Moderate Uptake Research Articles

Multimodality Approach for Surveillance of Cardiac Sarcoidosis After Heart Transplantation Based on a Case Series

<h3>Purpose</h3> Cardiac sarcoidosis is an inflammatory, granulomatous disease of a progressive nature, which may clinically present as sudden death, arrhythmias, or heart failure (HF). When advanced, heart transplantation (HT) emerges as a therapeutic option. The post-transplant outcomes of this patients, regarding survival and rejections, seem to be similar to those related to other etiologies. However, the involvement of multiple organs by the disease and its reactivation potential is a concern regarding its recurrence in the transplanted heart, but its diagnosis, screening and immunosuppression strategy in this scenario are still little explored in the literature. <h3>Methods</h3> We retrospectively reviewed the clinical course of 4 patients with cardiac sarcoidosis who underwent HT between 2014 and 2021. <h3>Results</h3> We followed 4 female patients submitted to HT due to sarcoidosis. The first one transplanted in 2014, aged 32 years, and reativated sarcoidosis after 1 year, diagnosed by cardiac magnetic resonance imaging (MRI) compatible with inflammatory cardiomyopathy and died in 2017 of a non-cardiac cause. Second patient transplanted in 2020, aged 55 years, had high troponin levels also after 1 year post HT, with no evidence of rejection - subsequently, underwent cardiac PET/CT with accentuated diffuse uptake, received treatment with increased steroid dose, with an improvement in the marker after. The third, transplanted in 2021 aged 50 years, presented cardiac MRI after 1 month with a non-ischemic late mesoepicardial enhancement and PET/CT with moderate FDG uptake in the corresponding region suggestive of active cardiac sarcoidosis, using corticosteroids in increased dose for a while, showing improvement in the control PET/CT pattern. Finally, fourth patient transplanted in 2015, aged 40, with no evidence of reactivation of the disease so far, but due to sarcoidosis diagnosis previous to HT, she has always received higher doses of steroids. <h3>Conclusion</h3> There are few reports of recurrence of sarcoidosis after heart transplantation, which makes management of these cases challenging. An integrated approach that includes advanced imaging methods, routine serial endomyocardial biopsies, and serum biomarkers may be useful in monitoring this patients after HT, giving early diagnosis and treatment, which may be lifesaving given it´s potential fatal prognosis.

Poly(p-terphenyl alkylene)s grafted with highly acidic sulfonated polypentafluorostyrene side chains for proton exchange membranes

Molecularly well-designed proton exchange membranes (PEMs) with a high local concentration of strongly acidic groups have the potential to fulfill the strict requirements for fuel cell operation under high temperature and low humidity. Here, we have prepared a series of well-defined and tunable PEMs based on poly( p -phenylene alkylene) backbones functionalized with sulfonated polypentafluorostyrene grafts having different ionic content, degree of grafting and molar mass. First, backbone copolymers were prepared by superacid-mediated polyhydroxyalkylations of p -terphenyl, 2,2,2-trifluoroacetophenone and 3-bromo-1,1,1-trifluoroacetone. Next, the bromomethyl groups of these copolymers were utilized as initiator sites for atom transfer radical polymerization (ATRP) of pentafluorostyrene. Finally, the polypentafluorostyrene grafts were quantitatively and selectively sulfonated to introduce highly acidic perfluorophenylsulfonic acid groups. Solvent cast PEMs displayed a microphase separated morphology with domains on the nanoscale, which gave a controlled water uptake that increased only very little between 20 and 80 °C. Under fully hydrated conditions, the PEMs reached a maximum proton conductivity of 154 mS cm −1 , exceeding that of Nafion NR212. Under reduced humidity, the conductivity was just slightly below that of NR212. In conclusion, the combination of ether-free stiff polymer backbones and the strongly acidic side chains gave rise to nanostructured PEMs with restricted water uptake, high proton conductivity, stability and robust mechanical properties, which merit further investigations of their performance in fuel cells. • Membranes with highly acidic perfluorophenylsulfonic acid groups. • Stiff p -terphenyl backbone polymers via polyhydroxyalkylations. • Grafting of pentafluorostyrene from the backbones, followed by complete sulfonation. • Distinctly microphase separated morphology. • High proton conductivity at moderate water uptake with low temperature dependence.

