bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium-glucose co-transporter 2 inhibitor use in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease
Authors: Takahara Mitsuyoshi , Soga Yoshimitsu , Fujihara Masahiko , Iida Osamu , Kawasaki Daizo
Published: October 2023

Background

This study aimed to reveal the prevalence of sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment and its association with restenosis risk in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease.

Methods

We used the database of a multicenter prospective study registering patients with symptomatic peripheral artery disease undergoing femoropopliteal drug-coated balloon treatment in Japan. The current analysis included 1058 patients with diabetes mellitus free from end-stage renal disease. The association of clinical characteristics with SGLT2 inhibitor use was investigated using the logistic regression model. The propensity score matching was adopted to compare the primary patency, i.e., freedom from restenosis, after endovascular therapy between patients treated with and without a SGLT2 inhibitor.

Results

The proportion of SGLT2 inhibitor treatment at revascularization was 14.8% (95% confidence interval, 12.8–17.1%). Younger age, increased body mass index, and increased hemoglobin A1c levels were independently associated with SGLT2 inhibitor use (all P < 0.05). The proportion of SGLT2 inhibitor reached 38.2% (95% confidence interval, 25.4–52.3%) in patients with the three associated factors. The propensity score-matching analysis demonstrated that primary patency was not different between patients treated with a SGLT2 inhibitor and those without it (72.0% [95% confidence interval, 64.1–80.9%] versus 67.8% [62.7–73.3%] at 2 years; P = 0.45).

Conclusions

SGLT2 inhibitors were not rarely used in patients with diabetes mellitus who underwent femoropopliteal endovascular therapy using a drug coated balloon for symptomatic peripheral artery disease in real-world settings. SGLT2 inhibitor treatment was not associated with an increased risk of restenosis.
Effect of ZnO nanoparticles on biofilm formation and gene expression of the toxin-antitoxin system in clinical isolates of Pseudomonas aeruginosa
Authors: Valadbeigi Hassan , Sadeghifard Nourkhoda , Kaviar Vahab Hassan , Haddadi Mohammad Hossein , Ghafourian Sobhan , Maleki Abbas
Published: October 2023

Background

Biofilm formation by Pseudomonas aeruginosa (P. aeruginosa) is known to be characteristic of this organism. This bacterium is considered one of the most life-threatening bacteria and has been identified as a priority pathogen for research by WHO. Biofilm-producing P. aeruginosa is a concern in many parts of the world due to antibiotic resistance. Alginate also plays an important role in the biofilm formation of P. aeruginosa as well as the emergence of antibiotic resistance in biofilms. In addition, the systems of toxin-antitoxin( TA) play an important role in biofilm formation. Metal nanoparticle(NP) such as zinc oxide (ZnO) also have extensive biological properties, especially anti-biofilm properties. Therefore, this study was conducted in relation to the importance of zinc oxide nanoparticles (ZnO NPs) in biofilm formation and also the correlation of gene expression of TA systems in clinical isolates of P. aeruginosa.

Methods

A total of 52 P. aeruginosa isolates were collected from burns (n = 15), UTI (n = 31), and trachea (n = 6) in hospitals in Ilam between May 2020 and October 2020. Biofilm formation was assessed using a microtiter plate assay. MIC and sub-MIC concentrations of ZnO NPs (10–30 nm with purity greater than 99.8%) in P. aeruginosa were determined. Subsequently, biofilm formation was investigated using sub-MIC concentrations of ZnO NPs. Finally, total RNA was extracted and RT- qPCR was used to determine the expression levels of genes of mazEF, mqsRA, and higBA of TA systems.

Results

Six isolates of P. aeruginosa were found to form strong biofilms. The results showed that ZnO NPs were able to inhibit biofilm formation. In our experiments, we found that the sub-MIC concentration of ZnO NPs increased the gene expression of antitoxins mazE and mqsA and toxin higB of TA systems treated with ZnO NPs.

Conclusions

In the present study, ZnO NPs were shown to effectively inhibit biofilm formation in P. aeruginosa. Our results support the relationship between TA systems and ZnO NPs in biofilm formation in P. aeruginosa. Importantly, the expression of antitoxins mazE and mqsA was high after treatment with ZnO NPs, but not that of antitoxin higA.
Naloxone prescriptions among patients with a substance use disorder and a positive fentanyl urine drug screen presenting to the emergency department
Authors: Ali Shawkut Amaan , Shell Jasmine , Harris Raymond , Bedder Marshall
Published: October 2023

Background

Over 109,000 people in the USA died from a drug overdose in 2022. More alarming is the amount of drug overdose deaths involving synthetic opioids other than methadone (SOOM), primarily fentanyl. From 2015 to 2020, the number of drug overdose deaths from SOOM increased 5.9-fold. SOOM are commonly being found in many other drugs without the user's knowledge. Given the alarming number of overdose deaths from illicit drugs with SOOM, naloxone should be prescribed for all persons using illicit drugs regardless of if they knowingly use opioids. How often providers prescribe naloxone for these patients remains unknown.

The aim of this study is to determine the rate of naloxone prescriptions given to patients with any substance use disorder, including when the patient has a urine drug screen positive for fentanyl. Secondary aims include determining what patient factors are associated with receiving a naloxone prescription.

