Clinical Implementation of Total-Body PET in China.

Total-body (TB) PET/CT is a groundbreaking tool that has brought about a revolution in both clinical application and scientific research. The transformative impact of TB PET/CT in the realms of clinical practice and scientific exploration has been steadily unfolding since its introduction in 2018, with implications for its implementation within the health care landscape of China. TB PET/CT's exceptional sensitivity enables the acquisition of high-quality images in significantly reduced time frames. Clinical applications have underscored its effectiveness across various scenarios, emphasizing the capacity to personalize dosage, scan duration, and image quality to optimize patient outcomes. TB PET/CT's ability to perform dynamic scans with high temporal and spatial resolution and to perform parametric imaging facilitates the exploration of radiotracer biodistribution and kinetic parameters throughout the body. The comprehensive TB coverage offers opportunities to study interconnections among organs, enhancing our understanding of human physiology and pathology. These insights have the potential to benefit applications requiring holistic TB assessments. The standard topics outlined in The Journal of Nuclear Medicine were used to categorized the reviewed articles into 3 sections: current clinical applications, scan protocol design, and advanced topics. This article delves into the bottleneck that impedes the full use of TB PET in China, accompanied by suggested solutions.

Intrinsic capacity assessment using World Health Organization Integrated Care for Older People Step 1, and the association with frailty in community dwelling older adults.

AIM: This study aimed to investigate the association between intrinsic capacity (IC) and frailty in community-dwelling older adults. Specifically, we examined the utility of the World Health Organization's Integrated Care for Older People Step 1 screen for identifying frail older persons in the community. METHODS: This is a cross-sectional analysis of a community frailty screening initiative. IC loss was ascertained using the World Health Organization's Integrated Care for Older People Step 1 questions. The Clinical Frailty Scale was used to categorize participants as robust (Clinical Frailty Scale S1-3) or frail (Clinical Frailty Scale ≥4). Logistic regression was used to analyze the association of individual and cumulative IC losses with frailty, adjusting for confounders. Additionally, the diagnostic performance of using cumulative IC losses to identify frailty was assessed. RESULTS: This study included 1164 participants (28.2% frail). Loss in locomotion (adjusted odds ratio [AOR] 1.47, 95% CI 1.07-2.02), vitality (AOR 1.58, 95% CI 1.04-2.39), sensory (AOR 1.99, 95% CI 1.51-2.64) and psychological capacities (AOR 1.92, 95% CI 1.45-2.56) were significantly associated with frailty. Loss in more than three IC domains was associated with frailty. Using loss in at least three ICs identifies frailty, with sensitivity of 38.6%, specificity of 83.5% and positive predictive value of 47.4%. Using loss in at least four ICs improved specificity to 96.9%, and is associated with the highest positive predictive value of 57.6% and highest positive likelihood ratio of 3.55 for frailty among all cut-off values. The area under the receiver operating characteristic curve was 0.64 (95% CI 0.61-0.68). CONCLUSIONS: IC loss as identified through World Health Organization's Integrated Care for Older People Step 1 is associated with frailty community-dwelling older adults. Geriatr Gerontol Int 2024; 24: 457-463.

Understanding and Mitigating Bias in Imaging Artificial Intelligence.

Artificial intelligence (AI) algorithms are prone to bias at multiple stages of model development, with potential for exacerbating health disparities. However, bias in imaging AI is a complex topic that encompasses multiple coexisting definitions. Bias may refer to unequal preference to a person or group owing to preexisting attitudes or beliefs, either intentional or unintentional. However, cognitive bias refers to systematic deviation from objective judgment due to reliance on heuristics, and statistical bias refers to differences between true and expected values, commonly manifesting as systematic error in model prediction (ie, a model with output unrepresentative of real-world conditions). Clinical decisions informed by biased models may lead to patient harm due to action on inaccurate AI results or exacerbate health inequities due to differing performance among patient populations. However, while inequitable bias can harm patients in this context, a mindful approach leveraging equitable bias can address underrepresentation of minority groups or rare diseases. Radiologists should also be aware of bias after AI deployment such as automation bias, or a tendency to agree with automated decisions despite contrary evidence. Understanding common sources of imaging AI bias and the consequences of using biased models can guide preventive measures to mitigate its impact. Accordingly, the authors focus on sources of bias at stages along the imaging machine learning life cycle, attempting to simplify potentially intimidating technical terminology for general radiologists using AI tools in practice or collaborating with data scientists and engineers for AI tool development. The authors review definitions of bias in AI, describe common sources of bias, and present recommendations to guide quality control measures to mitigate the impact of bias in imaging AI. Understanding the terms featured in this article will enable a proactive approach to identifying and mitigating bias in imaging AI. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Rouzrokh and Erickson in this issue.

