physical activity that has gained popularity. However, little is known about runners' running environments and how they differ from their residential environments. To fill this gap, this study examines runners' exposure to natural and built environments along their running routes and assesses the difference between running and residential environments. We collected running track data from Endmondo, a fitness data platform, and used it to determine runners' residency. Moreover, we used open geographical data to calculate a range of environmental variables within their residential areas and along their running trajectories. We applied t-tests to assess differences across objectively measured environmental variables between urban and rural runners, considering geographic, temporal and track-specific strata. We found that the running environments of urban and rural runners were diverse and had distinct characteristics. The results suggest policies to promote running acknowledging these differences between running environments in urban and rural areas.

Clinicopathological Characteristics of Breast Cancer Patients with HER-2 Low Expression Receiving Neoadjuvant Therapy.

INTRODUCTION: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. METHODS: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. RESULTS: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. CONCLUSIONS: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression.

Within-Physician Differences in Patient Sharing Between Primary Care Physicians and Cardiologists Who Treat White and Black Patients With Heart Disease.

BACKGROUND: Black-White disparities in heart disease treatment may be attributable to differences in physician referral networks. We mapped physician networks for Medicare patients and examined within-physician Black-White differences in patient sharing between primary care physicians and cardiologists. METHODS AND RESULTS: Using Medicare fee-for-service files for 2016 to 2017, we identified a cohort of Black and White patients with heart disease and the primary care physicians and cardiologists treating them. To ensure the robustness of within-physician comparisons, we restricted the sample to regional health care markets (ie, hospital referral regions) with at least 10 physicians sharing ≥3 Black and White patients. We used claims to construct 2 race-specific physician network measures: degree (number of cardiologists with whom a primary care physician shares patients) and transitivity (network tightness). Measures were adjusted for Black-White differences in physician panel size and calculated for all settings (hospital and office) and for office settings only. Of 306 US hospital referral regions, 226 and 145 met study criteria for all settings and office setting analyses, respectively. Black patients had more cardiology encounters overall (6.9 versus 6.6; P<0.001) and with unique cardiologists (3.0 versus 2.6; P<0.001), but fewer office encounters (31.7% versus 41.1%; P<0.001). Primary care physicians shared Black patients with more cardiologists than White patients (mean differential degree 23.4 for all settings and 3.6 for office analyses; P<0.001 for both). Black patient-sharing networks were less tightly connected in all but office settings (mean differential transitivity -0.2 for all settings [P<0.001] and near 0 for office analyses [P=0.74]). CONCLUSIONS: Within-physician Black-White differences in patient sharing exist and may contribute to disparities in cardiac care.

Naples score: a novel prognostic biomarker for breast cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND AND PURPOSE: The Naples Score (NPS) is a novel prognostic indicator that has been used in various cancers, but its potential in breast malignant tumor patients receiving neoadjuvant chemotherapy (NAC) has not been discovered. This study aimed to investigate the relationship between NPS and overall survival (OS) and disease-free survival (DFS) in breast cancer patients. METHODS: A total of 217 breast cancer patients undergoing NAC were incorporated into this retrospectively research. K-M survival curves and log-rank tests are used to determine OS and DFS. Cox regression model was used to evaluate the relationship between NPS and OS and DFS. Nomogram was developed based on the results of multivariate Cox regression analysis. Prognostic models were internally validated using bootstrapping and the consistency index (C-index). RESULTS: Age group was correlated with NPS (p < 0.05). Low and moderate Naples risk patients had higher 5-year OS and DFS rates than high risk Naples patients (93.8% vs. 75.4% vs. 60.0%; X2 = 9.2, P = 0.01; 82.4% vs 64.5% vs 43.7%; X2 = 7.4, P = 0.024; respectively). The nomogram based on demonstrated good performance in predicting OS and DFS (AUC = 0.728, 0.630; respectively). CONCLUSIONS: In breast cancer patients who have undergone NAC, NPS is a novel prognostic indicator. NPS combined with clinicopathological features showed good predictive ability, and its performance was better than that of traditional pathological TNM staging.

Relationship Between Asthma Control Status and Health-Related Quality of Life in Japan: A Cross-Sectional Mixed-Methods Study.

