Long-term strict ant-plant mutualism identity characterises growth rate and leaf shearing resistance of an Amazonian myrmecophyte.

Over 125 million years of ant-plant interactions have culminated in one of the most intriguing evolutionary outcomes in life history. The myrmecophyte Duroia hirsuta (Rubiaceae) is known for its mutualistic association with the ant Myrmelachista schumanni and several other species, mainly Azteca, in the north-western Amazon. While both ants provide indirect defences to plants, only M. schumanni nests in plant domatia and has the unique behaviour of clearing the surroundings of its host tree from heterospecific plants, potentially increasing resource availability to its host. Using a 12-year survey, we asked how the continuous presence of either only M. schumanni or only Azteca spp. benefits the growth and defence traits of host trees. We found that the continuous presence of M. schumanni improved relative growth rates and leaf shearing resistance of Duroia better than trees with Azteca. However, leaf herbivory, dry matter content, trichome density, and secondary metabolite production were the same in all trees. Survival depended directly on ant association (> 94% of trees died when ants were absent). This study extends our understanding of the long-term effects of strict ant-plant mutualism on host plant traits in the field and reinforces the use of D. hirsuta-M. schumanni as a model system suitable for eco-co-evolutionary research on plant-animal interactions.

Reductions in PTSD severity precede reductions in pain intensity among veterans receiving intensive treatment.

OBJECTIVE: Chronic pain often co-occurs with posttraumatic stress disorder (PTSD). The mutual maintenance hypothesis proposes that there may be shared underlying mechanisms of symptoms of pain exacerbating PTSD, and vice versa. The association between PTSD and pain intensity remains understudied. To elucidate the relationship, the present study examined the temporality of changes in PTSD severity and pain intensity in veterans undergoing intensive PTSD treatment. METHOD: Data from 332 veterans undergoing intensive 2-week cognitive processing therapy- (CPT-) based treatment (ITP) with adjunctive components (i.e., mindfulness, art therapy). Random intercepts cross-lagged panel models (RI-CLPMs) were used to examine within-subjects relationships between pain intensity and PTSD severity over the course of the program. RESULTS: Veterans experienced large PTSD severity reductions (Essg = 1.20; p < .001) and small pain severity reductions (Essg = 0.21; p < .001) over the course of treatment, despite pain not being a treatment target. RI-CLPMs revealed that PTSD severity significantly predicted subsequent pain severity. Results indicate the absence of a bidirectional relationship in that changes in pain intensity did not predict later PTSD severity improvement during the ITP. Time trends for both PTSD severity and pain intensity were generally consistent with respect to baseline demographic characteristics. CONCLUSION: Our findings support the mutual maintenance regarding the association between PTSD and pain intensity. Future research should investigate temporal associations in other evidence-based PTSD treatments and formats and evaluate the long-term impacts of PTSD treatment on pain intensity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.

Objective: Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context. Methods: We used zebrafish, rodents, and transplanted human islets comprising six different models of interrupted glucagon signaling to examine their impact on delta and beta cell proliferation and mass. We also used models with global deficiency of the cationic amino acid transporter, SLC7A2, and mTORC1 inhibition via rapamycin, to determine whether amino acid-dependent nutrient sensing was required for islet non-alpha cell growth. Results: Inhibition of glucagon signaling stimulated delta cell proliferation in mouse and transplanted human islets, and in mouse islets. This was rapamycin-sensitive and required SLC7A2. Likewise, gcgr deficiency augmented beta cell proliferation via SLC7A2- and mTORC1-dependent mechanisms in zebrafish and promoted cell cycle engagement in rodent beta cells but was insufficient to drive a significant increase in beta cell mass in mice. Conclusion: Our findings demonstrate that interruption of glucagon signaling augments islet non-alpha cell proliferation in zebrafish, rodents, and transplanted human islets in a manner requiring SLC7A2 and mTORC1 activation. An increase in delta cell mass may be leveraged for future beta cell regeneration therapies relying upon delta cell reprogramming.

Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments.