Early identification of patients at risk for iron-deficiency anemia using deep learning techniques.

OBJECTIVES: Iron-deficiency anemia (IDA) is a common health problem worldwide, and up to 10% of adult patients with incidental IDA may have gastrointestinal cancer. A diagnosis of IDA can be established through a combination of laboratory tests, but it is often underrecognized until a patient becomes symptomatic. Based on advances in machine learning, we hypothesized that we could reduce the time to diagnosis by developing an IDA prediction model. Our goal was to develop 3 neural networks by using retrospective longitudinal outpatient laboratory data to predict the risk of IDA 3 to 6 months before traditional diagnosis. METHODS: We analyzed retrospective outpatient electronic health record data between 2009 and 2020 from an academic medical center in northern Texas. We included laboratory features from 30,603 patients to develop 3 types of neural networks: artificial neural networks, long short-term memory cells, and gated recurrent units. The classifiers were trained using the Adam Optimizer across 200 random training-validation splits. We calculated accuracy, area under the receiving operating characteristic curve, sensitivity, and specificity in the testing split. RESULTS: Although all models demonstrated comparable performance, the gated recurrent unit model outperformed the other 2, achieving an accuracy of 0.83, an area under the receiving operating characteristic curve of 0.89, a sensitivity of 0.75, and a specificity of 0.85 across 200 epochs. CONCLUSIONS: Our results showcase the feasibility of employing deep learning techniques for early prediction of IDA in the outpatient setting based on sequences of laboratory data, offering a substantial lead time for clinical intervention.

Botulinum toxin A injection for post-stroke upper limb spasticity and rehabilitation practices from centers across Asian countries.

Purpose: Describe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings. Methods: Subgroup analysis of a prospective, observational study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described. Results: Overall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (p < 0.001). The majority (96.1%) of Asian patients were rated as having improved. Conclusion: In the Asian treatment setting, BoNT-A demonstrated a clinically significant effect on goal attainment for the real-life management of upper limb spasticity following stroke.

Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.

Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents.

Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 ± 3.37 µM against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 µM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.

Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment.

Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 µM, respectively. Meanwhile, MS87 (EC50 of 1.85 µM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 µM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 µM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.

Preoperative free access to water compared to fasting for planned cesarean under spinal anesthesia: a randomized controlled trial.

