High Uptake Research Articles

Development of 52Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2

PurposeDue to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 (52Mn, t1/2 = 5.6 d, β+ = 29.6%, E(βave) = 242 keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 (89Zr, t1/2 = 3.3 d, β+ = 22.7%, E(βave) = 396 keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with 52Mn under mild conditions using trastuzumab as a proof-of-concept.ProceduresTrastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [52Mn]MnCl2 at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2 + (BT474) and HER2- (MDA-MB-468) cell lines followed by in vivo studies.ResultsTrastuzumab-Oxo-DO3A was labeled within 30 min at 37 °C with a radiochemical yield (RCY) of 90 ± 1.5% and with the highest specific activity of the chelators investigated of 16.64 MBq/nmol. The labeled compound was purified with a resulting radiochemical purity of > 98% and retained a 67 ± 1.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in < 50 ± 2.5% (RCY) with similar specific activity. Mouse serum stability studies of [52Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5 days. Cell uptake studies showed higher uptake in HER2 + (12.51 ± 0.83% /mg) cells compared to HER2- (0.85 ± 0.10%/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02 ± 2.16%ID/g, 14 d) compared to MDA-MB-468 tumors (2.20 ± 0.80%ID/g, 14 d). Additionally, both models exhibited low bone uptake of < 1% ID/g.ConclusionThe bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of 52Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both in vitro and in vivo. High-quality PET/CT images of [52Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [52Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging.

Water sorption behavior of poly(norbornene)-based anion exchange polyelectrolytes: Experiments and simulation

Poly(norbornene)s (PNBs) are great potential candidates for anion exchange polyelectrolytes (AEPs), however, PNBs-based AEPs usually suffer from excessive water sorption. Herein, the underlying mechanism behind high water sorption was proposed by using the quaternized PNBs as a model AEP. With a moderate ionic content of 2.15 mmol/g, the hydrogenated AEP has a high water uptake of 253 % at 25 °C, which is caused by heterogeneous quaternization and weak interchain interactions. When the brominated AEP was immersed in trimethylamine aqueous (TMA/H2O) solution, TMA penetrates tightly packed polymer chains, seriously destroying vdW interchain interactions. Subsequently, the quaternized cationic groups induce spontaneous water sorption. Although ionic moieties possess strong interchain electrostatic interactions, the solid AEPs restrict polymer chains to form highly cohesive domains for resisting water sorption. Additionally, carbon–carbon double bonds in the PNBs preferentially interact with TMA/H2O, further increasing water uptake. This work provides theoretical guidance for preparing high-performance AEPs based on all-hydrocarbon aliphatic backbones.

A comprehensive analysis of the tubarial glands.

The tubarial glands (TGs) are a collection of salivary glands (SGs) located within the nasopharynx, proximal to the eustachian tube. Currently, there is no quantitative characterization of the TGs. We investigated the histological architecture of the TGs and compared it with the major and minor SGs for categorization. Tubarial, parotid, submandibular, sublingual, buccal, labial, and lingual glands were excised from human donors (8 male and 3 female). Hematoxylin and eosin-stained tissue sections were analyzed to measure the area of the largest lobule, number of ducts, number of mucinous acini, and mean mucinous acini area. Based on our observation, the TGs' histology resembles the minor SGs, while having some unique characteristics that distinguish them from both major and minor SGs. The area of the largest lobule in the TGs and minor SGs was smaller than the major SGs. TGs have a lower number of ducts than the major and minor SGs. TGs contain densely packed clusters of predominantly mucinous acini surrounded by loose connective tissue resembling minor SGs. This density may explain their previously observed high prostate-specific membrane antigen uptake. In our cohort of donors, sex-based differences were observed in the mean mucinous acini area between male and female TGs, submandibular and sublingual glands. Taken together, our findings suggest the histological characteristics of all SGs are better organized on a spectrum rather than discrete groups (major vs. minor) and provide information to open new avenues for research into the TGs' role in head and neck pathologies and sexual dimorphism of the SGs.

Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study.

β-amyloid (Aβ) pathology is not always coupled with Alzheimer's disease (AD) relevant cognitive decline. We assessed the accuracy of tau PET to identify Aβ(+) individuals who show prospective disease progression. 396 cognitively unimpaired and impaired individuals with baseline Aβ and tau PET and a follow-up of ≥ 2 years were selected from the Alzheimer's Disease Neuroimaging Initiative dataset. The participants were dichotomously grouped based on either clinical conversion (i.e., change of diagnosis) or cognitive deterioration (fast (FDs) vs. slow decliners (SDs)) using data-driven clustering of the individual annual rates of cognitive decline. To assess cognitive decline in individuals with isolated Aβ(+) or absence of both Aβ and tau (T) pathologies, we investigated the prevalence of non-AD comorbidities and FDG PET hypometabolism patterns suggestive of AD. Baseline tau PET uptake was higher in Aβ(+)FDs than in Aβ(-)FD/SDs and Aβ(+)SDs, independently of baseline cognitive status. Baseline tau PET uptake identified MCI Aβ(+) Converters and Aβ(+)FDs with an area under the curve of 0.85 and 0.87 (composite temporal region of interest) respectively, and was linearly related to the annual rate of cognitive decline in Aβ(+) individuals. The T(+) individuals constituted largely a subgroup of those being Aβ(+) and those clustered as FDs. The most common biomarker profiles in FDs (n = 70) were Aβ(+)T(+) (n = 34, 49%) and Aβ(+)T(-) (n = 19, 27%). Baseline Aβ load was higher in Aβ(+)T(+)FDs (M = 83.03 ± 31.42CL) than in Aβ(+)T(-)FDs (M = 63.67 ± 26.75CL) (p-value = 0.038). Depression diagnosis was more prevalent in Aβ(+)T(-)FDs compared to Aβ(+)T(+)FDs (47% vs. 15%, p-value = 0.021), as were FDG PET hypometabolism pattern not suggestive of AD (86% vs. 50%, p-value = 0.039). Our findings suggest that high tau PET uptake is coupled with both Aβ pathology and accelerated cognitive decline. In cases of isolated Aβ(+), cognitive decline may be associated with changes within the AD spectrum in a multi-morbidity context, i.e., mixed AD.

18 F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers.

To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers. We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan. In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261). FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.

Simultaneous capture of trace benzene and SO2 in a robust Ni(II)-pyrazolate framework

Benzene and SO2, coexisting as hazardous air pollutants in some cases, such as in coke oven emissions, have led to detrimental health and environmental effects. Physisorbents offer promise in capturing benzene and SO2, while their performance compromises at low concentration. Particularly, the simultaneous capture of trace benzene and SO2 under humid conditions is attractive but challenging. Here, we address this issue by constructing a robust pyrazolate metal-organic framework (MOF) sorbent featuring rich accessible Ni(II) sites with low affinity to water and good stability. This material achieves a high benzene uptake of 5.08 mmol g–1 at 10 Pa, surpassing previous benchmarks. More importantly, it exhibits an adsorption capacity of ~0.51 mmol g–1 for 10 ppm benzene and ~1.21 mmol g–1 for 250 ppm SO2 under 30% relative humidity. This work demonstrates that a pioneering MOF enables simultaneous capture of trace benzene and SO2, highlighting the potential of physisorbents for industrial effluent remediation, even in the presence of moisture.