Divergent total syntheses of binding pocket and peripherally modified tetrachlorovancomycins, a non-native synthetic glycopeptide, and their evaluation are disclosed. Central to the approach is the synthesis of a single late-stage intermediate that bears a residue 4 thioamide ([Ψ[C(═S)NH]Tpg4]tetrachlorovancomycin (3), LLS 15 steps, 14% overall) as a precursor to either of two key pocket modifications and their pairing with any combination of two peripheral modifications conducted without protecting groups. A stereochemical simplification achieved by the addition of two aryl chlorides removes two synthetically challenging atropisomer centers in native glycopeptides and streamlines the synthesis. Key features include in a convergent epimerization-free thioacylation of the AB ring system amine with an N-thioacylbenzotriazolyl DE tetrapeptide (85%) followed by simultaneous room-temperature SNAr macrocyclizations of the CD and DE ring systems (96%). The approach provided 3 from which [Ψ[C(═N)NH]Tpg4]tetrachlorovancomycin (4) and [Ψ(CH2NH)Tpg4]tetrachlorovancomycin (5) were prepared in a single-step and bear binding pocket modifications that convey dual d-Ala-d-Ala/d-Lac ligand binding to overcome vancomycin resistance. The newest maxamycin members are disclosed, bearing two additional peripheral modifications that introduce two independent synergistic MOAs that do not rely on native ligand binding for activity. Ligand binding properties of pocket-modified tetrachlorovancomycins 3-5, antibacterial activity of a key compound series, and PK assessments of two tetrachloromaxamycins are reported.

IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.

Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.

Impact of Chemotherapy Educational Videos for Patients with Acute Myeloid Leukemia.

Patient education in acute myeloid leukemia (AML) has become increasingly complex with the introduction of new treatments and chemotherapy regimens. Video education presents an opportunity to supplement traditional patient education and address some of the gaps associated with standard methods. This single-center study sought to assess the potential impact of supplemental video education on patients receiving induction chemotherapy for AML. Participants were consented to be randomized to receive their education with or without a supplemental video designed for their treatment regimen. We then provided a survey to each participant to assess knowledge retention, anxiety, and overall satisfaction with their care. Patients that received video education were found to have significantly improved knowledge retention compared to those that did not. There were no differences detected in anxiety or patient satisfaction. Video education appears to be an effective supplemental method for patient education in AML. Limitations include the single-center nature of the study at an urban academic medical center with a relatively well-educated, primarily Caucasian, younger population. Future research is warranted to assess the video in a diverse set of languages and to explore its broader benefits.

Rapid selection of milk mid-infrared spectra for creating a world representative spectral database of dairy cow population.

The advantage of employing mid-infrared spectrometry for milk analysis in breeding lies in its ability to quickly generate millions of records. However, these records may be biased if the calibration process does not account for their spectral variability when constructing the predictive model. So, this study introduces a novel method for developing a World Representative Spectral Database (WRSD) to reduce the risks of spectral extrapolation when predicting dairy traits in new samples. Utilizing a 2-phase selection procedure that is both efficient and minimizes memory usage, we first generate a decomposition matrix via Principal Component Analysis (PCA) on a data set of 2,324,443 records. The next phase iterates spectral selection based on a location index from PCA scores, calculating spectra occurrence frequency for refined barycenter estimations. The chosen spectra's barycenter closely aligns with the entire data set, proving the efficacy of using just 3 principal components (PCs). Applied to 4 varied data sets, totaling over 21 million records, we select 583,440 spectra to represent spectral diversity, with selection rates between 2.00% and 14.88%. This selection illustrates the spectral variability across different dairy populations and data providers. Demonstrated through a hypothetical calibration set of 71 samples, the WRSD's utility for algorithm developers becomes apparent. This calibration set covers between 91.42 to 98.50% of the WRSD variability, except for the Irish data set (3.50%), indicating a need for additional samples to accurately represent Irish variability and minimize spectral extrapolation. This study offers valuable insights into the representativeness of training sets for capturing spectral variability within targeted dairy populations. While the current WRSD does not fully encompass global milk spectral diversity, its development underscores the importance of gathering more data and standardizing spectral information across spectrometer brands. Ultimately, the WRSD proves crucial not just for trait prediction but also for identifying abnormal milk samples, also marking a significant relevance in dairy science technology.