BACKGROUND: Contemporary guidance for preoperative feeding allows solids up to 6 hours and clear fluids up to 2 hours before anesthesia. Clinical trial evidence to support this approach for cesarean delivery is lacking. Many medical practitioners continue to follow conservative policies of no intake from midnight to the time of surgery, especially in pregnant women. OBJECTIVE: This study aimed to evaluate the pragmatic approach of permitting free access to water up to the call to dispatch to the operating theater vs fasting from midnight in preoperative oral intake restriction for planned cesarean delivery under spinal anesthesia on perioperative vomiting and maternal satisfaction. STUDY DESIGN: A randomized controlled trial was conducted in the obstetrical unit of the University of Malaya Medical Centre from October 2020 to May 2022. A total of 504 participants scheduled for planned cesarean delivery were randomized: 252 undergoing preoperative free access to water up to the call to dispatch to the operating theater (intervention group) and 252 undergoing fasting from midnight (fasting arm). The primary outcomes were perioperative vomiting and maternal satisfaction. Analyses were performed using t test, Mann-Whitney U test, and chi-square test, as appropriate. RESULTS: Of note, 9 of 252 patients (3.6%) in the intervention group and 24 of 252 patients (9.5%) in the control group had vomiting at up to 6 hours after completion of cesarean delivery (relative risk, 0.38; 95% confidence interval, 0.18-0.79; P=.007), and the maternal satisfaction scores (0-10 visual numerical rating scale) were 9 (interquartile range, 8-10) in the intervention group and 5 (interquartile range, 3-7) in the control group (P<.001). Assessed before dispatch to the operating theater, feeling of thirst was reported by 69 of 252 patients (27.4%) in the intervention group and 134 of 252 patients (53.2%) in the control group (relative risk, 0.52; 95% confidence interval, 0.41-0.65; P<.001), capillary glucose levels were 4.8±0.7 mmol/L in the intervention group and 4.9±0.8 mmol/L in the control group (P=.048), and preoperative intravenous fluid hydration was commenced in 49 of 252 patients (19.4%) in the intervention group and 76 of 252 patients (30.2%) in the control group (relative risk, 0.65; 95% confidence interval, 0.47-0.88; P=.005). In the operating theater, ketone was detected in the catheterized urine in 38 of 252 patients (15.1%) in the intervention group and 78 of 252 patients (31.0%) in the control group (relative risk, 0.49; 95% confidence interval, 0.25-0.59; P<.001), and the numbers of doses of vasopressors needed to correct hypotension were 2.3±1.7 in the intervention group and 2.7±2.2 in the control (P=.009). The recommendation rates for preoperative oral intake regimen to a friend were 95.2% (240/252) in the intervention group and 39.7% (100/252) in the control group (relative risk, 2.40; 95% confidence interval, 2.06-2.80; P<.001), in favor of free access to water. Other assessed maternal and neonatal outcomes were not different. CONCLUSION: Compared with fasting, free access to water in planned cesarean delivery reduced perioperative vomiting and was strongly favored by women. In addition, several pre- and intraoperative secondary outcomes were improved. However, postcesarean delivery recovery and neonatal outcomes were not different.

Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes.

While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.

Long-Term Tissue Preservation at Ambient Temperature for Post-Mass Fatality Incident DNA-Based Victim Identification.

In a mass fatality incident (MFI), effective preservation of tissue samples is the cornerstone for downstream DNA-based identification of victims. This is commonly achieved through freezing of tissue samples excised from bodies/fragmented remains which may be buried or stored in refrigerated containers. This may, however, not be possible depending on the nature of the MFI; in particular, during armed conflict/war where extended periods of electrical outages would be expected. The present study compared the effectiveness of long-term tissue preservation at ambient temperatures using two commercial products (non-iodized kitchen salt and a 40% alcoholic beverage) against a chemical preservative (Allprotect™ Tissue Reagent (Qiagen, Germantown, MD, USA)) and freezing at -20 °C. Bovine muscle tissue, used as a proxy for human tissue, was treated with the four preservation methods and sampled at six different time-points over a 24-month period. All four methods were able to preserve the bovine tissue, generally yielding STR-PCR (Short Tandem Repeat-Polymerase Chain Reaction) amplicons > 200 bp in size even at the end of 24 months. Gel electrophoresis, however, indicated that salt was more effective in preserving DNA integrity with high-molecular-weight DNA clearly visible as compared to the low-molecular-weight DNA smears observed in the other methods. This study also proposes a simple process for the rapid and low-cost preservation of tissue samples for long-term storage at ambient temperatures in support of post-incident victim identification efforts.

The efficacy of short acquisition time using 18F-FDG total-body PET/CT for the identification of pediatric epileptic foci.

BACKGROUND: 18F-FDG positron emission tomography (PET) plays a crucial part in the evaluation for pediatric epileptic patients prior to therapy. Short-term scanning holds significant importance, especially for pediatrics epileptic individuals who exhibited involuntary movements. The aim was to evaluate the effects of short acquisition time on image quality and lesion detectability in pediatric epileptic patients using total-body (TB) PET/CT. A total of 25 pediatric patients who underwent TB PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Short acquisition times (60 s, 150 and 300 s) were simulated by truncating PET data in list mode to reduce count density. Subjective image quality was scored on a 5-point scale. Regions of interest analysis of suspected epileptogenic zones (EZs), corresponding locations contralateral to EZs, and healthy cerebellar cortex were used to compare the semi-quantitative uptake indices of short-time images and then were compared with 600 s images. The comparison of EZs detectability based on time-dependent PET images was performed. RESULTS: Our study demonstrated that a short acquisition time of 150 s is sufficient to maintain subjective image quality and lesion significance. Statistical analysis revealed no significant difference in subjective PET image quality between imaging at 300 s and 150 s (P > 0.05). The overall impression scores of image quality and lesion conspicuity in G60s were both greater than 3 (overall quality, 3.21 ± 0.46; lesion conspicuity, 4.08 ± 0.74). As acquisition time decreased, the changes of SUVmax and SD in the cerebellar cortex gradually increased (P < 0.01). There was no significant difference in asymmetry index (AI) difference between the groups and the AIs of EZs were > 15% in all groups. In 26 EZs of 25 patients, the lesion detection rate was still 100% when the time was reduced to 60 s. CONCLUSIONS: This study proposed that TB PET/CT acquisition time could be reduced to 60 s with acceptable lesion detectability. Furthermore, it was suggested that a 150 s acquisition time would be sufficient to achieve diagnostic performance and image quality for children with epilepsy.