Leveraging synergistic polar and nonpolar binding sites in a fluorinated metal–organic framework for efficient ethane/ethylene separation

Constructing favorable C2H6-selective adsorbents for one-step C2H4 purification from C2H6/C2H4 mixtures is a matter of considerable significance, but is still a very challenging task in the field of petrochemical industry. Herein, we report a well-designed ant-type metal–organic framework (NUM-16) with appropriate pore size and pore environment for preferential trapping C2H6. NUM-16a (activated NUM-16) performs a high C2H6 uptake of 4.39 mmol/g and a good adsorption selectivity for C2H6/C2H4 (10:90, v/v) mixture at 298 K and 1 bar. The separation mechanism, as unveiled by the grand canonical Monte Carlo simulations and density functional theory calculations, is mainly attributed to synergistic polar and nonpolar binding sites on the pore surface of NUM-16a, which provide stronger affinities to C2H6 than C2H4. Under ambient conditions, dynamic breakthrough experiments revealed that NUM-16a demonstrates the enormous potential for actual C2H6/C2H4 separation and is expected to be applied to the correlative industrial process. Both experiments and theoretical calculations distinctly demonstrated that the reasonable integration of polar and nonpolar binding sites in C2H6-preferred MOFs is a feasible strategy for efficient C2H6/C2H4 separation. This work afforded some useful insights into designing and developing high-powered MOF adsorbents to solve tricky industrial separation challenges.

Estimating the potential number of cases prevented by infant/ toddler immunisation with a MenACWY vaccine

Introduction: Meningococcal disease control in the UK relies on various vaccines, with the discontinuation of the Hib/MenC combination vaccine Menitorix® in 2018 necessitating reassessment of the immunisation strategy. The quadrivalent MenACWY vaccine emerges as a promising long-term solution, already integrated into the teenage immunisation regimen. While indirect control of group W and C cases is anticipated through existing programs, the high incidence of meningococcal disease in infancy underscores the potential benefits of infant/toddler vaccination.Methods: Utilizing data from two UK studies, we recalibrated age-specific carriage prevalence curves and estimated the proportion of meningococcal carriage attributed to ACWY and non-ACWY strains. Employing a dynamic transmission model, we evaluated the combined indirect effects of the teenage MenACWY vaccination initiative and the direct impact of administering MenACWY vaccine at either 3 or 12 months, alongside ongoing 4CMenB vaccination efforts. Given the pandemic-induced decline in cases and alterations in social contact patterns reported in prior research, we also simulated the transmission model to reflect periods of COVID-19 lockdown.Results: Our projections indicate effective control of carriage and disease associated with groups A, C, W, and Y through the teenage vaccination campaign. Assuming sustained high uptake of teenage vaccines amid pandemic scenario, we forecast MenACWY carriage prevalence to be below 1% by 2025. Across all scenarios, the impact of an infant/toddler MenACWY program on case reduction remains modest. Notably, administering the MenACWY dose at 3 months yields a greater number of prevented cases compared to administration at 12 months. With sustained uptake of teenage vaccination, our estimates suggest that between 3 and 22 cases could be averted in a 2025 birth cohort through a 3-month MenACWY dose.Conclusions: Provided teenage uptake remains high and the infant 4CMenB programme is maintained, we suggest that few cases will be prevented from an infant/ toddler MenACWY dose.

Radiosynthesis and preclinical evaluation of a 68Ga-labeled tetrahydroisoquinoline-based ligand for PET imaging of C-X-C chemokine receptor type 4 in an animal model of glioblastoma

