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The Genes journal retracts the article "Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test" [...].
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To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. SIGNIFICANCE: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL.
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Antineoplastic Combined Chemotherapy Protocols , Brentuximab Vedotin , Drug Resistance, Neoplasm , Hodgkin Disease , Ipilimumab , Nivolumab , Humans , Brentuximab Vedotin/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/immunology , Hodgkin Disease/blood , Nivolumab/therapeutic use , Nivolumab/administration & dosage , Ipilimumab/therapeutic use , Ipilimumab/administration & dosage , Ipilimumab/pharmacology , Female , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Middle Aged , Aged , Young AdultABSTRACT
The structural characterization of epoxy resins is essential to improve the understanding on their structure-property relationship for promising high-performance applications. Among all analytical techniques, scanning transmission electron microscopy-electron energy-loss spectroscopy (STEM-EELS) is a powerful tool for probing the chemical and structural information of various materials at a high spatial resolution. However, for sensitive materials, such as epoxy resins, the structural damage induced by electron-beam irradiation limits the spatial resolution in the STEM-EELS analysis. In this study, we demonstrated the extraction of the intrinsic features and structural characteristics of epoxy resins by STEM-EELS under electron doses below 1 e-/Å2 at room temperature. The reliability of the STEM-EELS analysis was confirmed by X-ray absorption spectroscopy and spectrum simulation as low- or non-damaged reference data. The investigation of the dependence of the epoxy resin on the electron dose and exposure time revealed the structural degradation associated with electron-beam irradiation, exploring the prospect of EELS for examining epoxy resin at low doses. Furthermore, the degradation mechanisms in the epoxy resin owing to electron-beam irradiation were revealed. These findings can promote the structural characterization of epoxy-resin-based composites and other soft materials.
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The mechanisms underlying the influence of the surface chemistry of inorganic materials on polymer structures and fracture behaviours near adhesive interfaces are not fully understood. This study demonstrates the first clear and direct evidence that molecular surface segregation and cross-linking of epoxy resin are driven by intermolecular forces at the inorganic surfaces alone, which can be linked directly to adhesive failure mechanisms. We prepare adhesive interfaces between epoxy resin and silicon substrates with varying surface chemistries (OH and H terminations) with a smoothness below 1 nm, which have different adhesive strengths by ~13 %. The epoxy resins within sub-nanometre distance from the surfaces with different chemistries exhibit distinct amine-to-epoxy ratios, cross-linked network structures, and adhesion energies. The OH- and H-terminated interfaces exhibit cohesive failure and interfacial delamination, respectively. The substrate surface chemistry impacts the cross-linked structures of the epoxy resins within several nanometres of the interfaces and the adsorption structures of molecules at the interfaces, which result in different fracture behaviours and adhesive strengths.
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OBJECTIVES: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization. METHODS: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM. RESULTS: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM. CONCLUSION: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM. CLINICAL RELEVANCE: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization.
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Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.
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PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.
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Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Nivolumab , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Multiomics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Immunotherapy , Lung/pathology , Epithelial Cells/pathology , Ipilimumab/therapeutic use , Tumor MicroenvironmentABSTRACT
BACKGROUND: Sex disparities have been noted across various aspects of total hip/knee arthroplasty (THA/TKA). Given incentives to standardize care, bundled payment initiatives including the Comprehensive Care for Joint Replacement (CJR) program may reduce disparities. This study aimed to assess the CJR program's impact on sex disparities in THA/TKA care and outcomes. METHODS: This retrospective cohort study included 259,673 THAs (61.7% women) and 506,311 TKAs (64.0% women) from a large national database (2013 to 2017). Sex disparities were assessed for care and outcomes related to the period (1) before surgery, (2) during hospitalization for THA/TKA, and (3) after discharge. Disparities were reported as women:men ratios. Difference-in-differences analyses estimated the impact of the CJR program on pre-existing sex disparities. RESULTS: For both THA and TKA, women were less likely than men to present with a Charlson-Deyo comorbidity index >0 (women:men ratio 0.88 to 0.92), but were more likely to require blood transfusions (women:men ratio 1.48 to 1.79) and be discharged to institutional postacute care (women:men ratio 1.50 to 1.66). Difference-in-differences models demonstrated that the CJR bundled payment program reduced sex disparities in institutional postacute care discharges (THA: -2.28%; 95% confidence interval [CI] -4.20 to -0.35%, P = .02; TKA: -2.07%; 95% CI -3.93 to -0.20%; P = .03) and THA 90-day readmissions (-1.00%, 95% CI -1.88 to -0.13%, P = .02), indicating a differential impact of CJR in women versus men for some outcomes. CONCLUSIONS: While sex disparities in THA/TKA persist, the CJR program demonstrates potential to impact such differences. Future research should focus on how potential mechanisms could be leveraged to reduce disparities.
