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Aims: The aim of this study was to create artificial intelligence (AI) software with the purpose of providing a second opinion to physicians to support distal radius fracture (DRF) detection, and to compare the accuracy of fracture detection of physicians with and without software support. Methods: The dataset consisted of 26,121 anonymized anterior-posterior (AP) and lateral standard view radiographs of the wrist, with and without DRF. The convolutional neural network (CNN) model was trained to detect the presence of a DRF by comparing the radiographs containing a fracture to the inconspicuous ones. A total of 11 physicians (six surgeons in training and five hand surgeons) assessed 200 pairs of randomly selected digital radiographs of the wrist (AP and lateral) for the presence of a DRF. The same images were first evaluated without, and then with, the support of the CNN model, and the diagnostic accuracy of the two methods was compared. Results: At the time of the study, the CNN model showed an area under the receiver operating curve of 0.97. AI assistance improved the physician’s sensitivity (correct fracture detection) from 80% to 87%, and the specificity (correct fracture exclusion) from 91% to 95%. The overall error rate (combined false positive and false negative) was reduced from 14% without AI to 9% with AI. Conclusion: The use of a CNN model as a second opinion can improve the diagnostic accuracy of DRF detection in the study setting. Cite this article: Bone Joint Res 2024;13(10):588–595.

Abstract Background Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects. Methods Targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) in 147 paired plasma-CSF samples from the Ace Alzheimer Center Barcelona and 58 CSF samples of MCI patients from the Mannheim/Heidelberg cohort. Linear regression was used to evaluate the association of metabolites with CSF levels of ATN biomarkers in the overall sample and stratified by Aβ-42 pathology and APOE genotype. We further evaluated the role of metabolites in MCI to AD dementia progression. Results Increased CSF levels of PGF2α, 8,12-iso-iPF2α VI, and 5-iPF2α VI were significantly associated (False discovery rate (FDR)

Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin αvβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin αvβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the αvβ6-binding peptide (αvβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin αvβ6-selective internalization, cell binding, and cytotoxicity. Integrin αvβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing αvβ6 (+) tumors (median survival: 77 days, vs αvβ6 (-) tumor group 49 days, and all other control groups 37 days).

Across the world, local communities are actively engaging in management and monitoring of natural resources. The underlying driver of most community-driven efforts goes beyond the utilizations of natural resources to entail a deeper relation to the place or ecosystem they are managing. The aim of this study is to understand what motivates a local volunteer group to spend considerable amount of time and resources to manage and restore a subarctic lake. We used a case study approach combining analysis of documents, participant observation and semi-structured interviews to explore their narrative. The findings show that values, such as care, responsibility, and stewardship, were the primary motivation of this effort and its ultimate goal. The project also promoted relational values like social cohesion, cultural identity, and knowledge-sharing. Despite no longer being essential for subsistence, the lake retains cultural and social significance, highlighting the need to document informal community-based monitoring and management practices for understanding ecological dynamics. The implications include the importance of recognizing relational values in shaping behaviour towards nature for achieving sustainability.

BackgroundAlthough mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness.MethodsComparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation.ResultsIonophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (

IntroductionWhile antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined.MethodsInterferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD).ResultsIn two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination.DiscussionOverall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Tipping points in the Earth system could be passed within the Paris Agreement's temperature goal range (1.5°C–2°C). Tipping processes are a feature of complex Earth system dynamics that present major governance challenges not addressed by existing global governance institutions. The common governance toolkit is a poor match for dealing with tipping processes, especially non-linear change, and radical intertemporality. To support the development of effective responses to anticipated, rapid state changes in the Earth system, there is an urgent need for new interdisciplinary research programs focused specifically on tipping-point governance. We distinguish two domains of action in a multi-phase framework - prevention and impact governance - and identify key research areas and questions that need to be addressed. These include developing governance principles, identifying actors and institutions that should be involved or need to be created, and determining the appropriate temporal and spatial scales for governance efforts.

