bluuebunny/crossref_metadata_2025 huggingface dataset:
Delay volterra integrodifferential models of fractional orders and exponential kernels: Well-posedness theoretical results and Legendre–Galerkin shifted approximations
Authors: Sweis Hind , Shawagfeh Nabil , Abu Arqub Omar
Published: May 2024

The utilized research work studies the well-posedness theoretical results and Galerkin-shifted approximations of delay Volterra integrodifferential models of fractional orders and exponential kernels in linear and nonlinear types in the Caputo–Fabrizio sense. Schauder’s and Arzela–Ascoli’s theorems are employed to prove a local existence theorem. After that, the Laplace continuous transform is employed to establish and confirm the global well-posedness theoretical results for the presented delay model. For numerical solutions, the Legendre–Galerkin shifted approximations’ algorithm has been used by the dependence on the orthogonal Legendre shifted polynomials to find out the required approximations. Utilizing this scheme, the considered delay model is reduced to an algebraic system with initial constraints. The algorithm precision, error behavior, and convergence are studied. Several numerical experiments together with several tables and figures are included to present the performance and validation of the algorithm presented. At last, some consequences and notes according to the given consequences were offered in the final section with several suggestions to guide future action.
Stability analysis and retrieval of new solitary waves of (2+1)- and (3+1)-dimensional potential Kadomtsev–Petviashvili and B-type Kadomtsev–Petviashvili equations using auxiliary equation technique
Authors: Sağlam Fatma Nur Kaya , Ahmad Shabir
Published: May 2024

The Kadomtsev–Petviashvili (KP) equations are nonlinear partial differential equations which are widely used for the modeling of wave propagation in hydrodynamic and plasma systems. This study aims to make a valuable contribution to the literature by providing new solitary waves to the (2+1)- and (3+1)-dimensional potential Kadomtsev–Petviashvili (pKP)-B-type Kadomtsev–Petviashvili (BKP) equations. For this, the auxiliary equation method associated with Bernoulli equation is used and new solutions for the considered equations are obtained. The stability of obtained solutions is demonstrated using nonlinear analysis. It is shown that this method for the considered pKP–BKP equations is an important step forward in an overall mathematical framework for similar equations.
Hygro-Thermo-Magneto-Elastic Vibration of Multidirectional Graded Porous Nanobeams with Axial Motion by Considering Rotary Inertia and Thickness Effects
Authors: Chen Xiaolan
Published: May 2024

Scale-dependent vibration and stability of three-dimensional functionally graded (FG) porous Rayleigh nanobeams with axial motion in varying environmental conditions are investigated by considering scale effects in the thickness orientation. It is supposed that the effective material characteristics of the nanobeam in the longitudinal, width, and thickness orientations are graded according to exponential and power-law functions. Different patterns involving uniform, non-uniform, and logarithmic distributions are considered to model the porosity impacts. Based on the nonlocal strain gradient Rayleigh beam model and incorporating thickness effects, the dynamical equation of the system is derived by considering linear, parabolic, and sinusoidal elastic foundations. The Galerkin discretization technique and Laplace transform are adopted to solve the eigenvalue problem and accomplish the stability analysis. Several comparative studies are performed with the available data in the open literature to validate the solution approach and results. Also, detailed parametric investigations are accomplished to interpret the importance of scale factor, rotary inertia factor, porosity characteristics, magneto-hygro-thermal loads, foundation parameters, gradient indices, and boundary conditions on the dynamical behavior, critical divergence, and flutter axial speeds. The results revealed that, contrary to the effect of the material gradient in thickness orientation, the longitudinal and width gradation of materials can lead to the increment of vibrational frequencies. The outcomes declared that the instability threshold improves significantly by considering the scale effects along the thickness orientation. Also, it is demonstrated that when the middle surface of the cross-section has the highest porosity, the stability regions expand by increasing the porosity coefficient. The present research outcomes can offer valuable insights into the optimum design of high-speed moving multi-directional graded porous nanosystems.
Investigation on the invariance of fractal characteristics preserved under horizontal linear stretching
Authors: Yu Binyan , Liang Yongshun
Published: May 2024

In this paper, we mainly make research on whether fractal characteristics of an object with a fractal curve shape will keep invariable under being subjected to horizontal linear stretching. For two continuous functions [Formula: see text] and [Formula: see text], it has been proven that the graph of [Formula: see text] has the same fractal dimensions with the graph of [Formula: see text] when [Formula: see text] is a linear function. Some examples have also been provided to corroborate our theoretical results. This work may contribute to the dimensional theory of fractal curves and have practical application significance in physics.
Parametrized predictor–corrector method for initial value problems with classical and Caputo–Fabrizio derivatives
Authors: Atangana Abdon , İğret Araz Seda
Published: May 2024