Kinetic analysis of cardiac dynamic 18F-Florbetapir PET in healthy volunteers and amyloidosis patients: A pilot study.

Objectives: This study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease. Materials & methods: The distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5-5 min) and late phase (SUVRLP, 50-60 min) were also calculated. Results: Ten participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t'(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t'(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t'(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P < 0.001) and DVR(r = 0.99, P < 0.001), respectively. The DVRs in the total myocardium region increased slightly as the size of FWHM increased and became stable at a Gaussian filter ≥6 mm. The secular equilibrium of SUVR was reached at around 50-min p.i. time. Conclusion: The DVR and R1 estimated from cardiac dynamic 18F-Florbetapir PET using pSRTM with kidney pseudo-reference tissue are suggested to quantify cardiac amyloid deposition and relative perfusion, respectively, in amyloidosis patients and healthy controls. We recommend a dual-phase scan: 0.5-5 min and 50-60 min p.i. as the appropriate time window for clinically assessing cardiac amyloidosis and perfusion measurements using 18F-Florbetapir PET.

Testicular Radiomics To Predict Pathology At Time of Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminomatous Germ Cell Tumor.

INTRODUCTION: Testicular germ cell tumors are the most common malignancy in young adult males. Patients with metastatic disease receive standard of care chemotherapy followed by retroperitoneal lymph node dissection for residual masses >1cm. However, there is a need for better preoperative tools to discern which patients will have persistent disease after chemotherapy given low rates of metastatic germ cell tumor after chemotherapy. The purpose of this study was to use radiomics to predict which patients would have viable germ cell tumor or teratoma after chemotherapy at time of retroperitoneal lymph node dissection. PATIENTS AND METHODS: Patients with nonseminomatous germ cell tumor undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) between 2008 and 2019 were queried from our institutional database. Patients were included if prechemotherapy computed tomography (CT) scan and postchemotherapy imaging were available. Semiqualitative and quantitative features of residual masses and nodal regions of interest and radiomic feature extractions were performed by 2 board certified radiologists. Radiomic feature analysis was used to extract first order, shape, and second order statistics from each region of interest. Post-RPLND pathology was compared to the radiomic analysis using multiple t-tests. RESULTS: 45 patients underwent PC-RPLND at our institution, with the majority (28 patients) having stage III disease. 24 (53%) patients had teratoma on RPLND pathology, while 2 (4%) had viable germ cell tumor. After chemotherapy, 78%, 53%, and 33% of patients had cystic regions, fat stranding, and local infiltration present on imaging. After radiomic analysis, first order statistics mean, median, 90th percentile, and root mean squares were significant. Strong correlations were observed between these 4 features;a lower signal was associated with positive pathology at RPND. CONCLUSIONS: Testicular radiomics is an emerging tool that may help predict persistent disease after chemotherapy.

Do friends get under the skin?: Everyday social encounters and cardiovascular functioning among Black and White adults in the United States.

