bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyruvate Dehydrogenase Kinase 4‐Deficiency Induces Hepatic Apoptosis by Activating NF‐κB/TNFα Signaling
Authors: Wu Jianguo , Choiniere Jonathon , Lin Matthew , Wang Li 
Published: November 2023

ObjectivePyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein and key metabolic regulator of glucose oxidation. However, the role of PDK4 in the development hepatocellular carcinoma (HCC) remains unknown, which is the focus of this study.MethodsIn vivo model: Male 15‐day‐old wild‐type (WT) or Pdk4 knockout (Pdk4−/−) mice given i.p. injections of a single dose of diethylnitrosamine(DEN) (25 mg/kg body weight). In vitro model: PDK4 knockdown Huh7 and Hep3B cells using shRNAs. Cell viability was evaluated by MTS and colony formation assays. Mitochondria function and cell apoptosis were determined by transmission electronic microscopy (EM), Seahorse assay, flow cytometry, and the measurement of caspase activity. Cell death gene expression was profiled with qPCR array and Western blot. TNFα levels were detected by ELISA. NF‐κB activity was determined by immunofluorescence (IF), CHIP assay, qPCR, and luciferase reporter assay. TNFα and NF‐κB signaling were inhibited by shRNAs against TNFR and NF‐κB/p65, respectively. The protein interaction was studied by GST‐pulldown and co‐immunoprecipitation (Co‐IP). Immunohistochemistry (IHC), liver histology, and TUNEL assay were used to detect apoptosis in mouse liver.ResultsPdk4−/− mice injected with DEN died within a week, whereas WT‐DEN showed no visible abnormalities. Pdk4−/−‐DEN had significantly decreased liver/body weight ratio and displayed disrupted liver structure. Pdk4−/−‐DEN liver exhibited severe apoptosis as determined by TUNEL staining, which was accompanied by increased caspase 3 activity, PARP1 cleavage, TNFα expression, and NF‐kB activity, as compared to WT‐DEN. Knockdown of PDK4 in Huh7 and Hep3B cells also caused a marked decrease in cell viability and increased apoptosis and caspase activities. Interestingly, EM revealed apoptotic body formation as well as mitochondria vacuolization in shPDK4 cells. Seahorse revealed marked increases in basal mitochondria respiration, and ATP and ROS production in shPDK4 cells. qPCR array identified a common upregulation of TNFα, BIRC3, and CCDC103 in shPDK4 Huh7 and Hep3B cells. At the molecular level, PDK4 protein sequestrated p65 and p50 in cytoplasm via direct protein‐protein interactions and knockdown of PDK4 resulted in their dissociation thus increased p65/p50 nuclear translocation. This in turn increased binding of p65 to TNFα, BIRC3, and CCDC103 promoters and the activation of their gene transcription.ConclusionsOur study elucidated PDK4 as a crucial new modulator of NF‐κB‐TNFα mediated apoptosis signaling in HCC.Support or Funding InformationGrant support: L.W. is supported by NIH R01DK104656, R01DK080440, R01ES025909, R21AA022482, R21AA024935, VA Merit Award 1I01BX002634, P30 DK34989 (Yale Liver Center) and the National Natural Scientific Foundation of China (Grant No. 81572443).
