Basic Science Research Articles

International Comparison of Qualification Process for Medical Product Development Tools.

Qualification of medical product evaluation tools is underway in the United States, Europe, and Japan to reflect the advancements in the basic science of medical products. In Europe and the U.S., Guidance of Guidances (GoG) policies that clarify regulators'processes, tasks, and methods of sponsor involvement are adopted to issue tool guidance. However, in Japan, a non-GoG type policy focusing on supporting the research and development for tools without defining a tool guidance-making process has been adopted. In this study, an analytical framework for the lifecycle of development tools was constructed, including pre- and post-tool qualification processes, to compare the two above-mentioned approaches. For this study, Japanese cases were selected as experimental cases, whereas Western cases served as controls. The progress of tool qualification and composition of deliverables were analyzed. It was indicated that in the GoG type policy, in which processes are defined, and involvement methods are clarified, tool qualification can progress more smoothly than in a non-GoG type policy. This policy indicates that deliverables may have a consistent composition. Contrastingly, GoG-type policies alone present challenges in connecting upstream tools for R&D support.

Whole person healthcare as social and environmental justice: new research directions toward a paradigmatic integration of an ecological whole system medicine framework

With increasing recognition of the interdependencies of human and planetary health, calls for a socially and environmentally just framework of health have centered on whole person healthcare (WPHC) approaches. This perspective piece proposes an argument for broadening the definition of human health from WPHC to one that is guided by the philosophical orientation of traditional whole system medicine (WSM) approaches, undergirded by the values of social and environmental justice, and supported by the practices of an allopathic-integrative medicine-based WPHC framework. This piece presents opportunities for praxis offered by a WSM–WPHC framework to address global inequity, environmental disparities, and sustainability challenges. An ecological WSM–WPHC framework envisages social and environmental justice in material and discursive ways by foregrounding environmental planetary ecological consciousness as constitutive of human consciousness and biopsychosocial composition. It argues for structural support through formalized programmatic pathways targeting funding opportunities and mechanisms that invite investigations addressing epistemic challenges of expanding definitions of evidence constituting basic science knowledge domains beyond mechanistic, causal, and formative paradigms. Furthermore, it calls for innovative research directions examining the integration and validation of evidence-based approaches incorporating the ontologically diverse and epistemically distinct ontological orientation of WSM and clinical approaches. A WSM–WPHC framework that positions human health within the parameters of social and environmental justice principles envisions the material enactment of the practice of health and medicine as a universal planetary value.

Abstracts From the First Annual Research Day Hosted by the Michigan State University College of Osteopathic Medicine, Novi, Michigan, May 15, 2023.

The Spartan Medical Research Journal (SMRJ) is pleased to publish abstracts from the First Annual Research Day hosted by the Michigan State University College of Osteopathic Medicine (MSUCOM), held in Novi, Michigan, on May 15, 2023. Sponsored by MSUCOM, the Statewide Campus System (SCS), and Research, Innovation, and Scholarly Engagement (RISE), this event showcased a total of 139 selected research abstracts following a meticulous blinded review by the MSUCOM Research Day Planning Committee and SMRJ editorial staff. These abstracts were subsequently presented at the MSUCOM First Annual Research Day in 2023, with awards for exceptional oral and poster presentations conferred on May 15, 2023. Of the 139 presentations that were ultimately chosen, 45 authors consented and elected to have their abstracts published in SMRJ. The abstracts from 2023 encompass a wide array of contemporary medical and clinical subjects, incorporating a variety of research designs that cover basic science, clinical research, case reports, medical education, and quality improvement. While abstracts offer concise overview of research projects or presentations, they do not permit a comprehensive evaluation of the scientific rigor employed in the respective works. Although these abstracts offer preliminary results that may necessitate further refinement and validation, they serve a vital function in disseminating novel research concepts and advancements in the discipline of medicine. This knowledge-sharing promotes meaningful dialogue among researchers, clinicians, and educators, thereby making a valuable contribution to the collective body of knowledge in the fields of medical sciences and osteopathic medicine. Andrea Amalfitano, DO, PhD Osteopathic Heritage Foundation Professor of Pediatrics, Microbiology and Molecular Genetics Professor, BioMolecular Science Gateway Editor-in-Chief, Spartan Medical Research Journal (SMRJ) MSU College of Osteopathic Medicine- Statewide Campus System C. Patricia Obando S., PhD Associate Dean and DIO, Graduate Medical Education Associate Professor- MSU College of Osteopathic Medicine- Statewide Campus System Rana Ismail, PhD, MSc, CPHQ Director of Research Editor, Spartan Medical Research Journal (SMRJ) MSU College of Osteopathic Medicine- Statewide Campus System Francis Akenami, BMLS, PhD, MSc, FIMLS Managing Editor Spartan Medical Research Journal (SMRJ) MSU College of Osteopathic Medicine- Statewide Campus System

Type IV Collagen Promotes Adipogenic Differentiation of Adipose Stem Cells.