Methods

The design was a single-center retrospective cohort study on patients that presented to the Augusta University Medical Center emergency department between 2019 through 2021 and had an ICD-10 diagnosis of a substance use disorder. Analyses were conducted by logistic regression and t-test or Welch’s t-test.

Results

A total of 10,510 emergency department visits were by 6787 patients. Naloxone was prescribed in 16.3% of visits with an opioid-related discharge diagnosis and 8.4% of visits with a non-opioid substance use-related discharge diagnosis and a urine drug screen positive for fentanyl. Patients with a fentanyl positive urine drug screen had higher odds of receiving a naloxone prescription (aOR 5.80, 95% CI 2.76–12.20, p < 0.001). Patients with a psychiatric diagnosis had lower odds of being prescribed naloxone (aOR 0.51, p = 0.03). Patients who received naloxone had a lower number of visits (mean 1.23 vs. 1.55, p < 0.001). Patients with a urine drug screen positive for cocaine had higher odds of frequent visits (aOR 3.07, p = 0.01).

Conclusions

Findings should remind providers to prescribe naloxone to all patients with a substance use disorder, especially those with a positive fentanyl urine drug screen or a co-occurring psychiatric condition. Results also show that cocaine use continues to increase healthcare utilization.
L-Fucose promotes enteric nervous system regeneration in type 1 diabetic mice by inhibiting SMAD2 signaling pathway in enteric neural precursor cells
Authors: Yao Hailing , Shi Huiying , Jiang Chen , Fan Mengke , Zhang Yurui , Qian Wei , Lin Rong
Published: October 2023

Background

Diabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain.

Methods

Genetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-β (TGF-β) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs.

Results

L-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p < 0.05), reduced total gastrointestinal transmission time (p < 0.001) and bead expulsion time (p < 0.05), as well as enhanced spontaneous contractility and electric field stimulation-induced contraction response in isolated colonic muscle strips (p < 0.001). The decrease in the number of neurons and glial cells in the ENS of diabetic mice were reversed by L-Fucose treatment. More importantly, L-Fucose treatment significantly promoted the proportion of ENPCs differentiated into neurons and glial cells both in vitro and in vivo, accompanied by inhibiting SMAD2 phosphorylation.

Conclusions

L-Fucose could promote neurogenesis and gliogenesis derived from ENPCs by inhibiting the SMAD2 signaling, thus facilitating ENS regeneration and gastrointestinal motility recovery in type 1 diabetic mice.
Antibody against apolipoprotein-A1, non-alcoholic fatty liver disease and cardiovascular risk: a translational study
Authors: Pagano Sabrina , Bakker Stephan J. L. , Juillard Catherine , Vossio Stefania , Moreau Dimitri , Brandt Karim J. , Mach François , Dullaart Robin P. F. , Vuilleumier Nicolas
Published: October 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease increasing cardiovascular disease (CVD) morbidity and mortality. Autoantibodies against apolipoprotein A-1 (AAA-1) are a possible novel CVD risk factor promoting inflammation and disrupting cellular lipid homeostasis, two prominent pathogenic features of NAFLD. We explored the role of AAA-1 in NAFLD and their association with CVD risk.

Methods

HepaRG cells and liver sections from ApoE−/− mice exposed to AAA-1 were used for lipid quantification and conditional protein expression. Randomly selected sera from 312 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND) general population cohort were used to measure AAA-1. A Fatty Liver Index (FLI) ≥ 60 and a 10-year Framingham Risk Score (FRS) ≥ 20% were used as proxy of NAFLD and high CVD risk, respectively.

Results

In-vitro and mouse models showed that AAA-1 increased triglyceride synthesis leading to steatosis, and promoted inflammation and hepatocyte injury. In the 112 PREVEND participants with FLI ≥ 60, AAA-1 were associated with higher FRS, alkaline phosphatase levels, lower HDL cholesterol and tended to display higher FLI values. Univariate linear and logistic regression analyses (LRA) confirmed significant associations between AAA-1, FLI and FRS ≥ 20%, while in adjusted LRA, FLI was the sole independent predictor of FRS ≥ 20% (OR: 1.05, 95%CI 1.01–1.09, P = 0.003). AAA-1 was not an independent FLI predictor.

Conclusions

AAA-1 induce a NAFLD-compatible phenotype in vitro and in mice. Intricate associations exist between AAA-1, CVD risk and FLI in the general population. Further work is required to refine the role of AAA-1 in NAFLD and to determine if the AAA-1 association with CVD is affected by hepatic steatosis.
Association between triglyceride glucose index and severity of diabetic foot ulcers in type 2 diabetes mellitus
Authors: Chen Weihao , Wang Xuedong , Jiang Qilin , Wu Jiyan , Shi Wanyan , Wang Xiaoxiao , Yin Yihu , Zheng Jiayin , Hu Xiang , Lin Cai , Zhang Xingxing
Published: October 2023

Background

Triglyceride glucose (TyG) index is a good surrogate biomarker to evaluate insulin resistance (IR). The study aimed to investigate whether the TyG index is related to the severity of diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 1059 T2DM patients were enrolled in this observational, retrospective, single‐center study. TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/ dl)/2]. The severity of DFUs was classified into mild‐to‐moderate DFUs (Wagner grade score < 3) and severe DFUs (Wagner grade score ≥ 3) based on Wagner classification. Patients were stratified according to the tertiles of TyG index. Logistic regression models were implemented to explore the association between TyG index and the severity of DFUs. Subgroup analyses were used to verify the reliability of results.