Metabolic Tumor Volume on 18-Fluorodeoxyglucose Positron Emission Tomography as a Prognostic Marker of Survival in Patients With Locally Advanced or Metastatic Neuroendocrine Neoplasms Treated With 177Lutetium-DOTA-Octreotate Peptide Receptor Radionuclide Therapy.

OBJECTIVE: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT). METHODS: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low). Main Outcomes were overall survival (OS) and progression-free survival (PFS) by MTV and TLG (high vs low). RESULTS: One hundred five patients were included. Median age was 64 years (50% male). Main primary NEN sites were small bowel (43.8%) and pancreas (40.0%). Median MTV was 3.8 mL and median TLG was 19.9. Dichotomization formed identical cohorts regardless of whether MTV or TLG were used. Median OS was 72 months; OS did not differ based on MTV/TLG high versus low (47.4 months vs not reached; hazard ratio, 0.43; 95% confidence interval [CI], 0.18-1.04; P = 0.0594). Median PFS was 30.4 months; PFS differed based on MTV/TLG high versus low (21.6 months vs 45.7 months; hazard ratio, 0.35; 95% CI, 0.19-0.64; P = 0.007). CONCLUSIONS: Low MTV/TLG on pre-treatment FDG-PET was associated with longer PFS in metastatic NEN patients receiving PRRT.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Changes in emotion regulation difficulties and PTSD symptom severity in an intensive treatment program for PTSD.

BACKGROUND: Greater difficulties in emotion regulation (ER) and decreased use of adaptive ER strategies have been associated with higher levels of posttraumatic stress disorder (PTSD) symptoms. To date, limited research has explored whether ER improves with PTSD treatment or whether such improvements are linked with improvements in PTSD symptoms. METHODS: Veterans and service members with PTSD (N = 223) participated in a 2-week intensive treatment program (ITP) based in Cognitive Processing Therapy (CPT). ER was measured using the Difficulties in Emotion Regulation Short Form (DERS-SF) at baseline and on days 4 and 9 of treatment. PTSD symptoms were reported on the PTSD Symptom Checklist for DSM-5 (PCL-5) at baseline, on days 3, 5, 6, and 8 of treatment, and at post-treatment. RESULTS: DERS-SF scores decreased during treatment (Mchange = 5.12, d = 0.38). Baseline DERS-SF did not predict overall PCL-5 scores across timepoints (p = .377). However, scores on the DERS-SF over time were significantly associated with PCL-5 improvement over the course of treatment (p < .001, R2b = 0.07). Finally, improvements in all subscales of the DERS-SF across time except clarity were significantly associated with improvement in PCL-5 over time. LIMITATIONS: Additional treatment components in the ITP beyond CPT may have contributed to ER improvements. Conclusions are also limited by the use of self-report data. CONCLUSIONS: An intensive CPT-based treatment program for veterans and service members can lead to improved ER in two weeks. ER improvements are associated with PTSD symptom severity during the ITP.

Computational Studies of Reactions of 1,2,4,5-Tetrazines with Enamines in MeOH and HFIP.

The reaction between 1,2,4,5-tetrazines and alkenes in polar solvents proceeds through a Diels-Alder cycloaddition along the C-C axis (C3/C6 cycloaddition) of the tetrazine, followed by dinitrogen loss. By contrast, the reactions of 1,2,4,5-tetrazines with enamines in hexafluoroisopropanol (HFIP) give 1,2,4-triazine products stemming from a formal Diels-Alder addition across the N-N axis (N1/N4 cycloaddition). We explored the mechanism of this interesting solvent effect through DFT calculations in detail and revealed a novel reaction pathway characterized by C-N bond formation, deprotonation, and a 3,3-sigmatropic rearrangement. The participation of an HFIP molecule was found to be crucial to the N1/N4 selectivity over C3/C6 due to the more favored initial C-N bond formation than C-C bond formation.