Ontogenetic Changes in the Terrestrial Locomotion of the American Alligator (Alligator mississippiensis)
Authors: Manfredi Kevin , Georgi Justin 
Published: November 2023

Ontogenetic changes in the musculoskeletal system, ecological niche, and feeding habits of the American alligator (Alligator mississippiensis) have all been hypothesized to relate to similar ontogenetic shifts in locomotion. Anecdotal evidence of the loss of galloping in some crocodilian taxa lends some support to this hypothesis. This study represents the first systematic evaluation of terrestrial locomotor mechanics across an ontogenetic series of crocodilian in order to evaluate if there is an identifiable change. American alligators representing 23 different sizes (ranging in length from 0.63 to 1.64 m in total length) were tracked with a VICON motion tracking system as they moved across a packed dirt floor. For all walking strides that included less than 20° of direction change, stride length, stride duration and duty factor were calculated from the 3D data. These stride parameters were compared to a geometric mean of skull measurements to calculate scaling factors. In addition to overall scaling patterns, the data were sorted into two large (n=11) and small (n=12) groups, correlating to the difference between juveniles and adults (less than or greater than approximately 1 m in length). Scaling patterns between these groups were then compared.Across all specimens, length and duration showed significant positive correlation with size (p << 0.001 and p = 0.016 respectively), but duty factor did not (p = 0.079). In only smaller alligators, length exhibited a positive correlation with size (p << 0.001), duty factor a strong negative correlation (p = 0.002) and duration no correlation (p = 0.288). In contrast, larger alligators demonstrated a different pattern with length and duty factor both showing positive correlations with size (p = 0.002 and p = 0.001 respectively) and no correlation between duration and size (p = 0.204). Comparisons between the large and small groups found significantly different scaling factors for both length (p = 0.008) and duty factor (p = 0.007). Thus, we have shown that there is a major shift in the scaling of the fundamental parameters of alligator locomotion at approximately the sub‐adult stage. This transition decreases the scaling factor of stride length from positive allometry (slope = 1.64) to negative (slope = 0.54) and completely reverses the scaling trend of duty factor from decreasing duty factor (slope = −0.18) to increasing duty factor (slope = 0.40).
Modeling Complex Cranial Joints in Varanus exanthematicus
Authors: Wilken Alec T. , Middleton Kevin M. , Sellers Kaleb C. , Cost Ian N. , Davis Julian L. , Holliday Casey M. 
Published: November 2023

In contrast to humans and other mammals which have relatively few mobile cranial joints, most lizards exhibit cranial kinesis, intracranial movement between bones, which they inherited from their amniote ancestors. Although the tissue‐level structure of kinetic joints has been described, how these joints are loaded during feeding remains relatively poorly known. Finite element analysis previously has been used to estimate joint loading; however, these studies have not modeled mobile joints, instead fusing bones across joints, creating a solid model. We have developed a new method of modeling mobile cranial joints, in which joint spaces are filled with materials that have the properties of cartilage, ligaments, and other tissues that are known to contribute to joint structure. Because their skulls house many different types of structurally and compositionally different joints, ranging from sutural to synovial, lizards make excellent model organisms for studying the relationship between the composition and loading of cranial joints. We created a 3D finite element model of the cranium of an individual of Varanus exanthematicus, a species with intermediate levels of kinesis for which comparative feeding data is available. Intracranial joints were modeled as flexible interfaces between bones and material properties of those joints could be assigned independently. Muscle force magnitudes were calculated from physiological cross‐sectional area estimates and oriented toward mandibular attachment sites. These forces and orientations mimicked feeding behavior. For each simulation, we changed the properties of the joint material to (1) cartilage, (2) ligament, and (3) bone, which represents a fused morphology. Comparisons among these models show lower overall strain energy when joints are modeled using ligament and cartilage, whereas joints modeled with bone showed areas of high stress concentrations. Modeling joints as non‐bony soft‐tissues produced deformations that more closely approximated in vivo feeding kinematics. This concordance affirms the model's ability to recreate feeding mechanics; therefore, the methods used to develop the varanid model can be used to more accurately model the feeding mechanics of fossils, which cannot be directly checked against in vivo feeding kinematics.Support or Funding InformationNational Science Foundation IOS 1457319
Comparative Anatomy and Biomechanics of the Feeding Apparatus of Parrots (Aves: Psittaciformes)
Authors: Cost Ian N. , Middleton Kevin M. , Witmer Lawrence M. , Echols M. Scott , Holliday Casey M. 