Type IV collagen is a major component of the extracellular matrix in adipose tissue. It is secreted during the lipogenic differentiation of mesenchymal stem cells, but its direct impact and mechanism on the differentiation of adipose-derived stem cells (ASCs) into lipids are unclear. In this study, ASCs were obtained from human liposuction samples and cultured. Lipogenic induction of ASCs was achieved using lipogenic induction medium. Immunofluorescence analysis revealed differential expression of type IV collagen during the early and late stages of adipogenic induction, displaying a distinct morphological encapsulation of ASCs. Silencing of type IV collagen using siRNA resulted in a significant decrease in adipogenic capacity, as indicated by reduced lipid droplet formation and downregulation of adipogenic-related gene transcription. Conversely, supplementation of the culture medium with synthetic type IV collagen demonstrated enhanced adipogenic induction efficiency, accompanied by upregulation of YAP/TAZ protein expression and its downstream target gene transcription. Furthermore, inhibition of the YAP/TAZ pathway using the inhibitor Blebbistatin attenuated the functionality of type IV collagen, leading to decreased lipid droplet formation and downregulation of adipocyte maturation-related gene expression. These findings highlight the crucial role of type IV collagen in promoting adipogenic differentiation of ASCs and suggest its involvement in the YAP/TAZ-mediated Hippo pathway.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Investigation of Two New Grafting Techniques for Dorsal Augmentation Rhinoplasty: An Experimental Study with New Zealand White Rabbits.

Cartilage is an important source in supporting the structure of the nose for dorsal augmentation rhinoplasty. However, it is known that its viability is not always on the ideal level. Various wrapping materials are used to increase the strength of cartilage. Donor site morbidity, which develops following the harvesting of both cartilage and fascia as one such cover material, has attracted interest in recent years. In this study, we aimed to investigate the potential of dermis and tendon autografts as alternatives to fascia and cartilage. The sample of the study included 16 New Zealand white rabbits. The right auricular cartilage of all rabbits was amputated, and it was transformed into diced cartilage autografts. The dermis autografts from the right gluteal areas of the rabbits were deepithelialized, and lumbosacral fascia autografts were harvested from the same incision. Additionally, the Achilles tendon of each rabbit was harvested and transformed into diced tendon autografts. Four different autografts were embedded under the skin of each rabbit from 4 different pouches opened in the back of the rabbit. These autografts included diced cartilage alone (Intervention 1), fascia-wrapped cartilage (Intervention 2), dermis-wrapped cartilage (Intervention 3) and fascia-wrapped tendon (Intervention 4) autografts. Intervention 1 had the most irregular appearance, the outcomes in Intervention 4 were volumetrically smaller and softer. Connective tissue formed between the diced pieces in all interventions, and it was observed that the dermis and fascia had a capsule-like appearance, and their viability was preserved. The differences between the initial and final measurements of the volumes of interventions 1, 2 and 3 were statistically significant (p<0.05). There was no significant difference between the initial and final volumetric measurements of intervention 4 (p>0.05). More peripheral proliferation was observed in the interventions of fascia-wrapped and dermis-wrapped diced cartilage compared to the other interventions. The intervention including fascia-wrapped diced tendon grafts had displayed more fibrosis, fragmentation and collagen fibers, while it showed a lower amount of elastic fiber. There were no significant differences among the intervention in terms of other histological parameters. Tendon autografts may be a good option for dorsal augmentation rhinoplasty as they are easily harvested and have minimal donor site morbidity. Dermis autograft usage is more advantageous than fascia usage in terms of accessibility and convenience. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1β), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Future of Basic Science: Development of the Next Generation of Mechanistic Researchers in Female Pelvic Medicine.

