Intermediate Stage Research Articles

Long-Term Planning for a Mixed Urban Freight Fleet with EVs and ICEVs in the USA

Commercial electric vehicles (EVs) have increasingly gained interest from urban freight companies in the past decade due to the introduction of economic and policy drivers. Although these factors promote urban freight electrification, some barriers hinder the transition to fully electric fleets, such as the significant monetary investment required to replace the current internal combustion engine vehicles (ICEV) and the lack of readily available electric freight vehicles. Due to these barriers, for the foreseeable future, urban freight companies will operate mixed fleets with a combination of EVs and ICEVs to balance their cost/benefit trade-offs. This intermediate operational stage will allow companies to adjust their operations, test EVs, and decide if a fully electric fleet is the best choice. This paper focuses on urban last-mile deliveries in the USA and proposes a long-term planning model to explore the effects of external factors (i.e., fuel costs) on planning decisions (i.e., EV share) for a mixed fleet. In the context of this paper long-term planning is the planning for the infrastructure needed for the introduction of EVs (i.e., fleet composition and charging station location). The goal of the proposed model is to minimize the fuel, EV, ICEV, and EV charger costs. The results show that the EV share of a mixed fleet is affected by gasoline and electricity prices and the distances traveled in a given network. This paper shows that the EV share of a mixed fleet increases when the gasoline cost increases and the electricity cost decreases.

Integrating technology into a successful apomorphine delivery program in Thailand: a 10-year journey of achievements with a five-motto concept.

Apomorphine, a potent dopamine agonist, is a therapeutic option for patients with Parkinson's disease and motor fluctuations. However, the adoption of and adherence to this therapy have been limited by the need for complex delivery devices and specialized care as well as resource consumption, posing challenges for new physicians. Thailand is a unique example of a developing nation that has successfully implemented and continued the use of this therapy by employing cooperative technology that has dramatically enhanced apomorphine delivery services. Establishing apomorphine delivery services requires significant resources and step-by-step solutions. We began our services by implementing various strategies in three chronological stages: the initial stage (2013-2015), intermediate stage (2016-2019), and current stage (2020-present), each presenting unique challenges. Together, we also implemented a proposed set of five mottos to strengthen our apomorphine delivery service. Using additive technology, we developed a patient registry platform that combined electronic data acquisition, video and remote monitoring using wearable sensors, and in-house mobile applications to support our service. At the initial stage, we assembled a team to enhance the efficacy and confirm the safety of apomorphine treatment in our hospital. At the intermediate stage, we expanded our apomorphine delivery services beyond just the patients at our hospital. We supported other hospitals in Thailand in setting up their own apomorphine services by educating both physicians and nurses regarding apomorphine therapy. With this educational undertaking, increased apomorphine-related knowledge among medical professionals, and a greater number of hospitals providing apomorphine services, an increasing number of patients were administered apomorphine in subsequent years. Currently, we are providing effective apomorphine delivery to improve patient outcomes and are seamlessly integrating technology into clinical practice. Incorporating integrative technologies in our apomorphine delivery program yielded positive results in data collection and support throughout patient care, in tracking patients' statuses, in the long-term use of this treatment, and in increasing medication adherence rates. This perspective paper describes how technology can help provide supportive healthcare services in resource-constrained environments, such as in Thailand, offering a step-by-step approach to overcoming several limitations. The valuable insights from our 10-year journey in successfully integrating technology into apomorphine delivery services can benefit new physicians seeking to replicate our success.

Fuzzy Optimized Quadratic Boost Converter for Photovoltaic Application

To enhance the Inverter and Quadratic Boost Converter utilizing Fuzzy Logic Control for the Solar Panels. The quadratic boost converter is the intermediate stage between the solar panel and the Voltage Source Inverter. In normal boost converter produces a medium level of output voltage, but a quadratic boost converter produces double voltage gain for example if you give the supply voltage 20V and duty cycle 0.7 it will be output voltage 220V produced. Key Words: Quadratic boost converter, Single phase Voltage source inverter, Fuzzy logic control,

To Estimate and Compare the Level of Serum Immunoglobulin A in Patients of Oral Submucous Fibrosis, Leukoplakia, and Control Group.

