Human Studies Research Articles

CUTTING-EDGE DEVELOPMENTS IN HPLC FOR IDENTIFYING PROCESS IMPURITIES: A REVIEW ON METHOD OPTIMIZATION AND VALIDATION

High-Performance Liquid Chromatography (HPLC) is a widely utilized column chromatography technique in biochemistry and analytical sciences for the separation, identification, and quantification of active compounds. Renowned as a leading separation technology, HPLC plays a pivotal role in detecting, separating, and quantifying pharmaceutical drugs. The development and validation of HPLC methods are essential in novel drug discovery, development, manufacturing, and various human and animal studies. This review highlights the comprehensive processes involved in the development and validation of HPLC methods. Method development is influenced by factors such as the chemical structure of molecules, synthetic pathways, solubility, polarity, pH, pKa values, and the activity of functional groups. Validation, as per ICH Guidelines, encompasses key parameters including accuracy, precision, specificity, linearity, range, limits of detection and quantification, robustness, and system suitability testing.

Carbapenem-resistant Enterobacter hormaechei uses mucus metabolism to facilitate gastrointestinal colonization.

The emergence and global spread of carbapenem-resistant Enterobacter cloacae complex species present a pressing public health challenge. Carbapenem-resistant Enterobacter spp. cause a wide variety of infections, including septic shock fatalities in newborns and immunocompromised adults. The intestine may be a major reservoir for these resistant strains, either by facilitating contamination of fomites and transfer to susceptible individuals, or through translocation from the gut to the bloodstream. For this reason, we sought to establish a neonatal mouse model to investigate the mechanisms underpinning gut colonization by carbapenem-resistant Enterobacter hormaechei. We describe a new mouse model to study gut colonization by Enterobacter spp., leading to vital insights into the adaptation of carbapenem-resistant E. hormaechei to the gut environment during the early stages of intestinal colonization. We observed successful colonization and proliferation of E. hormaechei in the 5-day-old infant mouse gut, with primary localization to the colon following oral inoculation. We also uncovered evidence that E. hormaechei uses mucus as a carbon source during colonization of the colon. Our findings underscore the importance of oxygen-dependent metabolic pathways, including the pyruvate dehydrogenase complex and N-acetyl-D-glucosamine metabolism, in gut colonization and proliferation, which aligns with previous human studies. These insights are essential for developing novel therapeutic strategies that can serve as decolonization therapies in at-risk populations.IMPORTANCEBloodstream infections caused by Enterobacter spp. pose a significant clinical threat. The intestine acts as the primary site for colonization and serves as a reservoir for infection. To combat this pathogen, it is crucial to understand how carbapenem-resistant Enterobacter spp. colonize the gut, as such knowledge can pave the way for alternative therapeutic targets. In this study, we developed a novel neonatal mouse model for gastrointestinal colonization by Enterobacter spp. and discovered that mucus plays a key role as a carbon source during colonization. Additionally, we identified two mucus catabolism pathways that contribute to intestinal colonization by carbapenem-resistant E. hormaechei. This new mouse model offers valuable insights into host-pathogen interactions and helps identify critical gastrointestinal fitness factors of Enterobacter, potentially guiding the development of vaccines and alternative therapeutic strategies to minimize intestinal carriage in patient populations at risk of infection with Enterobacter spp.

Targeting Ketone Body Metabolism Improves Cardiac Function and Hemodynamics in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

The impacts of elevated ketone body levels on cardiac function and hemodynamics in patients with heart failure (HF) remain unclear. The effects of ketone intervention on these parameters in patients with HF were evaluated quantitatively in this meta-analysis. We searched the PubMed, Cochrane Library, and Embase databases for relevant studies published from inception to April 13, 2024. Ketone therapy included ketone ester and β-hydroxybutyrate intervention. Seven human studies were included for the quantitative analysis. Our results showed that ketone therapy significantly improved left ventricular ejection fraction (standardized mean difference, 0.52 [95% CI, 0.25-0.80]; I2 = 0%), cardiac output (0.84 [95% CI, 0.36-1.32]; I2 = 68%) and stroke volume (0.47 [95% CI, 0.10-0.84]; I2 = 39%), and significantly reduced systemic vascular resistance (-0.92 [95% CI, -1.52 to -0.33]; I2 = 74%) without influencing mean arterial pressure (-0.09 [95% CI: -0.40 to 0.22]; I2 = 0%) in patients with HF. Subgroup analysis revealed that the enhanced cardiac function and favorable hemodynamic effects of ketone therapy were also applicable to individuals without HF. Ketone therapy may significantly improve cardiac systolic function and hemodynamics in patients with HF and in patients without HF, suggesting it may be a promising treatment for patients with HF and also a beneficial medical strategy for patients without HF or healthy individuals.