INTRODUCTION: There is limited information regarding multidimensional relationships between asthma control and health-related quality of life (HRQoL), work productivity, and asthma symptom burden in Japan. Furthermore, systematic qualitative investigations about asthma burden have not been performed. METHODS: This cross-sectional, mixed-methods study included Japanese patients (≥ 20 years) with asthma adherent to inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA). The primary endpoint was impact of asthma on HRQoL, measured using the Asthma Health Questionnaire-33 (AHQ-33). Secondary endpoints were cough burden (Japanese-adapted Leicester Cough Questionnaire [J-LCQ]) and impact of asthma on work/activities (asthma-specific Work Productivity and Activity Impairment Questionnaire [WPAI:Asthma]). Quantitative data were assessed for the overall population and for well-controlled (WC) and not well-controlled (NWC) asthma subgroups. Qualitative verbal interviews further assessed the impact of NWC asthma on patients' HRQoL; emergent themes were extracted using thematic analyses. RESULTS: Of 454 patients, 45.2% (n = 205) had NWC asthma. Patients with NWC asthma had significantly worse asthma- and cough-related HRQoL across all AHQ-33 and J-LCQ domains and significantly greater work and activity impairment versus patients with WC asthma, across all assessed WPAI:Asthma domains. AHQ-33 total score was highly correlated with J-LCQ total and domain scores (r = - 0.8132 to r = - 0.7407). Nine themes emerged from qualitative interviews and confirmed that patients with NWC asthma had considerable HRQoL impairment due to asthma symptoms. CONCLUSIONS: Patients with NWC asthma had higher symptom burden and worse HRQoL than patients with WC asthma, despite ICS/LABA adherence. Cough burden correlated with HRQoL, suggesting cough may be one of the key markers to inform treatment strategy for patients with asthma.

Prediction of nonsentinel lymph node metastasis in breast cancer patients based on machine learning.

BACKGROUND: Develop the best machine learning (ML) model to predict nonsentinel lymph node metastases (NSLNM) in breast cancer patients. METHODS: From June 2016 to August 2022, 1005 breast cancer patients were included in this retrospective study. Univariate and multivariate analyses were performed using logistic regression. Six ML models were introduced, and their performance was compared. RESULTS: NSLNM occurred in 338 (33.6%) of 1005 patients. The best ML model was XGBoost, whose average area under the curve (AUC) based on 10-fold cross-verification was 0.722. It performed better than the nomogram, which was based on logistic regression (AUC: 0.764 vs. 0.706). CONCLUSIONS: The ML model XGBoost can well predict NSLNM in breast cancer patients.

Ultrasound Triggered Tumor Metabolism Suppressor Induces Tumor Starvation for Enhanced Sonodynamic Immunotherapy of Breast Cancer.

Introduction: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression. Methods: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation. Results: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth. Conclusion: This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.

Suboptimally controlled asthma in patients treated with inhaled ICS/LABA: prevalence, risk factors, and outcomes.

This observational claims-linked survey study assessed the prevalence of and risk factors for suboptimal asthma control and healthcare utilization in adults with asthma receiving fixed-dose combination (FDC) inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA). Commercially insured adults from the Optum Research Database were invited to complete the Asthma Control Test (ACT) and Asthma Control Questionnaire-6 (ACQ-6). Among participants (N = 428), 36.4% (ACT-assessed) and 55.6% (ACQ-6-assessed) had inadequately controlled asthma. Asthma-related quality of life was worse and asthma-related healthcare resource utilization was higher in poorly controlled asthma. Factors associated with ACT-defined suboptimal asthma control in multivariate analysis included: frequent short-acting ß2-agonist (SABA) use, asthma-related outpatient visits, lower treatment adherence, and lower education levels. During follow-up, factors associated with asthma exacerbations and/or high SABA use included: inadequately controlled asthma (ACT-assessed), body mass index ≥30 kg/m2, and high-dose ICS/LABA. Approximately 35-55% of adults with asthma were inadequately controlled despite FDC ICS/LABA; poor control was associated with worse disease outcomes.

Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization.