OBJECTIVE: Studies have shown that contact with friends enhances emotional health, but little is known about whether friends influence cardiovascular health. This study investigated (a) whether encounters with friends and the quality of these encounters were associated with cardiovascular reactivity in everyday life and (b) whether these associations varied by race. METHOD: Participants were from the Stress and Well-being in Everyday Life Study which included Black (n = 76; aged = 34-76) and White (n = 87, aged = 34-91) adults residing in the United States. Participants provided background and social network information in a baseline interview, followed by a 4-day ecological momentary assessment in which they reported social encounters every 3 hr. Concurrently, participants wore an electrocardiogram monitor which collected physiological data in real time. To assess cardiovascular reactivity, heart rate variability (HRV) was analyzed. RESULTS: Multilevel models revealed that at times when individuals encountered friends (particularly positive encounters), they exhibited a momentary reduction in HRV (within-person association). But those with more friend encounters during the study period (particularly positive encounters) had higher HRV than those with fewer friend encounters during the study period (between-person association). These links were observed only among Black adults, but not among White adults. CONCLUSIONS: This study contributes to the conceptual model of social integration and enriches the literature on racial disparities in cardiovascular health from a social perspective. Findings highlight the implications of engagement with friends for momentary cardiovascular reactivity and suggest that friends may be more salient for Black adults' cardiovascular health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessing dynamic metabolic heterogeneity in prostate cancer patients via total-body [68Ga]Ga-PSMA-11 PET/CT imaging: quantitative analysis of [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs.

PURPOSE: This study aimed to quantitatively assess [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs in prostate cancer using the total-body [68Ga]Ga-PSMA-11 PET/CT and to characterize the dynamic metabolic heterogeneity of prostate cancer. METHODS: Dynamic total-body [68Ga]Ga-PSMA-11 PET/CT scans were performed on ten prostate cancer patients. Manual delineation of volume-of-interests (VOIs) was performed on multiple normal organs displaying high [68Ga]Ga-PSMA-11 uptake, as well as pathological lesions. Time-to-activity curves (TACs) were generated, and the four compartment models including one-tissue compartmental model (1T1k), reversible one-tissue compartmental model (1T2k), irreversible two-tissue compartment model (2T3k) and reversible two-tissue compartmental model (2T4k) were fitted to each tissue TAC. Various rate constants, including K1 (forward transport rate from plasma to the reversible compartment), k2 (reverse transport rate from the reversible compartment to plasma), k3 (tracer binding on the PSMA-receptor and its internalization), k4 (the externalization rate of the tracer) and Ki (net influx rate), were obtained. The selection of the optimal model for describing the uptake of both lesions and normal organs was determined using the Akaike information criteria (AIC). Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values for differentiating physiological and pathological [68Ga]Ga-PSMA-11 uptake. RESULTS: Both 1T1k and 1T2k models showed relatively high AIC values compared to the 2T3k and 2T4k models in both pathological lesions and normal organs. The kinetic behavior of pathological lesions was better described by the 2T3k model compared to the 2T4k model, while the normal organs were better described by the 2T4k model. Significant variations in kinetic metrics, such as K1, k2, and k3, and Ki, were observed among normal organs with high [68Ga]Ga-PSMA-11 uptake and pathological lesions. The high Ki value in normal organs was primarily determined by elevated K1 and low k3, rather than k2. Conversely, the high Ki value in pathological lesions, ranking second to the kidney and similar to salivary glands and spleen, was predominantly determined by the highest k3 value. Notably, k3 exhibited the highest performance in distinguishing between physiological and pathological [68Ga]Ga-PSMA-11 uptake, with an area under the curve (AUC) of 0.844 (95% CI, 0.773-0.915), sensitivity of 82.9%, and specificity of 74.1%. The k3 values showed better performance than SUVmean (AUC, 0.659), SUVmax (AUC, 0.637), and other kinetic parameter including K1 (AUC, 0.604), k2 (AUC, 0.634), and Ki (AUC, 0.651). CONCLUSIONS: Significant discrepancies in kinetic metrics were detected between pathological lesions and normal organs, despite their shared high uptake of [68Ga]Ga-PSMA-11. Notably, the k3 value exhibits a noteworthy capability to distinguish between pathological lesions and normal organs with elevated [68Ga]Ga-PSMA-11 uptake. This discovery implies that k3 holds promise as a prospective imaging biomarker for distinguishing between pathologic and non-specific [68Ga]Ga-PSMA-11 uptake in patients with prostate cancer.

Comparison of parametric imaging and SUV imaging with [68 Ga]Ga-PSMA-11 using dynamic total-body PET/CT in prostate cancer.