Published: November 2023

Parrots occupy varied dietary niches that require an agile, mobilized but sturdy feeding apparatus. Cranial kinesis, flexibility among intracranial joints, has a central role in the unique feeding apparatus of parrots. Parrots possess a highly mobile, streptostylic quadrate that drives the kinetic assemblage by moving the rod‐like pterygoids. The pterygoids, in turn, act as levers and rostrally actuate the tall, thin palatine bones which possess a robust articulation with the rostrum. This palatomaxillary system of articulation rotates the rostrum about the synovial craniofacial hinge, leading to extensive prokinetic movement between the frontal and nasal bones. In this study we analyze the size and orientations of jaw and palatal muscles as well as the biomechanical environment of the kinetic palate of five species of parrots: Psittacus erithacus, Eclectus roratus, Brotogeris jugularis, Strigops habroptilus, and Nestor notabilis. We compared feeding apparatuses across species using 3D data derived from muscle resultants, 3D modeling, and finite element analysis to identify shared patterns of cranial form and function. We digitally mapped jaw muscles onto the models, calculated 3D moments about multiple joints using BoneLoad, and evaluated force propagation through and strain patterns in the models using finite element analysis. Quantitative muscle orientations were visualized and compared using 3D spatial orientations. These data show relationships between muscle orientations and loading of cranial elements during feeding behaviors and highlight the morphological and dietary diversity of the parrot feeding apparatus. We found a wide diversity of orientations among parrot cranial muscles, however, jaw and palate muscles in the parrot species studied are highly specialized for cranial kinesis. Our results show that parrots have appreciably altered the conservative environment of the feeding apparatus by radically expanding their range of cranial kinesis. Understanding how parrot joint articulations work in a highly mobilized system can be applied to skull biomechanics, behavior, and our understanding of avian cranial kinesis. This new understanding will be applied to parrots of various morphologies with similar diets in future studies to assess the abilities of novel morphologies in performing similar tasks. More broadly, these new methods can be applied across other vertebrates to assess morphological performance capabilities of biomechanical tasks.Support or Funding InformationWe thank the National Science Foundation (NSF IOS‐1457319), Missouri Research Board, Missouri Research Council, and the Department of Pathology and Anatomical Sciences for funding this research.
Telequantum Medical Technologies Taught, Practiced, and Assessed by Medical Students in a Millennial Anatomy Lab Developing Telemedicine Skills
Authors: Benninger Brion , Chen Wilson 
Published: November 2023

IntroductionMedical school basic science curriculum is formally attempting a facelift from traditional curricula better preparing trainees to succeed in todays changing healthcare arena. Evolving technologies and patient care have created logical behavioral changes for both patient and physician. Teleporting units have continued to develop and evolve into better quality audiovisual transmissions with friendlier interfaces. Third/fourth year medical students(MS) and junior residents arrive with no or minimal formal training skills interacting with teleporting, tele‐emotion and telemedicine technology skills(TTS).ObjectiveTelequantum medical technologies(TqMedTech) successfully integrated into a millennial anatomy lab resulting in TTS.MethodsTqMTech were taught, used and assessed in a millennial anatomy lab during 1st year anatomy course. MS(n=103) participated with the following TqMTechs, Sectra cross‐sectional and 3D visualization table, PercuVision catheterization, SKY‐EYE camera system, Ultrasound Triple feedback technique, finger probe and 3D/4D ultrasound, robotic OPUS ultrasound simulator, C‐Link and novel scopes, Otoscope teleporting and Google Glass.ResultsMS successfully used all technologies as revealed by timed hands‐on assessment results(>80%) from anatomy lab examinations. Likert scale scores ranged 3.8–4.5 from questions addressing instruction, hands‐on time and perceived importance.DiscussionTelemedicine is growing and appears to have an invaluable contribution in today's health care system. Ideally suited for use between 7pm–7am weekdays and weekends when virtually all family practices are closed. MS appear to have the acumen to integrate TTS during basic science curriculum. MS incorporated TqMTech, skills, education and clinical benefits to improve.ConclusionThis pilot study successfully integrated telequantum medical technologies, skills and clinical uses demonstrated by MS in a millennial anatomy lab.Support or Funding InformationWith the cordial support of Jim & Heather McDaniel and Dr. Jeff Heatherington, as well as the gracious donors who donated themselves for science.
