bluuebunny/crossref_metadata_2025 huggingface dataset:
Aligned carbon nanotube–based electronics on glass wafer
Authors: Cheng Xiaohan , Pan Zipeng , Fan Chenwei , Wu Zhichen , Ding Li , Peng Lian-mao
Published: March 2024

Carbon nanotubes (CNTs), due to excellent electronic properties, are emerging as a promising semiconductor for diverse electronic applications with superiority over silicon. However, until now, the supposed superiority of CNTs by “head-to-head” comparison within a well-defined voltage range remains unrealized. Here, we report aligned CNT (ACNT)–based electronics on a glass wafer and successfully develop a 250-nm gate length ACNT-based field-effect transistor (FET) with an almost identical transfer curve to a “90-nm” node silicon device, indicating a three- to four-generation superiority. Moreover, a record gate delay of 9.86 ps is achieved by our ring oscillator, which exceeds silicon even at a lower supply voltage. Furthermore, the fabrication of basic logic gates indicates the potential for further digital integrated circuits. All of these results highlight ACNT-based FETs on the glass wafer as an effective solution/platform for further development of CNT-based electronics.
Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging
Authors: Saladino Giovanni M. , Brodin Bertha , Kakadiya Ronak , Toprak Muhammet S. , Hertz Hans M.
Published: March 2024

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.
Invasion of spontaneous germinal centers by naive B cells is rapid and persistent
Authors: van den Broek Theo , Oleinika Kristine , Rahmayanti Siti , Castrillon Carlos , van der Poel Cees E. , Carroll Michael C.
Published: March 2024

In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.
Antibiotic treatment modestly reduces protection against
Mycobacterium tuberculosis
reinfection in macaques
Authors: Ganchua Sharie Keanne , Maiello Pauline , Chao Michael , Hopkins Forrest , Mugahid Douaa , Lin Philana Ling , Fortune Sarah M. , Flynn JoAnne L.
Published: March 2024

Concomitant immunity is generally defined as an ongoing infection providing protection against reinfection . Its role in prevention of tuberculosis (TB) caused by
Mycobacterium tuberculosis
(Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection. Using cynomolgus macaques, molecularly barcoded Mtb libraries, positron emission tomography-computed tomography (PET CT) imaging, flow cytometry, and cytokine profiling, we evaluated the effect of antibiotic treatment after primary infection on immunological response and bacterial establishment, dissemination, and burden post-secondary infection. Our data provide evidence that, in this experimental model, treatment with antibiotics after primary infection reduced inflammation in the lung but was not associated with a significant change in bacterial establishment, dissemination, or burden in the lung or lymph nodes. Nonetheless, treatment of the prior infection with antibiotics did result in a modest reduction in protection against reinfection: none of the seven antibiotic-treated animals demonstrated sterilizing immunity against reinfection, while four of the seven non-treated macaques were completely protected against reinfection. These findings support that antibiotic-treated animals were still able to restrict bacterial establishment and dissemination after rechallenge compared to naïve macaques, but not to the full extent of non-antibiotic-treated macaques.
Place-based climate change: lowering students' psychological distance through a classroom activity
Authors: Duke Jessica , Holt Emily A.
Published: March 2024

Psychological distance (PD) can be a barrier to how students perceive climate change impacts and severity. Localizing climate change using place-based approaches is one way instructors can structure their curricula to help combat students' PD, especially from a spatial and social viewpoint. We created a novel classroom intervention that incorporated elements of place-based education and the Teaching for Transformative Experiences in Science model that was designed to lower undergraduate biology students' spatial and social distance of climate change. Our research questions sought to determine whether students' PD changed following our intervention and whether variables beyond our intervention might have contributed to changes we identified. To measure the efficacy of our intervention, we administered a survey that contained several instruments to measure students' recognition and psychological distance of climate change pre- and post-intervention. We found that students' psychological distance to climate change decreased after participating in our classroom intervention. Additionally, course level was the only outside variable we identified as a predictor of students' post-activity scores. Participation in our activity lowered our students' spatial and social psychological distance, which could have impacts beyond the classroom as these students become the next generation of scientists and voters.
Photoinduced Nonlinear Dynamics of Strongly Correlated Systems with Spin Crossover: Autocatalytic Spin Transition
Authors: Orlov Yu. S. , Nikolaev S. V. , Paklin N. N.
Published: March 2024

Nonlinear phenomena similar to the Belousov–Zhabotinsky reaction (autocatalytic oscillations of the population of high-spin and low-spin multielectron states of a transition metal ion) in open systems with spin crossover near bistability are considered. The conditions for possible experimental observation of autocatalytic oscillations of the magnetization in magnetically ordered systems with spin crossover are analyzed.
Do not attempt cardiopulmonary resuscitation decision-making process: scoping review
Authors: Doody Owen , Davidson Hope , Lombard John
Published: March 2024

Objectives

To conduct a scoping review to explore the evidence of the process of do not attempt cardiopulmonary resuscitation (DNACPR) decision-making.

