Electronic and Structural Disorder of the Epitaxial La0.67Sr0.33MnO3 Surface.

Understanding and tuning epitaxial complex oxide films are crucial in controlling the behavior of devices and catalytic processes. Substrate-induced strain, doping, and layer growth are known to influence the electronic and magnetic properties of the bulk of the film. In this study, we demonstrate a clear distinction between the bulk and surface of thin films of La0.67Sr0.33MnO3 in terms of chemical composition, electronic disorder, and surface morphology. We use a combined experimental approach of X-ray-based characterization methods and scanning probe microscopy. Using X-ray diffraction and resonant X-ray reflectivity, we uncover surface nonstoichiometry in the strontium and lanthanum alongside an accumulation of oxygen vacancies. With scanning tunneling microscopy, we observed an electronic phase separation (EPS) on the surface related to this nonstoichiometry. The EPS is likely driving the temperature-dependent resistivity transition and is a cause of proposed mixed-phase ferromagnetic and paramagnetic states near room temperature in these thin films.

A genetic risk score to predict treatment nonresponse in psychotic depression.

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.

Bio-based adsorption foam composed of MOF and polyethyleneimine-modified cellulose for selective anionic dye removal.

With the increase of sustainable development goal, the bio-based adsorption materials with high and selective dye removal are important for water treatment in the dyeing industry. In this paper, a bio-based adsorption foam composed of metal-organic frameworks (MOF) and polyethyleneimine (PEI)-modified cellulose was prepared by a three-step process, i.e., PEI modification of cellulose fibers (PC), MOF decoration of PEI-modified cellulose (MIL-53@PC), and in-situ foaming with polyurethane. PEI modification provides cellulose fiber with more active sites for both dye adsorption and MOF bonding. We found that MIL-53 crystals were tightly bonded on the surface of PC through hydrogen bonding. Because of the abundant adsorption sites (e.g., amines, iron oxide group), the MIL-53@PC demonstrated high adsorption capacity and selectivity for anionic dye (e.g., 936.5 mg/g for methyl orange) through electrostatic interaction and hydrogen bonding. Finally, MIL-53@PC particles were blended with a waterborne polyurethane prepolymer to prepare a three-dimensional hydrophilic foam (MIL-53@PC/PUF), which not only maintained high adsorption capacity and selectivity of MIL-53@PC and also improved its recyclability and reusability. The MIL-53@PC/PUF offers a promising solution for dye wastewater treatment.

The Relationship of Early Sleep Improvement With Response to Pharmacotherapy in Unipolar Psychotic Depression.

BACKGROUND: Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific. METHODS: This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks). RESULTS: EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome. CONCLUSIONS: Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.

Magnetic nanocellulose-based adsorbent for highly selective removal of malachite green from mixed dye solution.

Herein, a novel magnetic adsorbent (BC/AA/MN@Fe3O4) was successfully prepared from waste bamboo fiber tissue and montmorillonite, and subsequently applied for the highly selective removal of malachite green (MG, removal efficiency = 97.3 %) from the mixed dye solution of MG with methyl orange (MO, removal efficiency = 4.5 %). The magnetic adsorbent has a high porosity with abundant mesopores. In the single dye MG solution, the adsorbent could effectively remove MG over a wide pH range from 4 to 10, and the maximum adsorption capacity (qmax) was 2282.3 mg/g. Moreover, the magnetic adsorbent could remove MG from various solutions including mixed dye solution, high salinity solution, and real river water dye solution. The thermodynamic results proved that the adsorption process of MG was spontaneous and endothermic. The adsorption of MG was due to the comprehensive effects of electrostatic attraction, hydrogen bonding interactions and ions exchange, between the adsorbent and MG. Furthermore, the BC/AA/MN@Fe3O4 exhibited an excellent reusability with adsorption efficiency above 53.4 % after five consecutive cycles. Therefore, the prepared magnetic nanocellulose-based adsorbent was expected to be a promising material for highly selective adsorption and separation of MG from mixed dye solution.