Results

Compared with the reference lowest TyG tertile (T1), the highest tertile (T3) was associated with 0.377‐fold increased risk of prevalence of severe DFUs (odds ratio [OR] 1.377, 95% confidence interval [CI] 1.017–1.865) (P = 0.039). After adjusting for potential confounders, the multivariable‐adjusted OR and 95% CI were 1.506 (1.079–2.103) (P = 0.016) in patients with highest tertile. Moreover, subgroup analyses indicated that the association was stronger among men, patients with age ≥ 65 years, duration of diabetes more than 10 years, or without PAD.

Conclusions

Elevated TyG index is independently associated with severity of DFUs even after adjusting conventional confounders.
HycDemux: a hybrid unsupervised approach for accurate barcoded sample demultiplexing in nanopore sequencing
Authors: Han Renmin , Qi Junhai , Xue Yang , Sun Xiujuan , Zhang Fa , Gao Xin , Li Guojun
Published: October 2023

DNA barcodes enable Oxford Nanopore sequencing to sequence multiple barcoded DNA samples on a single flow cell. DNA sequences with the same barcode need to be grouped together through demultiplexing. As the number of samples increases, accurate demultiplexing becomes difficult. We introduce HycDemux, which incorporates a GPU-parallelized hybrid clustering algorithm that uses nanopore signals and DNA sequences for accurate data clustering, alongside a voting-based module to finalize the demultiplexing results. Comprehensive experiments demonstrate that our approach outperforms unsupervised tools in short sequence fragment clustering and performs more robustly than current state-of-the-art demultiplexing tools for complex multi-sample sequencing data.
The mechanism of dendritic cell-T cell crosstalk in rheumatoid arthritis
Authors: Wang Zhandong , Zhang Jinlong , An Fangyu , Zhang Jie , Meng Xiangrui , Liu Shiqing , Xia Ruoliu , Wang Gang , Yan Chunlu
Published: October 2023

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint pain and swelling, synovial hyperplasia, cartilage damage, and bone destruction. The mechanisms of dendritic cell (DC) and T cell-mediated crosstalk have gradually become a focus of attention. DCs regulate the proliferation and differentiation of CD4+ T cell subtypes through different cytokines, surface molecules, and antigen presentation. DC-T cell crosstalk also blocks antigen presentation by DCs, ultimately maintaining immune tolerance. DC-T cell crosstalk mainly involves chemokines, surface molecules (TonEBP, NFATc1), the PD-L1/PD-1 signalling axis, and the TGF-β signalling axis. In addition, DC-T cell crosstalk in RA is affected by glycolysis, reactive oxygen species, vitamin D, and other factors. These factors lead to the formation of an extremely complex regulatory network involving various mechanisms. This article reviews the key immune targets of DC-T cell crosstalk and elucidates the mechanism of DC-T cell crosstalk in RA to provide a basis for the treatment of patients with RA.
Organisational benefits of undertaking research in healthcare: an approach to uncover impact
Authors: Holliday Judith , Jones Natalie , Cooke Jo
Published: October 2023

There is increasing focus to review the societal impact of research through assessment and research excellence frameworks. These often link to financial and reputational incentives within the academic community. However, timeframes to demonstrate impact using these approaches are often long and are not designed to show benefit to service collaborators who require evidence of improvement and change to their services more immediately. Impacts that are measured this way may also miss out on unintended and positive impacts that occur as by-products of research, or through the ‘ripple effect’ that research may have on practice. Importantly, demonstrating how research makes a difference can improve the research culture in services, and motivations in service partners to become, and stay involved in research. This article describes, and provides access to, a tool called VICTOR (making Visible the ImpaCT Of Research) that was developed by a community of practice involving 12 NHS organisations through blending evidence from the literature, practice and service users. We describe the types of impact that have been collected by VICTOR and explore how collecting impact in this way might help research-practice partnerships and inform research methodologies and may be useful to show impacts alongside, and shortly after the research process.
Cognitive impairment indicator for the neuropsychological test batteries in the Canadian Longitudinal Study on Aging: definition and evidence for validity
Authors: O’Connell Megan E. , Kadlec Helena , Griffith Lauren E. , Wolfson Christina , Maimon Geva , Taler Vanessa , Kirkland Susan , Raina Parminder
Published: October 2023

Background

Prevalence of overall cognitive impairment based on each participant’s performance across a neuropsychological battery is challenging; consequently, we define and validate a dichotomous cognitive impairment/no cognitive indicator (CII) using a neuropsychological battery administered in a population-based study. This CII approximates the clinical practice of interpretation across a neuropsychological battery and can be applied to any neuropsychological dataset.