Methods

We conducted a systematic search and review of articles from 1 January 2013 to 6 April 2023 within eight databases. Through multi-disciplinary discussions and content analytical techniques, data were mapped onto a conceptual framework to report the data.

Results

Search results (n=66 207) were screened by paired reviewers and 58 papers were included in the review. Data were mapped onto concepts/conceptual framework to identify timing of decision-making, evidence of involvement, evidence of discussion, evidence of decision documented, communication and adherence to decision and recommendations from the literature.

Conclusion

The findings provide insights into the barriers and facilitators to DNACPR decision-making, processes and implementation. Barriers arising in DNACPR decision-making related to timing, patient/family input, poor communication, conflicts and ethical uncertainty. Facilitators included ongoing conversation, time to discuss, documentation, flexibility in recording, good communication and a DNACPR policy. Challenges will persist unless substantial changes are made to support and promote examples of good practice. Overall, the review underlined the complexity of DNACPR decision-making and how it is a process shaped by multiple factors including law and policy, resource investment, healthcare professionals, those close to the patient and of central importance, the patient.
Estimating fish production in wetlands
Authors: Tucker Caroline M. , Giacomini Henrique C. , Mandrak Nicholas E. , Wang Lifei , de Kerckhove Derrick T.
Published: March 2024

Fish production integrates changes in biomass from growth, reproduction, and mortality, and is a useful indicator for fisheries management. However, calculation of fish production has been limited by the intensive requirements for data on abundance, biomass, age structure, and vital rates, and so it is uncommon to find estimates of fish production for wetlands. We developed an approach to directly estimate production that is suitable for data-limited systems: a continuous time model of production describing individual growth over short time intervals with continuous time models of abundance and biomass over longer timescales. We applied this model for 18 Great Lakes coastal wetlands (GLCWs) on Lake Ontario, including Big Island Wetland (BIW). In BIW, most species were dominated in abundance and biomass by younger cohorts and, as a result, these young, fast-growing individuals contributed disproportionately to fish production. In total, BIW produced 336.1 kg·ha·year of fish and the other 17 neighbouring ranged between 447.7 and 1119.9 kg·ha·year. These are some of the first estimates of fish production for GLCWs, highlighting their value for managing Great Lakes fisheries.
Research on a work zone model with metering zone under mixed traffic flow environment
Authors: Liu Jun , Li Qi-Lang , Fu Ding-Jun , Wang Bing-Hong
Published: March 2024

In the upstream of the highway work zone, vehicles will change lanes automatically or forcibly, which has complexity and randomness. Most studies fail to consider the impact of actual mixed traffic characteristics on traffic flow. For example, the dependence of the lane-changing behaviors of Connected and Automated Vehicles (CAVs) on the length of the zone is ignored in upstream of work zone. In addition, it is assumed that vehicles in the merge lane of the work zone would “yield” or not consider an impact on vehicles in the through lane. This simplifies the complex dynamics of the interaction between the two streams of traffic, which leads to the results of the study and the actual situation inconsistency. Based on the Gipps model, the adaptive cruise control (ACC) and the collaborative adaptive cruise control (CACC) vehicle-following models, this paper proposes a continuous cellular automata model under Vehicle-Road Collaboration and studies the mixed traffic flow characteristics in the work zone. By setting a metering zone before the lane reduction sign, ACC/CACC can adjust headway by obtaining road information in advance. The simulation results indicate that ACC/CACC vehicles have better following response compared to human-driven vehicles. In other words, the platoon composed of ACC/CACC vehicles has stability and can improve the traffic capacity of the work zone. The results of the study also found that the insertion of vehicles from adjacent lane into the ACC/CACC vehicles platoon is detrimental, especially when the penetration rate [Formula: see text] is high. Furthermore, when the length of the metering zone [Formula: see text] is set at 120–150[Formula: see text]m, it can significantly improve the road congestion in the work zone.
GOVERNMENT INVESTMENT IN NATURAL CAPITAL BOOSTS ECONOMIC GROWTH: EVIDENCE FROM CHINA’S TRANSFER PAYMENT POLICY FOR NATIONAL KEY ECOLOGICAL FUNCTIONAL AREAS
Authors: LUO XI , ZHANG LINLING , LUO YONGMIN , GAO MIN
Published: March 2024