Keep bright in the dark: Multimodal emotional effects on donation-based crowdfunding performance and their empathic mechanisms.

How to raise donations effectively, especially in the E-era, has puzzled fundraisers and scientists across various disciplines. Our research focuses on donation-based crowdfunding projects and investigates how the emotional valence expressed verbally (in textual descriptions) and visually (in facial images) in project descriptions affects project performance. Study 1 uses field data (N = 3817), grabs project information and descriptions from a top donation-based crowdfunding platform, computes visual and verbal emotional valence using a deep-learning-based affective computing method and analyses how multimodal emotional valence influences donation outcomes. Study 2 conducts experiments in GPT-4 (Study 2a, N = 400) and humans (Study 2b, N = 240), manipulates the project's visual and verbal emotional valence through AI-generated stimuli and then assesses donation decisions (both GPT-4 and humans) and corresponding state empathy (humans). The results indicate a multimodal positivity superiority effect: both visual and verbal emotional valence promote initial whether-to-donate decisions, whereas only verbal emotional valence further promotes the how-much-to-donate decisions. Notably, such multimodal emotional effects can be explained through different mediating paths of empathic concern and empathic hopefulness. The current study theoretically facilitates our understanding of the emotional motivations underlying human prosociality and provides insights into crafting impactful advertisements for online donations.

The Value and Importance of a Professional Ethical Code for Medicines Development: IFAPP International Ethics Framework.

Pharmaceutical medicine professionals have to face many ethical problems during the entire life span of new medicines extending from animal studies to broad clinical practice. The primary aim of the general ethical principles governing research conducted in humans is to diminish the physical and psychological burdens of the participants in human drug studies but overlooks many additional social and ethical problems faced by medicine developers. These arise mainly at the interface connecting the profit-oriented pharmaceutical industry and the healthcare-centered medical profession cooperating in medicines development. In 2002, the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine developed the International Code of Ethical Conduct for Pharmaceutical Physicians for providing ethical advice for their members to manage the frequently competitive goals characteristic for their specialty. The ethical framework compiled by the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine serves its members by presenting morally acceptable or inacceptable behaviors in frequently encountered controversies arising from competing industrial and healthcare interests in medicines development. The authors selected this format to encourage reflection and debate for finding optimal moral conclusions in specific issues. Many recent examples of serious scientific-ethical misconduct, such as the oxycodone tragedy, the recommendations of unproven useless occasionally dangerous therapies during the coronavirus disease 2019 pandemic, and the withdrawal of many papers containing non-reproducible results, contributed to the increasing loss of trust by the public in science including pharmaceutical medicine. We are convinced that the ethical guidance developed by the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine will encourage its members to reflect intensively on optimal ethical behavior in drug development for strengthening the trust of society in innovative new medicines. Finally, considering the increasingly active participation of non-medically trained scientists in producing and applying complex biological medicines, distant monitoring methods coupled together with artificial intelligence technology in innovative clinical trials, the Ethics Working Group recommended already in 2017 measures to optimize their smooth cooperation and underlined their joint ethical responsibilities in guarding the safety and human dignity of trial participants.

Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE to improve treatment efficacy – protocol for the ERADICATE study: a phase II randomised controlled trial