Ordinary nonlinear differential equations with classical and fractional derivatives are used to simulate several real-world problems. Nonetheless, numerical approaches are used to acquire their solutions. While various have been proposed, they are susceptible to both disadvantages and advantages. In this paper, we propose a more accurate numerical system for solving nonlinear differential equations with classical and Caputo–Fabrizio derivatives by combining two concepts: the parametrized method and the predictor–corrector method. We gave theoretical analyses to demonstrate the method’s correctness, as well as several illustrated examples for both scenarios.
A Multi-Task Adversarial Attack against Face Authentication
Authors: Wang Hanrui , Wang Shuo , Chen Cunjian , Tistarelli Massimo , Jin Zhe
Published: May 2024

Deep learning-based identity management systems, such as face authentication systems, are vulnerable to adversarial attacks. However, existing attacks are typically designed for single-task purposes, which means they are tailored to exploit vulnerabilities unique to the individual target rather than being adaptable for multiple users or systems. This limitation makes them unsuitable for certain attack scenarios, such as morphing, universal, transferable, and counterattacks. In this article, we propose a multi-task adversarial attack algorithm called MTADV that are adaptable for multiple users or systems. By interpreting these scenarios as multi-task attacks, MTADV is applicable to both single- and multi-task attacks, and feasible in the white- and gray-box settings. Furthermore, MTADV is effective against various face datasets, including LFW, CelebA, and CelebA-HQ, and can work with different deep learning models, such as FaceNet, InsightFace, and CurricularFace. Importantly, MTADV retains its feasibility as a single-task attack targeting a single user/system. To the best of our knowledge, MTADV is the first adversarial attack method that can target all of the aforementioned scenarios in one algorithm.
Surface Modification of High Voltage Spinel LiNi0.5Mn1.5O4 Cathode Material Manufactured via Co-precipitation
Authors: Song Young-Woong , Lee Junghwan , Jung Younghoon , Lee Seulgi , Kim Min-Young , Lim Jinsub
Published: May 2024

Spinel-structured LiNi0.5Mn1.5O4 (LNMO) can provide high energy density due to its high operating voltage of 4.7 V. LNMO materials synthesized through co-precipitation are suitable for commercialization because of their easily controllable particles and structure. However, their practical application is difficult due to electrolyte and surface-side reactions. In this study, TiO2 was coated with LNMO using the sol–gel method to evaluate its electrochemical properties and thermal stability. Consequently, the TiO2 coating improved the rate performance and long-term battery cycling. Additionally, the cycling characteristics at high temperatures were improved by enhancing the thermal stability of the charged LNMO particles.
Transition Metals Co, Ni, Mn Based Bimetallic Sulfides as an Efficient Electrocatalyst for Hydrogen Evolution Using Graphite Counter Electrode Extracted from Spent Battery
Authors: Vijaya S. , Kennedy L. John
Published: May 2024

The clean and green hydrogen energy production by electrochemical process is gaining great attention in recent years. For this, designing an efficient and cost-effective electrocatalyst for the hydrogen evolution reaction (HER) is highly desirable. Herein, Co-Ni-Mn based bimetallic sulfides electrocatalysts are developed for HER in 1 M KOH. Owing to the presence of abundant electrochemical active sites and micro flower-like morphology, the fabricated Co-Ni-S, Ni-Mn-S, Co-Mn-S electrodes deliver the small overpotential of 136, 112, 75 mV to reach the current density of 10 mA cm−2. For practical applications, the commercially available 1.6 V battery is used to drive the overall water splitting process of the device fabricated with the two-electrode system (symmetric device). In addition to this, in this research work, a graphite rod extracted from a spent battery is directly used as a counter electrode for the entire electrochemical study to substitute platinum (Pt) counter electrode. This approach is sustainable as well as eco-friendly.
Is Aluminium Useful in NiMn Cathode Systems?: A Study of the Effectiveness of Al in Co-Free, Ni-Rich Positive Electrode Materials for Li-Ion Batteries
Authors: Hamam Ines , Omessi Roee , Ball Mitchell , Dahn J. R.
Published: May 2024

Aluminium has become a dopant of interest in many positive electrode materials, particularly the widely used LiNi1−x−yMnxCoyO2 (NMC). Despite the shift of the positive electrode active material space towards Co-free alternatives, the benefits of Al-doping in Co-free LiNixMn1−xO2 (NM) systems have yet to be extensively studied. In this work a series of polycrystalline NM and NMA pairs are compared head-to-head to better understand the effect of Al in Ni-rich, Co-free systems in terms of electrochemical, mechanical, surficial, and thermal stability. The materials tested vary in Ni-content, Al-doping amount as well as secondary particle size, as these parameters influence the effect of Al-presence on certain aspects of material performance. Although Al can bring certain advantages to NM materials, Al-substitution does not universally lead to improved performance in these systems.
Electro-Chemo-Mechanical Model for the Damage in Porous Electrodes of Lithium-Ion Batteries
Authors: Xi Yalu , Zhang Fangzhou , Huang Qiu-An , Bai Yuxuan , Zhang Jiujun
Published: May 2024