The International Urogynecological Association (IUGA) brought together senior and junior members actively engaged in scholarly and educational activities for a consensus conference centered on developing a strategy for sustainable training of the next generation of mechanistic researchers in female pelvic medicine. Four a priori identified major foci were explored in a half-day virtual consensus conference. Participants included representatives from various countries and disciplines with diverse backgrounds-clinicians, physician-scientists, and basic scientists in the fields of urogynecology, biomechanical engineering, and molecular biology.Following a keynote address, each focus area was first tackled by a dedicated breakout group, led by the Chair(s) of the most relevant IUGA committees. The break-out sessions were followed by an iterative discussion among all attendees to identify mitigating strategies to address the shortage of mechanistic researchers in the field of female pelvic medicine. The major focus areas included: research priorities for IUGA basic science scholar program; viable strategies for sustainable basic science mentorship; core competencies in basic science training; and the challenges of conducting complex mechanistic experiments in low-resource countries. Key gaps in knowledge and core competencies that should be incorporated into fellowship/graduate training were identified, and existing training modalities were discussed. Recommendations were made for pragmatic approaches to increasing the exposure of trainees to learning tools to enable sustainable training of the next generation of basic science researchers in female pelvic medicine worldwide. The attendees presented multiple perspectives to gain consensus regarding critical areas of need for training future generations of mechanistic researchers. Recommendations for a sustainable Basic Science Scholar Program were developed using IUGA as a platform. The overarching goal of such a program is to ensure a successful bench-to-bedside-and-back circuit in Urogynecology and Pelvic Reconstructive Surgery, ultimately improving lives of millions of women worldwide through scientifically rational effective preventative and therapeutic interventions.

Scrotoschisis: Review in clinical and embryological perspective of a rare anomaly

Scrotoschisis is a rare congenital anomaly affecting the scrotum and testes, characterized clinically by a defect in the scrotal wall and extrusion of testicular tissue. This literature review is based on reports gathered from PubMed, Science Direct, and Google Scholar using relevant keywords to explore the underlying basic science of this rare condition. The etiology and mechanism of scrotoschisis development remain largely unknown, with only theoretical explanations and a lack of empirical evidence regarding its pathogenesis, which is thought to be linked to embryological abnormalities during scrotal formation. Diagnosing scrotoschisis typically involves a straightforward visual examination of the extruded testes immediately after birth, although clinical presentations may vary, being either unilateral or bilateral. Surgical intervention, primarily through orchidopexy, is generally beneficial for repositioning the testes, closing defects, and preventing potential complications. The prognosis for individuals with this anomaly is generally favorable, although long-term testicular function has been inadequately documented. Further research, including additional clinical reports and investigations involving animal models or embryological studies, is warranted to enhance our understanding of this condition.

A Systematic Literature Review on the Use of Dried Biofluid Microsampling in Patients With Kidney Disease.

Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research. A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability. In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring. There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Evaluation of Different Fixation Methods Combinations After L-Shaped Osteotomy Reduction Malarplasty: An In Vitro Biomechanical Study.

This in vitro study compared the stability of different fixation method combinations for the zygomatic complex after simulated L-shaped osteotomy reduction malarplasty, a common facial contouring surgery in East Asia with high postoperative complications due to poor fixation methods. The study used 108 zygoma replicas with various fixation methods combinations in the zygomatic body (L-shaped plate with short wing on zygoma and on the maxilla, two bicortical screws, one bicortical screw with L-shaped plate, square plate, and rectangular plate) and zygomatic arch (Mortise-Tenon structure, 3-hole plate, and Mortise-Tenon structure plus short screw). The failure force under incremental load was applied through the Instron tensile machine to a well-stabilized model using a rubber band simulating the masseter muscle and recorded the increasing force digitally. ANOVA test was used for comparison between recorded values (P < 0.05). The results showed that the most stable combination was a six-hole rectangular plate and a Mortise-Tenon structure plus one short screw (358.55 ± 51.64 N/mm2). The results also indicated that the placement vector of the fixation methods around the L-shaped osteotomy and the use of the two-bridge fixation method were important factors in enhancing the stability of the zygomatic complex. The study suggested that surgeons should choose appropriate fixation methods based on these factors to reduce postoperative complications and improve surgical outcomes. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Abstract 1848: The Cellular Thermal Shift assay and its applications in Target ID, MoA determination and biomarker discovery