BackgroundThis study aimed to develop a novel positron emission tomography (PET) tracer, [68Ga]Ga-TD-01, for CXCR4 imaging. To achieve this goal, the molecular scaffold of TIQ15 was tuned by conjugation with the DOTA chelator to make it suitable for 68Ga radiolabeling.MethodsA bifunctional chelator was prepared by conjugating the amine group of TIQ15 with p-NCS-Bz-DOTA, yielding TD-01, with a high yield (68.92%). TD-01 was then radiolabeled with 68Ga using 0.1 M ammonium acetate at 60 °C for 10 min. A 1-h dynamic small animal PET/MRI study of the labeled compound in GL261-luc2 tumor-bearing mice was performed, and brain tumor uptake was assessed. Blocking studies involved pre-administration of TIQ15 (10 mg/kg) 10 min before the PET procedure started.Results[68Ga]Ga-TD-01 exhibited a radiochemical yield (RCY) of 36.33 ± 1.50% (EOS), with a radiochemical purity > 99% and a molar activity of 55.79 ± 1.96 GBq/µmol (EOS). The radiotracer showed in vitro stability in PBS and human plasma for over 4 h. Biodistribution studies in healthy animals revealed favorable kinetics for subsequent PET pharmacokinetic modeling with low uptake in the brain and moderate uptake in lungs, intestines and spleen. Elimination could be assigned to a renal-hepatic pathway as showed by high uptake in kidneys, liver, and urinary bladder. Importantly, [68Ga]Ga-TD-01 uptake in glioblastoma (GBM)-bearing mice significantly decreased upon competition with TIQ15, with a baseline tumor-to-background ratios > 2.5 (20 min p.i.), indicating high specificity.ConclusionThe newly developed CXCR4 PET tracer, [68Ga]Ga-TD-01, exhibited a high binding inhibition for CXCR4, excellent in vitro stability, and favorable pharmacokinetics, suggesting that the compound is a promising candidate for full in vivo characterization of CXCR4 expression in GBM, with potential for further development as a tool in cancer diagnosis.

Development of a Multiparticulate Metal-Organic Framework/Textile Fiber Swatch.

The versatility of metal-organic frameworks (MOFs) has led to groundbreaking applications in a wide variety of fields, especially in the areas of energy, environment, and sustainability. For example, MOFs can be designed for high uptake of toxic gases and pollutants, such as CO2, NH3, and SO2, but designing a single MOF that shows tangible uptake for all of these gases is challenging due to the differences in the chemical and physical properties of these molecules. To this end, integrating multiple MOFs onto textile fibers and crafting various structures have emerged as pivotal developments, enhancing framework durability and usability. MOF composites prepared on readily available textile fibers offer the flexibility essential for critical applications, including heterogeneous catalysis, chemical sensing, toxic gas adsorption, and drug delivery, while preserving the unique characteristics of MOFs. This study introduces a scalable and adaptable method for seamlessly embedding multiple high-performing MOFs onto a single textile fiber using a dip-coating method. We explored the uptake capacity of these multi-MOF composites for CO2, NH3, and SO2 and observed a performance similar to that of traditional powdered materials. Along with harmful gas adsorption, we also have evaluated the permeation and reactivity of these MOF/textile composites toward chemical warfare agents (CWAs) like GD (soman), HD (mustard gas), and VX. In combination, these results demonstrate a fundamental advancement toward establishing a consistent strategy for the hydrolysis of nerve agents in real-world scenarios. This approach can substantially increase the protection toward CWAs and enhance the effectiveness of protective equipment such as fabrics for protective garments. This dip-coating method for the integration of multiple MOFs on a single textile fiber unlocks a wealth of possibilities and paves the way for future innovations in the deployment of MOF-based composites.

Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2.

[18F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [11C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k2 and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [11C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [18F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions. Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [18F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate [Formula: see text](ref: CS) and DVRCER(ref: CER) values. For SRTM2, the population average of [Formula: see text] was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated. The 1TC k2 (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC [Formula: see text] was much higher than 1TC [Formula: see text], SRTMC underestimated BPND(ref: CS) and DVRCER by an average of 3% and 1% across regions, respectively, due to similar bias in k2 and [Formula: see text] estimation. SRTM underestimated BPND(ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVRCER underestimation varied by region (mean 10%). Using population average [Formula: see text] values, SRTM2 BPND and DVRCER showed the best agreement with 1TC estimates. Our findings support the use of population [Formula: see text] value in SRTM2 with [18F]SynVesT-1 for the estimation of [Formula: see text] or DVRCER, regardless of the choice of reference region.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program

IntroductionPatients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. MethodsThrough a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). ResultsMore than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). ConclusionsThe results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Exhaled Anesthetic Xenon Regeneration by Gas Separation Using a Metal–Organic Framework with Sorbent‐Sorbate Induced‐Fit

AbstractNoble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed‐circuit anesthetic Xe recovery and reusage process with highly effective CO2‐specific adsorbent CUPMOF‐5 that is promising to solve the anesthetic Xe supply problem. CUPMOF‐5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4 Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In situ single‐crystal X‐ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent‐sorbate induced‐fit strengthening binding interaction to CO2. CUPMOF‐5 can remove 5 % CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8 %) so far, as verified by breakthrough experiments. This endows CUPMOF‐5 great potential for the on‐line CO2 removal and Xe recovery from anesthetic closed‐circuits.