An electro-chemo-mechanical model is developed for lithium-ion battery (LIB) considering the damage of active material (AM) particles. The established model is used to evaluate the effect of stress and the effect of damage on the electro-chemo-mechanical behavior of cathode. The cathode is generated with a random distribution method. Computational results show that moderate stress is beneficial for the battery performance, while damage generated by high stress can considerably degrade the battery capacity. The impact of several structural factors on the electro-chemo-mechanical behaviors of LIB are investigated. Smaller particles are found beneficial for the battery performance. Furthermore, the computational results also suggest that an increasing particle size from the separator to the current collector leads to higher capacity. The presented model helps to understand the electro-chemo-mechanical coupling mechanism of LIB.
Role of STIM1 in stretch-induced signaling in human airway smooth muscle
Authors: Yao Yang , Zheng Mengning , Borkar Niyati A. , Thompson Michael A. , Zhang Emily Y. , Koloko Ngassie Maunick Lefin , Wang Shengyu , Pabelick Christina M. , Vogel Elizabeth R. , Prakash Y. S.
Published: May 2024

Mechanical forces on the airway can contribute to altered contractility and remodeling in airway diseases, but the mechanisms are not clearly understood. Using human airway smooth muscle cells exposed to cyclic forces with static stretch to mimic breathing and static pressure, we found that the effects of stretch are mediated through STIM1, resulting in the activation of multiple pathways, including Piezo channels and the inflammasome, with potential downstream influences on contractility and remodeling.
Repeatability of Platelet Aggregation Characteristics Using Impedance Aggregometry With and Without Aspirin Intervention
Authors: Williams Auni , Fisher Kat , Kenney W. Larry , Alexander Lacy
Published: May 2024

Nearly 40% of adults over 50-years-old regularly take aspirin for primary or secondary prevention of cardiovascular disease and/or adverse cardiovascular events. The effcacy of aspirin therapy is commonly assessed with light transmission aggregometry. However, this method requires removal of large platelets as well as the mechanical disturbance of platelets remaining to be tested in the sample. Impedance aggregometry presents a solution to this problem, but the repeatability of impedance aggregometry analysis remains to be tested. We hypothesized repeated impedance aggregometry analysis would show decreased platelet aggregation activity following aspirin intervention compared with control visits. Venous blood samples were obtained from ten participants on three occasions each, separated by at least two weeks. One sample followed seven days of aspirin intervention (81 mg once daily; ASA) and the other two with no intervention (control). Platelet aggregation was induced using 1 μg/ml collagen (Col1), 5 μg/ml collagen (Col5), and 0.5 mM arachidonic acid (AA) via impedance aggregometry to determine area under the aggregation curve (AUC, au), time to aggregation initiation following addition of reagent (Lag, s), the rate of aggregation (Slope), and the maximal aggregation (Amp, Ohms). These characteristics were statistically analyzed for an impact of aggregometer channel (intra-test repeatability), visit (inter-test repeatability), intervention (ASA or control), and incubation (samples were incubated with either saline or Terutroban solution to block thromboxane receptors). Results were analyzed by multiple paired t-tests and represented with lowest relevant p-value if insignificant or highest relevant p-value if significant. Impedance aggregometry revealed no difference in any aggregation characteristics (AUC, Lag, Slope, or Amp) for duplicate samples (all p ≥ 0.10) or visits (all p ≥ 0.06). ASA decreased AUC, Slope, and Amp while increasing or completely inhibiting Lag response to the addition of all reagents (all p ≤ 0.01). Terutroban incubation had no effect on aggregation characteristics following the ASA intervention (all p ≥ 0.09), but attenuated the AUC, Slope, and Amp (all p ≤ 0.01), and entirely prevented or substantially increased the Lag response to AA (p ≤ 0.01) without impacting the responses to Col1 or Col5 (all p ≥ 0.24). These findings suggest the impedance aggregometry approach is a repeatable method for platelet aggregometry analysis for the characteristics of AUC, Lag, Slope, and Amp.

NIH R01 Grant 1R01AG067471-01 NIH F31 Grant 1F31HL170616-01.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sodium Bicarbonate Decreases Alcohol Consumption in Mice
Authors: Lin Jason , Ye Yani , Ryu Clara , Choi Inyeong
Published: May 2024