Effective radiosensitizers are urgently needed due to the serious negative effects that high radiation doses might have. We created an integrated nano-system (Cuhemin-Au) made of Cuhemin nanosheets and Au nanoparticles (Au NPs) for sensitizing radiotherapy to solve this issue. This system can manifest enzyme-like activities to universally suppress the resistance pathways in breast cancer cells for amplifying radiation damage. Cuhemin-Au NPs increase the energy deposition of radiation owing to the high X-ray attenuation coefficient of Au. In addition, Cuhemin-Au has peroxidase (POD)-like and glucose oxidase (Gox)-like activity, and can also consume intracellular GSH, which can reduce intracellular GSH levels to reduce tumor cells' capacity to repair DNA and deplete intracellular glucose via their characteristic Gox-like catalytic activities, which can cause an increase in the oxidative stress and further produce H2O2. Cuhemin-Au then produced ˙OH, which upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity, after reacting with enough hydrogen peroxide in tumor cells. Cuhemin-Au combined with low dose RT (4 Gy) could significantly limit tumor development with fewer adverse effects, according to in vivo and in vitro experiments. This platform generated a fresh concept for the construction of a radiotherapy sensitization system and accomplished synergistic radiotherapy sensitization.

Serum Metabolomic Profiles for Distinguishing Lung Cancer From Pulmonary Tuberculosis: Identification of Rapid and Noninvasive Biomarker.

BACKGROUND: Pulmonary tuberculosis (PTB) and lung cancer (LC) have similar clinical symptoms and atypical imaging findings, which are easily misdiagnosed. There is an urgent need for a noninvasive and accurate biomarker to distinguish LC from PTB. METHODS: A total of 694 subjects were enrolled and divided into discovery set (n = 122), identification set (n = 214), and validation set (n = 358). Metabolites were identified by multivariate and univariate analyses. Receiver operating characteristic curve were used to evaluate the diagnostic efficacy of biomarkers. RESULTS: Seven metabolites were identified and validated. Phenylalanylphenylalanine for distinguishing LC from PTB yielded an area under the curve of 0.89, sensitivity of 71%, and specificity of 92%. It also showed good diagnostic abilities in discovery set and identification set. Compared with that in healthy volunteers (median [interquartile range], 1.57 [1.01, 2.34] µg/mL), it was elevated in LC (4.76 [2.74, 7.08] µg/mL; ratio of median, [ROM] = 3.03, P < .01) and reduced in PTB (1.06 [0.51, 2.09] µg/mL; ROM = 0.68, P < .05). CONCLUSIONS: The metabolomic profile of LC and PTB was described and a key biomarker identified. We produced a rapid and noninvasive method to supplement existing clinical diagnostic examinations for distinguishing LC from PTB.

Targeting GPR133 via miR-106a-5p inhibits the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of glioma cells.

Background: Glioma is the most common malignant brain tumor. GPR133 is a key factor in the progression of glioma. However, the role of GPR133 in glioma invasion and EMT and the microRNAs (miRNAs) associated with this pathway are still poorly understood.Objective: This study aims to elucidate the biological function of miR-106a-5p and GPR133 in glioma as well as the molecular mechanism of their interaction.Methods: The mRNA expression of miR-106a-5p and GPR133 in glioma specimens and cells was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of GPR133 and the levels of invasion- and EMT-related proteins were measured by western blotting. miR-106a-5p and GPR133 function in glioma cells was determined through cell counting kit-8 (CCK-8), transwell, wound healing, colony formation assays in vitro and xenograft assays in vivo. To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted.Results: A marked reduction in miR-106a-5p expression was observed in glioma cells and specimens. Patients with high expression of miR-106a-5p had a good prognosis, while patients with high expression of GPR133 had a shorter OS. Additionally, overexpression of miR-106a-5p or downregulation of GPR133 inhibited the progression of glioma cells. Furthermore, miR-106a-5p negatively regulated GPR133 expression by binding to its 3'-UTR, and restrained the invasion, migration, proliferation and EMT of glioma cells by targeting GPR133.Conclusions: miR-106a-5p is a tumor suppressor that negatively regulates GPR133. The miR-106a-5p/GPR133 axis could potentially serve as a therapeutic target for glioma.