Evaluation of ABD-Linked RM26 Conjugates for GRPR-Targeted Drug Delivery.

Targeting the gastrin-releasing peptide receptor (GRPR) with the bombesin analogue RM26, a 9 aa peptide, has been a promising strategy for cancer theranostics, with recent success in radionuclide imaging of prostate cancer. However, therapeutic application of the short peptide RM26 would require a longer half-life to prevent fast clearance from the circulation. Conjugation to an albumin-binding domain (ABD) is a viable strategy to extend the in vivo half-life of peptides and proteins. We previously reported an ABD-fused RM26 peptide targeting GRPR (ABD-RM26 Gen 1) that showed prolonged and stable tumor uptake over 144 h; however, the observed high kidney uptake indicated that the conjugate's binding to albumin was reduced and that this could be an obstacle for its use as a delivery system for targeted therapy, especially for radiotherapy. Here, we have designed, produced, and preclinically evaluated a series of novel ABD-RM26 conjugates with the aim of improving the conjugate's binding to albumin and decreasing the kidney uptake. We developed three second-generation constructs with varying formats, differing in the relative positions of the targeting moieties and the radionuclide chelator. The produced conjugates were radiolabeled with indium-111 and evaluated in vitro and in vivo. All constructs displayed improved biophysical characteristics, biodistribution, and lower kidney uptake compared to previously reported first-generation molecules. The ABD-RM26 Gen 2A conjugate showed the best biodistribution profile with a nearly 6-fold reduction in kidney uptake. However, the ABD-RM26 Gen 2A conjugate's binding to GRPR was compromised. This conjugate's assembly of albumin- and GRPR-binding moieties might be used for further development of drug conjugates for targeted therapy/radiotherapy of GRPR-expressing cancers.

Associations of CD4 Cell Count Measures With Infection-Related and Infection-Unrelated Cancer Risk Among People With HIV.

People with HIV are at higher risk of infection-related cancers than the general population, which could be due, in part, to immune dysfunction. Our objective was to examine associations between 4 CD4 count measures as indicators of immune function and infection-related and infection-unrelated cancer risk. We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada. Incident cancers were identified from January 1, 1997 to December 31, 2020. We estimated adjusted hazard ratios (aHR) for the associations between CD4 measures (baseline CD4, nadir CD4, time-updated CD4, time-updated CD4:CD8) and cancer incidence rates using competing risk analyses, adjusted for socio-demographic factors, history of hepatitis B or C infection, baseline viral load, smoking, and alcohol use. Among 4771 people with HIV, contributing 59,111 person-years of observation, a total of 549 cancers were observed. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI: 1.38 to 3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI: 1.49 to 2.71]), low time-updated CD4 (aHR 3.52 [95% CI: 2.36 to 5.24]) and time-updated CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI: 1.08 to 3.79]) were associated with an increased rate of infection-related cancer. No associations were observed for infection-unrelated cancers. Low CD4 counts and indices were associated with increased rates of infection-related cancers among people with HIV, irrespective of the CD4 measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may lead to improved immune function and could add to cancer prevention strategies such as screening and vaccine uptake.

Ultrastable Carboxyl-Functionalized Pore-Space-Partitioned Metal-Organic Frameworks for Gas Separation.