This paper studies the impact of the transfer payment policy for national key ecological functional areas (TPPNKEFA) on economic growth. As the most representative and extensive vertical ecological compensation policy in China, the TPPNKEFA plays an important role in protecting and restoring natural capital. Using the county-level TPPNKEFA data disclosed according to the application, we constructed a multi-stage DID model to identify the economic growth effect of TPPNKEFA. The results show that TPPNKEFA effectively improves the level of county economic development, which is more prominent in the counties located in the central and western regions, water conservation functional areas, low economic development level, large fiscal gap, and the counties where TPPNKEFA has been implemented for a long time. A mechanism analysis shows that industrial ecologization and ecological industrialization are important paths. The extension analysis shows that the original intention of TPPNKEFA to promote the restoration of natural capital and the improvement of people’s livelihoods has been well implemented. This study provides important evidence to support efforts to protect and restore natural capital, highlighting the need for governments to invest in natural capital and thus facilitate the transition to a low-carbon economy.
Heat transfer analysis of Cu–H2O/Al2O3–H2O nanofluid flow in wavy/microchannels: A review
Authors: Sharma Tarun , Sharma Pooja
Published: March 2024

The miniaturization of electronic devices without compromising their heat dissipation capacities is the main concern due to the rapid evolution in power industries and engineering fields. The conventional methods of cooling or heating the devices are changed and old tactics of using conventional fluids for heat dissipation are replaced with nanofluids of strong thermal efficiency. In the present context, the experimental as well as theoretical studies of nanofluids (Cu–H2O/Al2O3–H2O) flow inside the wavy and microchannels are elucidated and discussed for different physical conditions. It is found that the use of Cu–H2O/Al2O3–H2O nanofluid improves the thermal efficiency of heat exchangers. The complex shapes and sizes of heat exchangers such as multilayer heat exchangers, heat exchangers with twisted and square shapes and multijet heat exchangers are considered effective coolants as compared with straight microchannel heat exchangers. The use of Cu–H2O/Al2O3–H2O nanofluids improves the overall heat transfer efficacy of electronic devices, and it is considered a promising coolant for various applications including aerospace (spacecraft and satellites), automobile (cooling the engines and power management in electric vehicles), renewable energy (solar plants), microelectronic devices (heat dissipation through the microprocessor and cooling the other components of devices) and modern heat exchangers of engineering domains.
A homotopy-based computational scheme for two-dimensional fractional cable equation
Authors: Kumar C. V. Darshan , Prakasha D. G. , Veeresha P. , Kapoor Mamta
Published: March 2024

In this paper, we examine the time-dependent two-dimensional cable equation of fractional order in terms of the Caputo fractional derivative. This cable equation plays a vital role in diverse areas of electrophysiology and modeling neuronal dynamics. This paper conveys a precise semi-analytical method called the q-homotopy analysis transform method to solve the fractional cable equation. The proposed method is based on the conjunction of the q-homotopy analysis method and Laplace transform. We explained the uniqueness of the solution produced by the suggested method with the help of Banach’s fixed-point theory. The results obtained through the considered method are in the form of a series solution, and they converge rapidly. The obtained outcomes were in good agreement with the exact solution and are discussed through the 3D plots and graphs that express the physical representation of the considered equation. It shows that the proposed technique used here is reliable, well-organized and effective in analyzing the considered non-homogeneous fractional differential equations arising in various branches of science and engineering.
Optimizing Storage Efficiency Through Pipelining and Parallelization for Enhanced Data Deduplication
Authors: Nalini M. , Thilagavathy R. , Bhargavi K. , Thinakaran K.
Published: March 2024

Nowadays, huge devices are connected to the internet to deal with many cloud environments for storing data efficiently. Also, it is used to store big data determined in business activities. However, the data storage in the cloud avoids duplicate copies of files and reduces complexity issues. However, this platform is utilized by many users for storing the file in cloud and this creates a data redundancy problem. Also, fingerprint indexing is a major issue in data storage in the cloud. So in order to overcome this issue a novel Enhanced Arithmetic Optimization Algorithm with Mixed-Kernel-based Extreme Learning Machine-based Random Forest (EAOA-MKELM-RF) method is proposed that overcome the deduplication issues. In spite, the scalability issues are solved, and the limitations determined in fingerprint indexing. Further, the pipelining and parallelizing hash function values are utilized to address the scalability issue in the deduplication process. The data storage container organizes the programs and files into data blocks, metadata files and nonduplicate blocks. However, the proposed methods determine the similarity issues and accelerate the fingerprint queries for better scalability. The datasets employed to evaluate the proposed approach are CorrAL-100 dataset, Madelon dataset, XOR-100 dataset, Infocom’05 dataset and Linux kernel dataset. The experimentation results demonstrated that the proposed method attained a superior accuracy by 96.8% in terms of restoration accuracy, robustness and delivery ratio. Additionally, the proposed approach reduces buffer time, improving overall system performance. This validation optimized the storage resources, diminished storage costs and improved overall data management.
Statistical Inference Using Partially Accelerated Life Test Model for the Weibull Population Mean Unified Hybrid Censored Data
Authors: Rabie Abdalla , Abd-Elrahman Ayman M.
Published: March 2024