pH is an important biological factor in the brain as H+ alters the structure and function of many ion channels, transporters and receptors, thus affecting relevant synaptic activities and complex firing patterns. pH may change activities in the neural circuits responsible for motivation and reward, such that drug reward values or modulatory properties are modified to change drinking frequency and amount. In this study, we tested whether alcohol consumption can be affected by systemic pH in mice. C57BL/6J mice were given free access to 0.2 M NaHCO3 for 6 days, which resulted in a 0.2 pH unit increase compared to water-fed control mice ( p < 0.05; n = 6/group). Mice were then subjected to voluntary alcohol consumption in the two-bottle free choice procedure with one bottle containing water and the other containing 5-20% alcohol (5% increment for 4 days each). NaHCO3-fed mice consumed similar amounts of 5-15% alcohol as pair-fed mice but decreased the consumption of 20% alcohol (p < 0.05). Consistent with this result, NaHCO3-fed mice had decreased alcohol preference (i.e., alcohol intake/total fluid intake) at 20%. These changes were observed in both males and females. In separate experiments, mice were subjected to the two-bottle free choice procedure using water and 20% alcohol, with both bottles containing 0.05-0.4 M NaHCO3. The alcohol consumption was significantly decreased in the presence of 0.1 M or higher NaHCO3. The minimum effective dose of NaHCO3 was 0.08 g/kg body weight, calculated from the amount of alcohol mice consumed. Determined by the diarrhea scoring system, mice produced a normal state of feces after receiving 0.4 M NaHCO3 for 2 days, thus indicating negligible abdominal discomfort at this concentration. In other experiments, mice were given NaHCO3 by oral gavage and 1 hour later subjected to 20% alcohol in the drinking in the dark procedure. The alcohol consumption was significantly decreased in NaHCO3-fed mice, compared to pair-fed mice. In conclusion, our study shows that mildly raising blood pH by NaHCO3 decreases alcohol consumption in mice. Given that pH change has been considered as a consequence of alcohol metabolism, our data provide first evidence on the pH as a factor affecting alcohol consumption.

This work was supported by the grant from the National Institute of Alcohol Abuse and Alcoholism (R21AA028606).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Method of storage impacts graft immune cell populations in intestinal transplantation
Authors: McKinney-Aguirre Caroline , Schaaf Cecilia , Ludwig Elsa , Antezana Ariana , Freund John , Gonzalez Liara
Published: May 2024

Intestinal transplantation (IT) is the only treatment for intestinal failure patients who cannot tolerate parenteral nutrition. Although cold storage (CS) is the gold standard for intestinal allograft preservation, normothermic machine perfusion (NMP) has improved transplantation success in other organs. Allograft immune modulation is thought to contribute to this success. The objective of this study was to assess the impact of NMP on intestinal immune cell populations as it relates to ultimate allograft and recipient health. We hypothesized that NMP would stabilize overall immune cell populations while reducing pro-inflammatory cohorts, thus improving IT success. Porcine intestines were stored for 6H at 4°C (CS-T6, n=6) or perfused at 34°C (NMP-T6, n=8) and transplanted. Samples were collected following intestinal procurement (T0), storage (T6), 1-hour post-transplant (T1PT), and euthanasia (T48). Flow cytometric profiling and quantification of intraepithelial (IEL) and lamina propria (LP) lymphocytes and NK cells were performed at T0, T6, and T48. Immunofluorescence (IF) identified CD3+ T-cells at T1PT. One-way ANOVA analyzed cell counts with significance set at p< 0.05. Flow cytometry revealed that NMP preserved CD3+ IELs in the jejunum at T6 (63.74% vs 32.79%, p< 0.0001), and in the ileum at T6 (51.31% vs 42.77%, p< 0.0001) and at T48 (57.73% vs 34.21%, p<0.0001). Immunofluorescent cell quantification confirmed this preservation of CD3+ IEL at T1PT in the crypts of the jejunum (4.9% vs 2.1 %, p< 0.05) and ileum (6.9% vs 2.8%, p< 0.001) compared to CS. However, upon further subpopulation analyses using flow cytometry, ileal IEL T-cells were reduced throughout NMP compared to CS (T6 28.7% vs 44.0%; T48 16.65% vs 22.37%; p< 0.0001). NK cells were also decreased in ileal and jejunal LP at NMP-T6 compared to T0 (3.6% vs 5.6%, p< 0.01; 2.4% vs 4.3% p< 0.05). NMP reduces NK cells, a cell type known to be associated with rejection. Interestingly, NMP preserved the overall CD3+ T cell populations in the jejunum and ileum at T6, T1PT, and T48. The subpopulation of IELs, however, were reduced in the ileum following NMP. The role of these populations, specifically in IT, has yet to be determined. Further characterization of T-cell subpopulations and dynamics is needed. Complimentary evaluations of the microbiome and proteomic responses to IT NMP are ongoing. Understanding immune cell dynamics will improve IT outcomes for patients requiring this critical, lifesaving surgery.

U.S. Department of Defense PR181265; NIH K01OD010199 SERCA, T32OD011130-15.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Pharmacy Student Use of ChatGPT
Authors: Dirks-Naylor Amie
Published: May 2024