Veterans' 12-month PTSD and depression outcomes following 2- and 3-week intensive cognitive processing therapy-based treatment.

Background: Growing evidence indicates that daily delivery of evidence-based PTSD treatments (e.g. Cognitive Processing Therapy (CPT)), as part of intensive PTSD treatment programmes (ITPs), is feasible and effective. Research has demonstrated that a 2-week CPT-based ITP can produce equivalent outcomes to a 3-week ITP, suggesting shorter treatment can also be highly effective. However, the extent to which ITP length and composition impact longer-term outcomes needs further study.Objective: We examined whether PTSD and depression symptoms 3-, 6-, and 12-months following completion of a 2-week ITP could be considered non-inferior, or equivalent, to those of a 3-week ITP.Method: Data from 638 veterans who participated in a 2-week CPT-based ITP were evaluated against 496 veterans who participated in a 3-week CPT-based ITP. A Bayes factor approach was used to examine whether PTSD and depression severity outcomes of the 2-week ITP could be considered equivalent to the 3-week ITP.Results: Participants across both ITPs reported large PTSD (d = 0.98) and moderate to large depression symptom reductions (d = 0.69) from baseline to 12-month follow-up. The PTSD and depression symptom reductions seen in the 2-week ITP were determined to be equivalent to those of the 3-week ITP.Conclusions: Low follow-up completion was a limitation. Future research might replicate the present findings using samples with greater follow-up rates and explore whether adjunctive services impact other relevant constructs, such as quality of life and functioning.

This study demonstrated that intensive PTSD treatment programmes for veterans can produce large and lasting PTSD and depression symptoms reductions.A 2-week intensive PTSD treatment programme that offered 37 fewer clinical hours was just as effective as a 3-week programme for veterans, with lasting symptom improvement up to 12 months after treatment.The 2-week programme focused primarily on individual Cognitive Processing Therapy delivered twice per day whereas the 3-week programme combined individual and group CPT and had a much larger number of adjunctive services.

Human insulin as both antigen and protector in type 1 diabetes.

Type 1 diabetes (T1D) is characterized by T-cell responses to islet antigens. Investigations in humans and the nonobese diabetic (NOD) mouse model of T1D have revealed that T-cell reactivity to insulin plays a central role in the autoimmune response. As there is no convenient NOD-based model to study human insulin (hIns) or its T-cell epitopes in the context of spontaneous T1D, we developed a NOD mouse strain transgenically expressing hIns in islets under the control of the human regulatory region. Female NOD.hIns mice developed T1D at approximately the same rate and overall incidence as NOD mice. Islet-infiltrating T cells from NOD.hIns mice recognized hIns peptides; both CD8 and CD4 T-cell epitopes were identified. We also demonstrate that islet-infiltrating T cells from HLA-transgenic NOD.hIns mice can be used to identify potentially patient-relevant hIns T-cell epitopes. Besides serving as an antigen, hIns was expressed in the thymus of NOD.hIns mice and could serve as a protector against T1D under certain circumstances, as previously suggested by genetic studies in humans. NOD.hIns mice and related strains facilitate human-relevant epitope discovery efforts and the investigation of fundamental questions that cannot be readily addressed in humans.

Occupational Radiation Dose Trends in U.S. Radiologic Technologists Assisting with Fluoroscopically Guided Interventional Procedures, 1980-2020.