Methods

Using data from participants aged 45–85 in the Canadian Longitudinal Study on Aging receiving a telephone-administered neuropsychological battery (Tracking, N = 21,241) or a longer in-person battery (Comprehensive, N = 30,097), impairment was determined for each neuropsychological test based on comparison with normative data. We adjusted for the joint probability of abnormally low scores on multiple neuropsychological tests using baserates of low scores demonstrated in the normative samples and created a dichotomous CII (i.e., cognitive impairment vs no cognitive impairment). Convergent and discriminant validity of the CII were assessed with logistic regression analyses.

Results

Using the CII, the prevalence of cognitive impairment was 4.3% in the Tracking and 5.0% in the Comprehensive cohorts. The CII demonstrated strong convergent and discriminant validity.

Conclusions

The approach for the CII is a feasible method to identify participants who demonstrate cognitive impairment on a battery of tests. These methods can be applied in other epidemiological studies that use neuropsychological batteries.
RETRACTED ARTICLE: Enhancing throughput using channel access priorities in frequency hopping network using federated learning
Authors: Han Yu , Zhu Xiaowei
Published: October 2023

The data are sent by the nodes taking part in frequency hopping communications (FHC) utilising carrier frequencies and time slots that are pseudo-randomly assigned. Because of this, a high degree of protection against eavesdropping and anti-interference capabilities is provided. When using FHC in an environment, sharing time and frequency resources, avoiding collisions, and differentiating services are all made more complex as a result of this. A protocol for FHC that is based on dispersed wireless networks is presented by the authors of this research. It is a mechanism for multiple access control, which is prioritised and distributed. The ratio of empty channels metric can be found in the previous sentence. It is possible to provide priority in channel access by assigning different preset ratios of empty channel thresholds to the various traffic classes. Frames from frequency spread segments that have a partial collision are included as well. An analytical model is simulated for the analysis in terms of collision probability, transmission probability, and frame service time in order to carry out a theoretical examination of the performance of FHC. The objective of this inquiry is to determine how well FHC works. The analytical model has been proven correct by the exhaustive simulations as well as the theoretical findings. Cloud platforms are often used in the instruction of the most cutting-edge machine learning techniques of today, such as deep neural networks. This is done in order to take advantage of the cloud's capacity to scale elastically. In order to satisfy the criteria of these sorts of applications, federated learning, has been proposed as a distributed machine learning solution. This is done in order to fulfil the requirements of these kinds of applications. In federated learning (FL), even though everyone who uses the system works together to train a model, nobody ever shares their data with anybody else. Each user trains a local model with their own data, and then communicates the updated models with a FL server so that the data can be aggregated and a global model can be constructed. This process ensures that each user's model is unique. This process is repeated until a global model has been developed. This kind of training not only reduces the amount of network overhead that is necessary to transfer data to a centralised server, but it also safeguards the personal information of the users. Within the framework of this work, we looked at the feasibility of using the FL technique of learning on the many devices that are part of the dispersed network. On a centralised server, we conduct an analysis of the performance of the FL model by comparing its accuracy and the amount of time it takes to train using a range of various parameter value combinations. Additionally, the accuracy of these federated models may be made to reach a level that is comparable to that of the accuracy of central models.
An exploratory factor analysis of entrepreneurship psychological readiness (EPR) instrument
Authors: Farradinna Syarifah , Syafitri Nesi , Herawati Icha , Jayanti Wella
Published: October 2023

The purpose of this study was to develop an instrument for assessing psychological readiness for entrepreneurship. A well-designed measurement of entrepreneurship psychological readiness can provide early warning to policymakers, in this case the government, and provide education and funding to prospective entrepreneurs who must not only be examined physically, but also psychologically. Using Exploratory Factor Analysis (EFA) and reliability analysis, the validity and reliability of the Entrepreneurship Psychological Readiness (EPR) instrument were examined. An Exploratory Factor Analysis (EFA) found that the Entrepreneurship Psychological Readiness (EPR) instrument’s eight-factor model explained 57.44% of the variance among the items. To develop a fit model, it was necessary to exclude 26 items from the questionnaire, leaving 59 items left. The factors name identified by Personal Knowledge, Personal Adversity, Committed Certain Action, Willingness to Learn, Personal Relationship to Others, Personal Growth, Passion Achieved, and Related Person Support. All of the eight-factor models have excellent reliability of 0.96.
Decoding cell-type contributions to the cfRNA transcriptomic landscape of liver cancer
Authors: Safrastyan Aram , zu Siederdissen Christian Höner , Wollny Damian
Published: October 2023

Background

Liquid biopsy, particularly cell-free RNA (cfRNA), has emerged as a promising non-invasive diagnostic tool for various diseases, including cancer, due to its accessibility and the wealth of information it provides. A key area of interest is the composition and cellular origin of cfRNA in the blood and the alterations in the cfRNA transcriptomic landscape during carcinogenesis. Investigating these changes can offer insights into the manifestations of tissue alterations in the blood, potentially leading to more effective diagnostic strategies. However, the consistency of these findings across different studies and their clinical utility remains to be fully elucidated, highlighting the need for further research in this area.

Results

In this study, we analyzed over 350 blood samples from four distinct studies, investigating the cell type contributions to the cfRNA transcriptomic landscape in liver cancer. We found that an increase in hepatocyte proportions in the blood is a consistent feature across most studies and can be effectively utilized for classifying cancer and healthy samples. Moreover, our analysis revealed that in addition to hepatocytes, liver endothelial cell signatures are also prominent in the observed changes. By comparing the classification performance of cellular proportions to established markers, we demonstrated that cellular proportions could distinguish cancer from healthy samples as effectively as existing markers and can even enhance classification when used in combination with these markers.