BackgroundTumour hypoxia resulting from inadequate perfusion is common in many solid tumours, including prostate cancer, and constitutes a major limiting factor in radiation therapy that contributes to treatment resistance. Emerging research in preclinical animal models indicates that exercise has the potential to enhance the efficacy of cancer treatment by modulating tumour perfusion and reducing hypoxia; however, evidence from randomised controlled trials is currently lacking. The ‘Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE’ (ERADICATE) study is designed to investigate the impact of exercise on treatment response, tumour physiology, and adverse effects of treatment in prostate cancer patients undergoing external beam radiation therapy (EBRT).MethodsThe ERADICATE study is a two-arm, parallel group, phase II randomised controlled trial. Fifty patients diagnosed with prostate cancer will be randomised (1:1) to either an exercise intervention group (EBRT + exercise) or a usual care control group (EBRT only) for the duration of treatment (i.e., 2 to 8 weeks of EBRT). The exercise intervention will be clinic-based and supervised by exercise physiologists. Exercise sessions will include moderate- to vigorous-intensity aerobic and resistance exercise conducted two to three times per week for 60 min per session. Treatment response (primary outcome) will be assessed by change in tumour apparent diffusion coefficient derived from magnetic resonance imaging. Secondary outcomes will include acute and chronic changes in tumour perfusion and hypoxia, treatment-related toxicity, body composition, physical function, and quality of life. Survival outcomes will be assessed as exploratory endpoints. Study measurements will be conducted at baseline (i.e., prior to commencing EBRT), immediately after completion of EBRT, and during follow-up at 3 months as well as 2 years and 5 years post treatment. The study was approved by the Human Research Ethics Committee at Edith Cowan University.DiscussionThe ERADICATE study will investigate exercise as a novel therapeutic approach for sensitising prostate cancer to EBRT by targeting a known mechanism of treatment resistance. Improving treatment efficacy of EBRT with exercise may result in better patient outcomes clinically, while also addressing adverse effects of treatment and quality of life in prostate cancer patients.Trial registrationThe study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12624000786594) on 26/06/2024.

Human brain organoid research: An analysis of public attitudes and ethical concerns in Japan

Human brain organoids are three-dimensional neural structures derived from human pluripotent and tissue stem cells. They have become a focal point in scientific research due to their potential to elucidate brain functions, disease mechanisms, and therapeutic strategies. However, the ethical implications of this research have sparked significant debate, particularly concerning the potential for consciousness and effects of transplanting organoids into animals. Given the complexity and novelty of these issues, it is essential to gauge public opinion to ensure that the research aligns with societal values and ethical standards. To understand public perceptions of human brain organoid research, we conducted an online survey targeting Japanese individuals. The survey explored expectations, concerns, and agreements regarding this type of research. The results revealed high expectations for applied and clinical outcomes but significant ethical concerns, particularly regarding unanticipated risks and commercialization. Moreover, comprehension test scores were positively correlated with support for various research objectives, indicating that informed individuals may view this type of research favorably. These findings underscore the need for public engagement and informed discussions to foster responsible innovation in this emerging field.

Advances in RNA editing in hematopoiesis and associated malignancies.

Adenosine-to-inosine (A-to-I) RNA editing is a prevalent RNA modification essential for cell survival. The process is catalyzed by the Adenosine Deaminase Acting on RNA (ADAR) enzyme family that converts adenosines in double-stranded RNAs (dsRNAs) into inosines, which are read as guanosines during translation. Deep sequencing has helped to reveal that A-to-I editing occurs across various types of RNAs to affect their functions. RNA editing detection is now so sophisticated that we can achieve a high level of accuracy and sensitivity to identify low abundance edited events. Consequently, A-to-I editing has been implicated in various biological processes, including immune and stress responses, cancer progression and stem cell fate determination. In particular, a crucial role for this process has been recently reported in hematopoietic cell development and hematologic malignancy progression. Results from genetic mouse models have demonstrated the impact of ADARs' catalytic activity on hematopoietic cells, complemented by insights from human cell studies. Meanwhile clinical studies have implicated ADAR enzymes and RNA editing events in hematologic malignancies and highlighted their potential as prognostic indicators. In this review, we outline the regulatory mechanisms of RNA editing in both normal hematopoiesis and hematologic malignancies. We then speculate on how targeting ADAR expression and site-specific RNA substrates might serve as a therapeutic avenue for affected patients.

Concomitant Cartilage Procedures With Meniscal Allograft Transplantation Do Not Substantially Alter Failure or Survival Rates Relative to Meniscal Allograft Transplantation Without Cartilage Procedures: A Systematic Review.