To estimate and compare the level of serum immunoglobulin A in patients of oral submucous fibrosis (OSMF), leukoplakia, and control group. OSMF is a well-recognized potentially malignant condition in the oral cavity, and a transformation rate as high as 7.6% over a period of 10 years has been reported from India. Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Quantia IgA is a turbidometric immunoassay for the detection of IgA in human serum and is based on the principle of agglutination reaction. The test specimen is mixed with the activation buffer (R1) and then with antihuman IgA reagent (R2) and allowed to react. For the estimation of serum IgA, 500 μl of Quantia IgA activation buffer R1 is taken in a clean test tube. Serum sample is diluted in the ratio of 1:5 with normal saline. Ten microliters of diluted serum sample are added to R1. After incubation for 10 min, 50 μl of R2 is added, which is Quantia IgA antihuman IgA reagent to the sample, and the reading is recorded at wavelength 340 nm at 37°C. The level of IgA will be estimated by a semi-automatic biochemical analyzer machine and then data analysis will be done. The immunologic alterations observed by us in OSMF and leukoplakia are almost similar or nearer to the alterations observed in oral cancer, so it is reasonable to assume that OSMF and leukoplakia can be an intermediate stage in the transformation process of a normal cell to oral malignancy. Prevention and early detection is the best way to reduce the incidence and mortality of premalignant disorders and oral cancer. There are many ways and methods of early detection of premalignant disorders and oral cancer, and the immunological method is one of them.

Survey of current practices in the management of cervical cancer by Moroccan radiotherapists

ObjectiveTo assess the applicability degree of the international guidelines by Moroccan radiotherapists, in order to improve the management of cervical cancer (CC), since CC is the second most common cancer for women in Morocco. MethodsThis cross-sectional study was carried out using a questionnaire sent online to Moroccan radiotherapists. The questionnaire covered participants' characteristics, initial assessment and treatment preparation, techniques and indications for radiotherapy and brachytherapy, dose and indications, as well as on the protocol adopted in the intermediate stages and the location of adjuvant treatments and assessments' follow-up. Results74 radiotherapists out of 300 have responded to the survey. Only 27.0% of practitioners reported discussing patient records systematically in a multidisciplinary consultation meeting (MCM). For the initial assessment, 77.0% requested pelvic magnetic resonance imaging (MRI). It is significantly less requested in regional oncology centers (ROCs) than in university hospital centers (UHCs) or the private sector (P ​< ​0.001). Furthermore, Clinicians in ROCs do not have access to new techniques of radiotherapy. In 83.8% of cases, the most prescribed radiotherapy protocols were 45–46 ​Gy in 1.8–2 ​Gy per fraction. Three-dimensional gynaecological brachytherapy high-throughput dose guided by dosimetric scanner was available in 75.5% of structures while interstitial gynaecological brachytherapy was only available in 23% of centers. The two most prescribed dose protocols were 4 ​× ​7 ​Gy and 3 ​× ​7 ​Gy in 74.4% and 21.6% of cases, respectively. Finally, monitoring during the first two years was based mainly on pelvic MRI (82.2%) while PET/CT was recommended by only less than 10%. ConclusionsThe findings obtained show that our radiotherapists generally comply with international guidelines for the cervical cancer management. However, they should still enhance their practices for the first staging evaluation, the use of systematic MCMs, the doses and treatment techniques used, and the follow-up evaluation.

Relationship between microfinance institutions' self‐sustainability and financing sources: Moderating role of external governance

AbstractThe self‐sustainability of microfinance institutions (MFIs) is a growing concern as they work as non‐profit organizations to achieve global poverty reduction goals. This study aims to examine the MFIs' self‐sustainability using an efficiency measurement technique based on Data Envelopment Analysis (DEA). It also determines the influence of different financing sources on MFIs' self‐sustainability as well as the moderating impact of external governance on this relationship. It uses the Generalized Method of Moments (GMM) estimator to analyze the panel data from 661 MFIs in 86 countries during the 2010–2018 period. The DEA analysis reveals that MFIs are still in the intermediate stage of self‐sustainability in terms of technical and cost efficiency. The second‐stage regression results reveal that financing sources such as retained earnings and equity have a robust positive and statistically significant effect on the MFIs' self‐sustainability, implying that MFIs that rely more on these two sources are more likely to be self‐sustainable. The moderation analysis reveals that good governance accelerates the positive effect of financing sources on MFIs' efficiency. Given these empirical findings, MFIs' decision‐makers can benefit from considering their own funding and equity. Quality governance can be ensured by government agencies and regulatory bodies to support the MFIs' sustainability.