Conclusions

Our comprehensive analysis of liver cell-type composition changes in blood revealed robust effects that help classify cancer from healthy samples. This is especially noteworthy, considering the heterogeneous nature of datasets and the etiological distinctions of samples. Furthermore, the observed differences in results across studies underscore the importance of integrative and comparative approaches in the future research to determine the consistency and robustness of findings. This study contributes to the understanding of cfRNA composition in liver cancer and highlights the potential of cellular deconvolution in liquid biopsy.
Solid–liquid extraction of bioactive compounds as a green alternative for developing novel biostimulant from Linum usitatissimum L.
Authors: Szparaga Agnieszka , Kocira Sławomir , Kapusta Ireneusz , Zaguła Grzegorz
Published: October 2023

Background

The interest expressed by the agriculture in the category of innovative biostimulants is due to the intensive search for novel preparations based on natural substances i.a. allelochemicals. Scientific research into the design and testing of next-generation biostimulants marks advances for sustainable agricultural production.

Results

Our research represents an innovative and comprehensive approach to the use of Linum usitatissimum L. seed extracts in soybean cultivation using foliar treatments. A multi-tiered approach was adopted, involving both the assessment of soybean responses at the agronomic, morphological and biochemical levels. It was hypothesized that the extract would improve the growth and yield of soybean through mechanisms based on improved physiological and biochemical processes. The study showed that the extract was rich in micro- and macro-nutrients (in particular potassium and zinc), amino acids (with the largest proportion of glutamic acid), fatty acids (predominant oleic + elaidic acids) and carbohydrates (sucrose and glucose). Soybean responded positively by increased in plant height, number of pods and seed yield. The results confirmed that the tested biostimulant is not only an environmentally friendly product, but also is capable of increasing the growth and productivity of soybeans, thus increasing farmers' profit. The obtained yield was characterized by a lower total proteins pool (average decrease approx. 2%). The extract caused changes in the amino acid profile (especially in the case of proline and lysine) and fatty acid composition (significantly higher content of acids: heptadecanoic, octadecanoic, eicosanoic, eicosapentaenoic, docosanoic, erucic, tricosanoic).

Conclusions

All the observations made confirm that the extract positively affected the soybean crop. Based on the study, it was concluded that solid–liquid extraction could be considered as a green alternative for prototyping a novel and ecological biostimulant.

Graphical Abstract
Analysis of iron-rich hydrochloric acid solutions for uranium, thorium, rare-earth elements and other heavy metals
Authors: Sunilkumar Beena , Krishnakumar M. , Patwardhan A. A.
Published: October 2023

A simple solvent extraction method is described for the separation of trace elements including uranium (U), thorium (Th) and rare-earth elements (REEs) from industrially processed iron-rich hydrochloric acid solutions. Iron (Fe) causes severe spectral interference during the analysis of trace elements using inductively coupled plasma optical emission spectrometer (ICP-OES) and U by light-emitting diode (LED)-based fluorimeter (LEDF). The spectral interferences of Fe on trace elements are studied and documented. Sequential solvent extractions using methyl isobutyl ketone (MIBK) effectively removed the highly interfering Fe from these processed acid solutions, thereby enabling accurate and sensitive determination of Cd, Zn, Pb, Co, Ni, Cr, V, Cu, Sr, Zr, Ti, REEs including radioactive elements like U and Th. Solvent extraction parameters like the number of extractions, aqueous-organic ratio and acidity have been optimized for removal of Fe. The accuracy of the method has been established by analyzing synthetically prepared hydrochloric acid solutions by spiking-recovery method. Ion exchange separation of REEs using Dowex 50 × 8 cation exchange resin has been also studied and reported. The precision obtained has been well within ± 10% RSD for elements having concentration above 10 mg L−1 and ± 15% for elements having concentration below 10 mg L−1 for replicate (n = 5) measurements.
Artificial intelligence in diagnosis and management of Huntington’s disease
Authors: Parekh Neel , Bhagat Anjali , Raj Binith , Chhabra Raunak Singh , Buttar Harpal Singh , Kaur Ginpreet , Ramniwas Seema , Tuli Hardeep Singh
Published: October 2023

Background

Huntington’s disease is one of the rare neurodegenerative diseases caused because of genetic mutation of the Huntingtin gene. The major hallmarks of the condition include motor impairment, cognitive decline, and psychiatric symptoms. With no cure and only symptomatic treatments available, early detection and personalized therapy are warranted for managing the disease effectively. Artificial Intelligence has emerged as a transformational tool in healthcare, revolutionizing many parts of medical practice and research, thus holding the potential in detecting, monitoring, and managing Huntington’s disease.

Main body of abstract

Artificial Intelligence’s role in Huntington’s disease includes a variety of applications like medical image analysis and predictive analytics. AI-driven algorithms are utilized to analyze brain imaging data in medical image analysis. Deep learning and convolutional neural networks (CNNs) aid in the detection of subtle brain changes and the identification of illness biomarkers, allowing for the early diagnosis of the disease. Additionally, the predictive analytics capabilities of AI are used to analyze disease development and forecast clinical outcomes. AI models can identify illness patterns, estimate the rate of functional decline, and assist doctors in making educated decisions about treatment methods and care planning by analyzing patient data.