Timely recognition and addressing of concomitant cartilage damage at the time of meniscal allograft transplantation (MAT) is critical to warrant future success. However, there remains a scarcity of data comparing outcomes between MAT with and without cartilage procedures. To compare patient-reported outcomes and rates of complications, failures, reoperations, and graft survivorship after MAT with concomitant cartilage procedures (MAT/Cart) and MAT without (MAT/NoCart). Systematic review; Level of evidence, 4. A literature search was performed according to the 2020 PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) using the Scopus, PubMed, and Embase computerized databases from inception to January 7, 2024. Human clinical studies with levels of evidence 1 to 4 were included that evaluated patient-reported outcomes, postoperative complications, failures, reoperations, and graft survivorship with a minimum mean follow-up of 2 years. Study quality was assessed using the Methodological Index for Non-randomized Studies criteria and Modified Coleman Methodology Score. Twenty-six studies from 2006 to 2024 consisting of 1031 patients were included. Thirteen studies (n = 367) reported on MAT/Cart with a mean patient age of 37.6 years and mean follow-up of 72.9 months. Thirteen studies (n = 665) reported on MAT/NoCart procedures in patients with a mean age of 33.6 years and mean follow-up of 58.6 months. Postoperatively, both study groups had improved clinical outcomes, with International Knee Documentation Committee scores ranging from 55.3 to 74.4 in the MAT/Cart group versus 61.7 to 89.8 in the MAT/NoCart group and Lysholm scores from 62.5 to 85.9 versus 72 to 92.4, respectively. The incidence of failure ranged from 0% to 33% after MAT/Cart versus 3.8% to 43.7% after MAT/NoCart. All included patients either had well-aligned lower extremities in the coronal plane, within 3° to 5° of neutral on the affected side, or underwent correction via an osteotomy before or during the MAT procedure. Subsequent surgery not related to failure was higher in the MAT/Cart group (range, 11.8%-83.3%) as compared with the MAT/NoCart group (range, 4.3%-30.8%). The mean survival rates after MAT/Cart ranged from 86.2% to 100% at 2 years, 75% to 97.9% at 5 years, and 70% to 85% at 10 years. The mean survival rates after MAT/NoCart ranged from 83.5% to 93% at 2 years, 82.6% to 85% at 5 years, and 55% to 90% at 10 years. Decreased range of motion and arthrofibrosis were the most frequently reported complications in each group. In patients with normal lower limb coronal plane alignment, performing cartilage restoration procedures in combination with MAT does not substantially alter clinical outcomes or complication, failure, and survival rates relative to isolated MAT.

Boosting human immunology: harnessing the potential of immune organoids.

Studying the human immune system in vivo is challenging and often not possible. Therefore, most human immunology studies have been predominantly confined to peripheral blood analyses, which by themselves have inherent limitations, as many immune reactions take place within tissues. For example, potent antibody responses that contribute to fighting infections and provide protection following vaccination require cellular interactions between B cells and T cells in specialized micro-anatomical structures called germinal centers, which are found in secondary lymphoid organs such as spleen, lymph nodes, and tonsils. Thus, there is a clear demand for novel enhanced experimental systems that faithfully recapitulate the intricate dynamics of the human immune system as much as possible. In this review, we discuss recent advances in versatile human tonsil/adenoid tissue-based ex vivo immune organoid cultures as well as related cancer and autoimmunity-focused experimental setups. These systems have been implemented as translational immunology platforms for in-depth analyses of human B and T cell-mediated immune responses, thereby facilitating mechanistic studies as well as drug and vaccine testing in a human-first approach.

Neuro-reproductive toxicity and carcinogenicity of 1-bromopropane - studies for evidence-based preventive medicine (EBPM).

Bromopropane was introduced commercially as an alternative to ozone-depleting and global warming solvents. The identification of 1-bromopropane neurotoxicity in animal experiments was followed by reports of human cases of 1-bromopropane toxicity. In humans, the most common clinical features of 1-bromopropane neurotoxicity are decreased sensation, weakness in extremities, and walking difficulties. Moreover, decreased cognition, abnormal findings on brain magnetic resonance imaging, urinary incontinence, and numbness in the perineal area have also been described in workers exposed to 1-bromoporopane. Murine histological studies showed that exposure to 1-bromopropane reduced the density of brain noradrenergic axons. Furthermore, proteome studies demonstrated 1-bromopropane-induced changes in the expression of proteins in the hippocampus of rats, similar to the changes seen in mice exposed to acrylamide, suggesting a common mechanism of electrophile-induced neurotoxicity. In addition to its neurotoxicity, 1-bromopropane also induces male reproductive toxicity in rats, though the targeted areas in the reproductive system differ from those affected by 2-bromopropane. However, exposure to high levels of 1-bromopropane was reported to induce spermatogenic cell degeneration, similar to that caused by 2-bromopropane, suggesting common mechanism(s) underlying 1- and 2-bromopropane-induced male reproductive toxicity. Plural approaches, including human, animal and mechanistic studies, are useful for identification of 1-bromopropane neurotoxicity. The International Agency for Research on Cancer (IARC) summarized that 1-bromopropane as well as 2-bromopropane share several key characteristics of carcinogens. Plural approaches can establish evidence-based preventive medicine (EBPM) by modification of the conventional evidence-based medicine (EBM), which has been developed for therapeutic medicine and represented by the EBM pyramid.