In this paper, estimates of the parameters and the acceleration factor of a new distribution known as the Weibull Population Mean Distribution (WPMD) are explored. We propose the use of the model suggested by Abd-Elrahman [A better alternative to the generalized Bilal distribution: A new model and applications, Int. J. Reliab. Qual. Saf. Eng. 30(6) (2023) 2350027, doi: 10.1142/S0218539323500274 ] for estimating these parameters. To accomplish this, we employ the maximum likelihood estimation method via a Constant-Stress Partially Accelerated Life Test (CSPALT) model. In this study, we have utilized Unified Hybrid (UH) censored data obtained from the WPMD. Confidence intervals for the model parameters and the acceleration factor are constructed based on the approximate Fisher information matrix. The average and Mean Squared Error (MSE) of estimates are computed to evaluate the performance of the proposed method under the CSPALT model. Additionally, a real data set is provided for illustrative purposes, and a numerical analysis of the UH Censoring Scheme (UHCS) is carried out. Finally, concluding remarks are presented.
EFFECTS OF PROLOTHERAPY WITH HYPERTONIC DEXTROSE IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED CLINICAL TRIAL
Authors: Sahebari Maryam , Mirfeizi Zahra , Noorabadi Parisa , Rezaieyazdi Zahra , Khodashahi Mandana , Hashemzadeh Kamila , Nobakht Zohreh , Dadgarmoghaddam Maliheh , Abbasi Bita , Amerizadeh Forouzan , Salari Masoumeh
Published: March 2024

Background: The role of prolotherapy in the healing process of damaged tissues has been confirmed in patients with degenerative joint disease. Hypertonic dextrose has been introduced as the most common solution in prolotherapy for reducing pain and improving mobility in people with knee osteoarthritis (KOA). This study aimed to compare the KOA patients undergoing hypertonic dextrose prolotherapy (DPT) with the placebo in terms of pain intensity and functional level.

Methods: This triple-blind study randomized clinical trial (RCT) was conducted on patients with mild to moderate KOA who were referred to the Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran, in the year 2021. Patients were randomly assigned to two groups of the DPT ([Formula: see text] = 47) and normal saline placebo prolotherapy ([Formula: see text] = 50) intra- and peri-articular knee joints. Treatment was monthly for three months. Western Ontario and McMaster Universities’ Arthritis Index (WOMAC) and Anterior Knee Pain Scale (AKPS) were completed before and after intervention (weeks 0, 4, 8, 12, and 16). The variables were compared between the two study groups at a significance level of less than 0.05 ([Formula: see text] < 0.05).

Results: The WOMAC score improved significantly compared to the baseline in both groups ([Formula: see text] < 0.005). An increase in WOMAC score (the last follow-up compared to baseline) was 97.4% and 85.7% in DPT and placebo groups, respectively ([Formula: see text]= 0.06). Before the intervention and also after the first injection, the AKPS score in the normal saline group was significantly better than the dextrose group ([Formula: see text]= 0.03). The AKPS score did not differ significantly between the two groups ([Formula: see text] > 0.05) in the next two visits and two-month follow-ups. Improvement of AKPS score in the last follow-up compared to baseline was reported in 66.7% and 68.4% of patients in the normal saline group and dextrose group, respectively, ([Formula: see text]= 0.86).