The integration of artificial intelligence (AI) tools into educational environments has become a subject of increasing interest. This study delves into the utilization of ChatGPT, a cutting-edge conversational AI technology, among pharmacy students. By investigating how these students engage with ChatGPT, the research aims to shed light on the impact of AI on academic practices, discern the various purposes for which ChatGPT is employed, and offer insights into the potential enhancements and challenges this technology presents in pharmacy education. It is hypothesized that the majority of pharmacy students in a PharmD program have used ChatGPT to assist with academic work of various types. An anonymous Qualtrics survey was emailed to all students matriculating in a Doctor of Pharmacy program in October of 2023. The survey consisted of 11 Likert-scale type questions and two text-entry questions. The overall response rate was 54.3%, however, the response rate by class was P1= 84%, P2=87%, P3=79%, and P4=6%. The P4 students are those no longer taking didactic courses on campus and are matriculating in clinical rotations, thus, may explain the difference in response rate. 26.6% of respondents were not aware of ChatGPT. Of those aware of ChatGPT, 66.7% have never used ChatGPT for academic purposes. Responders not aware of ChatGPT or never used it for academic purposes did not continue with the survey, by design. Thus, only 22% (27/121) of initial responders used ChatGPT for academic purposes and continued with the survey. The most often cited academic uses of ChatGPT were: studying for course exams and quizzes (41%), calculations (26%), interpreting clinical trials (22%), patient case questions used in pharmacotherapy courses (22%), and preparing presentations for classes or rotations (22%), among several other listed uses. The majority of users found ChatGPT to be moderately effective to highly effective assisting with academic work. Most users agreed that they were able to write effective prompts to receive effective responses from ChatGPT. 85% of users agreed that they always cross-check the responses to ensure accuracy. 78% were confident in their ability to use ChatGPT without plagiarizing. 18% of users agreed that in hindsight they may have unintentionally plagiarized an assignment with 19% neither agreeing or disagreeing. 89% agreed that they are confident in their judgement to determine when it is appropriate or not appropriate to use ChatGPT to assist with academic work. 89% were confident that use of ChatGPT was not hindering their learning of material or development of skills/abilities and 88% were confident that use enhanced their learning and development. In conclusion, a minority of pharmacy students have used ChatGPT for academic work, which was unexpected.

None.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Calcium-activated chloride channels in pericytes shape capillary electrical signaling
Authors: Xiang Liuruimin , Longden Thomas
Published: May 2024

The brain vasculature, composed of penetrating arterioles (PAs) giving rise to the dense capillary network, facilitates continuous energy substrate delivery to neurons and glia by tightly controlling blood flow. The capillaries are covered by perivascular cells known as pericytes, which exhibit varying morphological and physiological properties based on their location in relation to the terminal arteriole, and these contribute to blood flow control within the capillary network in distinct ways. Thin-strand pericytes —the focus of this study—are located in the deep capillary bed. Serendipitously, we have discovered a robust chloride current during perforated patch clamp experiments on these thin-strand pericytes. We hypothesized that this current is mediated by calcium-activated chloride channels (CaCCs), which may influence electrical signaling and thereby regulate blood flow. Our data reveal that this robust current is dependent on external calcium concentration and can be blocked by voltage-gated calcium channel blockers, depletion of endoplasmic reticulum calcium stores, and calcium-activated chloride channel blockers. This suggests a mechanism wherein calcium entry into the cytosol via voltage-gated channels and intracellular calcium release govern the activity of CaCCs in the thin-strand pericyte membrane. Using two-photon microscopy, we further observed that blocking CaCCs led to PA dilation and hyperemia. Together, our data indicate a novel role for CaCCs in thin-strand pericytes, where they modulate electrical signaling across the capillary bed in response to intracellular calcium activity. By providing a depolarizing signal countering hyperpolarizing electrical signaling, these channels contribute to the intricate regulation of blood flow and vessel dilation.

This work was supported by the NIH (grants 1R01AG066645, 5R01NS115401, 1DP2NS121347-01), and the American Heart Association (19IPLOI34660108).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
AI-Powered Web Applications for Enhanced Clinical, Research, and Professional Development
Authors: Melvin Ryan , Godwin Ryan
Published: May 2024

Introduction: The rapid growth of technology in the field of anesthesiology offers unique opportunities to leverage artificial intelligence (AI) for enhancing clinical, research, and administrative operations. Our team, consisting of anesthesiologists and data scientists, sought to develop a suite of web applications using generative AI to address specific challenges faced by anesthesiology departments. Objective: To design, develop, and evaluate the feasibility of a range of AI-powered web applications tailored for anesthesiologists to streamline research feasibility, literature searches, protocol drafting, text simplification, work promotion, grant writing, professional advancement, and secure communication. AI Tools developed: Data Feasibility Analysis: AI-assisted search of descriptions and schemas of multiple data warehouses to assess the feasibility of various clinical and research ideas. AI-Powered PubMed Search: AI-assisted search to effciently navigate and extract relevant publications from PubMed, including summarizing the literature found. IRB Protocol Generation: Automated drafting process for Institutional Review Board (IRB) protocol forms, ensuring adherence to regulatory standards. Text Simplification: Tool to distill complex clinical, research, or regulatory text to an 8th-grade reading level, enhancing accessibility — e.g., for patient consent forms. Work Promotion and Amplification: drafts blog posts, “tweets,” and layperson summaries of research abstracts. NIH Grant Drafting: Drafts Specific Aims page and Research Strategy sections for National Institutes of Health (NIH) style applications, ensuring compliance and coherence. Professional Advancement Assistance: Drafts Promotion & Tenure portfolios and letters of recommendations Secure AI Conversations: Integrated generative AI technology in an encrypted and secured platform, safeguarding sensitive information. Conclusions: The suite of AI-powered web applications, developed in collaboration between anesthesiologists and data scientists, showcases potential in enhancing the effciency and impact of various processes integral to anesthesiology research. The integration of these tools into daily operations can potentially revolutionize how anesthesiologists engage with research, patient care, professional development, and communication. Future endeavors will focus on rigorous validation and widespread deployment to harness the full potential of these innovations.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Role for the Carotid Chemoreceptors in Glucose Tolerance in Human Type 2 Diabetes
Authors: Pipkins Aubrey , Lis Eric , Ott Elizabeth , Harper Jennifer , Manrique-Acevedo Camila , Limberg Jacqueline
Published: May 2024