Conclusions

With clinical practice and research integrated with Artificial Intelligence technologies, we can significantly improve the quality of life of individuals affected with Huntington’s disease. This integration holds the potential to develop effective personalized interventions. Nevertheless, collaborative efforts among doctors, researchers, and technology sound developers would be key to the successful implementation of AI in HD.

Graphical Abstract
Assessment of nasal outcomes after endoscopic removal of large midline skull base tumors with nasoseptal flap reconstruction
Authors: Ibrahim Anwar Abdelatty , Negm Hazem , Hamdan Ahmad M.
Published: October 2023

Background

There have been several reconstructive methods with free flaps or vascular pedicled flaps constituting a large portion of the rebuilding of the skull base. The vascularized pedicled nasoseptal flap, however, appears to be the “gold standard” flap in the restoration of the integrity of the cranial base among all of the foregoing alternatives. This study aimed to assess the postoperative outcomes of endoscopic removal of large midline skull base tumors with nasoseptal flap reconstruction in 21 patients. Patients were assessed at 1 week postoperative using Sinonasal Outcome Test 22 (SNOT 22) to assess postoperative nasal symptoms. An endoscopic assessment of the nose was done at 1 week postoperative to assess the degree of crusting and at 4 weeks postoperative to assess the degree of nasal adhesions and the presence or absence of gangrene of the nasoseptal flap. Postoperative complications were assessed.

Results

The study patients included 12 cases with pituitary macroadenoma, five cases with anterior cranial fossa meningioma, and four cases with petroclival chordoma. The skull base defect size ranged from 2.5 to 4.5 cm. The most troublesome postoperative symptoms were decreased sense of smell/taste. Postoperatively, 10 patients had mild, 7 patients had moderate, and 4 patients had severe nasal crusting. Three cases had epistaxis and two cases had postoperative cerebrospinal fluid rhinorrhea. Ten cases had no nasal adhesions, four cases had mild, four cases had moderate, and three cases had severe nasal adhesions. No cases had gangrene of the nasoseptal flap.

Conclusion

The nasoseptal flap is an effective option for large skull base defect reconstruction after endoscopic resection of large skull base tumors with an acceptable postoperative patient quality of life and a low incidence of postoperative complications.
Obstructive sleep apnea in patients with type 2 diabetes mellitus in Egyptian population
Authors: Sweed Rania Ahmad , Wahab Nashwa Hassan Abd El , El Hooshy Mona Saeed , Morsy Eman Youssef , Shetta Dina Mohsen
Published: October 2023

Background

Sleep disordered breathing (SDB) is a widespread disorder with a wide range of harmful outcomes including obstructive sleep apnea (OSA), central sleep apnea (CSA), or sleep-related hypoventilation.

Purpose

The aim of the present study was to screen for the occurrence of sleep apnea syndrome in patients with type 2 diabetes mellitus (DM) and to evaluate the relation between the presence of sleep apnea and the level of glycemic control.

Methods

This was a prospective clinical study that enrolled 59 patients who were previously diagnosed as type 2 DM. Sleep study level IV was done using overnight recording of oxygen saturation and pulse.

Results

Among the studied patients, 42 were females and 17 were males, Their mean age was 59.76 ± 11.13 years. Obstructive sleep apnea was diagnosed in 46 patients (78%). Thirty three (86.8%) patients among those with uncontrolled glycemic level were diagnosed as OSA, whereas 13(61.9%) patients with controlled glycemic level were diagnosed as OSA showing statistically significant difference, p = 0.047. There was no correlation between either HbA1c, age, Mallampati score, or BMI and ODI but there was a correlation between STOP-BANG questionnaire and ODI (P = 0.036). The variables that were significantly related to presence of OSA, were comorbidities, ESS, Mallampati score, STOP-BANG, and sleep symptoms (nocturia and snoring) P value (0.029), (0.031), (0.022), (0.005), (0.049), and (0.012), respectively.

Conclusion

Patients with type 2 diabetes showed a significant high prevalence of OSA. With significant higher prevalence among patients with uncontrolled DM versus controlled DM.
Volume estimation of fluid intake using regression models
Authors: Hassan E. A. , Morsy A. A.
Published: October 2023

Monitoring of water intake is critical for managing the health and wellness of individuals with various health conditions, including young children, sick adults, the elderly, and individuals seeking better weight control. The research presented in this paper studies the use of different regression methods to estimate water intake using wireless surface electromyography (sEMG). The advantage of using regression is that it can provide more consistent values for different swallow volumes. In addition, the setup reported in this research employs a less controlled environment, providing stronger evidence of the practical feasibility of the used setup. Neural networks-based regression achieved an R2 of 0.99 and a root-mean-squared error of 0.14 and 0.08 after feature selection. The relative immunity of sEMG as a sensing technique and the accuracy levels achieved with the used mobile sEMG device can provide a robust system for volume estimation of fluid intake in real-world situations.
Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer
Authors: Duska Linda R. , Zamarin Dmitriy , Hamilton Erica , Oza Amit , Fleming Gini , Spira Alexander , Yeku Oladapo O. , Richardson Debra L. , Walling Jackie , Inokuchi Kerry , Matusow Bernice , Bollag Gideon , Swisher Elizabeth M.
Published: October 2023

PURPOSE

The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with ARID1A loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members.