Conclusion: Prolotherapy as intra- and peri-articular injections of hypertonic dextrose could be used to relieve pain and improve functional status in patients with mild to moderate KOA as much as a placebo does. Although no remarkable difference was observed between dextrose and placebo in the outcomes, the rate of improvement (last follow-up compared to the baseline) was relatively higher in the dextrose group than in the normal saline group.
Characterizations of some (weak) Grothendieck topologies
Authors: Khanjanzadeh Zeinab , Madanshekaf Ali
Published: March 2024

Let [Formula: see text] be a small well-powered category which has pullbacks. The aim of this paper is to study and characterize two (weak) topologies on presheaf category [Formula: see text], one of these is constructed by means of a subfunctor of the Yoneda functor which corresponds to an ideal of [Formula: see text], called (weak) ideal topology, and another constructed by a dominion. Naturally, these (weak) topologies of [Formula: see text] introduce two (weak) Grothendieck topologies on [Formula: see text]. To find and study their relations, using the induced presheaf [Formula: see text] given by the fixed dominion [Formula: see text] on [Formula: see text] we construct an action of [Formula: see text] on the subobject classifier [Formula: see text] of [Formula: see text]. Then, we investigate which one of (weak) Grothendieck topologies corresponds one-to-one to the ideals of [Formula: see text] and which one is a sub [Formula: see text]-set of [Formula: see text]. Moreover, among other things, we give some conditions under which the Grothendieck topologies on [Formula: see text] associated to the double negation topology [Formula: see text] and two topologies [Formula: see text] and [Formula: see text] (mentioned above) are sub [Formula: see text]-sets of [Formula: see text].
Numerical approximations of groundwater flow problem using fractional variational iteration method with fractional derivative of singular and nonsingular kernels
Authors: Kumar Pravindra , Yadav Mahaveer Prasad
Published: March 2024

This study aims to present the numerical approximations of groundwater flow problem, namely the time-fractional Boussinesq equation using the fractional variational iteration method. Fractional derivatives in time variable are taken in Caputo and Caputo–Fabrizio sense. This work compares the solutions of the time-fractional Boussinesq equation for the Caputo and Caputo–Fabrizio fractional operators. Graphical representation of the water table head’s behavior for different time values is shown.
Sensitivity and bifurcation analysis of corruption dynamics model with control measures
Authors: Gutema Tesfaye Worku , Wedajo Alemu Geleta , Koya Purnachandra Rao
Published: March 2024

Corruption is an old and complex phenomenon that affects many countries in different forms. Despite many countries using various techniques to control corruption transmission, the problem is still present. Hence, we developed and analyzed a nonlinear deterministic mathematical model that explains the dynamics of corruption to investigate the effect of control measures on the transmission of corruption. Depending on the corruption status we classified the total population into five compartments, which is an extension of the SCJH model, and techniques of reducing corruption transmission were also examined. We have computed the basic reproduction number [Formula: see text] of the model by using the next-generation matrix method and analyzed the stability of the equilibrium point. The stability analysis reveals that corruption-free equilibrium (CFE) is both locally and globally asymptotically stable for [Formula: see text], but the corruption-endemic equilibrium (CEE) is both locally and globally stable for [Formula: see text]. In the model, we established a sufficient condition for the presence of forward bifurcation. We used the normalized forward sensitivity approach to compute the most sensitive parameters that reduce the spread of corruption. The model was simulated by using ode45 code in MATLAB and results indicate that the effective transmission contact rate [Formula: see text] and taking of adequate penalties rate [Formula: see text] reduce corruption. Therefore, this study recommends that reducing the effective transmission contact rate and taking adequate penalty rate were better strategies to reduce the spread of corruption.
Computational analysis of fractional kinetic equations having Bessel–Maitland function
Authors: Shukla Akanksha , Shekhawat Shalini , Modi Kanak
Published: March 2024

This paper’s objective is to arrange fractional active conditions while taking into account the Bessel–Maitland capability reported by Khan et al. The solution’s final form is expressed in terms of the Wright hypergeometric function, which allows us to define numerous additional fractional kinetic equation solutions. Generally, fractional kinetic condition is applied to many problems in astronomy and material science.
Role of the circulating milieu in age-related arterial dysfunction: a novel ex vivo approach
Authors: Mahoney Sophia A. , VanDongen Nicholas S. , Greenberg Nathan T. , Venkatasubramanian Ravinandan , Rossman Matthew J. , Widlansky Michael E. , Brunt Vienna E. , Bernaldo de Quirós Yara , Seals Douglas R. , Clayton Zachary S.
Published: March 2024

Changes in the circulating milieu with advancing age may be a mechanism underlying age-related arterial dysfunction. Ex vivo exposure of young mouse arteries to the circulating milieu from old mice or midlife/older adults impairs arterial function whereas exposure of old mouse arteries to the circulating milieu from young mice or young adults improves arterial function. These findings establish that the circulating milieu directly influences arterial function with aging.
Three-dimensional object geometry of mitochondria-associated signal: 3-D analysis pipeline for two-photon image stacks of cerebrovascular endothelial mitochondria
Authors: Gonzales Christopher R. , Moca Eric N. , Chandra Partha K. , Busija David W. , Rutkai Ibolya
Published: March 2024