18F-FDG PET/CT Findings in HIV-Positive Patient With Primary Pancreas Lymphoma and CMV Pancreatitis.

A 35-year-old HIV-positive man with abdominal pain was referred to 18F-FDG PET/CT for metabolic characterization of mass in pancreas. PET/CT images showed intense FDG uptake in head of the pancreas, as well as diffuse moderate uptake throughout body and tail of the pancreas. Histopathological results revealed Epstein-Barr virus (EBV) associated large B-cell lymphoma and pancreatitis caused by cytomegalovirus.

Proton exchange membranes containing densely alkyl sulfide sulfonated side chains for vanadium redox flow battery

Due to further increase the performance of aromatic sulfonated proton exchange membrane (PEM) and make it play a better role in vanadium redox flow battery (VRFB), a series of poly(aryl ether sulfone)s containing eight alkyl sulfide sulfonated side chains (8SPAES-xx) are designed and synthesized. Their molecular structure, phase morphology and some selective properties were investigated in detail, respectively. It is confirmed that 8SPAES-xx membranes have clear hydrophilic/hydrophobic phase separation morphology. These membranes with the ion exchange capacity values of 1.08–1.61 mmol/g exhibit excellent ionic conductivity as well as moderate water uptake and good dimensional stability, and their values are in the range of 25–96 mS/cm, 8–28% and 5–17% at 30 °C, respectively. Among them, the proton conductivity of 8SPAES-12 membrane is 82 mS/cm at 30 °C, which exceeds the ionic conductivity of Nafion 117 (79 mS/cm). The membrane also shows high ion selectivity and excellent battery performance. At current density of 60 mA/cm 2 , the highest energy efficiency of VRFB with 8SPAES-12 membrane is 87.3%, which is higher than that of Nafion 117 (83.8%). Furthermore, the efficiency of VRFB with 8SPAES-12 membrane remains good cycle stability. • PEMs containing eight alkyl sulfide sulfonated side chains are prepared for VRFB. • 8SPAES-xx shows clear hydrophilic/hydrophobic phase separation morphology. • 8SPAES-12 has excellent ionic conductivity and high ion selectivity. • 8SPAES-12 membrane exhibits high cell efficiency as well as good stability.

Inclusion of CO2, NH3, SO2, Cl2 and H2S in porous N4O4-donor macrocyclic Schiff base

The removal and detection of highly toxic and environmentally harmful gases such as SO2, H2S and CO2 is a hot topic of the scientific community. Porous organic compounds, in particular, imine-based macrocycles, are promising materials for this purpose. In this paper we have used porous N4O4-donor macrocyclic Schiff base (1,6,20,25-tetraaza-2,5:8,9:17,18:21,24:27,28:36,37-hexabenzo-10,16,29,35-tetraoxa-cyclooctatriakonta-1,6,20,25-tetraen) (1) for sorption of NH3, SO2, Cl2, CO2 and H2S. Five novel inclusion compounds 1xNH3, 1xSO2, 1xCl2, 1xCO2 and 1xH2S were prepared by a single-crystal to single-crystal (SC-SC) transformation. Single-crystal X-ray diffraction (SCXRD) analysis of 1xCO2 and 1xNH3 inclusion compounds have shown that CO2 molecule resides in the plane of the macrocyclic ring connected by weak C–O … π interactions to the host, and no host-guest interactions in 1xNH3 were observed. The relative thermal stabilities of the host-guest systems (Ton – Tb parameter) is in the range from 93 (1xNH3) to 132 °C (1xH2S), indicating the formation of stable inclusion compounds. Although used gases are highly reactive and corrosive, FT-IR and powder diffraction studies indicate that the molecular and crystal structure of the host is constant upon gas sorption. The activated compound displays moderate uptake (0.35 mmol/g) of CO2 at 298 K. The relatively high thermal stability, constant molecular and crystal structure of inclusion compounds with interesting optical properties (determined by solid state UV–Vis) make this material potentially useful for the detection of toxic gases.