Abstract With the Cellular Thermal Shift Assay (CETSA) celebrating its first decade since the PoC publication, the method has gained much interest in the basic science field as well as become an industry standard in applied drug discovery setting. In the last few years it has become apparent that in addition to providing information about drug-protein interaction, CETSA based thermal profiling of cells can help describe additional aspects of cell biology as it gives insight into the activating and rewiring of protein-protein interaction networks inside the cell upon stimuli. In the work presented here, we have used CETSA coupled to high resolution mass spectrometric readout to profile the response patterns of about 8000 proteins to several hundred molecular probes and marketed drugs. The goal has been to provide a map of wanted and unwanted effects following treatment and to correlate it to alternative readouts, by for example cellular imaging and cell death assays. We have applied the CETSA protocol for close to five hundred compounds, many in several cell-lines (HepG2, U87MG and K562). The experimental setup includes the step of treating the cells with a certain compound at a fixed concentration. After incubation for an hour, we heated the cells to a range of temperatures, followed by a lysis protocol and pooling of the samples. After this, the samples have been centrifuged to separate the soluble from insoluble fraction. The soluble fraction has then been prepared for MS acquisition using TMT based multiplexing. Typically, this allowed us to monitor changes in thermal stability among more than 8,000 proteins, as a consequence of compound treatment. This data reveals specific compound “fingerprints” that can be used to decipher mode of action and identify biomarkers. Despite the short incubation time, proteins with compound-induced thermal stability shifts are not only targets/off-targets (direct binders), but also downstream, and sometimes upstream, pathway members and general cellular responses. All data combined makes the basis of the Target Engagement Atlas. Here we can see clusters of compounds, sharing similar protein binding profiles. Among the most prominent ones are mTOR inhibitors, NSAIDs, as well as tubulin binders. Alternatively, one can use this resource to reveal clusters of “pharmacologically” associated protein networks. We show that pharmacological perturbation allows identification of clusters representing tight protein complexes (for example ribosomes), known metabolic pathways (folate biosynthesis), molecular functions (kinases), as well as networks of proteins linked only by ligand binding specificity. CETSA MS allows for unbiased, cellular, and molecular profiling of compound effects. Together with data from clinical settings, as well as in vivo/in vitro end point assays it is possible to correlate the CETSA patterns to wanted but also unwanted responses. Citation Format: Tomas Friman, Alexey Chernobrovkin, Tuomas Tolvanen, Erin Gilson, Stina Lundgren, Victoria Brehmer, Daniel Martinez Molina. The Cellular Thermal Shift assay and its applications in Target ID, MoA determination and biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1848.

Abstract 7315: Collaboration between NIDCR and NCI promotes innovative research in head and neck cancers

Abstract The Oral and Salivary Cancer Biology Program at National Institute of Dental and Craniofacial Research (NIDCR) supports research activities that improve early detection and treatment of cancers of the oral cavity, pharynx, and salivary glands. We promote basic science research on the regulatory pathways and transformation process of pre-cancerous lesions to primary and metastatic tumors, as well as translational science activities to develop novel technologies and therapeutics for the diagnosis, prognosis, and treatment of cancers. NIDCR and National Cancer Institute (NCI) have established long-term collaborations to promote and co-manage awards funded through The Immuno-Oncology Translational Network (IOTN) of the Cancer Moonshot program, Specialized Programs of Research Excellence (SPOREs), and Early Detection Research Network (EDRN) program. NIDCR and NCI have co-developed Notice of Special Interest (NOSI) and Request for Application (RFA) on Advancing Head and Neck Cancer Early Detection Research (AHEAD), which co-funded seven research projects to discover and develop molecular signatures of early detection and diagnosis of HPV positive and negative head and neck cancer (HNC). To further strengthen NIDCR and NCI collaboration, we jointly organized the symposium to promote HNC early detection and biomarker identification at the American Head and Neck Society (AHNS) 11th International Conference on Head and Neck Cancer in July 2023. In addition, NIDCR has organized a symposium to promote HNC research at the 2024 annual meeting of American Association for Dental, Oral, and Craniofacial Research (AADOCR) to celebrate the 75th anniversary of NIDCR. This AADOCR symposium will feature the collaboration between NIDCR with NCI in the Cancer Moonshot program focusing on immunoprevention and immunotherapy, HNC early detection and biomarker research in AHEAD and EDRN, and investigation of HPV positive and negative HNC and clinical translational research under SPORE. At this 2024 AACR annual meeting, NIDCR and NCI program directors will present the collaborations and funding opportunities between NIDCR and NCI, focusing on early cancer detections and biomarker discovery and validation. Collaboration between NIDCR with NCI provides a unique opportunity to promote basic, translational, and clinical research in advancing HNC early detection to benefit cancer patients. Citation Format: Zhong Chen, Wendy Wang. Collaboration between NIDCR and NCI promotes innovative research in head and neck cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7315.