Objectives: The carotid body (CB) chemoreceptors have been implicated in the development and progression of type 2 diabetes (T2D). CB denervation can prevent the development and worsening of T2D in pre-clinical models — although these data have yet to be translated to humans. We examined CB chemosensitivity in T2D, as well as the contribution of the CB to glucose tolerance. We hypothesized: 1) individuals with T2D would exhibit exaggerated CB sensitivity to hypoxia (hypoxic ventilatory response, HVR), 2) attenuation of CB chemoreceptor activity (i.e., hyperoxia) would improve glucose tolerance in T2D, and 3) the magnitude of the effect of hyperoxia on glucose tolerance would be related to the level of CB chemosensitivity. Methods: HVR was assessed in sixteen adults with T2D (6M/10F, 55±11 yrs, HbA1c 7.7±1.4%) and twenty-one healthy controls (9M/12F, 50±13 yrs, HbA1c 5.2±0.4%)(NCT05219994). A subset (n=9 per group) completed two additional visits randomized to normoxia (0.21 FiO2) and hyperoxia (1.0 FiO2). During each visit, blood glucose and plasma insulin were measured every 15 min for 2 hrs following consumption of a 75 g glucose drink and responses were calculated as area under the curve (AUC). Pearson correlations between HVR and the difference in AUC glucose and insulin between visits (ΔAUC = hyperoxia-normoxia) were conducted. Results: HVR was augmented in T2D compared to control (control, -0.47±0.39; T2D, -0.83±0.50 L/min/%; p=0.02). There was no effect of hyperoxia on AUCglucose (control, p=0.77; T2D, p=0.73) or AUCinsulin (control, p=0.70; T2D, p=0.41). Correlations were observed between HVR and ΔAUCglucose (R=0.67, p=0.047) and ΔAUCinsulin (R=-0.55, p=0.16)] in adults with T2D, but not in controls [ΔAUCglucose (R=-0.32, p=0.40), ΔAUCinsulin (R=-0.18, p=0.67)]. Conclusions: Individuals with T2D exhibit exaggerated CB sensitivity to hypoxia. Glucose tolerance was unaffected by attenuation of CB chemoreceptor activity; however, when examined in relation to CB sensitivity, glucose tolerance improved with hyperoxia in T2D adults with the highest HVR. Present data advance our understanding of the pathophysiology of T2D and support a potential role for the CB chemoreceptors in glucose tolerance in human T2D.

MizzouForward Undergraduate Research Training Grant, University of Missouri Research Council, University of Missouri Alumni Association Richard Wallace Research Incentive Fund.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Lysosomal Regulation of Gasdermin D Pore Formation in Podocytes Determined by Acid Sphingomyelinase
Authors: Huang Dandan , Ren Jenna , Zou Yao , Kidd Jason , Gehr Todd , Li Pin-Lan , Li Guangbi
Published: May 2024

Recent studies have shown that gasdermin D (GSDMD) pore may be involved in inflammasome product release and pyroptosis in podocytes. Nevertheless, the molecular mechanism by which GSDMD pore formation is regulated in these cells remains poorly understood. Given the important role of acid sphingomyelinase (ASM)-ceramide signaling pathway in glomerular inflammation and sclerosis under pathological conditions, the present study tested whether ASM controls lysosome-dependent autophagic degradation of GSDMD-NT and GSDMD pore repair to determine GSDMD pore formation in podocytes. WT/WT, ASM knockout (KO), and ASM overexpression (OE) podocytes were isolated from wild type, Smpd1 (gene code of ASM) gene KO, and podocyte-specific Smpd1 gene OE mice for experiments. We first demonstrated that palmitic acid (PA) as an obesity-related danger factor induced NLRP3 inflammasome activation, GSDMD pore formation on plasma membrane, and IL-1β secretion in podocytes, which was blocked by Smpd1 gene KO but exaggerated by Smpd1 gene OE. Also, it was found that PA-induced pyroptosis was prevented by ASM KO but amplified by ASM OE in podocytes. By confocal microscopy and super-resolution microscopy, we observed that PA treatment enhanced the formation of autophagosomes containing GSDMD-NT but inhibited lysosome-autophagosome interaction in podocytes. Also, FasL-induced lysosome fusion to plasma membrane was reduced by PA. All these pathological changes were remarkably attenuated by ASM KO or amitriptyline but significantly augmented by ASM OE. To further dissect the molecular mechanism by which ASM determines GSDMD pore formation, we examined whether ASM controls lysosomal TRPML1 channel-mediated Ca2+ release to regulate lysosome traffcking and associated lysosomal functions. By GCaMP3 Ca2+ imaging, we found that PA treatment significantly inhibited TRPML1 channel activity in podocytes, which was exaggerated by ASM OE. Correspondingly, PA-induced reduction of lysosome traffcking was more remarkable in ASM OE podocytes compared to WT/WT podocytes. Moreover, PA-induced decrease in lysosome-autophagosome interaction and increase in GSDMD pore formation in podocytes were hindered by ML-SA5 (TRPML1 channel agonist) but enhanced by ML-SI1 (TRPML1 channel inhibitor). In summary, our findings suggest that ASM plays a crucial role in lysosomal regulation of GSDMD pore formation via control of TRPML1 channel activity and lysosome traffcking in podocytes.