Analysis pipeline for 3-D mitochondria-associated signal geometry of two-photon image stacks of brain vasculature.
Physiological basis for xenotransplantation from genetically modified pigs to humans
Authors: Peterson Leigh , Yacoub Magdi H. , Ayares David , Yamada Kazuhiko , Eisenson Daniel , Griffith Bartley P. , Mohiuddin Muhammad M. , Eyestone Willard , Venter J. Craig , Smolenski Ryszard T. , Rothblatt Martine
Published: March 2024

The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor’s (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.
The Importance of a PM&R Consultation for Becker Muscular Dystrophy Patients Admitted with Cardiomyopathy
Authors: Cherin Neyha , Patel Shivani , Jukic Michelle
Published: March 2024

Becker muscular dystrophy (BMD) is a rare genetic disorder that is associated with significant cardiac compromise, including heart failure and cardiomyopathy. Given the significant cardiac impact of the disease, patients are commonly hospitalized under the care of cardiologists. While it is imperative to address the acute cardiac challenges these patients face, it is crucial to not disregard the musculoskeletal derangement that occurs from this underlying disease and how acute hospitalization can exacerbate these issues. While literature focuses heavily on providing management protocols to address these acute cardiac complications, it is also important for providers to feel supported in addressing the functional implications that hospitalized BMD patients may face. An early PM&R consultation in the inpatient setting can be useful in identifying and addressing the functional impairments and subsequent comorbidities of BMD patients. PM&R teams can provide oversight from multiple avenues including the psychosocial, neurocognitive, durable medical equipment, and pain management perspectives and assist with transition of care to the postacute rehabilitation setting. The ultimate goal of the PM&R provider is to work alongside the primary service and patient in order to assist with retaining independence, improving patient satisfaction, and most importantly improving quality of life both inside and outside of the hospital setting.
Confronting Barriers to Equitable Care: A Qualitative Analysis of Factors That Inform People with Mobility Disabilities’ Decisions to Self‐Advocate in the Context of Healthcare
Authors: VanPuymbrouck Laura , Magasi Susan
Published: March 2024

Background. One in 5 people in the United States live with disability; however, the public health needs of this community have been largely overlooked. Although U.S. law mandates the availability of accessible medical exam equipment, people with mobility disabilities (PWMD) frequently encounter barriers that require self‐advocacy to receive basic primary care. Objective. The purpose of this study was to qualitatively explore the impact of healthcare access barriers—specifically, the experiences of the need to self‐advocate and factors that inform decisions to make accommodation requests—for PWMD. Methods. Qualitative semistructured interviews were performed across two phases of data collection with each of the 6 participants. Interpretative phenomenological analysis was used to highlight the essence of participants’ experiences in making decisions to request healthcare accommodation. Results. Participants included a purposive sample of self‐advocates with physical disabilities (3 men and 3 women). While individual approaches to self‐advocacy varied, participants identified a process of “recognizing the normalization of disability discrimination and disability stigma” which necessitates the development of “agency in self‐advocacy.” This process has a lasting impact on people that includes a shared embodied experience of disability, as well as a sense of empowerment based on their collective and individual identities. Conclusions. Findings have implications for supporting individual disability consumer advocacy efforts as well as the need to address the normalization of disability discrimination within healthcare systems levels.
Abstract 1012: Colorectal cancer in the American Indian and Alaska Native community: A holistic review
Authors: Monetathchi Angela R. , Carson William , Little Alyssa , Cordova-Marks Felina M. , Erdrich Jennifer
Published: March 2024

Colorectal cancer (CRC) is ranked third in the United States for both cancer incidence and mortality. Despite a decline in both categories, CRC continues to be a great concern in American Indian/Alaska Native (AI/AN) communities. AI/AN populations have also experienced the largest increase in early-onset colorectal cancer, have the second highest CRC incidence rates, and the AN community has the highest rates of CRC worldwide. AI/AN populations face numerous barriers and are susceptible to risk factors that may contribute to these findings. Currently, a significant amount of research is on screening efforts. Through conducting a literature review of 63 articles, as well as an additional 11 supplemental sources, this manuscript aims to look at several aspects of CRC including demographics, diet, screening, and the impact of geography. This review presents and organizes available research on CRC in the AI/AN population and explores research beyond screening because a more comprehensive and population-specific fund of knowledge on the totality of the subject is critical to directing more effective prevention, earlier detection, and management. Evaluating different components of CRC honors the holistic approach to health practiced by AI/AN communities.