Isoreticular chemistry, which enables property optimization by changing compositions without changing topology, is a powerful synthetic strategy. One of the biggest challenges facing isoreticular chemistry is to extend it to ligands with strongly coordinating substituent groups such as unbound -COOH, because competitive interactions between such groups and metal ions can derail isoreticular chemistry. It is even more challenging to have an isoreticular series of carboxyl-functionalized MOFs capable of encompassing chemically disparate metal ions. Here, with the simultaneous introduction of carboxyl functionalization and pore space partition, a family of carboxyl-functionalized materials is developed in diverse compositions from homometallic Cr3+ and Ni2+ to heterometallic Co2+/V3+, Ni2+/V3+, Co2+/In3+, Co2+/Ni2+. Cr-MOFs remain highly crystalline in boiling water. Unprecedentedly, one Cr-MOF can withstand the treatment cycle with 10m NaOH and 12m HCl, allowing reversible inter-conversion between unbound -COOH acid form and -COO- base form. These materials exhibit excellent sorption properties such as high uptake capacity for CO2 (100.2 cm3g-1) and hydrocarbon gases (e.g., 142.1 cm3g-1 for C2H2, 110.5 cm3g-1 for C2H4) at 1 bar and 298K, high benzene/cyclohexane selectivity (up to ≈40), and promising separation performance for gas mixtures such as C2H2/CO2 and C2H2/C2H4.

Probing the Distribution and Mobility of Aminopolymers after Multiple Sorption-Regeneration Cycles: Neutron Scattering Studies.

Solid-supported amines are effective CO2 adsorbents capable of capturing CO2 from flue gas streams (10-15 vol % CO2) and from ultradilute streams, such as ambient air (∼400 ppm CO2). Amine sorbents have demonstrated promising performance (e.g., high CO2 uptake and uptake rates) with stable characteristics under repeated, idealized thermal swing conditions, enabling multicycle application. Literature studies suggest that solid-supported amines such as PEI/SBA-15 generally exhibit slowly reducing CO2 uptake rates or capacities over repeated thermal swing capture-regeneration cycles under simulated DAC conditions. While there are experimental reports describing changes in supported amine mass, degradation of amine sites, and changes in support structures over cycling, there is limited knowledge about the structure and mobility of the amine domains in the support pores over extended use. Furthermore, little is known about the effects of H2O on cyclic applications of PEI/SBA-15 despite the inevitable presence of H2O in ambient air. Here, we present a series of neutron scattering studies exploring the distribution and mobility of PEI in mesoporous silica SBA-15 as a function of thermal cycling and cyclic conditions. Small-angle neutron scattering (SANS) and quasielastic neutron scattering (QENS) are used to study the amine and H2O distributions and amine mobility, respectively. Applying repeated thermal swings under dry conditions leads to the thorough removal of water from the sorbent, causing thinner and more rigid wall-coating PEI layers that eventually lead to slower CO2 uptake rates. On the other hand, wet cyclic conditions led to the sorption of atmospheric water at the wall-PEI interfaces. When PEI remains hydrated, the amine distribution (i.e., wall-coating PEI layer thickness) is retained over cycling, while lubrication effects of water yield improved PEI mobility, in turn leading to faster CO2 uptake rates.

N-Heteroatom Engineered Nonporous Amorphous Self-Assembled Coordination Cages for Capture and Storage of Iodine.

Radioactive iodine isotopes from nuclear-related activities, present substantial risks to human health and the environment. Developing effective materials for the capture and storage of these hazardous molecules is paramount. Traditionally, nonporous solids were historically considered ineffective for adsorbing target species. In this study, we investigate the potential of four nonporous, amorphous, self-assembled coordination cages (C1, C2, C3, and C4) featuring varying numbers of nitrogen atoms within the core (pyridyl/triazine unit) and specific cavity sizes for iodine adsorption. These coordination cages demonstrate remarkable adsorption abilities for iodine in both vapor and solution phases, facilitated by enhanced electron-pair interactions. The cages exhibit high uptake capacities of up to 3.16 g g-1 at 75 °C, the highest among metal-organic cages and up to 434.29 mg g-1 in solution, highlighting the efficiency of these materials across different phases. Even at ambient temperature, they show significant iodine capture efficiency, with a maximum value of 1.5 g g-1. Furthermore, these robust materials can be recycled, enduring at least five reusable cycles without apparent fatigue. Overall, our findings present a "N-heteroatom engineering" approach for the development of recyclable amorphous containers for the capture and storage of iodine, contributing to the mitigation of nuclear-related risks.