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BACKGROUND: Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied. METHODS: Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children's Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures. RESULTS: A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention ( P =0.033). CONCLUSIONS: Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone.
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Animal Assisted Therapy , Hematology , Needlestick Injuries , Neoplasms , Animals , Child , Dogs , Humans , Allied Health Personnel , Anxiety/etiology , Pain/etiology , Child, Preschool , AdolescentABSTRACT
BACKGROUND: Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care. METHODS: In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20-25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items. RESULTS: Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., "maturation". Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction. CONCLUSION: This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset.
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COVID-19 , Telemedicine , Humans , United States , COVID-19/epidemiology , Telemedicine/methods , Surveys and Questionnaires , Pandemics , Primary Health CareABSTRACT
The interaction of two subsequent ultra-short sub-milli-Joule laser pulses with a thin water flow results in an emission of a strong single-cycle THz pulse associated with enhanced soft X-ray emission. In this paper, a chain of processes produced in this interaction is analyzed and compared with other THz generation studies. It is demonstrated that the enhanced THz and X-ray emissions are produced by an energetic electron beam accelerated in the interaction of a main laser pulse with liquid water ejected from the surface by the pre-pulse. This scheme thus provides an efficient laser energy conversion in a THz pulse, avoiding laser self-focusing and filamentation in air.
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BACKGROUND: Few studies have assessed the relationship between the quantity of preoperative corticosteroid injections (CSIs) or hyaluronic acid injections (HAIs) and postoperative infection risk after total knee or hip arthroplasty (TKA, THA). We aimed to (1) determine whether the number of injections administered before TKA/THA procedures is associated with postoperative infections and (2) establish whether infection risk varies by injection type. METHODS: This retrospective cohort study included 230,487 THAs and 371,511 TKAs from the 2017 to 2018 Medicare Limited Data Set. The quantity of CSI or HAI, defined as receiving either CSI or HAI ≤2 years before TKA/THA, was identified and categorized as 0, 1, 2, or >2. The primary outcome was 90-day postoperative infection. Multivariable regression models measured the association between the number of injections and 90-day postoperative infection. Odds ratios and 95% confidence intervals were reported. RESULTS: The percentage of THA patients receiving 1, 2, and >2 preoperative CSIs was 6.1%, 1.6%, and 0.8%, respectively. Receiving >2 CSIs within 2 years before THA was associated with higher odds of 90-day postoperative infection (odds ratios = 1.74, 95% CI = 1.11 to 2.74, P = 0.02). The percentage of TKA patients receiving 1, 2, and >2 CSIs was 3.0%, 1.2%, and 1.1%, respectively. For HAIs in TKA patients, percentage receiving injections was 98.3%, 0.6%, 0.2%, and 0.9%, respectively. Quantity of CSIs or HAIs administered was not associated with postoperative infection among TKA patients. CONCLUSION: Patients receiving >2 injections before THA had higher odds of 90-day postoperative infection. This finding was not observed in TKA patients. These results suggest that the use of >2 injections within 2 years of THA should be avoided.
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Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , United States/epidemiology , Humans , Aged , Arthroplasty, Replacement, Hip/adverse effects , Hyaluronic Acid/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Retrospective Studies , Medicare , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Adrenal Cortex Hormones/adverse effectsABSTRACT
Knowledge of digestion mechanism of starch nanoparticles are crucial for their utilization and potential applications. In this study, molecular structural evolution and digestion kinetics of starch nanoparticles from green banana (GBSNPs) during digestion (0-180 min) was investigated. Distinctive topographic changes of the GBSNPs during digestion with decreased particle size and increased surface roughness were detected. The GBSNPs showed markedly decreased average molecular weight and polydispersity in the initial digestion phase (0-20 min), and these two structural characteristics remained nearly unchanged thereafter. The GBSNPs exhibited a B-type polymorph throughout digestion, while their crystallinity decreased with increasing digestion duration. The infrared spectra revealed that the initial digestion phase led to the increased absorbance ratios 1047/1022 and 1047/1035 cm-1, reflecting the markedly increased short-range molecular order that was substantiated by the blue-shifting of COH-bending band. Logarithm of slope analysis of digestogram revealed that the GBSNPs were digested by a two-phase process that reflected the surface barrier effect exerted by the increased short-range order. The short-range molecular order strengthening induced from the initial digestion phase was responsible for the increased enzymatic resistance. The results can help to elucidate the gastrointestinal fate of starch nanoparticles for their potential applications as health-promoting ingredients.