PURPOSE: To summarize dose trends from 1980 to 2020 for 19,651 U.S. Radiologic Technologists who reported assisting with fluoroscopically guided interventional procedures (FGIPs), overall and by work history characteristics. MATERIALS AND METHODS: A total of 762,310 annual personal dose equivalents at a 10-mm reference depth (doses) during 1980-2020 for 43,823 participants of the U.S. Radiologic Technologists (USRT) cohort who responded to work history questionnaires administered during 2012-2014 were summarized. This population included 19,651 technologists who reported assisting with FGIP (≥1 time per month for ≥12 consecutive months) at any time during the study period. Doses corresponding to assistance with FGIP were estimated in terms of proximity to patients, monthly procedure frequency, and procedure type. Box plots and summary statistics (eg, medians and percentiles) were used to describe annual doses and dose trends. RESULTS: Median annual dose corresponding to assistance with FGIP was 0.65 mSv (interquartile range [IQR], 0.60-1.40 mSv; 95th percentile, 6.80). Higher occupational doses with wider variability were associated with close proximity to patients during assistance with FGIP (median, 1.20 mSv [IQR, 0.60-4.18 mSv]; 95th percentile, 12.66), performing ≥20 FGIPs per month (median, 0.75 mSv [IQR, 0.60-2.40 mSv]; 95th percentile, 9.44), and assisting with high-dose FGIP (median, 0.70 mSv [IQR, 0.60-1.90 mSv]; 95th percentile, 8.30). CONCLUSIONS: Occupational doses corresponding to assistance with FGIP were generally low but varied with exposure frequency, procedure type, and proximity to patients. These results highlight the need for vigilant dose monitoring, radiation safety training, and proper protective equipment.

Nuclear factor kappa B-dependent persistence of Salmonella Typhi and Paratyphi in human macrophages.

Salmonella serovars Typhi and Paratyphi cause a prolonged illness known as enteric fever, whereas other serovars cause acute gastroenteritis. Mechanisms responsible for the divergent clinical manifestations of nontyphoidal and enteric fever Salmonella infections have remained elusive. Here, we show that S. Typhi and S. Paratyphi A can persist within human macrophages, whereas S. Typhimurium rapidly induces apoptotic macrophage cell death that is dependent on Salmonella pathogenicity island 2 (SPI2). S. Typhi and S. Paratyphi A lack 12 specific SPI2 effectors with pro-apoptotic functions, including nine that target nuclear factor κB (NF-κB). Pharmacologic inhibition of NF-κB or heterologous expression of the SPI2 effectors GogA or GtgA restores apoptosis of S. Typhi-infected macrophages. In addition, the absence of the SPI2 effector SarA results in deficient signal transducer and activator of transcription 1 (STAT1) activation and interleukin 12 production, leading to impaired TH1 responses in macrophages and humanized mice. The absence of specific nontyphoidal SPI2 effectors may allow S. Typhi and S. Paratyphi A to cause chronic infections. IMPORTANCE: Salmonella enterica is a common cause of gastrointestinal infections worldwide. The serovars Salmonella Typhi and Salmonella Paratyphi A cause a distinctive systemic illness called enteric fever, whose pathogenesis is incompletely understood. Here, we show that enteric fever Salmonella serovars lack 12 specific virulence factors possessed by nontyphoidal Salmonella serovars, which allow the enteric fever serovars to persist within human macrophages. We propose that this fundamental difference in the interaction of Salmonella with human macrophages is responsible for the chronicity of typhoid and paratyphoid fever, suggesting that targeting the nuclear factor κB (NF-κB) complex responsible for macrophage survival could facilitate the clearance of persistent bacterial infections.

Muscle and joint mechanics during maximum force biting following total temporomandibular joint replacement surgery.

Total temporomandibular joint replacement (TMJR) surgery is the established treatment for severe temporomandibular joint disorders. While TMJR surgery is known to increase mouth-opening capacity, reduce pain and improve quality of life, little is known about post-surgical jaw function during activities of daily living such as biting and chewing. The aim of this study was to use subject-specific 3D bite force measurements to evaluate the magnitude and direction of joint loading in unilateral total TMJR patients and compare these data to those in healthy control subjects. An optoelectronic tracking system was used to measure jaw kinematics while biting a rubber sample for 5 unilateral total TMJR patients and 8 controls. Finite element simulations driven by the measured kinematics were employed to calculate the resultant bite force generated when compressing the rubber between teeth during biting tasks. Subject-specific musculoskeletal models were subsequently used to calculate muscle and TMJ loading. Unilateral total TMJR patients generated a bite force of 249.6 ± 24.4 N and 164.2 ± 62.3 N when biting on the contralateral and ipsilateral molars, respectively. In contrast, controls generated a bite force of 317.1 ± 206.6 N. Unilateral total TMJR patients biting on the contralateral molars had a significantly higher lateral TMJ force direction (median difference: 63.6°, p = 0.028) and a significantly lower ratio of working TMJ force to bite force (median difference: 0.17, p = 0.049) than controls. Results of this study may guide TMJ prosthesis design and evaluation of dental implants.