Simple ultrasonic integration of shapeable, rebuildable, and multifunctional MIL-53(Fe)@cellulose composite for remediation of aqueous contaminants.

Metal-organic frames (MOFs) have been recognized as one of the best candidates in the remediation of aqueous contaminants, while the fragile powder shape restricts the practical implementation. In this work, a shapeable, rebuildable, and multifunctional MOF composite (MIL-53@CF) was prepared from MIL-53 (Fe) and cellulose fiber (CF) using a simple ultrasonic method for adsorption and photocatalytic degradation of organic pollutants in wastewater. The results showed MIL-53(Fe) crystals were uniformly growth on CF surfaces and bonded with surface nanofibrils of CF through physical crosslinking and hydrogen bonding. Because of the high bonding strength, the MIL-53@CF composite exhibited an excellent compressive strength (3.53 MPa). More importantly, the MIL-53@CF composite was rebuildable through mechanical destruction followed by re-ultrasonication, suggesting the excellent reusability of MIL-53@CF for water remediation. The MIL-53@CF composite also had high adsorption capacities for methyl orange (884.6 mg·g-1), methylene blue (198.3 mg·g-1), and tetracycline (106.4 mg·g-1). MIL-53@CF composite could degrade TC through photocatalysis. The photocatalytic degradation mechanism was attributed to the Fe(II)/Fe(III) transform cycle reaction of MIL-53 crystal located on MIL-53@CF. Furthermore, the mechanical property and remoldability of MIL-53@CF composite increased its practicability. Comprehensively, MIL-53@CF composite provided a possible strategy to practically apply MOF in the remediation of aqueous contaminants.

Preclinical evaluation of EpCAM-binding designed ankyrin repeat proteins (DARPins) as targeting moieties for bimodal near-infrared fluorescence and photoacoustic imaging of cancer.

PURPOSE: Fluorescence-guided surgery (FGS) can play a key role in improving radical resection rates by assisting surgeons to gain adequate visualization of malignant tissue intraoperatively. Designed ankyrin repeat proteins (DARPins) possess optimal pharmacokinetic and other properties for in vivo imaging. This study aims to evaluate the preclinical potential of epithelial cell adhesion molecule (EpCAM)-binding DARPins as targeting moieties for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of cancer. METHODS: EpCAM-binding DARPins Ac2, Ec4.1, and non-binding control DARPin Off7 were conjugated to IRDye 800CW and their binding efficacy was evaluated on EpCAM-positive HT-29 and EpCAM-negative COLO-320 human colon cancer cell lines. Thereafter, NIRF and PA imaging of all three conjugates were performed in HT-29_luc2 tumor-bearing mice. At 24 h post-injection, tumors and organs were resected and tracer biodistributions were analyzed. RESULTS: Ac2-800CW and Ec4.1-800CW specifically bound to HT-29 cells, but not to COLO-320 cells. Next, 6 nmol and 24 h were established as the optimal in vivo dose and imaging time point for both DARPin tracers. At 24 h post-injection, mean tumor-to-background ratios of 2.60 ± 0.3 and 3.1 ± 0.3 were observed for Ac2-800CW and Ec4.1-800CW, respectively, allowing clear tumor delineation using the clinical Artemis NIRF imager. Biodistribution analyses in non-neoplastic tissue solely showed high fluorescence signal in the liver and kidney, which reflects the clearance of the DARPin tracers. CONCLUSION: Our encouraging results show that EpCAM-binding DARPins are a promising class of targeting moieties for pan-carcinoma targeting, providing clear tumor delineation at 24 h post-injection. The work described provides the preclinical foundation for DARPin-based bimodal NIRF/PA imaging of cancer.

Evaluation of Potential Targets for Fluorescence-Guided Surgery in Pediatric Ewing Sarcoma: A Preclinical Proof-of-Concept Study.

Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients.

[Prevention of delirium in the Intensive Care Unit]. / Preventie van delier op de intensive care.

Delirium is highly prevalent in the Intensive Care Unit (ICU) and is strongly associated with negative patient outcomes. We aimed to present an overview of the effectiveness of non-pharmacological and pharmacological interventions to prevent delirium in ICU patients. Multicomponent non-pharmacological interventions are proven effective in the prevention of delirium. These interventions are aimed at multiple domains, including re-orientation, providing a safe and healing environment, cognitive stimulation, mobilization and family engagement. A special type of multicomponent intervention is the ''A-F bundle'', comprising both non-pharmacological and pharmacological interventions. Multicomponent non-pharmacological interventions and the ''A-F bundle'' are recommended. There is insufficient evidence for the effectiveness of pharmacological prophylaxis using antipsychotics, dexmedetomidine, melatonin or thiamin, except for delirium due to substance withdrawal. Therefore, pharmacological interventions should be aimed at minimizing delirogenousmedication (especially benzodiazepines and opiates), adequate pain management and the prevention of deep and continuous sedation.

[Consider (es)ketamine for treatment-resistant depression]. / Overweeg (es)ketamine bij therapieresistente depressie.

Major depressive disorder has a high prevalence globally. Although pharmacotherapy and psychotherapy are effective for most patients, about one third is treatment resistant. Ketamine, known as an anesthetic, is a new treatment option that can be effective in patients with treatment-resistant depression. (es)ketamine works relatively fast. However, the long-term effects are still relatively unknown. In the Netherlands, S-Ketamine is currently administered in various forms, of which only the nasal spray is registered for treatment-resistant depression. Currently, many studies have been conducted on the use of (es)ketamine. In this article we describe the latest state of affairs regarding its effectiveness and safety.

Nanocellulose-based polyurethane foam adsorbent for pressure-driven dye-contaminated water purification.

Dye-contaminated water has caused a worldwide pollution, which is threatening aquatic organisms and human health. In this work, a pressure-driven foam adsorbent (PFA) was bioinspired from the tapestry turban for purifying the dye-contaminated water. The PFA was prepared using an one-step method from nanocellulose (NC), amino-functionalized ZIF-8 (ZIF-8-NH2), and high resilience polyurethane foam (PUF). It was applied to efficiently remove methyl orange (MO) and crystal violet (CV) dyes from dye-contaminated waste solutions. The maximum adsorption capacity of PFA for MO and CV was 225.9 mg/g (25 °C, pH = 2) and 41.6 mg/g (25 °C, pH = 10), respectively, which were acceptable as compared with the reported works. The dyes could be efficiently removed from various river water samples. After 5 cycles, the removal efficiencies of MO and CV decreased from 92.0% and 85.7% to 84.7% and 76.1%, respectively. Moreover, the PFA relied on pressure-driven force to release the purified water under a low pressure.

Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding (i.e. pharmaceutical or medical device companies). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last guidelines from the Collège National des Gynécologues et Obstétriciens Français on the management of women with AUB were published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescents; idiopathic AUB; endometrial hyperplasia and polyps; type 0-2 fibroids; type 3 or higher fibroids; and adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and evidence profiles were compiled. The GRADE® methodology was applied to the literature review and the formulation of recommendations. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 are strong and 17 weak. No response was found in the literature for 14 questions. We chose to abstain from recommendations rather than providing advice based solely on expert clinical experience. CONCLUSIONS: The 36 recommendations make it possible to specify the diagnostic and therapeutic strategies for various clinical situations practitioners encounter, from the simplest to the most complex.

Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects. Objective: To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). Design, Setting, and Participants: This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications. Intervention: In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage. Main Outcomes and Measures: The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores). Results: Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT. Conclusions and Relevance: In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03548675.

C/EBPß-LIP mediated activation of the malate-aspartate shuttle sensitizes cells to glycolysis inhibition.