Abstract Augmented reality (AR) apps, in which the virtual and real world are combined, can recreate instrumental activities of daily living (IADL) and are therefore promising to measure cognition needed for IADL in early Alzheimer’s disease (AD) both in the clinic and in the home settings. The primary aim of this study was to distinguish and classify healthy controls (HC) from participants with AD pathology in an early AD stage using an AR app. The secondary aims were to test the association of the app with clinical cognitive and functional tests and investigate the feasibility of at-home testing using AR. We furthermore investigated the test-retest reliability and potential learning effects of the task. The digital score from the AR app could significantly distinguish HC from preclinical AD (preAD) and prodromal AD (proAD), and preAD from proAD, both with in-clinic and at-home tests. For the classification of the proAD group, the digital score (AUCclinic_visit = 0.84 [0.75–0.93], AUCat_home = 0.77 [0.61–0.93]) was as good as the cognitive score (AUC = 0.85 [0.78–0.93]), while for classifying the preAD group, the digital score (AUCclinic_visit = 0.66 [0.53–0.78], AUCat_home = 0.76 [0.61–0.91]) was superior to the cognitive score (AUC = 0.55 [0.42–0.68]). In-clinic and at-home tests moderately correlated (rho = 0.57, p

Abstract Environmental monitoring and long-term research produce detailed understanding, but its collective effort does not add up to ‘the environment’ and therefore may be difficult to relate to. Local knowledge, by contrast, is multifaceted and relational and therefore can help ground and complement scientific knowledge to reach a more complete and holistic understanding of the environment and changes therein. Today’s societies, however, are increasingly fleeting, with mobility potentially undermining the opportunity to generate rich community knowledge. Here we perform a case study of High Arctic Svalbard, a climate change and environmental science hotspot, using a range of community science methods, including a Maptionnaire survey, focus groups, interviews and cognitive mapping. We show that rich local knowledge on Svalbard could indeed be gathered through community science methods, despite a high level of transience of the local population. These insights complement environmental monitoring and enhance its local relevance. Complex understanding of Svalbard’s ecosystems by the transient local community arose because of strong place attachment, enabling environmental knowledge generation during work and play. We conclude that transience does not necessarily prevent the generation of valuable local knowledge that can enrich and provide connection to scientific understanding of the environment.

Abstract Background Systematic literature screening is a key component in systematic reviews. However, this approach is resource intensive as generally two persons independently of each other (double screening) screen a vast number of search results. To develop approaches for increasing efficiency, we tested the use of text mining to prioritize search results as well as the involvement of only one person (single screening) in the study selection process. Method Our study is based on health technology assessments (HTAs) of drug and non-drug interventions. Using a sample size calculation, we consecutively included 11 searches resulting in 33 study selection processes. Of the three screeners for each search, two used screening tools with prioritization (Rayyan, EPPI Reviewer) and one a tool without prioritization. For each prioritization tool, we investigated the proportion of citations classified as relevant at three cut-offs or STOP criteria (after screening 25%, 50% and 75% of the citation set). For each STOP criterion, we measured sensitivity (number of correctly identified relevant studies divided by the total number of relevant studies in the study pool). In addition, we determined the number of relevant studies identified per single screening round and investigated whether missed studies were relevant to the HTA conclusion. Results Overall, EPPI Reviewer performed better than Rayyan and identified the vast majority (88%, Rayyan 66%) of relevant citations after screening half of the citation set. As long as additional information sources were screened, it was sufficient to apply a single-screening approach to identify all studies relevant to the HTA conclusion. Although many relevant publications (n = 63) and studies (n = 29) were incorrectly excluded, ultimately only 5 studies could not be identified at all in 2 of the 11 searches (1x 1 study, 1x 4 studies). However, their omission did not change the overall conclusion in any HTA. Conclusions EPPI Reviewer helped to identify relevant citations earlier in the screening process than Rayyan. Single screening would have been sufficient to identify all studies relevant to the HTA conclusion. However, this requires screening of further information sources. It also needs to be considered that the credibility of an HTA may be questioned if studies are missing, even if they are not relevant to the HTA conclusion.