Fatty acids characterisation by GC-MS, antiglycation effect at multiple stages and protection of erythrocytes cells from oxidative damage induced by glycation of albumin of Opuntia ficus-indica (L.) Mill seed oil cultivated in Eastern Morocco: Experimental and computational approaches

Ethnopharmacological relevanceOpuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. Aim of the studyThe aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. Materials and methodsThe assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of β-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC–MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. ResultsIn vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. ConclusionThe identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.

The puzzling ecology of African Marantaceae forests.

Marantaceae forests are tropical rainforests characterized by a continuous understory layer of perennial giant herbs and a near absence of tree regeneration. Although widespread in West-Central Africa, Marantaceae forests have rarely been considered in the international literature. Yet, they pose key challenges and opportunities for theoretical ecology that transcend the borders of the continent. Specifically, we ask in this review whether open Marantaceae forests and dense closed-canopy forests can be considered as one of the few documented examples of alternative stable states in tropical forests. First, we introduce the different ecological factors that have been posited to drive Marantaceae forests (climate, soil, historical and recent anthropogenic pressures, herbivores) and develop the different hypotheses that have been suggested to explain how Marantaceae forests establish in relation with other vegetation types (understory invasion, early succession after disturbance, and intermediate successional stage). Then, we review the underlying ecological mechanisms that can explain the stability of Marantaceae forests in the long term (tree recruitment inhibition, promotion of and resilience to fire, adaptive reproduction, maintenance by megaherbivores). Although some uncertainties remain and call for further empirical and theoretical research, we found converging evidence that Marantaceae forests are associated with an ecological succession that has been deflected or arrested. If verified, Marantaceae forests may provide a useful model to understand critical transitions in forest ecosystems, which is of particular relevance to achieve sustainable forest management and mitigate global climate change.

Effect of applied stress on microstructural evolution during the sintering of nanocrystalline tetragonal zirconia below 1000 °C

Microstructural evolution during the sintering of tetragonal ZrO2 nanoparticles was investigated using stress-free sintering and sinter forging. The green body prepared via gel casting had a densely packed structure with a narrow pore size distribution. Special attention was paid to the evolution of pore structures in the initial and intermediate stages of sintering. Pore coarsening, which is considered an important issue in the nanoceramics densification, was not remarkable in sinter forging. The accelerated densification rate, coupled with the retention of finer pore size than that in stress-free sintering throughout densification, lowered the sintering temperature requirement. This temperature reduction effectively inhibited grain growth, allowing samples prepared via pressure-assisted sintering to maintain a nanometric structure.

Dynamics of Structural and Functional Changes of Patients with Dry Form Age-related Macular Degeneration after Double Filtration Plasmapheresis