OBJECTIVE: Cancer cells use glycolysis for generation of metabolic intermediates and ATP needed for cell growth and proliferation. The transcription factor C/EBPß-LIP stimulates glycolysis and mitochondrial respiration in cancer cells. We initially observed that high expression of C/EBPß-LIP makes cells vulnerable to treatment with the glycolysis inhibitor 2-deoxyglucose. The aim of the study was to uncover the involved mechanisms of C/EBPß-LIP induced sensitivity to glycolysis inhibition. METHODS: We used genetically engineered cell lines to examine the effect of C/EBPß-LIP and -LAP protein isoforms on glycolysis and NADH/NAD+ metabolism in mouse embryonic fibroblasts (MEFs), and triple negative breast cancer (TNBC) cells that endogenously express high levels of C/EBPß-LIP. Analyses included assays of cell proliferation, cell survival and metabolic flux (OCR and ECAR by Seahorse XF96). Small molecule inhibitors were used to identify underlying metabolic pathways that mediate sensitivity to glycolysis inhibition induced by C/EBPß-LIP. RESULTS: The transcription factor C/EBPß-LIP stimulates both glycolysis and the malate-aspartate shuttle (MAS) and increases the sensitivity to glycolysis inhibition (2-deoxyglucose) in fibroblasts and breast cancer cells. Inhibition of glycolysis with ongoing C/EBPß-LIP-induced MAS activity results in NADH depletion and apoptosis that can be rescued by inhibiting either the MAS or other NAD+-regenerating processes. CONCLUSION: This study indicates that a low NADH/NAD+ ratio is an essential mediator of 2-deoxyglucose toxicity in cells with high cytoplasmic NAD+-regeneration capacity and that simultaneous inhibition of glycolysis and lowering of the NADH/NAD+ ratio may be considered to treat cancer.

Urokinase-Type Plasminogen Activator Receptor (uPAR) Cooperates with Mutated KRAS in Regulating Cellular Plasticity and Gemcitabine Response in Pancreatic Adenocarcinomas.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers. Given the currently limited therapeutic options, the definition of molecular subgroups with the development of tailored therapies remains the most promising strategy. Patients with high-level gene amplification of urokinase plasminogen activator receptor (uPAR/PLAUR) have an inferior prognosis. We analyzed the uPAR function in PDAC to understand this understudied PDAC subgroup's biology better. METHODS: A total of 67 PDAC samples with clinical follow-up and TCGA gene expression data from 316 patients were used for prognostic correlations. Gene silencing by CRISPR/Cas9, as well as transfection of uPAR and mutated KRAS, were used in PDAC cell lines (AsPC-1, PANC-1, BxPC3) treated with gemcitabine to study the impact of these two molecules on cellular function and chemoresponse. HNF1A and KRT81 were surrogate markers for the exocrine-like and quasi-mesenchymal subgroup of PDAC, respectively. RESULTS: High levels of uPAR were correlated with significantly shorter survival in PDAC, especially in the subgroup of HNF1A-positive exocrine-like tumors. uPAR knockout by CRISPR/Cas9 resulted in activation of FAK, CDC42, and p38, upregulation of epithelial makers, decreased cell growth and motility, and resistance against gemcitabine that could be reversed by re-expression of uPAR. Silencing of KRAS in AsPC1 using siRNAs reduced uPAR levels significantly, and transfection of mutated KRAS in BxPC-3 cells rendered the cell more mesenchymal and increased sensitivity towards gemcitabine. CONCLUSIONS: Activation of uPAR is a potent negative prognostic factor in PDAC. uPAR and KRAS cooperate in switching the tumor from a dormant epithelial to an active mesenchymal state, which likely explains the poor prognosis of PDAC with high uPAR. At the same time, the active mesenchymal state is more vulnerable to gemcitabine. Strategies targeting either KRAS or uPAR should consider this potential tumor-escape mechanism.

Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method.

INTRODUCTION: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons' ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). METHODS: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. RESULTS: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. CONCLUSION: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.

Colorectal polyps: Targets for fluorescence-guided endoscopy to detect high-grade dysplasia and T1 colorectal cancer.

BACKGROUND: Differentiating high-grade dysplasia (HGD) and T1 colorectal cancer (T1CRC) from low-grade dysplasia (LGD) in colorectal polyps can be challenging. Incorrect recognition of HGD or T1CRC foci can lead to a need for additional treatment after local resection, which might not have been necessary if it was recognized correctly. Tumor-targeted fluorescence-guided endoscopy might help to improve recognition. OBJECTIVE: Selecting the most suitable HGD and T1CRC-specific imaging target from a panel of well-established biomarkers: carcinoembryonic antigen (CEA), c-mesenchymal-epithelial transition factor (c-MET), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FRα), and integrin alpha-v beta-6 (αvß6). METHODS: En bloc resection specimens of colorectal polyps harboring HGD or T1CRC were selected. Immunohistochemistry on paraffin sections was used to determine the biomarker expression in normal epithelium, LGD, HGD, and T1CRC (scores of 0-12). The differential expression in HGD-T1CRC components compared to surrounding LGD and normal components was assessed, just as the sensitivity and specificity of each marker. RESULTS: 60 specimens were included (21 HGD, 39 T1CRC). Positive expression (score >1) of HGD-T1CRC components was found in 73.3%, 78.3%, and 100% of cases for CEA, c-MET, and EpCAM, respectively, and in <40% for FRα and αvß6. Negative expression (score 0-1) of the LGD component occurred more frequently for CEA (66.1%) than c-MET (31.6%) and EpCAM (0%). The differential expression in the HGD-T1CRC component compared to the surrounding LGD component was found for CEA in 66.7%, for c-MET in 43.1%, for EpCAM in 17.2%, for FRα in 22.4%, and for αvß6 in 15.5% of the cases. Moreover, CEA showed the highest combined sensitivity (65.0%) and specificity (75.0%) for the detection of an HGD-T1CRC component in colorectal polyps. CONCLUSION: Of the tested targets, CEA appears the most suitable to specifically detect HGD and T1 cancer foci in colorectal polyps. An in vivo study using tumor-targeted fluorescence-guided endoscopy should confirm these findings.

Intraoperative Imaging Techniques to Improve Surgical Resection Margins of Oropharyngeal Squamous Cell Cancer: A Comprehensive Review of Current Literature.

Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.

Bamboo Nanocellulose/Montmorillonite Nanosheets/Polyethyleneimine Gel Adsorbent for Methylene Blue and Cu(II) Removal from Aqueous Solutions.

In recent years, the scarcity of pure water resources has received a lot of attention from society because of the increasing amount of pollution from industrial waste. It is very important to use low-cost adsorbents with high-adsorption performance to reduce water pollution. In this work, a gel adsorbent with a high-adsorption performance on methylene blue (MB) and Cu(II) was prepared from bamboo nanocellulose (BCNF) (derived from waste bamboo paper) and montmorillonite nanosheet (MMTNS) cross-linked by polyethyleneimine (PEI). The resulting gel adsorbent was characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS), etc. The results indicated that the MB and Cu(II) adsorption capacities of the resulting gel adsorbent increased with the solution pH, contact time, initial concentration, and temperature before equilibrium. The adsorption processes of MB and Cu(II) fitted well with the fractal-like pseudo-second-order model. The maximal adsorption capacities on MB and Cu(II) calculated by the Sips model were 361.9 and 254.6 mg/g, respectively. The removal of MB and Cu(II) from aqueous solutions mainly included electrostatic attraction, ion exchange, hydrogen bonding interaction, etc. These results suggest that the resulting gel adsorbent is an ideal material for the removal of MB and Cu(II) from aqueous solutions.