bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of PI3K-AKT-mTOR signaling pathway-related circular RNAs in the diagnosis and prognosis of hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Wang Shuaiyang , Wu Mei , Xie Bei , Tian Ye , Ma Xingyuan , Li Jing , Ma Bin , Li Linjing
Published: June 2024

Background
Several studies have demonstrated that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-related circular RNAs (circRNAs) play a role in the development and progression of hepatocellular carcinoma (HCC). However, a systematic review and meta-analysis of the role of PI3K/AKT-related circRNAs in the diagnosis and prognosis of HCC has not been reported at present. Herein, we systematically reviewed the literature and conducted a meta-analysis of the potential role of PI3K/AKT/mTOR-related circRNAs in the diagnosis and prognosis of HCC.
Method
PubMed, EMBASE, Cochrane Library, Web of Science, Scoups, Wanfang, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI) and Chinese Science and Technique Journals Database (VIP) databases were searched for relevant studies from inception to April 19, 2024. Pooled odds ratio (OR) was used to evaluate clinical case characteristics, sensitivity and specificity. Prognostic overall survival (OS) was estimated using the hazard ratio (HR). Subgroup analyses were conducted according to sample type, country and control group type. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool or the Newcastle-Ottawa Scale (NOS) method, and Egger’s tests were used to assess potential publication bias. STATA (version 17.0) software was used for statistical analysis.
Results
Twenty five eligible articles, including ten diagnostic studies and sixteen prognostic studies, involving 2995 HCC patients, 435 healthy controls and 338 controls with benign lesions were included in this meta-analysis. The pooled sensitivity and specificity were 0.80 (95% CI: 0.75–0.84) and 0.86 (95% CI: 0.77–0.92), respectively. Higher levels of PI3K/AKT/mTOR pathway-associated circRNAs are significantly associated with poor patient prognosis (OS:HR = 1.49, 95% Cl: 0.89–2.48, P < 0.001). Elevated levels of highly expressed circRNAs in patients were significantly associated with HbsAg positivity, MVI positivity, and worse TMN staging in patients with HCC, and elevated levels of low expressed circRNAs in patients were associated with MVI negativity in patients with HCC. No publication bias was found.
Conclusion
PI3K/AKT/mTOR-related circRNAs are potential biomarkers for HCC, especially in the diagnosis of HCC. Due to the small number of included articles and the limitation of the included population, more studies on the diagnostic and prognostic value of PI3K/AKT/mTOR pathway-related circRNAs are needed in the future.
The Nutritional Impact of Metallic Taste in Head and Neck Cancer Patients: Explorations and Clinical Implications
Authors: Buiret Guillaume , Brignot Hélène , Septier Chantal , Thomas-Danguin Thierry , Féron Gilles
Published: June 2024

PURPOSE: Metallic taste (MT) is frequently observed during head and neck cancer treatments, but very little is known about its impact on nutritional status. The aim of this study was to explore the impact of MT on the quality of life and nutritional status in patients with head and neck cancer expressing MT disorder.
METHODS: Questionnaires on quality of life, MT, weight, and food intake were filled out by 44 patients with head and neck cancer before, during, and up to one year after their treatment. Patients were divided into two groups based on the occurrence of MT.
RESULTS: MT was commonly observed (27.2%), always during the treatment phase and mostly linked with radiotherapy or radiochemotherapy. MT intensity was moderate (40%) to high (26.7%). MT had a significant negative impact on QoL linked to dysgeusia (p=0.025). The negative impacts of MT on food intake and on weight were not significant, possibly due to a combination of sample size, dropouts, and duration of observation. Further research in this area could provide additional insights into how to better address the issue related to MT and enhance the quality of care provided to this patient population.
CONCLUSION: Metallic taste, experienced by 27.2% of head and neck patients, contributes to dysgeusia and results in a significant decline in quality of life.
ClinicalTrials.gov trial registration number: NCT03558789
Association of social isolation and depressive symptoms with workplace productivity loss: A multi- ethnic Asian study
Authors: Ha Joey Wei Yee , Yip Wan Fen , Ge Lixia , Yap Chun Wei , Pereira Michelle Jessica
Published: June 2024