PURPOSE: Standardized uptake value (SUV) has been prevalently used to measure [68 Ga]Ga-PSMA-11 activity in prostate cancer, but it is susceptible to multiple factors. Parametric imaging allows for absolute quantification of tracer uptake and provides a better diagnostic accuracy that is crucial for lesion detection. However, the clinical significance of total-body parametric imaging of [68 Ga]Ga-PSMA-11 remains to be fully assessed. Therefore, the aim of our study is to delve into the diagnostic implications of total-body parametric imaging of [68 Ga]Ga-PSMA-11 PET/CT for patients with prostate cancer. METHODS: Twenty prostate cancer patients were included and underwent a dynamic total-body [68 Ga]Ga-PSMA-11 PET/CT scan. An irreversible two-tissue compartment model (2T3k) was fitted for each tissue time-to-activity curve, and the net influx rate (Ki) was obtained. The image quality and semi-quantitative analysis of lesion-to-background ratio (LBR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between parametric images and SUV images. RESULTS: Kinetic modeling using 2T3k demonstrated favorable model fitting in both normal organs and lesions. All of the lesions detected on SUV images (55-60 min) could be detected on Ki images. The correlation between Ki, SUVmean, and SUVmax in both normal organs and pathological lesions was found to be positive and statistically significant. Conversely, a moderate positive correlations were found between Ki and K1 (R = 0.69, P < 0.001; R = 0.61, P < 0.001) and Ki and k3 (R = 0.69, P < 0.001; R = 0.62, P < 0.001), in normal organs and pathological lesions, respectively. Visual assessment in Ki images showed less image noise and higher lesions conspicuity compared to SUV images. Ki image-derived LBR, SNR, and CBR of pathological lesions including primary tumors (PTs), lymph node metastases (LNMs) and bone metastases (BMs), exhibited remarkably higher folds (1.4-3.6 folds) compared to those derived from SUV of corresponding lesions. CONCLUSIONS: Total-body parametric imaging of [68 Ga]Ga-PSMA-11 enhanced lesion contrast and improved lesion detectability compared to SUV images. This may potentially serve as an imaging biomarker and theranostic tool for precise diagnosis and treatment evaluation in prostate cancer patients.

Using item response theory to estimate interpretation threshold values for the Frailty Index in community dwelling older adults.

BACKGROUND: Although the frailty index (FI) is designed as a continuous measure of frailty, thresholds are often needed to guide its interpretation. This study aimed to introduce and demonstrate the utility of an item response theory (IRT) method in estimating FI interpretation thresholds in community-dwelling adults and to compare them with cutoffs estimated using the receiver operating characteristics (ROC) method. METHODS: A sample of 1,149 community-dwelling adults (mean[SD], 68[7] years) participated in this cross-sectional study. Participants completed a multi-domain geriatric screen from which the 40-item FI and 3 clinical anchors were computed - namely, (i)self-reported mobility limitations (SRML), (ii)"fair" or "poor" self-rated health (SRH), and (iii) restricted life-space mobility (RLSM). Participants were classified as having SRML-1 if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty and SRML-2 if they reported having walking and stair climbing difficulty. Participants with a Life Space Assessment score <60 points were classified as having RLSM. Threshold values for all anchor questions were estimated using the IRT method and ROC analysis with Youden criterion. RESULTS: The proportions of participants with SRML-1, SRML-2, Fair/Poor SRH, and RLSM were 21 %, 8 %, 22 %, and 9 %, respectively. The IRT-based thresholds for SRML-2 (0.26), fair/poor SRH (0.29), and RLSM (0.32) were significantly higher than those for SRML-1 (0.18). ROC-based FI cutoffs were significantly lower than IRT-based values for SRML-2, SRH, and RLSM (0.12 to 0.17), and they varied minimally and non-systematically across the anchors. CONCLUSIONS: The IRT method identifies biologically plausible FI thresholds that could meaningfully complement and contextualize existing thresholds for defining frailty.

Individual and combined associations of sarcopenia, osteoporosis and obesity with frailty in a multi-ethnic asian older adult population.