Test-retest repeatability and interobserver variation of healthy tissue metabolism using 18F-FDG PET/CT of the thorax among lung cancer patients.

ObjectivesThe aim of this study was to assess the test-retest repeatability and interobserver variation in healthy tissue (HT) metabolism using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) of the thorax in lung cancer patients.MethodsA retrospective analysis was conducted in 22 patients with non-small cell lung cancer who had two PET/CT scans of the thorax performed three days apart with no interval treatment. The maximum, mean and peak standardized uptake values (SUV) in different HTs were measured by a single observer for the test-retest analysis and two observers for interobserver variation. Bland-Altman plots were used to assess the repeatability and interobserver variation. Intrasubject variability was evaluated using within-subject coefficients of variation (wCV).ResultsThe wCV of test-retest SUVmean measurements in mediastinal blood pool, bone marrow, skeletal muscles and lungs were <20%. The left ventricle (LV) showed higher wCV (>60%) in all SUV parameters with wide limits of repeatability. High interobserver agreement was found with wCV of <10% in SUVmean of all HT, but up to 22% was noted in the LV.ConclusionHT metabolism is stable in a test-retest scenario and has high interobserver agreement. SUVmean was the most stable metric in organs with low FDG-uptake and SUVpeak in HTs with moderate uptake. Test-retest measurements in LV were highly variable irrespective of the SUV parameters used for measurements.

Native and Oxidized Low-Density Lipoproteins Increase the Expression of the LDL Receptor and the LOX-1 Receptor, Respectively, in Arterial Endothelial Cells.

Atherosclerotic artery disease is the major cause of death and an immense burden on healthcare systems worldwide. The formation of atherosclerotic plaques is promoted by high levels of low-density lipoproteins (LDL) in the blood, especially in the oxidized form. Circulating LDL is taken up by conventional and non-classical endothelial cell receptors and deposited in the vessel wall. The exact mechanism of LDL interaction with vascular endothelial cells is not fully understood. Moreover, it appears to depend on the type and location of the vessel affected and the receptor involved. Here, we analyze how native LDL (nLDL) and oxidized LDL (oxLDL) modulate the expression of their receptors—classical LDLR and alternative LOX-1—in endothelial cells derived from human umbilical artery (HUAECs), used as an example of a medium-sized vessel, which is typically affected by atherosclerosis. Exposure of HUAECs to nLDL resulted in moderate nLDL uptake and gradual increase in LDLR, but not LOX-1, expression over 24 h. Conversely, exposure of HUAECs to oxLDL, led to significant accumulation of oxLDL and rapid induction of LOX-1, but not LDLR, within 7 h. These activation processes were associated with phosphorylation of protein kinases ERK1/2 and p38, followed by activation of the transcription factor AP-1 and its binding to the promoters of the respective receptor genes. Both nLDL-induced LDLR mRNA expression and oxLDL-induced LOX-1 mRNA expression were abolished by blocking ERK1/2, p-38 or AP-1. In addition, oxLDL, but not nLDL, was capable of inducing LOX-1 through the NF-κB-controlled pathway. These observations indicate that in arterial endothelial cells nLDL and oxLDL signal mainly via LDLR and LOX-1 receptors, respectively, and engage ERK1/2 and p38 kinases, and AP-1, as well as NF-κB transcription factors to exert feed-forward regulation and increase the expression of these receptors, which may perpetuate endothelial dysfunction in atherosclerosis.

Rational regulation of acetylene adsorption and separation for ultra-microporous copper-1,2,4-triazolate frameworks by halogen hydrogen bonds.