Background
The association between health-related productivity loss (HRPL) with social isolation and depressive symptoms is not well studied. We aim to examine the association between social isolation and depressive symptoms with productivity loss.
Methods
The National Healthcare Group (NHG) Population Health Index (PHI) study is a population-based study on community-dwelling employed adults aged ≥21 years, residing in the Central and Northern of Singapore.
The severity of depressive symptoms and social isolation were assessed using the 9-item Patient Health Questionnaire (PHQ-9) and Lubben Social Network Scale-6 (LSNS-6) respectively. Productivity loss was assessed using the Work Productivity and Activity Impairment Questionnaire (WPAI). We used Generalised Linear Models, with family gamma, log link for the analysis. Models were adjusted for socio-demographic variables (including age, gender, ethnicity, employment status, housing type) and self-reported chronic conditions (including the presence of diabetes, hypertension, and dyslipidemia).
Results
There were 2,605 working (2,143 full-time) adults in this study. The median reported percentage of unadjusted productivity loss was 0.0%, 10.0% and 20.0% for individuals with social isolation, depressive symptoms, and both, respectively. In the regression analysis, mean productivity loss scores were 2.81 times (95% Confidence Interval: 2.12, 3.72) higher in participants with depressive symptoms than those without. On the other hand, social isolation was not found to be associated with productivity loss scores (1.17, 95% Confidence Interval: 0.96, 1.42). The interaction term of depressive symptoms with social isolation was statistically significant, with an effect size of 1.89 (95% Confidence Interval: 1.04, 3.44). It appears that productivity loss was amplified when social isolation and depressive symptoms are concomitant.
Conclusions
Our results suggested associations between depressive symptoms and social isolation with productivity loss. The findings highlighted the potential impact of depressive symptoms and social isolation on work performance and draw attention to the importance of having a holistic work support system that promotes mental wellbeing, social connectedness and work productivity.
Current profile of pyrethroid resistance in Rhipicephalus microplus populations sampled from Marathwada region of Maharashtra state, India
Authors: Khating Sandip , Jadhav Nitin , Vijay M. , Sharma Anil Kumar , Srivast Anand , Jadhao Suresh , Kumar Sachin , Kalwaghe Shrikant , Siddiqui M. F.M.F. , Narawade Mahima , Dhabale Ankush , Chigure Gajanan
Published: June 2024

This study examined the pattern of resistance to widely applied synthetic pyrethroids i.e. cypermethrin and deltamethrin, against larvae of Rhipicephalus microplus ticks sampled from Marathwada region in Maharashtra, India. The study also examined the role of α and β-esterase’s and glutathione-S-transferase (GST) in resistance development. All eight R. microplus isolates tested were resistant to deltamethrin (RL IV), having RR50 values from 6.88 to 131.26. LPT analysis exhibited the resistance level II deltamethrin resistance in Beed and Hingoli, III in Dharashiv, and IV in Sambhajinagar, Parbhani, Latur, Jalna, and Nanded isolates. The LIT analysis showed that Dharashiv field isolates had the lowest LC50 value of 229.09 ppm against cypermethrin, while Sambhajinagar field isolates had the highest at 489.78 ppm. The RR50 ranged from 1145.45 to 2448.9. Seven isolates were level I resistant to cypermethrin while the Jalna isolate was level II resistant. In larvae treated with deltamethrin and cypermethrin, the activity of α and β-esterase enzymes increased significantly compared to control groups. The enzyme ratios in treated larvae ranged from 0.7533 to 1.7023 for α-esterase and 0.7434 to 3.2054 for β-esterase. The Hingoli isolate treated with cypermethrin exhibited the highest α-esterase activity (903.261), whereas, Sambhajinagar isolate had the highest GST enzyme ratio (2.8224) after deltamethrin exposure. When exposed to cypermethrin, the Hingoli isolate showed the highest GST enzyme ratio, 2.0832.
Efficacy and safety of combined anti-vascular and two-staged stereotactic radiosurgery therapy for brain metastases with brainstem compression: a retrospective multicenter study
Authors: Zhu Xiuming , Zhou Jia , Chen Qun , Chen Haining , Li Renli , Zhu Yucun , Wang Zheng
Published: June 2024