BACKGROUND: We explored the relationships between sarcopenia (SP), osteoporosis (OP), obesity (OB), (alone and in combination) with physical frailty (PF) in a multi-ethnic, population-based study of Asians aged ≥ 60 years. METHODS: Participants were enrolled from the PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study (PIONEER) study. PF was defined using the modified Fried phenotype; SP using the Asian Working Group for Sarcopenia 2019; OP using bone mineral density scores; and OB using the fat mass index. Modified Poisson regression models investigated the associations between exposures and PF, and the relative excess rates of PF due to interactions (RERI) to determine synergistic or antagonistic interactions. RESULTS: Of the 2643 participants, 54.8% was female; and 49.8%, 25.1%, 25.0% were Chinese, Indians, and Malays, respectively. 25%, 19.0% and 6.7% participants had OB only, SP only, and OP only, respectively. A total of 356 (17.5%), 151 (7.4%) and 97 (4.8%) had osteosarcopenia (OSP), sarcopenic obesity (SOB) and osteo-obesity (OOB), respectively; while 70 (3.5%) had all 3 morbid conditions (osteosarcopenic obesity, OSO). Both SP only and OB only were strongly associated with increased rates of PF (RR: 2.53, 95% CI: 1.95, 3.29; RR: 2.05, 95% CI: 1.58, 2.66 respectively); but not OP. Those with OSP, OOB and SOB were also associated with high risks of PF (RR: 2.82, 95% CI: 2.16, 3.68; RR: 2.34, 95% CI: 1.69, 3.23; and RR: 2.58, 95% CI: 1.95, 3.41, respectively) compared to robust individuals. Critically, individuals with OSO had the highest relative risk of having PF (RR: 3.06, CI: 2.28, 4.11). Only the sarcopenia-obesity interaction was significant, demonstrating negative synergism (antagonism). The concurrent presence of SP and OB was associated with a 100% lower rate of PF compared to the sum of the relatively rates of SP only and OB only. CONCLUSION: The prevalence of SP, OB and OP, alone and combined, is substantial in older Asians and their early identification is needed to mitigate the risk of frailty. OB may interact with SP in an antagonistic manner to moderate rates of frailty. Further longitudinal studies are needed to address causality and mechanistic underpinnings our findings.

Exploring YouTube's Recommendation System in the Context of COVID-19 Vaccines: Computational and Comparative Analysis of Video Trajectories.

BACKGROUND: Throughout the COVID-19 pandemic, there has been a concern that social media may contribute to vaccine hesitancy due to the wide availability of antivaccine content on social media platforms. YouTube has stated its commitment to removing content that contains misinformation on vaccination. Nevertheless, such claims are difficult to audit. There is a need for more empirical research to evaluate the actual prevalence of antivaccine sentiment on the internet. OBJECTIVE: This study examines recommendations made by YouTube's algorithms in order to investigate whether the platform may facilitate the spread of antivaccine sentiment on the internet. We assess the prevalence of antivaccine sentiment in recommended videos and evaluate how real-world users' experiences are different from the personalized recommendations obtained by using synthetic data collection methods, which are often used to study YouTube's recommendation systems. METHODS: We trace trajectories from a credible seed video posted by the World Health Organization to antivaccine videos, following only video links suggested by YouTube's recommendation system. First, we gamify the process by asking real-world participants to intentionally find an antivaccine video with as few clicks as possible. Having collected crowdsourced trajectory data from respondents from (1) the World Health Organization and United Nations system (nWHO/UN=33) and (2) Amazon Mechanical Turk (nAMT=80), we next compare the recommendations seen by these users to recommended videos that are obtained from (3) the YouTube application programming interface's RelatedToVideoID parameter (nRTV=40) and (4) from clean browsers without any identifying cookies (nCB=40), which serve as reference points. We develop machine learning methods to classify antivaccine content at scale, enabling us to automatically evaluate 27,074 video recommendations made by YouTube. RESULTS: We found no evidence that YouTube promotes antivaccine content; the average share of antivaccine videos remained well below 6% at all steps in users' recommendation trajectories. However, the watch histories of users significantly affect video recommendations, suggesting that data from the application programming interface or from a clean browser do not offer an accurate picture of the recommendations that real users are seeing. Real users saw slightly more provaccine content as they advanced through their recommendation trajectories, whereas synthetic users were drawn toward irrelevant recommendations as they advanced. Rather than antivaccine content, videos recommended by YouTube are likely to contain health-related content that is not specifically related to vaccination. These videos are usually longer and contain more popular content. CONCLUSIONS: Our findings suggest that the common perception that YouTube's recommendation system acts as a "rabbit hole" may be inaccurate and that YouTube may instead be following a "blockbuster" strategy that attempts to engage users by promoting other content that has been reliably successful across the platform.