It is well known that the introduction of exposed fluorine (F) sites into metal-organic frameworks (MOFs) can effectively promote acetylene (C2H2) adsorption via C-H⋯F hydrogen bonds. However, such super strong hydrogen bonding interactions usually lead to very high acetylene adsorption enthalpy and thus require more energy during the adsorbent regeneration process. As the same group elements, chlorine (Cl), bromine (Br) and iodine (I) also can act as hydrogen bond acceptors but with relatively weak forces. So, it is speculated that the decoration of Cl, Br or I sites on the pore surface of MOF adsorbents may enhance acetylene adsorption but with lower energy consumption. Herein, ultra-microporous MOFs constructed by Cu4X4 (X = Cl, Br, I) motifs and 1,2,4-triazolate linkers, namely, [Cu8X4(TRZ)4]n (TRZ = 3,5-diethyl-1,2,4-triazole or detrz for SNNU-313-X, and 3,5-dipropyl-1,2,4-triazole or dptrz for SNNU-314-X), provide an ideal platform to investigate the effect of C-H⋯X (X = Cl, Br, I) hydrogen bonding on C2H2 adsorption and purification performance. Benefiting from the small pore size and pore environment, the C2H2 uptake and separation properties of this series of MOFs are systematically regulated. Detailed gas adsorption results show that with the same organic linker, the C2H2 uptake and separation (C2H2/C2H4 and C2H2/CO2) performance decrease clearly with the electronegativity of halogen ions (SNNU-313-Cl > SNNU-313-Br > SNNU-313-I). With the same halogen ion, the gas adsorption decreases with the bulk of decorated alkyl groups (SNNU-313-Cl > SNNU-314-Cl). Remarkably, SNNU-313/314 series MOF adsorbents exhibit moderate C2H2 uptake capacity and high separation ability, but the C2H2 adsorption enthalpies are much lower than those of MOF materials with exposed F sites. Dynamic fixed-bed column breakthrough experiments and Grand Canonical Monte Carlo (GCMC) simulations further indicate the critical effects of halogen hydrogen bonds on acetylene adsorption and separation. Overall, this work demonstrated an effective regulation of acetylene adsorption and separation by rational C-H⋯X hydrogen bonding, which may provide a new route for the exploration of energy-efficient acetylene adsorbent materials.

A positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain.

The two tandem bromodomains of BET (bromodomain and extra-terminal domain) proteins (BD1 and BD2) may play distinct and critical roles in neurological diseases. To better understand the underlying mechanisms of the BD1 bromodomain and facilitate brain permeable domain-selective inhibitor development, we describe here the development of the first BET BD1 positron emission tomography (PET) radioligand [11C]1a. Compound 1a was tested to possess potent binding affinities and good selectivity (>20-fold over BD2) for BD1 bromodomains of BRD2 (Kd = 25 nM), BRD3 (Kd = 24 nM), and BRD4 (Kd = 19 nM). Physicochemical characterization of 1a indicated the brain permeability and specific binding. [11C]1a was radiosynthesized in a good radiochemical yield (RCY: 25-30%) and molar activity (258 GBq μmol-1). The PET imaging studies of [11C]1a in mice showed moderate brain uptake (with peak SUV = 0.7) and binding specificity. Furthermore, [11C]1a demonstrated translational potential in the non-human primate (NHP) PET imaging study, which sets the stage for clinical translation.

Preparation of the 5-(4-((4-[18F] fluorobenzyl) oxy)- 3-methoxybenzyl) pyrimidine-2, -diamine as a radioligand for positron emission tomography scanning of the tyrosine kinase b/C receptor

Objective: The present research describes a new radiosynthesis of 5-(4-((4-[18F]fluorobenzyl)oxy)-3-methoxybenzyl)pyrimidine- 2,4-diamine as a potential radioligand for colony-stimulating factor 1 receptor (CSF-1R) and tyrosine kinase B/C (TrkB/C) neuroreceptors. Methods: Radiofluorination of a boronic acid precursor followed by thermal deprotection of Boc-protecting groups avoided acidcatalyzed protodeboronation in 8.7 ± 2.8% radiochemical yield. Results: Competitive autoradiographic binding research indicated a high unspecific binding, and that binding to TrkB/C could be blocked while binding to CSF-1R was not. In a rat model, a positron emission tomography (PET) scan indicated a moderate brain uptake and slow clearance rate. Conclusion: Moreover, the poor pharmacokinetic features of 5-(4-((4-[18F]fluorobenzyl)oxy)-3-methoxybenzyl)pyrimidine-2,4- diamine prevented its utilization as a PET radioligand in brain scanning, but 1-pot synthesis (which is a strategy to improve the effectiveness of the chemical reaction occurring by the use of copper, 18F-fluorination, and Boc deprotection) is an approach to the radio-synthesis of PET tracers (which are sensitive to acid).