Malnutrition exacerbating neuropsychiatric symptoms on the Alzheimer's continuum is relevant to the cAMP signaling pathway: Human and mouse studies.

Malnutrition correlates with neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD); however, the potential mechanism underlying this association remains unclear. Baseline and longitudinal associations of nutritional status with NPSs were analyzed in 374 patients on the AD continuum and 61 healthy controls. Serum biomarkers, behavioral tests, cerebral neurotransmitters, and differentially gene expression were evaluated in standard and malnourished diet-fed transgenic APPswe/PSEN1dE9 (APP/PS1) mice. Poor nutritional status and increased cerebral blood flow in the midbrain and striatum were associated with severe general NPSs and subtypes, especially depression, anxiety, and apathy. APP/PS1 mice fed a malnourished diet showed poor nutritional status, depression- and anxiety-like behaviors, altered neurotransmitter levels, and downregulated c-Fos expression in the midbrain and striatum; these were associated with suppressed cyclic adenosine monophosphate (cAMP) signaling pathway. Malnutrition exacerbating NPSs is relevant to suppressed cAMP pathway in the midbrain and striatum, suggesting the potential for targeted nutritional interventions to mitigate NPSs in the AD continuum. Poor nutritional status linked to general and specific neuropsychiatric symptom (NPS) deterioration. Malnutrition affects NPSs, usually involving the midbrain and striatum. Malnourished diet induces depression- and anxiety-like behaviors in APP/PS1 mice. Malnutrition exacerbates NPSs associated with cAMP signaling pathway in the midbrain and striatum.

Engineering mycobacteria for vaccination and controlled human infection studies.

Engineering mycobacteria for vaccination and controlled human infection studies.

Optimal aspiration pressure of suction pump for oocyte retrieval in infertile patients undergoing in vitro fertilization.

The oocyte retrieval is a critical step in assisted reproductive technologies, including in vitro fertilization and fertility preservation. Despite evolving techniques, the optimal aspiration pressure during retrieval remains debatable, with limited in vivo human studies. Existing studies, primarily in vitro and on animals, suggest that inappropriate aspiration pressures can impair oocyte quality. This study aims to compares the effects of two different aspiration pressures, 120mmHg and 150mmHg, on oocyte recovery, damage, and subsequent embryo development and pregnancy outcomes in infertile women undergoing transvaginal ultrasound-guided oocyte retrieval. This retrospective study analyzed data from 891 women at Seoul National University Hospital between May 2018 and August 2023. A total of 400 cycles were included, with 202 at 120 mmHg and 198 at 150 mmHg aspiration pressures. The primary outcomes were the number of retrieved, matured, fractured oocytes, embryos, and good-grade embryos. Pregnancy outcomes were evaluated by comparing the clinical pregnancy rates and live birth rates. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship between aspiration pressure, clinical pregnancy, and live birth rates. There was statistically significant difference in the number of retrieved oocytes and mature oocytes between the 120 mmHg group and the 150 mmHg group (6.3±5.2 vs. 7.7±6.7, p = 0.018; 4.4±3.7 vs. 5.6±5.3, p = 0.011). The number of embryos and good grade embryos also differed significantly (3.3±3.1 vs. 4.2±3.9, p = 0.011; 1.0±1.6 vs. 1.5±2.6, p = 0.031). However, there were no significant differences in clinical pregnancy and live birth rates between the two groups in multivariate logistic regression analysis (adjusted OR = 0.725, p = 0.519; adjusted OR = 0.370, p = 0.170). Increasing the aspiration pressure to 150mmHg led to a higher yield of oocytes and embryos than 120mmHg, without any negative impact on oocyte quality or live birth rates. These findings provide valuable insights for clinical decision-making in infertility treatments, suggesting that 150mmHg may be a more effective pressure for oocyte retrieval in in vitro fertilization and embryo transfer.