Greater Risk Taking in Cosmetic Surgery Acceptance and History: An Experimental and Computational Study.

Cosmetic surgery is ever more affordable and accessible, but carries physical and psychological risks. Yet, no study to date has directly examined risk-taking behaviour under controlled conditions, beyond self-report and in relation to cosmetic surgery attitudes. We used the Balloon Analogue Risk Task and advanced computational modelling to measure decision-making behaviour and identify the latent parameters driving behaviour associated with cosmetic surgery attitudes in women with no cosmetic surgery history (N = 265) and a subsample of women with a cosmetic surgery history (N = 24). Risk taking was higher in women with greater acceptance and history of cosmetic surgery. Computational modelling revealed increased risk taking in women with greater acceptance of cosmetic surgery when decisions were made with greater knowledge of loss (risk) and not when the likelihood of loss was unknown (uncertainty). When women with greater acceptance of cosmetic surgery made decisions, they also placed less emphasis on possible losses (reduced loss aversion). Our findings suggest that women seeking cosmetic procedures may be less sensitive to losses and thus make more risky decisions. Greater emphasis should be placed on communicating potential losses rather than just the associated risks to women considering cosmetic procedures.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Medical Informatics as a Concept and Field-Based Medical Informatics Research: The Case of Turkey

Aim: This study aimed to evaluate the position of Turkey in the field of Medical Informatics and assess the general structure of research by analyzing Medical Informatics research with bibliometric methods. Material and Methods: In this study, we conducted a bibliometric analysis of research and review articles generated between 1980 and 2023 from the Web of Science bibliometric data source, utilizing bibliometric methods through the R bibliometrix tool and VosViewer. Results: In the field of medical informatics research in Turkey, the country holds the 27th position with 905 articles, 15,610 citations, and an impressive impact factor of 51, along with an average citation rate of 17.25 per article, based on bibliometric analysis conducted between 1980 and 2023. Notable institutions in this field include Middle East Technical University, Hacettepe University, and Selçuk University. The prominent research topics encompass "neural network(s), machine learning, support vector, health care, decision support, deep learning, EEG signals, classification accuracy," reflecting the areas of intensive investigation. Conclusion: In Turkey, the field of medical informatics has lagged slightly behind basic engineering sciences or medical sciences. The domain exhibits a multidisciplinary structure intersecting with various engineering fields such as computer science, software engineering, industrial engineering, artificial intelligence engineering, and electronic engineering. To enhance productivity in this field, greater collaboration with other research areas can be pursued. Additionally, it is recommended to urgently establish four-year undergraduate programs specifically dedicated to medical informatics or health informatics at universities.

ChatGPT-3.5 and Bing Chat in ophthalmology: an updated evaluation of performance, readability, and informative sources.

Experimental investigation. Bing Chat (Microsoft) integration with ChatGPT-4 (OpenAI) integration has conferred the capability of accessing online data past 2021. We investigate its performance against ChatGPT-3.5 on a multiple-choice question ophthalmology exam. In August 2023, ChatGPT-3.5 and Bing Chat were evaluated against 913 questions derived from the Academy's Basic and Clinical Science Collection collection. For each response, the sub-topic, performance, Simple Measure of Gobbledygook readability score (measuring years of required education to understand a given passage), and cited resources were collected. The primary outcomes were the comparative scores between models, and qualitatively, the resources referenced by Bing Chat. Secondary outcomes included performance stratified by response readability, question type (explicit or situational), and BCSC sub-topic. Across 913 questions, ChatGPT-3.5 scored 59.69% [95% CI 56.45,62.94] while Bing Chat scored 73.60% [95% CI 70.69,76.52]. Both models performed significantly better in explicit than clinical reasoning questions. Both models performed best on general medicine questions than ophthalmology subsections. Bing Chat referenced 927 online entities and provided at-least one citation to 836 of the 913 questions. The use of more reliable (peer-reviewed) sources was associated with higher likelihood of correct response. The most-cited resources were eyewiki.aao.org, aao.org, wikipedia.org, and ncbi.nlm.nih.gov. Bing Chat showed significantly better readability than ChatGPT-3.5, averaging a reading level of grade 11.4 [95% CI 7.14, 15.7] versus 12.4 [95% CI 8.77, 16.1], respectively (p-value < 0.0001, ρ = 0.25). The online access, improved readability, and citation feature of Bing Chat confers additional utility for ophthalmology learners. We recommend critical appraisal of cited sources during response interpretation.