Actuality. One of the significant ophthalmic diseases is a dry form age-related macular degeneration (dAMD). The issues of etiology and pathogenesis are not completely cleared nowadays and they signify the subject of discussion. There are risk factors of dAMD (age, heredity, lifestyle etc.) which can cause metabolic disorders, changes hemorheological parameters which promote activation of druseogenesis and as a result an angiogenesis. Mostly an outcome of dAMD is geographical atrophy and decrease of central visual acuity. At the same time, it is known that similar metabolic and rheological disorders detected in other diseases are effectively corrected by extracorporeal rheoaferesis, in particular, using double filtration plasmapheresis. Thus, using of extracorporeal rheoaferesis with dAMD patients is pathogenetically well-reasoned, but in the available literature, a correct analysis of the effectiveness and safety of double filtration plasmapheresis in patients with intermediate stage of dAMD is presented poorly.Objective. To study along with data of OCT, OCT angiography, visometry, microperimetry and electroretinography structural and functional changes in the macular zone in patients with a dry form of age-related macular degeneration after the using of double filtration plasmapheresis.Patients and methods. The study included 63 patients (94 eyes) with an intermediate stage of dAMD. The patients were separated into two groups randomly. The first (main) group included 34 patients (52 eyes) who were performed double filtration plasmapheresis (DFPP) on an OctoNova device using a Plasmaflo plasma filter and a Cascadeflo EC40 fractionator in the amount of 4 procedures with a frequency of 1 time per week for 1 month. The second group (control) included 29 patients (42 eyes) who did not receive any specific treatment. In the main group of patients, OCT, OCT angiography, microperimetry and electroretinography were additionally performed in addition to standard ophthalmological examination before the DFPP course, after the DFPP course (1 month after the start of follow-up), 6 and 12 months later. Patients in the control group also underwent a similar examination at the specified time — 1, 6, 12 months after the start of follow-up.Results. In this study we found according to optical coherence tomography, optical coherence tomography-angiography, visometry, microperimetry and electroretinography, positive dynamics of structural and functional parameters of the macular retina is observed in patients with a dry form of age-related macular degeneration with using double filtration plasmapheresis. At the same time, a statistically significant difference between the two groups begins at 1 month and persists for 12 months of follow-up, which points to stabilization of the pathological process during the specified period.Conclusions. This study showed that after applying the double filtration plasmapheresis in patients with dry form of age-related macular degeneration, there is an improvement in structural and functional parameters of the macular zone, consisting in a decrease volume DOPES and stabilization of retinal light sensitivity.

DEVELOPMENT OF A VISUAL ODOMETRY MODEL BASED ON SENSORS AND VIDEO STREAM ANALYSIS

The article is devoted to the development of a visual odometry model based on sensors of an inertial measuring device and the analysis of a video stream arriving in real time. Modeling is based on the analysis and evaluation of methods for measuring the correct coordinates of a moving object, systems for estimating the movement of an object in three-dimensional space, algorithms at intermediate stages of image processing, principles for selecting special points on the frame and optical flow for selected points.

Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.

HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.

The prediction value of lipiodol retention pattern on post-TACE CT scan for local progression of HCC after complete response

BackgroundHepatocellular carcinoma (HCC) is classified as the sixth commonest cancer over the world and the fourth common in Egypt, representing the third leading cause of cancer-related mortality. Trans-arterial chemoembolization (TACE) is considered as one of the most effective treatment option for intermediate stage HCC. Lesions showing complete response (CR) after TACE can be classified according to their lipiodol retention pattern into complete (C-Lip, covering the entire tumor volume) or incomplete (I-Lip). The purpose of this study was to assess the prediction value of post-TACE lipiodol retention pattern on the local disease progression after complete response and thus to decide which patient should be carefully observed and considered to be incompletely treated.ResultsThe study included 45 HCC lesions treated with TACE and showed complete response in the first follow-up CT performed 4–6 weeks after the procedure; 23 cases showed incomplete lipiodol retention pattern and 22 with complete lipiodol retention pattern which was carefully assessed on non-contrast CT images done 4 to 6 weeks after treatment. Follow-up CT was then performed every 3 months for at least 12 months or until local progression occurred. On the follow-up CT studies, 20 out of the 45 lesions showed persistent complete response (i.e., no local progression), while 25 of them showed local progression. Among the 25 cases with disease progression upon correlation with their lipiodol retention pattern, it was found that local progression occurred in 31.8% of tumors showed CR with complete lipiodol retention, as opposed to 78.2% of tumors showed CR with incomplete lipiodol retention with significant statistical difference and p value 0.010.ConclusionsLipiodol retention pattern of HCC after TACE can predict the potential tumor local outcome. Lesions with incomplete lipiodol retention are at a higher risk of local tumor progression and therefore should probably observed and can be retreated; on the other hand, tumors with complete lipiodol retention have a much lower risk of local disease tumor progression.