325 Dealing with cardiac amyloidosis diagnosis: keep calm and use the magnifying glasses!

Abstract Methods and results Case report— male, 71 years old. Past medical history—arterial hypertension, dyslipidemia, tobacco abuse. COPD on nocturnal CPAP therapy. Rheumatic polymyalgia on steroid therapy. Previous unprovoked deep vein thrombosis on anticoagulation with rivaroxaban. Bilateral carpal tunnel surgeries 8 years ago. Spontaneous left biceps tendon rupture 4 year ago. IgA kappa monoclonal gammopathy of undetermined significance (MGUS). Mild interventricular septum (IVS) hypertrophy on echocardiography since 2018. In 2019 IVS was 18 mm with granular sparkling appearance. In February 2020 he was hospitalized for initial heart failure and COPD exacerbation. In 2021 he developed worsening dyspnoea. He underwent cardiological evaluation in a spoke hospital and a cardiac magnetic resonance (CMR) suggested infiltrative cardiomyopathy. Bone scintigraphy showed moderate cardiac uptake (Perugini Score 2). Following haematological evaluation, fat pad biopsy was performed, and amyloid was detected on Congo red staining. Classification of the amyloid fibril protein was not performed. Bone marrow biopsy, even though of suboptimal quality, was negative for amyloid and for plasma cellular infiltration. Bone marrow aspirate showed 11% of plasma cells and multiple myeloma was therefore hypothesized. Recent medical history—he was evaluated in our Cardiac Amyloid Outpatient Clinic in May 2021. He was symptomatic for dyspnoea (NYHA class III) and exercise intolerance, diffuse osteo-muscolar pain, and extremities paresthesia. His blood pressure was on the low side of normality with necessity of anti-hypertensive therapy downgrading. Signs and symptoms of hematological disease were not present. We required to analyse the fat pad specimen in order to perform amyloid fibril protein typing; with immunoelectron microscopy, transthyretin (TTR) was identified as the amyloid fibrils precursor (no light chains could be identified). We considered performing endomyocardial biopsy to exclude the coexistence of ATTR amyloidosis and light chains (AL) amyloidosis in the heart but, given the history, clinical picture, and fat pad biopsy results, we felt that cardiac ATTR was the most probable diagnosis and we decided to proceed with a close cardiological and haematological follow-up. TTR genetic testing is ongoing. Conclusions ATTR cardiac amyloidosis is an emerging cause of heart failure, especially with preserved ejection fraction, in the older population. However, these patients frequently present with dysproteinemias and bone marrow abnormalities, up to multiple myeloma, raising the issue of differential diagnosis between ATTR and AL amyloidosis. According to the latest European Consensus Document, in the presence of cardiac uptake at bone scintigraphy (Grades 1–3) and positive haematologic tests, histological confirmation (usually cardiac) is necessary to subtype amyloid infiltration. In our case, the patient had positive Congo Red-stained fat pad biopsy, but the typing of the amyloid deposition was not performed. After referral to a Center with a Cardiac Amyloid Outpatient Clinic with a specialized Pathology Unit, we could further proceed with diagnostic workup and identify the amyloid deposition as ATTR; of note, fat pad biopsy is positive in just 15–25% of ATTR amyloidosis. Moreover, close collaboration with Hematology was necessary to assess the risk of AL amyloidosis and to provide a close and targeted follow-up. Endomyocardial biopsy was not performed after consideration of the various elements suggestive for ATTR cardiac amyloidosis, but the patient will be evaluated periodically and closely to potentially reassess this decision.