Radioisotope production using lasers: From basic science to applications

The discovery of chirped pulse amplification has led to great improvements in laser technology, enabling energetic laser beams to be compressed to pulse durations of tens of femtoseconds and focused to a few micrometers. Protons with energies of tens of MeV can be accelerated using, for instance, target normal sheath acceleration and focused on secondary targets. Under such conditions, nuclear reactions can occur, with the production of radioisotopes suitable for medical application. The use of high-repetition lasers to produce such isotopes is competitive with conventional methods mostly based on accelerators. In this paper, we study the production of 67Cu, 63Zn, 18F, and 11C, which are currently used in positron emission tomography and other applications. At the same time, we study the reactions 10B(p,α)7Be and 70Zn(p,4n)67Ga to put further constraints on the proton distributions at different angles, as well as the reaction 11B(p,α)8Be relevant for energy production. The experiment was performed at the 1 PW laser facility at Vega III in Salamanca, Spain. Angular distributions of radioisotopes in the forward (with respect to the laser direction) and backward directions were measured using a high purity germanium detector. Our results are in reasonable agreement with numerical estimates obtained following the approach of Kimura and Bonasera [Nucl. Instrum. Methods Phys. Res., Sect. A 637, 164–170 (2011)].

Implementation of a teen sleep app in Canadian high schools: Preliminary evidence of acceptability, engagement, and capacity for supporting healthy sleep habits.

High school students suffer from mental health challenges and poorer academic performance resulting from sleep disturbances. Unfortunately, approaches to this problem sometimes focus on increasing sleep duration by going to bed early; a strategy with limited success because teens experience a phase delay in bedtimes. There is a need for approaches that leverage behavioural sleep science and are accessible, scalable, and easily disseminated to students. DOZE (Delivering Online Zzz's with Empirical Support) is a self-management app that is grounded in sleep and circadian basic science. Although initial testing supports it as a feasible and acceptable app in a research context, it has not been tested as a strategy to use in schools. The present study tested DOZE in private high schools in Canada. Two-hundred and twenty-three students downloaded the app and completed daily sleep diaries over 4 weeks. Students reported a more regularised routine for bedtime, Mdiff = -0.43 h, p < 0.001, 95% CI [-0.65, -0.21], and rise time, Mdiff = -0.61 h, p < 0.001, 95% CI [-0.84, -0.38], in addition to a higher total sleep time, Mdiff = 0.18 h, p < 0.008, 95% CI [0.05, 0.31]. Students also rated DOZE to be highly acceptable. The evidence suggests that students find DOZE to be acceptable and engagement in this nonclinical population was reasonably high under minimal researcher supervision. This makes DOZE an attractive option and a step towards broad-based sleep health services. High powered replications with control groups are needed to increase empirical rigour.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.

O148: Unlocking Enhanced Immunity in Pancreatic Ductal Adenocarcinoma: Activins Interplay with CAF-Stroma Mechanisms

Abstract SMAD4 is a tumour suppressor gene that is mutated in up to 60% of pancreatic ductal adenocarcinoma (PDAC) tumours. Activins are members of the TGF-b signalling superfamily which signal through SMAD4 and are generally associated with an oncogenic process, with differing effects on tumour and stromal cells, such as cancer associated fibroblasts (CAFs). We sought to further elucidate the role of activin within PDAC and perturb activin signalling in vitro and in vivo. Analysis was performed of publicly available human datasets alongside human and murine single-cell RNA-sequencing datasets to study the effect of activin expression on survival and tumourigenesis. We developed anti-activin monoclonal antibodies to perturb activin signalling in PDAC mice, with deep analysis of tumour composition including immune cells and CAFs via a multitude of basic science techniques. We demonstrated that circulating activin levels are higher in PDAC patients than in healthy volunteers, whilst activin overexpression is associated with reduced overall survival in PDAC patients. Activin was shown to be predominantly expressed by contractile (collagen-depositing) CAFs, as opposed to inflammatory CAFs. Activin expression co-localises with fibroblasts, and anti-activin antibodies can reduce the collagen content of dense PDAC tumours. Additionally, anti-activin antibodies led to a statistically significant increase in CD4 and CD8 T-cell infiltration into murine PDAC tumours. We have shown that activin is overexpressed in PDAC, and high expression is associated with a more aggressive disease process. Anti-activin antibodies can alter the composition of desmoplastic PDAC tumours and increase the immune infiltrate of these typically “immune cold” tumours.