METHODS

We conducted a multicenter and open-label study with two parallel arms: a phase IIa study of PLX2853 monotherapy in patients with advanced gynecologic malignancies with an ARID1A mutation and a phase Ib/IIa combination study of PLX2853 plus carboplatin in women with platinum-resistant OC. The primary objectives were safety and tolerability for phase Ib and efficacy for both phase IIa portions. Thirty-four of 37 enrolled patients completed at least one post-baseline response assessment.

RESULTS

Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a best overall response of partial response (PR), 5 (35.7%) had stable disease (SD), and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable patients on the combination arm, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD.

CONCLUSION

This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with ARID1A-mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway.
OR10-02 Effect Of Phosphodiesterase 4 Inhibitors On Weight Loss And Energy Homeostasis In Mice With Obesity Induced By A High-fat-diet
Authors: de Andrade Maria Amelia A M , da Silva Hellen , Jesus Aline Alves , de Paula Francisco J A , Elias Lucila
Published: October 2023

Disclosure: M.A. de Andrade: None. H. da Silva: None. A.A. Jesus: None. F.J. de Paula: None. L. Elias: None.

INTRODUCTION: Obesity is a worldwide health problem and the incidence of associated diseases such as type 2 diabetes is increasing. Leptin (Lep) resistance arises from obesity-related inflammation, enhancing the appetite. The expression of phosphodiesterase 4 enzymes (PDE4) is increased in inflammatory conditions. Rolipram (Rol) acts to inhibit PDE4 reducing adiposity and peripheral inflammation. Notwithstanding, the effects of Rol on Lep sensitivity and energy balance are still unknown. Objective: To evaluate the effect of PDE4 inhibition on energy homeostasis and Lep sensitivity and glucose tolerance in mice with obesity induced by a high-fat diet (HFD). Methodology: Four-week-old male C57BL6 mice were fed a HFD (60%, Research Diets) or chow diet (C) for 10 weeks. In the 8th week, they received daily subcutaneous Rol injections (2mg/kg) or vehicle (V) and food intake and body weight were daily measured. Energy expenditure (EE) was measured on the 8th day of treatment using a metabolic cage (Oxymax). After treatment, mice underwent 6h fasting and subsequent intraperitoneal (i.p.) glucose injection (2g/kg). Fasting blood glucose (FG) and 120 minutes after glucose (GTT) were measured. On the last day of treatment, 90 minutes after the Rol or V injection, i.p. Lep (5mg/kg in 100ul) or saline (S) was injected, and weight and food intake were measured 14 and 24h later. Results: 5-10 mice were analyzed in each group (chow + V, CV; chow + Rol, CR; HFD + V, HV; HFD + Rol, HR). There was a significant difference in body weight between HR and HV: absolute weight (HR 35+-4.18; HV 38.8+-3.88g; p 0.038) and weight variation (HR -2.26+-0.99; HV -0.19+-1.25g; p 0.002), but no difference between CR and CV (27.98+-2.25; 26.8 +- 2.22g, p 0.97). Rol effectively reduced ingestion in both diets (CR 42.85+-2.7; CV 48.13+-4.51g; p 0.03) (HR 24.75+-2.44; HV 28.31 +-2.81g; p 0.01). In the HFD groups, compared to V, Rol increased VO2 (p 0.04) and energy expenditure (p 0.049) as well as the heat (p 0.03). There was no difference in VCO2 nor motor activity. Lep sensitivity was evaluated in the HFD group and there was a significant reduction in food intake 24h after the Lep application compared to S (Lep 2.18+-0.2; S 2.47+-0.18g, p 0.04). There was no difference in food intake 14h after Lep or weight after injection at either time point (14/24h). Rol was ineffective to improve FG/GTT in the HFD group. Conclusion: Rolipram, a PDE4 inhibitor, effectively reduces the body weight of diet-induced obesity by reducing food intake, increasing basal energy expenditure and improving leptin sensitivity. PDE4 appears as a potential target to treat obesity.

Presentation: Friday, June 16, 2023
FRI005 Appetite Response To Short-term Energy Restriction In Young Healthy Women
Authors: Choi Gloria E , Okigbo Chinelo , Tonleu Joselyne Tessa , Shekhar Skand , Leka Helen F , Kim Anne E , Purse Bona , Hisch Katie R , Smith-Ryan Abbie E , Hall Janet E
Published: October 2023

Disclosure: G.E. Choi: None. C. Okigbo: None. J. Tessa Tonleu: None. S. Shekhar: None. H.F. Leka: None. A.E. Kim: None. B. Purse: None. K.R. Hisch: None. A.E. Smith-Ryan: None. J.E. Hall: None.