Construction of Highly Porous and Robust Hydrogen‐Bonded Organic Framework for High‐Capacity Clean Energy Gas Storage

Development of highly porous and robust HOFs for high‐pressure methane and hydrogen storage remains a grand challenge due to the fragile nature of hydrogen bonds. Herein, we report a strategy of constructing double‐walled framework to target highly porous and robust HOF (ZJU‐HOF‐5a) for extraordinary CH4 and H2 storage. ZJU‐HOF‐5a features a minimized twofold interpenetration with double‐walled structure, in which multiple supramolecular interactions are existed between the interpenetrated walls. This structural configuration can notably enhance the framework robustness while maintaining its high porosity, affording one of the highest gravimetric and volumetric surface areas of 3102 m2 g−1 and 1976 m2 cm−3 among the reported HOFs so far. ZJU‐HOF‐5a exhibits an extremely high volumetric H2 uptake of 43.6 g L−1 at 77 K/100 bar and working capacity of 41.3 g L−1 under combined swing conditions, and also impressive methane storage performance with a 5−100 bar working capacity of 187 (or 159) cm3 cm−3 at 270 K (or 296 K). SCXRD studies on CH4‐loaded ZJU‐HOF‐5a reveal that abundant supramolecular binding sites combined with ultrahigh porosities account for its high CH4 storage capacities. Combined with high stability, super‐hydrophobicity, and easy‐recovery, ZJU‐HOF‐5a is placed among the most promising materials for H2 and CH4 storage applications.

Exploring the value of FAP-targeted PET/CT in differentiating breast cancer molecular subtypes: a preliminary study.

This prospective study aims to evaluate the value of [18F]AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography-computed tomography (PET/CT) in predicting molecular subtypes of breast cancer. The study consecutively recruited patients suspected of having breast cancer from a single center who were prospectively enrolled from July 2023 to May 2024 and underwent [18F]AlF-NOTA-FAPI-04 PET/CT. This study compared the differences in tracer uptake among breast cancers with different adverse prognostic factors and molecular subtypes. The classification performance for each molecular subtype of breast cancer was assessed using a receiver operating characteristic (ROC) curve. Fifty-three participants (mean age, 51 ± 11 years; 52 females) were evaluated. Breast cancer lesions with adverse prognostic factors showed higher tracer uptake. The five different molecular subtypes exhibited varying levels of uptake. The luminal A and luminal B (HER2-negative) subtypes had relatively low uptake, while the luminal B (HER2-positive), HER2-positive, and triple-negative subtypes had relatively high uptake. ROC analysis identified the max standardized uptake value (SUVmax) as a significant classifier (AUC = 0.912, P = 0.0005) for the luminal A subtype, with 100% sensitivity and 83% specificity. For predicting the luminal B (HER2-negative) subtype, SUVmax had an AUC of 0.770 (P = 0.0015). SUVmax, with an AUC of 0.781 (P = 0.003), was used to identify the triple-negative subtype tumors, resulting in a sensitivity of 100% and specificity of 51%. Lastly, the ROC curve showed the cut-off 15.40 (AUC = 0.921, P < 0.0001) could classify luminal A & luminal B (HER2-negative), and luminal B (HER2-positive) & HER2-positive & triple-negative, yielding a sensitivity of 94% and specificity of 79%. The uptake of [18F]AlF-NOTA-FAPI-04 is significantly correlated with the molecular subtypes of breast cancer, and [18F]AlF-NOTA-FAPI-04 PET/CT is a potential tool for noninvasive identification of luminal A subtypes and guidance of FAP-targeted therapies.