Extracellular vesicles in malaria: proteomics insights, in vitro and in vivo studies indicate the need for transitioning to natural human infections.

Globally, an estimated 2.1 billion malaria cases and 11.7 million malaria deaths were averted in the period 2000-2022. Noticeably, despite effective control measurements, in 2022 there were an estimated 249 million malaria cases in 85 malaria-endemic countries and an increase of 5 million cases compared with 2021. Further understanding the biology, epidemiology, and pathogenesis of human malaria is therefore essential for achieving malaria elimination. Extracellular vesicles (EVs) are membrane-enclosed nanoparticles pivotal in intercellular communication and secreted by all cell types. Here, we will review what is currently known about EVs in malaria, from biogenesis and cargo to molecular insights of pathophysiology. Of relevance, a meta-analysis of proteomics cargo, and comparisons between in vitro and in vivo human studies revealed striking differences with those few studies reported from patients. Thus, indicating the need for rigor standardization of methodologies and for transitioning to human infections to elucidate their physiological role. We conclude with a focus on translational aspects in diagnosis and vaccine development and highlight key gaps in the knowledge of EVs in malaria research.

Abstract IA08: Theragnostics & external beam radiation dose absorbed - Similarities, differences and thoughts for the future

Abstract External Beam Radiotherapy (EBRT) and theragnostics share a key core characteristic – the use of radiation to exert its therapeutic benefit. However, the role radiation dose absorbed plays is significantly different between these two modalities in clinical practice. On the one hand it is a critical element of EBRT prescriptions (e.g. cGy), while on the other it is not even a requirement to document in theragnostic practices, where prescriptions are expressed as administered activities (e.g. GBq). Radiation dose absorbed by tumor and normal tissues is recognized to be variable across patients. It is acknowledged to be a critical metric in the safe use of radiopharmaceuticals and is required for all first in human studies and a priority for the development of any novel radiopharmaceutical. The process of individualized dosimetry is well described, enabling radiation dose absorbed estimates to regions of interest. There is an active debate currently as to when, in whom and how individualized dosimetry should be incorporated into clinical practice. The lack of high quality evidence to support radiation dose absorbed to patient outcomes, the lack of standardized methodologies to enable comparability of dose absorbed data across institutions, the burden on patients to return for dosimetry scans post treatment, the burden on the health care system to incorporate individualized dosimetry into treatment workflows and the lack of reimbursement codes for these activities are the main barriers cited against routine clinical use. In this session, we will review some of the theoretical and logistic considerations as well as evidence behind this debate. We will also take a broader view, of theragnostics as a rapidly growing modality, that patients and their oncology teams would need radiation absorbed dose information when considering “re-irradiation”, be it re-challenge with theragnostics, or to provide safety estimates when using different forms of radiation along patients’ cancer journey in the real world. Through a recently completed multi-center trial as a case study, we will review the processes involved in setting up individualized dosimetry across four academic institutions and our subsequent transition into standard of care. We will discuss the value of radiation dose information for our patients, at the systems and academic levels. Finally, we will consider radiation dose absorbed in the future of theragnostics - as a prognostic factor for response and toxicity, as a factor in understanding the mechanism of treatment resistance, as a strategy to create novel dosing approaches and as part of combined modality to strive for superior patient outcomes. We propose that we are at a critical time, where a collaborative strategy across theragnostic practices is critical. The adoption of the reporting of radiation dose absorbed as a quality metric, blending lessons learned across theragnostics and EBRT will set the stage for the future with excellent quality of care and accelerated discoveries for our patients. (458 words). Citation Format: Rebecca K.S. Theragnostics & external beam radiation dose absorbed - Similarities, differences and thoughts for the future. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA08

Analysis of "Dose Accuracy and Reliability of a Connected Insulin Pen System".

In an article in the Journal of Diabetes Science and Technology, Backfish and coauthors examined the dose accuracy and reliability of the Tempo Pen and Tempo Smart Button connected insulin pen system. This study sponsored by Eli Lilly and Company found that this system met the International Organization for Standardization 11608-1:2014 requirements for dose accuracy at a range of doses, as well as the data transfer requirements after all injections. While these results are very encouraging, they were based on simulated human factors data while data from a human factors validation study where individuals successfully dialed and administered correct doses was not reported. There is a need for further studies in a variety of populations that would greatly benefit from this enhanced insulin pen technology to facilitate optimization of dose adjustments based on accurate and reliable insulin dosing data.