The Mechanism of Folding of Human Frataxin in Comparison to the Yeast Homologue – Broad Energy Barriers and the General Properties of the Transition State

The funneled energy landscape theory suggests that the folding pathway of homologous proteins should converge at the late stages of folding. In this respect, proteins displaying a broad energy landscape for folding are particularly instructive, allowing inferring both the early, intermediate and late stages of folding. In this paper we explore the folding mechanisms of human frataxin, an essential mitochondrial protein linked to the neurodegenerative disorder Friedreich's ataxia. Building upon previous studies on the yeast homologue, the folding pathway of human frataxin is thoroughly examined, revealing a mechanism implying the presence of a broad energy barrier, reminiscent of the yeast counterpart. Through an extensive site-directed mutagenesis, we employed a Φ -value analysis to map native-like contacts in the folding transition state. The presence of a broad energy barrier facilitated the exploration of such contacts in both early and late folding events. We compared results from yeast and human frataxin providing insights into the impact of native topology on the folding mechanism and elucidating the properties of the underlying free energy landscape. The findings are discussed in the context of the funneled energy landscape theory of protein folding.

What are the effects of aquatic physiotherapy exercises on speed and complex gait-related activities in individuals with Parkinson's disease?

Parkinson's disease (PD) is a central nervous system disease that results in deficits in motor activities such as walking. Gait speed and step length are frequently reduced. Aquatic physiotherapy serves as a form of complementary treatment to promote improvements in the disease's motor symptoms. The purpose of this study was to examine the effect of an aquatic physiotherapy training program on gait in individuals with PD. This is an interventional clinical study in which a group of participants with PD participated in an assessment on the ground of their usual and maximum gait speed using the 10-m Walk Test and complex activities related to gait using the Dynamic Gait Index (DGI) at baseline and 12 weeks of an aquatic physiotherapy intervention, twice a week for 50 min. For statistical analysis, the paired t-test and the Wilcoxon test were used. The study included 10 individuals with PD, in the intermediate stage of PD - H&Y 2 (60%) and 3 (40%), of both sexes with a mean age of 65.8 ± 13.69 years. There was a significant increase in usual gait speed (p = 0.001) and in the DGI score (p = 0.05), but there was no improvement in maximum gait speed (p = 0.119). The aquatic physiotherapy exercise program improved habitual gait speed and the performance of complex activities related to gait in this group individuals with PD.

Clinical and functional eye condition changes in the dry form of age macular degeneration depending on the AREDS stage

Purpose: to assess the functional state of the eyes in age-related macular degeneration depending on the AREDS classification stage.Material and methods. A clinical study of 60 patients (120 eyes) with the dry AMD form, aged 55.1 ± 4.2 years, involved 30 patients (60 eyes) aged 52.7 ± 3.9 years with AREDS 2 category (initial AMD stage, group1) and 30 patients (60 eyes) aged 57.9 ± 7.8 years with AREDS 3 category (intermediate AMD stage, group 2). The complex research involved visual acuity measurement, including the assessment of near vision in various illumination conditions according to the authors’ methodology, fluorescein angiography, refractometry, tonometry, optical coherence tomography (OCT), ultrasound duplex scanning of the eye; and an immunological study aimed at determining interleukins and interferons in blood serum.Results. Visual acuity was found to depend on test illumination in healthy subjects and to substantially drop at all illumination levels in AMD, especially in the 3rd stage. With the development of AMD, the activity of the immune response was recorded.The patients of groups 1 and 2 showed an increase in the inflammatory response and a depression of the anti-inflammatory response. In group 1, an increase was recorded in IL-I by 23.5% (p &lt; 0.05), in IL5 by 25.4% (p &lt; 0.05), and in IL8 by 19.9% (p &lt; 0.05). In group 2, the value of these parameters exceeded the norm by 32.1, 39.5 and 25.4% (p &lt; 0.05), respectively. The parameters of anti-inflammatory immunity (IL10 and TGF l) were lower than the reference level by 18.3 and 24.6% (p &lt; 0.05) of patients of group 1 and by 24.3 and 30.75 (p &lt; 0.05) of group 2. It was established that the degree of imbalance of the immune system is associated with the stage of AREDS. In group 2 patients with AREDS 3, the content of pro-inflammatory interleukins exceeded those of group 1: IL-I by 12.5% (p &lt; 0.05), IL5 by 11.9% (p &lt; 0.05), IL8 by 11, 2% (p &lt; 0.05). IL10 and TGF l in group 2 were lower than in group 1 by 10.2 and 11.8% (p &lt; 0.05).Conclusion. Near visual acuity measurement depending on test illumination may be used as a sensitive diagnostic test in AMD in patients. At an early stage of AMD development, a disorder in the immune defense is observed, taking the form of activation of the pro-inflammatory spectrum and depression of the anti-inflammatory component, as well as microcirculatory changes Homeostatic changes of the eye appear at an early stage of the disease and are progressing as the clinical picture is deteriorating. The changes are the greatest at patients with stage 3 of AREDS.