Impact of an adolescent meningococcal ACWY immunisation programme to control a national outbreak of group W meningococcal disease in England: a national surveillance and modelling study

In August, 2015, the UK implemented an emergency adolescent immunisation programme with the meningococcal ACWY conjugate vaccine to combat a national outbreak of meningococcal group W (MenW) disease due to a hypervirulent ST-11 complex strain, which is currently causing regional and national outbreaks worldwide. This immunisation programme specifically targeted adolescents aged 13-18 years, an age group with low disease incidence but high nasopharyngeal carriage, with the aim of interrupting transmission and providing indirect (herd) protection across the population. Here, we report the impact of the first 4 years of the programme in England. Public Health England conducts meningococcal disease surveillance in England. Laboratory-confirmed cases of invasive meningococcal disease during the academic years 2010-11 to 2014-15 (Sept 1 to Aug 31) were used to predict post-vaccination trends, based on the assumption that cases would plateau 1 year after vaccine implementation (conservative scenario) or that cases would continue to rise for 4 years after vaccine implementation (extreme scenario). Vaccine uptake evaluated in August, 2019, was 37-41% in adolescents aged 18 years immunised in primary care and 71-86% in younger teenagers routinely vaccinated in school. Vaccine effectiveness was estimated with the indirect screening method. MenW and MenY cases plateaued within 12 months and then declined, while MenC cases remained low throughout. Significant reductions were observed among adolescents aged 14-18 years for MenW (incidence rate ratio [IRR] 0·35 [95% CI 0·17-0·76]) and MenY (0·21 [0·07-0·59]) cases, with a non-significant reduction in MenC cases (0·11 [0·01-1·01]). Based on conservative and extreme scenarios, 205-1193 MenW cases were prevented through the indirect effects of the programme and 25 through direct protection. For MenY, an estimated 60-106 cases were prevented through the indirect effects of the programme and 19 through direct protection. Ignoring any residual effect from an earlier MenC-containing vaccine, the overall vaccine effectiveness against MenCWY disease combined was 94% (95% CI 80-99). A meningococcal immunisation programme specifically targeting adolescent carriers succeeded in rapidly controlling a national MenW outbreak, even with moderate initial vaccine uptake. Public Health England.

Structure-Based design of Marine-derived Meridianin C derivatives as glycogen synthase kinase 3β inhibitors with improved oral bioavailability: From aminopyrimidyl-indoles to the sulfonyl analogues

Glycogen synthase kinase 3β (GSK-3β) has become an attractive target for the treatment of diabetes. Compound I is an indole-based GSK-3β inhibitor designed from the Meridianin C, a marine natural product (MNP) isolated from Aplidium meridianum. However, this compound has a moderate inhibitory activity toward GSK-3β (IC50 = 24.4 μM), moderate glucose uptake (38%), and especially, a low oral bioavailability (F = 11.4%). In the present study, applying the structure-based design strategy, a series of derivatives modified on the indole moiety were synthesized based on the lead compound I, followed by evaluating their cytotoxic activity, antihyperglycemic activity, and kinase inhibitory activity. Among this series, compound 6x with a sulfonyl group displayed the highest glucose uptake (83.5%) in muscle L6 cells, showing much higher inhibitory activity against GSK-3β (IC50 = 5.25 μM). Molecular docking indicated that compound 6x was properly inserted into the ATP-binding binding pocket of GSK-3β with a higher docking score (-8.145 kcal/mol) compared with that of compound I (-6.950 kcal/mol), interpreting the higher kinase inhibitory activity toward GSK-3β. Remarkably, compound 6x showed favorable drug-like properties, including significantly better oral bioavailability (F = 47.4%) and no two-week acute toxicity at a dose of 1 g/kg. Our findings suggest that these MNP-derived sulfonyl indole derivatives could be used as lead compounds for the development of anti-hyperglycemic drugs.