This study was supported by NIH grants DK054927 and DK120491.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Heavy Metal-Laden Particulate Dust Alters Transcriptional Regulation in Human Colonoids
Authors: Appell Lidia , Atanga Roger , In Julie
Published: May 2024

Chronic heavy metals exposure in the southwestern United States co-occurs with greater incidences of metabolic and digestive diseases, particularly in the Indigenous and Hispanic populations. There is a need to understand how particulate heavy metals drive this dysbiotic state and propose a molecular explanation as a result of these exposures. Previously, our group demonstrated human colonoids to be a relevant model for investigating the physiological impact of environmental toxicants on the intestinal tract. The objective of this study is to elucidate the mechanism behind the transcriptional and cellular changes present in the intestinal epithelia upon acute exposure to non fissile uranium particulate dust. We hypothesize that non-fissile uranium exposure biases the differentiation of progenitor cells in the crypt to secretory roles through miRNA regulation. Colonoids were exposed (18 hours) to non-fissile uranium dust obtained from the Jackpile uranium mine, one of the largest open pit uranium mines, located on the Laguna Pueblo in New Mexico. Control and dust-exposed colonoids (n=3 unique donors) were digested into single cells and processed for droplet-based single cell sequencing (scRNAseq). Upon exposure, enteroendocrine cells (EEC) expanded >4 fold, along with increases in serotonin and PYY, as well as goblet cells (>3 fold) which indicates changes to the secretory lineage. Downstream pathway analysis found microRNAs miR-625-3p, miR-320a, miR-29b-3p to be differentially expressed. These results suggest that acute uranium dust exposure induces changes in differentiation pathways which are modulated by regulatory miRNAs. We would like to expand these findings by performing miRNA sequencing and comparing miRNA expression profiles between UBD exposed and control samples. Our results also provide an improved understanding of uranium dust’s impact on the gastrointestinal system, which may inform other physiological studies on the health of individuals exposed to heavy metals.

This study was funded by K01DK106323, R56ES034400, P42ES025589, P20GM121176, P20GM130422, and AGA SURF.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Previous exercise training history reduces drug addiction through brain orexinergic pathway in rodents: Conditioned Place Preference (CPP) model
Authors: Fayazmilani Rana , Ahmadpour Mansoureh , Modaberi Shaghayegh , Haghparast Abbas
Published: May 2024

Methamphetamine, commonly known as METH, is a potent and highly addict-forming stimulant substance that has a significant impact on the brain and poses a substantial health challenge in certain areas. Previous studies have pointed to the involvement of orexinergic pathway in reward-related behavior which is directly involved in acquisition phase of METH induced conditioned place preference (CPP). Besides, while numerous studies have explored the impact of exercise training on METH addiction, there is a limited body of research investigating as a form of preconditioning to prevent drug dependence. In this study, 48 male Wistar rats were assigned into six groups: Saline control, METH1 control, METH2 control, METH1 exercise, METH2 exercise. The exercise groups underwent eight weeks of forced running wheel training, five days a week, at 65% of their maximum running speed (Vmax). Following preconditioning with exercise training, METH groups received intraperitoneal (IP) methamphetamine injections at doses of 1 mg/kg (METH1 control, METH1 exercise) and 2 mg/kg (METH2 control, METH2 exercise) for five days to induce addiction (acquisition phase) according to the CPP model. Immediately following conditioning, hippocampus tissues were extracted to measure OX1R levels using western blotting. The results of the study indicated the conditioning of rats in both METH1 and METH2 control groups while preconditioning with exercise training prevent the addiction with low does of METH and only induced acquisition with double does in METH2 exercise group represented with reduced CPP scores in compare with METH2 control group (p<0.05). Molecular analysis revealed a significant increased in OX1R levels according to METH administration in hippocampus, although exercise training appeared to inhibit OX1R expression. Only conditioning with a high dose of METH was able to increase OX1R levels significantly. As these molecular results are in line with CPP scores it could further support the role of orexinergic pathway in addiction behavior in hippocampus. Furthermore, previous exercise training seems to affect this pathway and prevent conditioning with METH in an effective manner which suggests adaptation in the mesolimbic reward pathway protecting against methamphetamine addiction. Further investigation is warranted to find out the effectiveness of different training interventions in orexinergic pathway to inhibit dependance to METH.