Link of Serum Esterase Enzymes with Cognitive Impairment in Diabetic Patients

Cognitive impairment is one of the main complications of diabetes and patients with cognitive impairment are considered to be in an intermediate stage of decreased cognition with higher risk of developing dementia and Alzheimer's disease. This study aimed at evaluating serum activity of two esterase enzymes including cholinesterase and paraoxonase 1 (PON 1) in diabetic patients and association with cognitive performance and metabolic parameters. In this crosssectional study, 128 diabetic patients were enrolled. Cognitive performance was evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Body mass index, fasting blood glucose, fasting blood insulin, insulin resistance, serum cholinesterase and paraoxonase 1 activity were measured. Prevalence of cognitive impairment was found to be 77% in the study population. Serum cholinesterase activity was found to be higher in diabetic patients with cognitive impairment than the patients with normal cognitive performance (p &lt; 0.04). Further, a negative correlation was found between cognitive performance and cholinesterase activity, albeit statistically non-significant. Alteration in the activity of cholinesterase enzyme was shown to be associated with cognitive impairment in diabetic patients and future studies are required to find the pathophysiological mechanisms of diabetic cognitive dysfunction.

Abstract 4357: Examining the role of end-stage kidney as a potential intermediate stage in the development of renal cell carcinomas; understanding the pathogenesis allowing for early detection

Abstract Introduction: Clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC) are both thought to arise from the renal proximal tubules. End stage renal disease (ESRD) patients have an increased incidence of developing PRCC and CCRCC. Some studies showed a progenitor cell population that is inherently present in renal tubules, and is significantly increased after renal injury. The studies have also illustrated similarities between these progenitor cells and PRCC &amp; CCRCC; hypothesizing that they are the cell of origin of these tumors. This trend was not observed in other renal cell carcinomas such as chromophobe renal cell carcinoma (chRCC). This study aims to further examine the possible role of ESRD in the development of PRCC and CCRCC to understand this initial step of renal cell carcinoma pathogenesis. Methods: A cohort of n = 39 PRCC, 25 CCRCC, 63 normal, 10 end-stage and 18 chRCC cases were selected. RNA sequencing was performed and differential-gene-expression analysis was conducted between normal, ESRD and tumor using DESeq2 software. Pathway analysis was performed using GSEA. Genes from oncogenic pathways that have been studied to be involved in renal cancer development were selected to perform consensus clustering analysis on Genepattern. Results: Oncogenic and developmental pathways enriched in ESRD are consistently overlapping with that of CCRCC and PRCC tumors. 50% of end-stage developmental pathways are found in both CCRCC and PRCC but only 4.5% in chRCC. 62.4% and 46.4% of end-stage oncogenic pathways are found in CCRCC and PRCC respectively but only 16% in chRCC. Clustering analysis showed ESRD cases clustered together with CCRCC and PRCC groups and not with chRCC. Overall, the ESRD cases exhibited a gene expression profile more closely resembling that of CCRCC and PRCC than chRCC. Conclusion: Our findings support the hypothesis that ESRD provides a favorable environment for tumor growth promoting pathogenesis of both PRCC and CCRCC. The enrichment of the same developmental pathways in both ESRD and the tumors suggests that the progenitor cell population in the renal tubules, mentioned above, could be the origin of both PRCC and CCRCC lesions. Further analysis would allow the uncovering of the pathways that lead to tumor progression from these cells of origin, and can be used to determine biomarkers for early detection of CCRCC and PRCC. This is of particular benefit for those with increased risk as the ESRD patients. Citation Format: Mingyuan Wan, Vincent Castillo, Rola Saleeb. Examining the role of end-stage kidney as a potential intermediate stage in the development of renal cell carcinomas; understanding the pathogenesis allowing for early detection [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 4357.