From botany to bedside: a review of the health benefits of Lycium barbarum as a functional food

Native to East Asia and predominantly cultivated in regions such as the Ningxia Hui and Xinjiang Uyghur Autonomous Regions of China, Lycium barbarum (L. barbarum), commonly known as goji berry, has a long history in traditional medicine and is gaining recognition in contemporary health research. This review provides a comprehensive exploration of its botanical characteristics, pharmacokinetics, and safety, alongside a critical evaluation of human clinical studies investigating its therapeutic potential. Key health benefits include immune modulation, antioxidative effects, mental health support, ocular health preservation, and metabolic and cardiovascular regulation. Furthermore, its role in addressing age-related macular degeneration and chronic conditions such as cancer and metabolic syndrome is highlighted. The bioactivity of L. barbarum is attributed to its rich composition of polysaccharides, carotenoids, flavonoids, and other bioactive compounds, which exhibit anti-inflammatory, neuroprotective, and metabolic-regulating properties. This review also examines the safety profile of L. barbarum, considering its side effects, toxicity, potential contamination, and interactions with medications, emphasising the importance of balancing its health-promoting properties with cautious consumption. Despite promising findings, gaps in the evidence base, including the need for larger, long-term, and rigorously controlled trials, remain significant barriers to clinical translation. By integrating traditional medicinal knowledge with modern scientific insights, this review underscores L. barbarum’s potential as a functional food and therapeutic agent. Its unique pharmacological properties and broad applicability position it as a valuable tool for health promotion and disease prevention, while highlighting areas requiring further research to optimise its safe and effective use.

Ultrasound-Based Local Lung Motion Assessment Using Synthetic Lateral Phase.

Ultrasound lung surface motion measurement is valuable for the evaluation of a variety of diseases. Speckle tracking or Doppler-based techniques are limited by the loss of visualization as a tracked point moves under ribs or is dependent. We developed a synthetic lateral phase-based algorithm for tracking lung motion to overcome these limitations. To validate the technique, we generated simulated lung motion images. We also obtained lung ultrasound cines from a healthy volunteer and a mechanically ventilated COVID-19 patient. In the healthy volunteer, the respiratory pattern varied between breath-hold, regular, and rapid shallow breathing. The measured displacement was within 3% of the ground truth for simulated cines. In both the healthy volunteer and COVID-19 patients, measured displacement was greatest in the lower and lateral zones of the lung when the ipsilateral side was compared. In the healthy volunteer, when the respiratory pattern was varied, measured displacement was greater in regular breathing compared to rapid shallow breathing and compared to breath-hold patterns in both the upper and lower lung zones. Estimation of lung surface displacement using a synthetic lateral phase-based approach is feasible. Future human studies should validate this approach against a direct measurement of lung surface movement.

The Impact of Dietary Fiber on Cardiovascular Diseases: A Scoping Review

Background/Objectives: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, placing an ever-increasing burden on healthcare systems. Dietary factors play a crucial role in the development and progression of CVD. Among them, dietary fiber has emerged as a potential modifiable factor with the potential to impact CVD risk. However, the specific and independent effects of dietary fiber on CVD are still not fully understood, making this area of research both challenging and of great significance. Methods: The publications of human studies involving the impact of dietary fiber on CVD were retrieved from databases including PubMed, Embase, Web of Science, Scopus, Cochrane Library, CBM, and China National Knowledge Infrastructure (CNKI). A search was conducted within these databases for studies published between 2014 and 20 March 2024. The included literature was screened and summarized. Results: A total of seven articles were included, and the related studies encompassed various types of dietary fiber, including soluble and insoluble dietary fiber, as well as research from different countries and regions. The outcome indicators involved an important measure known as the hazard ratio (HR). Conclusions: Increasing the intake of dietary fiber could reduce the risk of cardiovascular diseases through various mechanisms. To increase the consumption of dietary fiber from multiple sources, it would be beneficial to develop and promote healthcare interventions to enhance people’s awareness of the health benefits of dietary fiber, promote the consumption of fiber-rich foods, and advocate for a healthier diet.