A Formal Interprofessional Ultrasound Curriculum between Medical and Physical Therapy Students in the First Year Gross Anatomy Course
Authors: Gibbs Christopher M , Knight Jennifer A , Van Nuland Sonya E , Bhagra Anjali , Hellyer Nathan J , Langley Natalie R 
Published: November 2023

Ultrasound has been used more frequently in the anatomical sciences to reinforce core anatomy concepts in the classroom and introduce commonly applied imaging technologies encountered in a clinical setting. Interprofessional Education (IPE) is being incorporated into health sciences training as a learning model for real world interactions. The primary objective of the current study was to determine the impact of an IPE ultrasound curriculum on students' anatomy and ultrasound knowledge, as well as attitudes towards interprofessional collaboration. We hypothesized that students who participated in an IPE experience would have improved recall of anatomical and ultrasound concepts as well as improved attitudes and perceptions towards IPE when compared to students who did not participate in an IPE session. First year medical students (MD, n = 40) and first year physical therapy students (PT, n = 25) were randomly assigned to PT‐only, MD‐only, or mixed PT‐MD ultrasound instruction groups studying the shoulder. Students were assessed using an anatomy and ultrasound knowledge test and University of the West of England Interprofessional Questionnaire (UWEIPQ) prior to and following the session. The results of this study suggest that while ultrasound instruction significantly improves ultrasound post‐test scores when compared to pre‐test scores regardless of group assignment (PT‐only: p < 0.001; MD‐only: p = 0.007; PT‐MD: p < 0.001), learning in an interprofessional PT‐MD group did not significantly impact knowledge recall of ultrasound concepts when compared to non‐IPE groups. Interestingly, students in PT‐MD groups had significantly higher anatomy post‐test scores when compared to the MD‐only groups (PT‐MD post‐test = 93.2%; MD‐only post‐test = 84.1%; p = 0.041), but not when compared to the PT‐only groups. Additionally, the results of the UWEIPQ are consistent with the impression that students who participate in an IPE experience are more likely to be cognizant of inherent biases in the interactions between different health professionals as well as demonstrate increased confidence in their interprofessional relationships. In conclusion, our study reinforces that IPE programs should quantify knowledge recall in order to assess the effectiveness of a specific program. Furthermore, such endeavors should assess important competencies including communication, teamwork, and interdisciplinary respect that are necessary to succeed in a multidisciplinary health care team.Support or Funding InformationDepartment of Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN; Social Science and Humanities Research Council, Government of Canada
Tutor Group Assessments (TGAs): Criteria Based Monitoring of Medical Student Performance, Participation and Behavior in Small (Tutor) Group Sessions in a Problem Based Learning Curriculum
Authors: Viscomi Natalie S , DiLalla Lisabeth F , Henry Nancy , Clough Rich W 
Published: November 2023

Southern Illinois University School of Medicine developed and initiated a Problem Based Learning (PBL) curriculum 27 years ago, in 1990, for ½ of the medical school class. Owing to success, this approach was expanded to the entire class in year 2000 and we have maintained the PBL approach to date. In our theme‐based PBL curricular units, students are placed into faculty‐facilitated small groups of 6–8 (~Tutor Group, TG) for the entirety of any particular Unit (approx. 3 months). Students, and their faculty tutor, meet 3h/3x/week across approximately 2 years to develop learning issues, discuss clinical and basic science topics, generate and refine differential diagnoses, etc., and learn about the process of doctoring through electronic simulated patient cases. Participation of each student in TG is essential and expected. Moreover, participation is highly valuable to inculcate professionalism, seek, gain and offer knowledge, develop communication skills, develop diagnostic reasoning, etc. Accordingly, we have developed an assessment tool to monitor student performance in the TG process. Periodic TGAs (Tutor Group Assessments) allow students to both provide and receive feedback about performance and other attributes of TG participation. Initially, our TGAs were open‐ended forms that gave both