Abstract 3873: Understanding spatial organization of cellular plasticity in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is notorious for poor survival rates, underscoring the urgency of understanding factors that drive tumor progression. A key player in this process is epithelial-mesenchymal transition (EMT), known for its role in enhancing cancer cell adaptability, resistance to treatment, and metastasis. Our study focuses on EMT within PDAC, using single-cell spatial transcriptomics to explore how the tumor microenvironment influences changes in cellular states. We introduce a novel method involving Gaussian mixture models (GMM) to categorize EMT stages in single-cell data and utilize deep learning for label transfer of these tumor cell states, including intermediate cell states, onto spatial transcriptomic data with limited gene panels and sparse count profiles. We find strong spatial autocorrelation of classical cells and a dispersion of basal cells alongside other cells at intermediate stages of the EMT spectrum. By leveraging the spatial proximity of clonally related cells, we confirm that cells transition along the EMT spectrum in a gradient and infer transition rates. We next leverage density gradients of tumor cells in different states to identify distinct neighborhoods with varying EMT subtype composition. We observe significant variations in cell density among different EMT states. A focus on cancer-associated fibroblasts (CAFs) and macrophages reveals differences in these cells across density contours. We also examine differential ligand-receptor interactions across cell state gradients to better understand the cellular interactions that drive EMT transitions and alter the tumor environment. By leveraging spatial transcriptomics, this research aims to provide new biological insights into PDAC intratumoral heterogeneity, potentially leading to the identification of novel therapeutic targets to disrupt treatment resistance. Citation Format: Izabella Zamora, Milan Parikh, Bidish K. Patel, Lynn Bi, Doron Haviv, Jingyi Cao, Carina Shiau, Martin Hemberg, William L. Hwang, Nir Hacohen, David T. Ting, Arnav Mehta. Understanding spatial organization of cellular plasticity in pancreatic ductal adenocarcinoma [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 3873.

A Fully Coupled Gas–Water–Solids Mathematical Model for Vertical Well Drainage of Coalbed Methane

The coupling relationship between the deformation field, the diffusion field, and the seepage field is an important factor in fluid transport mechanisms in the long-term coalbed methane (CBM) exploitation process. A mathematical model of gas–water two-phase fluid–structure coupling in a double-porosity medium in coal reservoirs is established in this paper. Taking Hancheng Block, a typical production block in Qinshui Basin, as the geological background critical desorption pressure, reservoir permeability anisotropy is considered in the model. COMSOL Multiphysics (COMSOL_6.0) was used to create the model. The accuracy and rationality of the model were verified by comparing field production data with the results of the simulation. Using the simulation, the influence law of various reservoir geological characteristics parameters (Langmuir strain constant, ratio of critical desorption pressure to reservoir pressure of coal seam (CDPRP), elastic modulus, initial water saturation, Langmuir pressure, etc.) on CBM productivity, reservoir pressure, and permeability ratio was discussed, and a thorough analysis of the factors affecting productivity was obtained using the orthogonal test method. The findings of this study indicate that the change in permeability is the result of the superposition effect of many factors. Different stages of drainage have different primary regulating factors. Rock skeleton stress has a consequence on coal matrix permeability in the early drainage stage, and coal matrix shrinkage is primarily impacted in the later drainage stage. Besides the initial water saturation, other reservoir geological parameters (e.g., CDPRP, Langmuir volume, Langmuir strain constant, elastic modulus) have a strong relationship with productivity. When the value of coal geological parameters increases, the degree of productivity release is higher (as the initial water saturation increases, the production decreases correspondingly). Different coal and rock parameters have varying levels of impact on the drainage stage of CBM wells. The influences of the CDPRP, Langmuir volume, Langmuir strain constant, and elastic modulus on gas production are mainly concentrated in the initial and intermediate drainage stages and begin to fall off during the last drainage stage. Per the multi-factor analysis, the main coal–rock parameters affecting the productivity release are the Langmuir strain constant, followed by the CDPRP and other parameters. The analysis findings can offer theoretical guidance for CBM well selection and layer selection and enhance the block’s overall CBM development level. The improved productivity prediction model for CBM, which is based on fluid–structure coupling theory, can offer a new technical benchmark for CBM well productivity prediction.