In this study, there was no external funding or financial support provided. This work was entirely self-funded by the authors.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Influence of Microinjection of Kynurenic acid into the Pre-Botzinger Complex on Swallowing in the Cat
Authors: Bolser Donald , Shen Tabitha , Poliacek Ivan , Rose Melanie , Musselwhite M. Nicholas , Kotmanova Zuzana , Martvon Lukas
Published: May 2024

Recent evidence supports the involvement of the pre-BÖtzinger complex (pre-BOT) in spatiotemporal features of swallowing and swallowing-breathing coordination in mice. We hypothesized that pharmacological disruption of glutamate neurotransmission in this brainstem region would perturb the swallow motor pattern in anesthetized cats. Electromyograms (EMGs) of upper airway muscles were recorded in anesthetized, spontaneously breathing cats (n=5). Swallowing was induced by injection of 3 cc of water into the oropharynx. Multi-barrel micropipettes were employed to inject artificial cerebrospinal fluid or kynurenic acid (KYN; 50 mM, 44±3 nL per injection) bilaterally into the region of the pre-BOT. Microinjection sites were confirmed histologically by detection of fluorescent beads that were suspended in the microinjectate. Blocking glutamate-related neuronal excitation by bilateral microinjections of the nonspecific glutamate receptor antagonist kynurenic acid had no effect on the number of swallows induced by water injection (control 2.3±0.3; KYN 3.0±0.7; P<0.32). Swallow durations were significantly increased following microinjections of KYN from 691±54 ms to 812±81 ms (p<0.04). KYN significantly reduced the magnitudes of geniohyoid (control 97±3 % of median; Kyn 47±12% of control median, p<0.02), thyrohyoid (control 100±3% of median; KYN 69±8% of control median, p<0.01), and posterior cricoarytenoid (control 103±2% of median; KYN 74±8% of control median, p<0.04) muscle EMGs during swallowing. There was no significant effect of microinjection of KYN on the magnitudes of thyroartytenoid, mylohyoid, or thyropharyngeus electromyograms during swallowing. The results suggest that disruption of glutamate neurotransmission in the preBOT has preferential effects consistent with actions on motor drive to hypoglossal and ventrolateral motoneuron pools that participate in swallowing. Lengthening of swallow duration induced by KYN supports a role for the preBOT in modulating the excitability of the swallow oscillatory circuit.

NIH HL163008; NIH HL 131716; HL 155721.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Metabolomic and transcriptomic alterations in the colon of mice with metabolic syndrome in the absence of inflammation
Authors: Rivas Jaclyn , Castillo Eliseo , Scieszka David , Peralta-Herrera Eduardo
Published: May 2024

Metabolic syndrome (MetS) is characterized by a cluster of conditions including abdominal obesity, elevated blood pressure, altered lipid profiles and high blood sugar levels. These factors collectively elevate risks for cardiovascular diseases, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). MetS impacts approximately a third of the US populace and a quarter of the global population. Despite its widespread prevalence, there are no existing medications to specifically treat MetS. With the global rise in MetS cases, understanding its underlying mechanisms is paramount. Our research emphasizes the potential physiological and metabolic disruptions within the gastrointestinal (GI) tract that might contribute to MetS manifestation. Using a mouse model of MetS (MS NASH) and healthy lean controls (C57BL/6J), we investigated the colon environment. 16S rRNA sequencing from fecal samples revealed a distinct microbiota profile in MS NASH mice, highlighted by an increase in the Lactobacillus genus. Colonic metabolome and transcriptome in MS NASH mice displayed an upregulation in anabolic pathways, like glycolysis, the pentose phosphate pathway, and the tryptophan/kynurenine pathway. Subsequent integrated analysis of these datasets unveiled potential compensatory mechanisms and pathway crosstalk, within the colonic environment. Despite these alterations, MS NASH mice showed no signs of intestinal inflammation, a finding confirmed through detailed histological and LCN-2 assessments. Additionally, there were no changes detected in genes typically associated with increased intestinal inflammation or permeability. This study provides insight in the nuanced relationship between the metabolic state, gut microbiota, and potential progression towards other metabolic disorders. Our findings highlight the significance of multi-omics data convergence in understanding the changes within the colonic environment and their implications for MetS onset and/or progression.

Supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) through grant no. UL1TR001449 (E.F.C.) and in part by NIH grant P20GM121176 (E.F.C.), and the University of New Mexico Comprehensive Cancer Center with grant P30CA118100.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.