CS-1 Cerebellar liponeurocytoma; Report of two cases with detailed metabolic, immunohistochemical, and genetic evaluations

Cerebellar liponeurocytoma (cLNC), World Health Organization grade II neoplasm, is a rare brain tumor characterized by advanced neuronal/neurocytic differentiation and focal lipid accumulation in neuroepithelial tumor cells. However, the expression and genetic profiling of cLNC, as well as metabolic imaging characteristics, have been poorly studied. Two patients with lower vermian tumors were operated on with telovelar approach. Moderate methionine uptake in positron emission tomography was observed in both cases. Histologically, the tumor was composed of small, uniform cells with round nuclei in a sheet-like fashion. Vacuolate cells with displacement of nuclei suggested the lipid accumulation, which was further supported by immunohistochemical staining of S-100. Although the extent of lipidization was relatively low compared with the reported cLNC cases, the immunohistochemical findings confirmed the diagnosis of cLNC. Next-generation sequencing of tumoral DNA in one case detected a splice site mutation of the ATRX gene, which is the first observation in the literature. Neither chemotherapy nor radiotherapy were administered postoperatively in both cases. In one case with spinal dissemination, residual tumor demonstrated progression 7 months after the resection. Long term follow-up data of cLNC cases with detailed expression and genetic profiles are essential for precise diagnosis and better understanding of the oncogenic pathway as well as the natural history of cLNC.

Construction of Quaternized Polysulfone/Polyquaternium‐10 Anion Exchange Membrane with Semi‐Interpenetrating Network for Alkaline Fuel Cell

AbstractThe quaternized polysulfone/polyquaternium‐10 (QPSU/PQ‐10) anion exchange membranes (AEMs) with a semi‐interpenetrating network are prepared by the simple solution casting method. The effects of the mass ratio of chloromethylated polysulfone (CMPSU) to PQ‐10 and the molar ratio of quaternized chloromethyl (QCM) to cross‐linked chloromethyl (CCM) on the performance of AEM are systematically investigated. The results show that the introduction of PQ‐10 endows the QPSU/PQ‐10 AEM with excellent mechanical performance. More specifically, the QPSU/PQ‐10 AEM has moderate water uptake, swelling ratio, and ion exchange capacity (IEC) at an appropriate composition ratio and crosslinking degree. In particular, the tensile strength and elongation at break of the QP0.5‐1 membrane with the optimal composition ratio and crosslinking degree are 23.63 MPa and 20.07%, respectively; and its ion conductivity is up to 69.91 mS cm−1 at 80 °C. Furthermore, the peak power density of the single fuel cell assembled from the QP0.5‐1 membrane is 75.64 mW cm−2 at 60 °C. Herein, the QPSU/PQ‐10 AEM has good thermal oxidation stability, mechanical properties, and ion conductivity, highlighting the potential of bio‐based PQ‐10 as an ion‐conducting functional molecule in AEMs.

Hot needles can confirm accurate lesion sampling intraoperatively using [18F]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer

PurposeProstate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling.MethodsIn this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson’s test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC).ResultsIn 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100–200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156–2079 cpm).Conclusions[18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy.Trial registration numberNCT03187990, 15/06/2017.

CONCOMITANT LATENT POLYCYTHEMIA VERA AND MGUS.