Serum albumin binding moieties (ABMs) such as the Evans blue (EB) dye fragment and the 4-(p-iodophenyl)butyryl (IP) have been used to improve the pharmacokinetic profile of many radiopharmaceuticals. The goal of this work was to directly compare these two ABMs when conjugated to an integrin αvβ6 binding peptide (αvβ6-BP); a peptide that is currently being used for positron emission tomography (PET) imaging in patients with metastatic cancer. The ABM-modified αvβ6-BP peptides were synthesized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) chelator for radiolabeling with copper-64 to yield [64Cu]Cu DOTA-EB-αvβ6-BP ([64Cu]1) and [64Cu]Cu DOTA-IP-αvβ6-BP ([64Cu]2). Both peptides were evaluated in vitro for serum albumin binding, serum stability, and cell binding and internalization in the paired engineered melanoma cells DX3puroβ6 (αvβ6 +) and DX3puro (αvβ6 −), and pancreatic BxPC-3 (αvβ6 +) cells and in vivo in a BxPC-3 xenograft mouse model. Serum albumin binding for [64Cu]1 and [64Cu]2 was 53−63% and 42−44%, respectively, with good human serum stability (24 h: [64Cu]1 76%, [64Cu]2 90%). Selective αvβ6 cell binding was observed for both [64Cu]1 and [64Cu]2 (αvβ6 (+) cells: 30.3−55.8% and 48.5−60.2%, respectively, vs. αvβ6 (−) cells 3-fold improvement over the non-ABM parent peptide and thereby providing improved PET images. Comparing [64Cu]1 and [64Cu]2, the IP-ABM-αvβ6-BP [64Cu]2 displayed higher serum stability, higher tumor accumulation, and lower kidney and liver accumulation, resulting in better tumor-to-organ ratios for high contrast visualization of the αvβ6 (+) tumor by PET imaging.

CD8+ T cells have key protective roles in many viral infections. While an overall Th1-biased cellular immune response against SARS-CoV-2 has been demonstrated, most reports of anti-SARS-CoV-2 cellular immunity have evaluated bulk T cells using pools of predicted epitopes, without clear delineation of the CD8+ subset and its magnitude and targeting. In recently infected persons (mean 29.8 days after COVID-19 symptom onset), we confirm a Th1 bias (and a novel IL-4-producing population of unclear significance) by flow cytometry, which does not correlate to antibody responses against the receptor binding domain. Evaluating isolated CD8+ T cells in more detail by IFN-γ ELISpot assays, responses against spike, nucleocapsid, matrix, and envelope proteins average 396, 901, 296, and 0 spot-forming cells (SFC) per million, targeting 1.4, 1.5, 0.59, and 0.0 epitope regions respectively. Nucleocapsid targeting is dominant in terms of magnitude, breadth, and density of targeting. The magnitude of responses drops rapidly post-infection; nucleocapsid targeting is most sustained, and vaccination selectively boosts spike targeting. In SARS-CoV-2-naïve persons, evaluation of the anti-spike CD8+ T cell response soon after vaccination (mean 11.3 days) yields anti-spike CD8+ T cell responses averaging 2,463 SFC/million against 4.2 epitope regions, and targeting mirrors that seen in infected persons. These findings provide greater clarity on CD8+ T cell anti-SARS-CoV-2 targeting, breadth, and persistence, suggesting that nucleocapsid inclusion in vaccines could broaden coverage and durability.

Background: Toxoplasmosis has been of public health concern due to direct associations with socioeconomic vulnerability and inadequate living conditions. Methods: Accordingly, the present study aimed to assess antibodies against T. gondii, historical reported toxoplasmosis cases and associated socio-environmental risk factors in Pinhais, a full urban area of Curitiba, currently the eighth biggest metropolitan area of Brazil. Anti-Toxoplasma gondii antibodies were assessed by an indirect immunofluorescence reaction (RIFI). Owner and dog samples were also tested by IFAT to anti-Leishmania spp. and anti-Trypanosoma cruzi antibodies. Results: Overall, 20/135 (14.8%) persons and 13/133 (9.8%) dogs from 25 different households were considered seropositive to T. gondii. All samples were seronegative to Leishmania spp. and Trypanosoma cruzi. Conclusions: Although no significant covariates were found in the regression model, statistically associated risk factors in the bivariate analysis included no public water use (p = 0.016) and drinking raw milk (p = 0.041) for owners, and obesity (p = 0.028) and tick infestation (p = 0.03) for dogs. In addition, a spatial cluster of T. gondii seropositivity for both owners and their dogs overlapped the location of historic reported cases of human acquired, gestational and congenital toxoplasmosis. Finally, the results herein showed tick infestation as an indicator of socio-environmental risk for T. gondii exposure in the household environment, and dogs may be used as sentinels for human toxoplasmosis cases.