[18F]FDG PET/CT-Avid Discordant Volume as a Biomarker in Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Study.

[18F]FDG PET/CT and [68Ga]Ga-DOTATATE PET/CT are both used to predict tumor biology in neuroendocrine neoplasms. Although the presence of discordant ([18F]FDG-avid/non-[68Ga]Ga-DOTATATE-avid) disease predicts poor prognosis, the significance of the volume of such discordant disease remains undetermined. The aim of this study is to investigate discordant tumor volume as a potential biomarker in patients with advanced gastroenteropancreatic neuroendocrine neoplasms (GEPNENs). Methods: A multicenter retrospective study in patients with advanced GEPNENs and paired [18F]FDG and [68Ga]Ga-DOTATATE PET/CT no more than 85 d apart was conducted. Patients with discordant disease were identified by the NETPET score, and discordant lesions were contoured with a flat [18F]FDG SUV cutoff of 4. The primary variable of interest was the total discordant volume (TDV), which was the sum of the volumes of discordant lesions. Patients were dichotomized into high- and low-TDV cohorts by the median value. The primary endpoint was overall survival. Results: In total, 44 patients were included (50% men; median age, 60 y), with primary cancers in the pancreas (45%), small bowel (23%), colon (20%), and other (12%). Of the patients, 5% had grade 1 disease, 48% had grade 2 disease, and 48% had grade 3 disease (24% well differentiated, 67% poorly differentiated, 10% unknown within the grade 3 cohort). The overall median survival was 14.1 mo. Overall survival was longer in the low-TDV cohort than in the high-TDV cohort (median volume, 43.7 cm3; survival time, 23.8 mo vs. 9.4 mo; hazard ratio, 0.466 [95% CI, 0.229-0.948]; P = 0.0221). Patients with no more than 2 discordant intrahepatic lesions survived longer than those with 2 or more lesions (31.8 mo vs. 10.2 mo, respectively; hazard ratio, 0.389 [95% CI, 0.194-0.779]; P = 0.0049). Conclusion: TDV is a potential prognostic biomarker in GEPNENs and should be investigated in future neuroendocrine neoplasm trials.

A practical method for assessing quantitative scanner accuracy with long-lived radionuclides: The ARTnet insert.

Objectives: To address the problem of using large volumes of long-lived radionuclides in test phantoms to check calibration accuracy of PET and SPECT systems we have developed a test object which (a) contains less radioactivity, (b) has a low total volume, and (c) is easier to store than currently used phantoms, while still making use of readily-available "standardised" test objects. Methods: We have designed a hollow acrylic cylindrical insert compatible with the NEMA/IEC PET Body Image Quality (IQ) phantom used in NU 2 performance testing of PET systems. The insert measures 90 mm internal diameter and 70 mm internal height and so is sufficiently large to not be subject to partial volume effects in PET or SPECT imaging. The volume of the insert is approximately 500 mL. It has been designed as a replacement for the standard long cylindrical "lung insert" in the IQ phantom without needing to remove the fillable hollow spheres of the phantom. The insert been tested with 18F, 68Ga and 124I PET/CT and 99mTc, 131I and 177Lu SPECT/CT on scanners that had previously been calibrated for these radionuclides. Results: The scanners were found to produce accurate image reconstructions in the insert with  5% of the true value without any confounding uncertainty from partial volume effects when compared to NEMA NU 2-2018 Phantom measurement. Conclusions: The "ARTnet Insert" is simple to use, inexpensive, compatible with current phantoms and is suitable for both PET and SPECT systems. It does not suffer from significant partial volume losses permitting its use even with the poor spatial resolution of high-energy imaging with 131I SPECT. Furthermore, it uses less radioactivity in a smaller volume than would be required to fill the entire phantom as is usually done. Long-term storage is practical while allowing radioactive decay of the insert contents.