Citation Format: Angela R. Monetathchi, William Carson, Alyssa Little, Felina M. Cordova-Marks, Jennifer Erdrich. Colorectal cancer in the American Indian and Alaska Native community: A holistic review [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 1012.
Abstract 1054: Reciprocal circRNA-miRNA expression axes indicative of early tumor initiation in breast
Authors: Maatouk Nour Abbas , Marei Sarah Hussein , Kurdi Abdallah Bilal , Hamade Nadim Shady , Nasr Rihab Raif , Talhouk Rabih Shakib
Published: March 2024

Cancer prevention and early detection are the most effective tools for cancer control. In this study, we adopt a novel approach of identifying a network of proteins/mRNA-circRNA-miRNA axes. We hypothesize that mutation of oncogenes or tumor suppressor genes during pre-oncogenic stage result in aligned change in levels of circular RNAs-derived genes, as well as, reciprocally, in corresponding sponged miRNAs. These epigenetic risk predictive proteins/mRNA-circRNA-miRNA axes serve as potential tool for early detection of changes leading to breast cancer (BC) and can be further used as non-invasive screening biomarkers of patients’ blood in populations susceptible to cancer. BC patients in GDC Data Portal, TCGA-BRCA project are selected based on several criteria such as their age at diagnosis (20-50 years old), early clinical stage of cancer (stage I) and disease type (ductal and lobular neoplasms). Differentially expressed genes are acquired from mRNA sequencing data by comparing Stage I Breast cancer versus normal primary tissues using R Studio. Then, mRNAs whose expression is aligned with the differentially expressed circRNAs and their host genes acquired from Gene Expression Omnibus (GEO) (GSE182471, Triple Negative Breast cancer tissues versus normal tissues) are selected. Differentially expressed miRNAs, in reciprocal expression with circRNAs, are defined using miRNA sequencing data of the same previously chosen TCGA BRCA patients. Selected miRNAs are hypothesized to be sponged with high confidence by selected circRNAs based on a context percentile binding score in CircInteractome. Using KM Plotter, the survival analysis of corresponding miRNAs in grade I BC patients is examined. The predicted miRNA expression was correlated with lower survival rates among stage I BC patients in KM Plotter. MiRNA-enrichment analysis is used to further validate the involvement of selected miRNAs in early tumorigenic events through exploring in which molecular pathways their downstream genes are enriched. We have constructed more than 20 potential proteins/mRNA-circRNA-miRNA axes for non-invasive screening of patients’ body fluid (i.e. Blood) in populations susceptible to BC using RNA and miRNA sequencing data available in online databases and further validate the proposed axes using in-silico tools. The described axes, once validated in clinical samples could provide a potential tool for early-stage BC prediction and prevention.

Citation Format: Nour Abbas Maatouk, Sarah Hussein Marei, Abdallah Bilal Kurdi, Nadim Shady Hamade, Rihab Raif Nasr, Rabih Shakib Talhouk. Reciprocal circRNA-miRNA expression axes indicative of early tumor initiation in breast [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 1054.
Abstract 1109: LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis
Authors: Xu Qingqing , Sun Ciming , Zhang Suixian , Li Xuan , Chen Lei , Chen Ming
Published: March 2024

Background: Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown.

Methods: LINC01770 expression was determined using quantitative real-time reverse transcription PCR, and its prognostic value was evaluated using Kaplan-Meier survival analysis. RNA sequencing and bioinformatic analysis were used to determine the potential function of LINC01770, and its biological effects were investigated using in vitro and in vivo experiments. Mass spectrometry-coupled RNA pull-down assays and western blotting identified LINC01770 interacting proteins, followed by confirmation using RNA immunoprecipitation (RIP) assays. Ferroptosis and lipid peroxidation were detected using flow cytometry.

Results: LINC01770 was overexpressed in NPC tissues according to microarray screening. Patients with NPC showing high LINC01770 expression experienced shorter survival and worse prognosis. In vitro and in vivo experiments suggested that knockdown of LINC01770 expression significantly inhibited the proliferation, migration, and invasion of NPC cells. Sequencing and functional complementation experiments showed that LINC01770 regulates the proliferation and metastasis of NPC through TEA domain transcription factor 1 (TEAD1). Meanwhile, RIP and PCR experiments suggested that LINC01770 and TEAD1 were common targets of microRNAs miR-615-5p and miR-1293. Overexpression of LINC01770 promoted ferroptosis in vitro and in vivo through the TEAD1/Acyl-CoA synthetase long chain family member 4 (ACSL4)/transferrin receptor (TFRC) pathway.