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Musa , Nanoparticles , Kinetics , Starch , DigestionABSTRACT
PURPOSE: To evaluate the effectiveness and safety of intra-arterial imipenem/cilastatin sodium (IPM/CS) infusion for painful interphalangeal joint osteoarthritis (OA). MATERIALS AND METHODS: Fifty-eight patients with interphalangeal joint OA who underwent intra-arterial IPM/CS infusion were retrospectively evaluated. Intra-arterial infusions were performed via percutaneous wrist arterial access. The Numerical Rating Scale (NRS), Functional Index for Hand Osteoarthritis (FIHOA), and Patient Global Impression of Change (PGIC) scale scores were assessed at intervals of 1, 3, 6, 12, and 18 months. Clinical success was evaluated based on PGIC. RESULTS: All patients were followed up for at least 6 months after treatment. Of them, 30 and 6 patients were followed up for 12 and 18 months, respectively. No severe or life-threatening adverse events were encountered. The mean NRS score was 6.0 ± 1.4 at baseline, which significantly decreased to 2.8 ± 1.4, 2.2 ± 1.9, and 2.4 ± 1.9 at 1, 3, and 6 months after treatment, respectively (all P < .001). The mean NRS scores were 2.8 ± 1.7 and 2.9 ± 1.9 at 12 and 18 months, respectively, in the remaining patients. The mean FIHOA score significantly decreased from 9.8 ± 5.0 at the baseline to 4.1 ± 3.5 at 3 months (P < .001). The mean FIHOA score was 4.5 ± 3.3 at 12 months in the remaining 30 patients. The clinical success rates based on PGIC at 1, 3, 6, 12, and 18 months were 62.1%, 77.6%, 70.7%, 63.4%, and 50.0%, respectively. CONCLUSIONS: Intra-arterial IPM/CS infusion is a potential treatment option for interphalangeal joint OA refractory to medical management.
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Bacterial Infections , Osteoarthritis , Humans , Cilastatin, Imipenem Drug Combination/therapeutic use , Imipenem/adverse effects , Cilastatin/adverse effects , Infusions, Intra-Arterial , Retrospective Studies , Osteoarthritis/diagnosis , Osteoarthritis/drug therapy , Osteoarthritis/chemically induced , Arthralgia/diagnosis , Arthralgia/drug therapy , Arthralgia/etiologyABSTRACT
Bifunctional catalysts can facilitate two different electrochemical reactions with conflicting characteristics. Here, a highly reversible bifunctional electrocatalyst for rechargeable zinc-air batteries (ZABs) is reported featuring a "core-shell structure" in which N-doped graphene sheets wrap around vanadium molybdenum oxynitride nanoparticles. Single Mo atoms are released from the particle core during synthesis and anchored to electronegative N-dopant species in the graphitic shell. The resultant Mo single-atom catalysts excel as active oxygen evolution reaction (OER) sites in pyrrolic-N and as active oxygen reduction reaction (ORR) sites in pyridinic-N environments. ZABs with such bifunctional and multicomponent single-atom catalysts deliver high power density (≈376.4 mW cm-2 ) and long cycle life of over 630 h, outperforming noble-metal-based benchmarks. Flexible ZABs that can tolerate a wide range of temperatures (-20 to 80 °C) under severe mechanical deformation are also demonstrated.
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We report two cases of traumatic iliopsoas hemorrhage, without hemoperitoneum, initially detected by ultrasound. Flexion hip contracture in the first case and incomplete femoral nerve palsy in the second case alerted the sonographer to the possibility of traumatic iliopsoas hemorrhage. The first case involved a 54-year-old man who complained of progressive right flank pain and difficulty in walking after falling to the ground. The second case involved a 34-year-old man who complained of severe lower back pain and numbness and weakness of the left leg after a motorcycle accident. In both cases, iliopsoas hemorrhage was confirmed on subsequent multidetector computed tomography.
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Imaging and computational processing fusion technologies have expanded the wavelength range that can be visualized. However, it is still challenging to realize a system that can image a wide range of wavelengths, including non-visible regions, in a single system. Here, we propose a broadband imaging system based on femtosecond-laser-driven sequential light source arrays. The light source arrays allow us to form ultra-broadband illumination light depending on the excitation target and irradiated pulse energy. We demonstrated X-ray and visible imaging under atmospheric pressure by using a water film as an excitation target. Furthermore, by applying a compressive sensing algorithm, the imaging time was reduced while maintaining the number of pixels in the reconstructed image.
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THz emission in air under the irradiation of a pair of tightly-focused femtosecond laser pulses (800nm, 35fs) with nanosecond time delay and micro-meter spatial offsets is studied with polarization-sensitive THz time-domain spectroscopy and time-resolved imaging. The pre-pulse irradiation induces air-breakdown at its focus, which results in the expansion of shockwave front traveling outward. When the main pulse irradiates such shockwave front far from the pre-pulse focus with nanosecond delay, THz emission intensity was enhanced up to â¼13-times and its linear polarization was aligned along the line between the two focus positions of the pre- and the main pulses which is parallel to the expansion direction of the shockwave front. Asymmetric density profiles of the shockwave fronts prepared by the pre-pulse irradiation define the polarization of THz emission. Mechanisms are discussed from the viewpoint of electron diffusion in such asymmetric density profiles.