With the introduction of changes in the diagnostic criteria for polycythemia vera (PV) in the 2016 WHO classification, it became necessary to revise the diagnosis in some patients. Cases with latent (masked) polycythemia vera (LPV) were identified. Bone marrow trepanobiopsy takes one of the most important place in the differential diagnosis of LPV with other myeloproliferative diseases.We describe a case with coexistence of LPV and MGUS in a patient at the onset of the disease. Patient F.I., aged 62, was admitted with complaints of burning sensation in both feet, pain in the left lower extremity, back pain, nocturia 2-3 times per night and weight loss of 6-7 kg.Lumbar and whole spinal MRI revealed changes in the intensity of the medullary signal, mild decrease in the height of L2-L3 and T10 . EMG revealed polyneuropathy.PET showed a moderate uptake of FDG in the localization of the bone marrow. The spleen was enlarged-size-157 mm. Laboratory findings: hemogram-WBC-11.15 × 103/µL, Hgb-15g / dL, HCT-48%, PLT-604 × 103/µL. Bone marrow biopsy, imprint, aspiration revealed moderately hipercellular bone marrow with increasing in all 3 series, groupings in megakaryocytes, containing limited (3-4%) kappa monoclonal plasma cell population; moderately increasing reticulin fibers (grade 1 according to WHO). Karyotype 46, XY; multiple myeloma FISH panel: translocation 4; 14 and translocation 11; 14 (+). JAK2V617F-50.48% (+). The key point in the diagnosis was trilineage hyperplasia of the bone marrow,because the reticulin fibrosis may occurs in 20% of PV cases. Thus, the patient was diagnosed with LPV. Due to the detection of plasma cells in the bone marrow (3-4%), kappa light chains, with the diagnosis of LPV, the diagnosis of MGUS was established.The patient was prescribed ASS 100 mg per os, Hydrea at a dose of 500 mg every other day. For MGUS, the “wait and watch” tactic was chosen. In the diagnosis of LPV, along with molecular genetic research, trepanobiopsy of the bone marrow plays a leading role. The possibility of a combination of myeloproliferative and other diseases should not be ruled out.

Preparation and performance of bisimidazole cationic crosslinked addition-type polynorbornene-based anion exchange membrane

The late transition metal catalyst system (η3-allyl)Pd(PPh3)Cl/Li[B(C6F5)4]·2.5Et2O (Li[FABA]) was used to catalyze 5-norbornene-2-methylenehexyl ether (NB-MHE) and 5-norbornene-2-methylene-(6-bromohexyl) ether (NB–O–Br) controllable addition copolymerization to obtain post-functionalized vinyl addition-type block copolymer aP(NB-O-Br-b-NB-MHE). 1,6-Bis(2-methylimidazole)hexane (Bis-MeIm) was used as a crosslinking agent to prepare a series of anion exchange membranes (AEMs) CL-aP(NB-O-Br-b-NB-MHE). The initial thermal decomposition temperature of the obtained addition-type polynorbornene-based AEM was about 250 °C. The AEM had moderate water uptake (WU) and swelling ratio (SR), and obvious micro-phase separation structure that could be observed from the AFM phase diagram. It could maintain high OH− conductivity (85.07 mS cm−1, 80 °C) and alkali resistance stability (soaking alkali for more than 500 h at 25 °C). In the single cell test of the H2/O2 fuel cell assembled by CL5-aP(NB-O-Br-b-NB-MHE), the peak power density was 177 mW cm−2.

68Ga-EMP-100 PET/CT\u2014a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma\u2014first in-human biodistribution and imaging results

Background68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC.MethodsTwelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually.ResultsOverall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86–29.16)), followed by bone metastases (SUVmax 5.56 (0.97–15.85)), and lymph node metastases (SUVmax 3.90 (2.13–6.28)) and visceral metastases (SUVmax 3.82 (0.11–16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines.ConclusionTargeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

Nationwide rollout reveals efficacy of epidemic control through digital contact tracing

Fuelled by epidemiological studies of SARS-CoV-2, contact tracing by mobile phones has been put to use in many countries. Over a year into the pandemic, we lack conclusive evidence on its effectiveness. To address this gap, we used a unique real world contact data set, collected during the rollout of the first Norwegian contact tracing app in the Spring of 2020. Our dataset involves millions of contacts between 12.5% of the adult population, which enabled us to measure the real-world app performance. The technological tracing efficacy was measured at 80%, and we estimated that at least 11.0% of the discovered close contacts could not have been identified by manual contact tracing. Our results also indicated that digital contact tracing can flag individuals with excessive contacts, which can help contain superspreading related outbreaks. The overall effectiveness of digital tracing depends strongly on app uptake, but significant impact can be achieved for moderate uptake numbers. Used as a supplement to manual tracing and other measures, digital tracing can be instrumental in controlling the pandemic. Our findings can thus help informing public health policies in the coming months.