Conclusions: LINC01770 is a prognostic biomarker for NPC and participates in the regulation of TEAD1 signaling pathway through competitive binding to miRNA-615-5p and miRNA-1293, resulting in NPC metastasis and progression. Radiation resistant cells are in a delicate balance between lipid peroxidation and increased vulnerability to ferroptosis, suggesting that ferroptosis could be used to kill NPC cells and reverse their radiotherapy resistance during the malignant progression of NPC caused by high expression of LINC01770. Thus, inducing ferroptosis could be used to treat recurrent and refractory NPC.

Citation Format: Qingqing Xu, Ciming Sun, Suixian Zhang, Xuan Li, Lei Chen, Ming Chen. LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis [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 1109.
Abstract 1144: Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery
Authors: Harwood Dylan , Pedersen Vilde , Bager Nicolai S. , Schmidt Ane Y. , Stannius Tobias O. , Areskeviciute Ausrine , Josefsen Knud , Nørøxe Dorte S. , Scheie David , Rostalski Hannah E. , Lassen Ulrik , Bagger Frederik O. , Weischenfeldt Joachim , Heiland Dieter H. , Vitting-Seerup Kristoffer , Michaelsen Signe R. , Kristensen Bjarne W.
Published: March 2024

Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by concomitant and adjuvant temozolomide chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the brain parenchyma, where they give rise to the recurrent tumor. Based on gene expression, the tumor core can be subtyped into mesenchymal, proneural and classical areas, each being associated with differences in genetic alterations and cellular composition. In contrast, the tumor periphery where migrating tumor cells infiltrate brain parenchyma is less characterized in patients. Using spatial transcriptomics (n = 11), we show that specific malignant states colocalize in tumor core areas with necrosis and microvascular proliferation. Malignant cells within proneural or mesenchymal subtyped cores displayed, as expected, many differences in genetic expression, although such differences disappeared in the tumor periphery. Malignant cells residing in the tumor periphery had increased expression of genes related to neurodevelopmental pathways and synaptic connectivity. Our findings show similarities in cellular states across tumor subtypes with implications for post-operative treatment and provide an updated view of the spatial landscape of glioblastomas.

Citation Format: Dylan Harwood, Vilde Pedersen, Nicolai S. Bager, Ane Y. Schmidt, Tobias O. Stannius, Ausrine Areskeviciute, Knud Josefsen, Dorte S. Nørøxe, David Scheie, Hannah E. Rostalski, Ulrik Lassen, Frederik O. Bagger, Joachim Weischenfeldt, Dieter H. Heiland, Kristoffer Vitting-Seerup, Signe R. Michaelsen, Bjarne W. Kristensen. Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery [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 1144.
Abstract 116: Generation of humanized PD-1/PD-L1/CD94/NKG2A mice for evaluating novel combination therapies
Authors: He Fang , Yuan Jiangfeng , Shan Yawen , Bahetiyaer Huwatibieke , Xu Qingqing , Frame Jenna , Lin Qingcong , Zhou Xiaofei , Shang Chengzhang
Published: March 2024

NKG2A and its co-receptor, CD94, are expressed on the surface of NK cells, and function to send inhibitory signals to NK cells upon recognition of the HLA-E complex on adjacent cells. Blockade of the NKG2A/CD94 complex is a promising strategy for cancer immunotherapy, due to the potential to trigger NK-mediated tumor killing. Previously, we generated humanized NKG2A/CD94 mice for testing novel therapeutics targeting human NKG2A/CD94. To explore the potential that this complex could be targeted as part of a novel combination therapy, we crossed humanized NKG2A/CD94 mice with humanized PD-1/PD-L1 mice, which were previously engineered to express the extracellular regions of human PD-1/PD-L1. Flow cytometric data from splenocytes isolated from the quadruple humanized mice confirmed expression of human NKG2A and CD94 in NK cells and activated CD8 T cells, as well as PD-1/PD-L1 on the surface of T cells. To test the efficacy of antibodies targeting these checkpoints in vivo, B-hHLA-E plus/hPD-L1 MC38 colon cancer cells were subcutaneously implanted into the quadruple humanized mice and treated with antibodies targeting human NKG2A, human PD-L1, or both antibodies. Results indicate that the combination therapy significantly reduced tumor growth when compared to NKG2A single antibody treatment. Together, these data suggest that humanized PD-1/PD-L1/CD94/NKG2A mice are a validated model for further evaluation of novel combination therapies.

Citation Format: Fang He, Jiangfeng Yuan, Yawen Shan, Huwatibieke Bahetiyaer, Qingqing Xu, Jenna Frame, Qingcong Lin, Xiaofei Zhou, Chengzhang Shang. Generation of humanized PD-1/PD-L1/CD94/NKG2A mice for evaluating novel combination therapies [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 116.