Abstract The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous $$\nu _e$$ ν e appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV $$^2$$ 2 . After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

Abstract Background Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness. Methods Comparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation. Results Ionophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (

Summary: Background: Sensory impairment has been related to age-associated cognitive decline. While these associations were investigated primarily in the auditory and visual domain, other senses such as touch have rarely been studied. Thus, it remains open whether these results are specific for particular sensory domains, or rather point to a fundamental role of sensory deficits in cognitive decline. Methods: Data from 31 participants with mild cognitive impairment (MCI), 46 participants with frailty, and 23 non-clinical control participants (NCCs) were included. We assessed sensory function using visual acuity and contrast sensitivity, hearing threshold, and mechanical detection threshold. Cognitive function in participants with MCI was assessed using associative memory performance. Group differences on sensory thresholds were tested using analyses of covariance with age, sex, and years of education as covariates. Associations between measures within participants with MCI were evaluated using Spearman correlations. Findings: We found a significant difference in mechanical detection threshold between the groups (p

ABSTRACTFacing rapid fluctuations in their natural environment, extremophiles, like the hyperthermophilic archaeon Pyrococcus furiosus, exhibit remarkable adaptability to extreme conditions. However, our understanding of their dynamic cellular responses remains limited. This study integrates RNA-sequencing and mass spectrometry data, thereby elucidating transcriptomic and proteomic responses to heat and cold shock stress in P. furiosus. Our results reveal rapid and dynamic changes in gene and protein expression following these stress responses. Heat shock triggers extensive transcriptome reprogramming, orchestrated by the transcriptional regulator Phr, targeting a broader gene repertoire than previously demonstrated. For heat shock signature genes, RNA levels swiftly return to baseline upon recovery, while protein levels remain persistently upregulated, reflecting a rapid but sustained response. Intriguingly, cold shock at 4°C elicits distinct short- and long-term responses at both RNA and protein levels. Cluster analysis identified gene sets with either congruent or contrasting trends in RNA and protein changes, representing well-separated arCOG groups tailored to their individual cellular responses. Particularly, upregulation of ribosomal proteins and significant enrichment of 5′-leadered sequences in cold-shock responsive genes suggest that translation regulation is important during cold shock adaption. Further investigating transcriptomic features, we reveal that thermal stress genes are equipped with basal sequence elements, such as strong promoter and poly(U)-terminators, facilitating a regulated response of the respective transcription units. Our study provides a comprehensive overview of the cellular response to temperature stress, advancing our understanding of stress response mechanisms in hyperthermophilic archaea and providing valuable insights into the molecular adaptations that facilitate life in extreme environments.IMPORTANCEExtreme environments provide unique challenges for life, and the study of extremophiles can shed light on the mechanisms of adaptation to such conditions. Pyrococcus furiosus, a hyperthermophilic archaeon, is a model organism for studying thermal stress response mechanisms. In this study, we used an integrated analysis of RNA-sequencing and mass spectrometry data to investigate the transcriptomic and proteomic responses of P. furiosus to heat and cold shock stress and recovery. Our results reveal the rapid and dynamic changes in gene and protein expression patterns associated with these stress responses, as well as the coordinated regulation of different gene sets in response to different stressors. These findings provide valuable insights into the molecular adaptations that facilitate life in extreme environments and advance our understanding of stress response mechanisms in hyperthermophilic archaea.

Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naı̈ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naı̈ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naı̈ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naı̈ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

PurposeThe αvβ6-BP peptide selectively targets the integrin αvβ6, a cell surface receptor recognized as a prognostic indicator for several challenging malignancies. Given that the 4-[18F]fluorobenzoyl (FBA)-labeled peptide is a promising PET imaging agent, radiolabeling via aluminum [18F]fluoride chelation and introduction of an albumin binding moiety (ABM) have the potential to considerably simplify radiochemistry and improve the pharmacokinetics by increasing biological half-life.ProceduresThe peptides NOTA-αvβ6-BP (1) and NOTA-K(ABM)-αvβ6-BP (2) were synthesized on solid phase, radiolabeled with aluminum [18F]fluoride, and evaluated in vitro (integrin ELISA, albumin binding, cell studies) and in vivo in mouse models bearing paired DX3puroβ6 [αvβ6(+)]/DX3puro [αvβ6(-)], and for [18F]AlF 2, BxPC-3 [αvβ6(+)] cell xenografts (PET imaging, biodistribution).ResultsThe peptides were radiolabeled in 23.0 ± 5.7 % and 22.1 ± 4.4 % decay-corrected radiochemical yield, respectively, for [18F]AlF 1 and [18F]AlF 2. Both demonstrated excellent affinity and selectivity for integrin αvβ6 by ELISA (IC50(αvβ6) = 3-7 nM vs IC50(αvβ3) > 10 μM) and in cell binding studies (51.0 ± 0.7 % and 47.2 ± 0.7 % of total radioactivity bound to DX3puroβ6 cells at 1 h, respectively, vs. ≤ 1.2 % to DX3puro for both compounds). The radiotracer [18F]AlF 1 bound to human serum at 16.3 ± 1.9 %, compared to 67.5 ± 1.0 % for the ABM-containing [18F]AlF 2. In vivo studies confirmed the effect of the ABM on blood circulation (≤ 0.1 % ID/g remaining in blood for [18F]AlF 1 as soon as 1 h p.i. vs. > 2 % ID/g for [18F]AlF 2 at 6 h p.i.) and higher αvβ6(+) tumor uptake (4 h: DX3puroβ6; [18F]AlF 1: 3.0 ± 0.7 % ID/g, [18F]AlF 2: 7.2 ± 0.7 % ID/g; BxPC-3; [18F]AlF 2: 10.2 ± 0.1 % ID/g).ConclusionBoth compounds were prepared using standard chemistries; affinity and selectivity for integrin αvβ6 in vitro remained unaffected by the albumin binding moiety. In vivo, the albumin binding moiety resulted in prolonged circulation and higher αvβ6-targeted uptake.

The true impact and long-term damage to organs such as the lungs after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain to be determined. Noninvasive molecularly targeted imaging may play a critical role in aiding visualization and understanding of the systemic damage. We have identified αvβ6 as a molecular target; an epithelium-specific cell surface receptor that is low or undetectable in healthy adult epithelium but upregulated in select injured tissues, including fibrotic lung. Herein we report the first human PET/CT images using the integrin αvβ6-binding peptide (18F-αvβ6-BP) in a patient 2 mo after the acute phase of infection. Minimal uptake of 18F-αvβ6-BP was noted in normal lung parenchyma, with uptake being elevated in areas corresponding to opacities on CT. This case suggests that 18F-αvβ6-BP PET/CT is a promising noninvasive approach to identify the presence and potentially monitor the persistence and progression of lung damage.

We developed a set of two precision, small-scale, water balance lysimeters to provide accurate measurements of bare soil evaporation. Each lysimeter comprises a soil tank, a balance assembly with load cell, a wicking drainage system, and a stilling well to measure drained water. Fiberglass wicks installed at the bottom of the soil tanks provide −60 cm of tension to the base of the soil column, and soil water drainage is quantified to close the water balance within the lysimeter. The calibrated lysimeters return mass changes with uncertainties ranging from 3 to 8 g, corresponding to uncertainties of 0.02–0.05 mm of water. Installed at a semi-arid site in northern Nevada, the two lysimeters are filled with uniform construction sand and silt loam. Over a six-month pilot observation period, bare soil evaporation rates of 0.19 and 0.40 mm/day were measured for the construction sand and silt loam, respectively, which is consistent with meteorological data and models of potential evapotranspiration at the site. The design of the lysimeter can be adapted to specific research goals or site restrictions, and these instruments can contribute significantly to our ability to close the soil water balance.