the students and the tutor a forum to discuss any aspect of the tutor group process. This resulted in inconsistencies between groups and curricular units and complacency in the process, and it sometimes left students unsure of what is expected from them. In an effort to standardize TGAs and provide a more consistent method of evaluation between the different groups and units, we created a rubric style TGA form to evaluate the most critical components of tutor group performance. We modeled our new TGAs after the ACGME's rubrics for residency milestones because we wanted students to more accurately and objectively characterize their own, and their peers', performance in TG. This style of assessment is more robust than before because it combines a Likert scale with subjective comments, providing objective context to assessment categories for students and faculty (tutors) to evaluate performance. In conclusion, since adopting the new TGA approach, our students are now more aware of their specific strengths and/or deficiencies (apart from test scores) and can use the TGAs to better target improvements in their group performance. The new TGA also provides a more consistent longitudinal measurement of student performance throughout the curriculum and provides valuable insights into student behavior over time.Support or Funding InformationSupported by SIU School of Medicine
Improved Medical Student Perception of Ultrasound Using a Paired Anatomy Teaching Assistant and Clinical Instructor Model
Authors: Smith Jacob , Kendall John , Royer Danielle 
Published: November 2023

BACKGROUNDUltrasound (US) is an important component of modern clinical practice, creating the need for US exposure and training during medical school. Incorporating US into medical education allows trainees to develop fundamental skills that help ensure that they are adequately prepared for residency.GOALThis study describes and evaluates a new teaching model for US training during medical gross anatomy at the University of Colorado School of Medicine.METHODSDuring gross anatomy, students participated in five 1‐hour, small‐group, peer scanning sessions: introduction to US, musculoskeletal, cardiothoracic, abdominopelvic, and head and neck. In the 2014 academic year (AY), US sessions were led by a single clinical instructor; in the 2015 AY, the sessions used a new teaching model comprised of an anatomy teaching assistant (TA) paired with a clinical instructor. Both cohorts (N = 184 each) were invited to complete an IRB‐exempt anonymous questionnaire with five Likert‐scale items (1 = strongly disagree; 4 = strongly agree) measuring perceptions of US and anatomy. Ratings were compared using the Mann‐Whitney U test. The 2015AY questionnaire also solicited student views on the effectiveness of the anatomy TAs using three Likert‐scale items (1 = strongly disagree; 5 = strongly agree).RESULTSResponse rates were 89% (2014AY) and 80% (2015AY). Ratings for “US advanced my ability to learn anatomy” increased significantly from 2.91±0.77 in 2014AY to 3.35±0.68 in 2015AY (p<0.0001). Similarly, responses to the statement “Incorporating US increased my interest in anatomy” increased significantly from 3.05±0.84 in 2014AY to 3.50±0.71 in 2015AY (p<0.0001). There was a significant increase from 3.36±0.63 in 2014AY to 3.54±0.53 in 2015AY for the statement “US is relevant to my current educational needs” (p=0.015), and also a significant increase in students agreeing that US training should start in Phase I (2014AY = 3.36±0.71, 2015AY = 3.56±0.59; p=0.010). However, student responses for “US is a valuable tool for my future medical practice” were not significantly different between cohorts (2014AY = 3.75±0.52, 2015AY = 3.73±0.46; p=0.536). 86% of students who experienced the new teaching model agreed or strongly agreed that the anatomy TAs were sufficiently proficient in US (mean = 4.24±0.86), 85% that the TAs enhanced their understanding of anatomy during US (mean = 4.18±0.86), and 85% that TAs were a valuable aspect of the US sessions (mean = 4.23±0.89).CONCLUSIONSThe significant improvement in student perception of US as a tool to enhance anatomy education is attributed to the new teaching model utilizing anatomy TAs paired with clinical instructors. Furthermore, medical students viewed the TAs as knowledgeable in both anatomy and US, and considered them a valuable addition to the US sessions. The anatomy TA‐clinical instructor pair is a simple yet powerful teaching model that can improve student learning of anatomy through US.