Short-term caloric restriction, also referred to as energy restriction (ER), is commonly used by women across the weight spectrum to address their weight or health. Chronic ER is associated with increased appetite, but the relationship is poorly characterized in short-term ER or in the absence of obesity. We investigated the impact of controlled short-term ER on appetite and relevant hormone mediators in young women. In the early follicular phase of two menstrual cycles, 19 healthy non-obese women aged 23.36 ± 2.08 years (mean ± SD) with a BMI of 23.15 ± 2.34 kg/m2 (mean ± sem) underwent two five-day diet and exercise interventions: neutral energy availability (NEA) = 45 kcal/kg lean body mass (LBM)/day and deficient energy availability (DEA) = 20 kcal/kg LBM/day. On day 5 of both interventions, a visual analog scale (VAS) appetite questionnaire, body weight, fasting leptin and orexin-A were measured. We used paired t-tests for comparisons of changes from NEA to DEA. Principal-component factor analysis divided VAS items into appetite, satiety, and hunger (Cronbach alphas >0.80). We utilized linear regression models to determine how changes (Δ) in body weight, leptin, and orexin-A affect appetite, satiety, hunger, and cravings. From NEA to DEA, appetite and hunger increased (55% vs 76%; p<0.001 and 52% vs 71%; p<0.001, respectively), while satiety and cravings decreased (42% vs 19%; p <0.01 and 49% to 38%; p<0.01, respectively). DEA resulted in a weight loss of 1.0±0.22 kg (p<0.001), a decrease in leptin of 3.13±0.95 ng/ml, p=0.002), and increased orexin-A (0.06±0.02 ng/ml, p=0.018). Δ body weight was positively associated with Δ leptin (p=0.001) but not Δ orexin-A. When adjusting for leptin and orexin-A, increased appetite was associated with weight loss (p=0.011). Δ satiety was independently correlated with Δ body weight (p=0.002) and Δ leptin (p=0.033). Δ hunger was positively correlated with Δ body weight (p=0.043), independent of Δ orexin-A). Δ leptin, orexin-A, or body weight did not correlate with Δ craving. Thus, even in non-obese women, short-term ER results in a profound effect on homeostatic mechanisms designed to maintain weight; increased appetite and decreased satiety are mediated by even a minor degree of weight loss, both independently and through decreased leptin. It is likely that changes in ghrelin also contribute to these adaptations to ER, however it was not measured in this study for technical reasons. Interestingly, the effect of short-term ER on specific food cravings is overwhelmed by the overall increase in appetite.

Presentation: Friday, June 16, 2023
FRI014 Exploring The Epigenetic Fingerprint Of Sedentary Behavior
Authors: Brener Avivit , Lorber Dana , Reuveny Adriana , Lebenthal Yael , Volk Talila
Published: October 2023

Disclosure: A. Brener: None. D. Lorber: None. A. Reuveny: None. Y. Lebenthal: None. T. Volk: None.

Eating habits and physical activity play a central role among the environmental factors that modulate biological aging. Sedentary lifestyle, characterized by increased waking time spent in minimal energy expenditure activity, is closely associated with increased cardiometabolic risk, a principal hallmark of aging. The biological mechanisms linking a sedentary lifestyle with metabolic derangements are incompletely understood. Exercise was reported as a stimulator of epigenetic modifications of the DNA in human muscle cell nuclei (myonuclei). Exploring the specific impact of sedentary behavior on epigenetics, especially among younger individuals, requires the exclusion of the effects of inflammatory and nutritional contributors to medical conditions. We developed an experimental animal model that imitates sedentary behavior in which a chromatin epigenetic landscape could be explored. We used third-instar Drosophila larvae carrying a temperature-sensitive mutation in the shibire gene coding for GTPase involved in neuronal synaptic vesicle transport. Shibire homozygous mutant larvae are paralyzed at restrictive temperature (>∼29°C) due to inhibition of neuromuscular junction vesicular transport, while muscle contraction is abolished without affecting other systems. Shibire and control (y,w) larvae were kept at 18°C or 30°C without food for six hours. They were then dissected, fixed and double-labeled with antibodies specific for epigenetic marks of active (H3K9ac) and repressive (H3K27me3) histone modifications. An anti-lamin fluorescent antibody served for nuclear membrane demarcation. Immunofluorescence images of epigenetic marks were acquired on a confocal microscope Zeiss LSM 800, after which a quantitative analysis of epigenetics marks was performed. At the restrictive temperature (30°C), the crawling motion of shibire mutant larvae ceased in contrast to control (shibire at 18°C). The crawling motion of the y,w larvae was similar at 18°C and 30°C. The mean repressive mark H3K27me3 decreased (p<0.001), while the mean active H3KPac increased (p<0.001) in the myonuclei of sedentary shibire larvae (30°C). The mean myonuclear active/repressed ratio of epigenetic marks (H3K9ac/H3K27me) was similar in both active shibire (18°C) and y,w at 18°C, while it increased significantly in sedentary shibire (30°C) (p<0.001). In contrast, this ratio decreased in the control larvae (y,w at 30°C) (p<0.001). The findings of this model, which was aimed at reflecting sedentary behavior in youth, revealed that muscle inactivity changed the epigenetic fingerprint in myonuclei, with a balance shift towards decreased chromatin methylation relative to acetylation. Our finding suggests a decline in the epigenetic control of gene transcription, reminiscent of decreased epigenetic repression described with aging.

Presentation: Friday, June 16, 2023