Stereotactic radiosurgery poses a significant risk when treating brain metastases in close proximity to the brainstem. To address this issue, a novel approach known as "combined anti-vascular therapy" has been devised for these metastases. This treatment regimen involves a one-week course of two-staged stereotactic radiosurgery (2-SSRS), supplemented with the administration of the anti-vascular agent bevacizumab during the radiosurgery interval. The objective of this study is to assess the efficacy and safety of a combined anti-vascular and two-staged stereotactic radiosurgery therapy for brain metastases with brainstem compression. A retrospective analysis was conducted on patients treated at five gamma knife treatment centers to assess changes in tumor size and peritumoral edema volume. Clinical symptom changes were evaluated using the Headache Scale (VAS), Dizziness Disorder Inventory (DHI), Vomiting Scale (VS), and Glasgow Coma Scale (GCS). The Karnofsky Task Scale (KPS) and Barthel Index (BI) were used to assess overall physical fitness and physical activity rehabilitation. Tumor local control (TLC) and overall survival (OS) rate were also calculated for the patients. Among the 36 patients with brain metastases with brainstem compression, 36 received combined anti-vascular therapy. Both edema volume and tumor volume significantly decreased during the treatment period and post-treatment 3 months (p < 0.01). Clinical symptoms, as indicated by median scores of VAS, DHI, VS, and GCS, showed significant improvement during treatment and at the 3-month follow-up (p < 0.01). Median changes in KPS and BI, reflecting overall physical fitness and physical activity rehabilitation, were also similar and statistically significant (p < 0.01). The patient cohort exhibited a median overall survival of 14.2 months, with corresponding 6-month and 12-month survival rates of 91.7% and 80.0%, respectively. Tumor local control rates at 6 and 12 months were 94.7% and 78.9%, respectively.The combination of anti-vascular therapy with 2-SSRS demonstrates safety and efficacy in treating patients with brain metastases with brainstem compression. This approach rapidly alleviates patient symptoms, effectively manages tumor progression, extends overall survival, and exhibits manageable adverse effects.
Development of an in Vitro Model of the Neurovascular Unit for BBB Permeability Linked Neuroactivity Screening
Authors: Lubin Kelsey E. , Xu Zhuangyan (Monica) , Sluka James P. , Knipp Gregory
Published: June 2024

Many potential neurotherapeutic agents fail in the later stages during development due to insufficient blood-brain barrier (BBB) permeability or neurotoxic effects. To address this, we developed an in vitro model incorporating the neurovascular unit (NVU) — astrocytes, pericytes, neurons, and brain microvessel endothelial cells — designed to simulate the in vivo BBB and improve early drug screening. This model uses a direct contact triculture system enhanced by integrating SH-SY5Y neuron-like cells, enabling the study of permeability-linked neuronal responses. Our results show that this expanded NVU model, employing a Transwell® system, enhances the BBB’s restrictive properties and neuronal viability, potentially due to improved cell-cell signaling. Additionally, the model demonstrated increased efflux transporter expression, providing a more physiologically relevant assessment of neuroactivity in relation to BBB permeability. This innovative NVU model offers a predictive and robust tool for evaluating neurotherapeutic agents, facilitating the prioritization of candidates in large compound libraries and potentially reducing attrition rates in drug development. It represents a significant advancement in the methodology for early-stage neurotherapeutic screening, aligning in vitro findings more closely with in vivo responses.
Grid cell populations maintain their hexagonal firing patterns on a circular track
Authors: Yim Man Yi , Walton Steven , Hedrick Kathryn
Published: June 2024

In an open 2D environment, grid cells in the medial entorhinal cortex are known to be active in multiple locations, displaying a striking periodic hexagonal firing pattern covering the space. According to attractor network theory, grid cell activity in any stable 1D environment is a slice through an underlying 2D hexagonal pattern, but this underlying pattern has not been observed in some experimental studies on a circular track. Grid cells are believed to play a fundamental role in path integration, and understanding their behavior in various environments is crucial for understanding the flow of information through the entorhinal-hippocampal system. We analyzed the activity of grid cells when rats traversed a circular track. A previous study involving this data set analyzed individual grid cell activity patterns separately, but we found that individual grid cells provide insufficient data for determining the underlying spatial activity pattern. To circumvent this, we compute the population autocorrelation, which pools together population responses from grid cells within the same module. This novel approach recovers the underlying six-peak hexagonal pattern that was not observable in the individual autocorrelations. We also use the population autocorrelation to infer the population lattice properties, revealing how the lattice differs across environments. Furthermore, the population autocorrelation of the linearized track reveals that at the population level, grid cells have an allocentric code for space. These results are strong support for the attractor network theory for grid cells, and our novel approach can be used to analyze grid cell activity in undersampled environments.
Insights into structural features and phylogenetic implications of the complete mitochondrial genome of Fasin rainbow fish (Melanotaenia fasinensis)
Authors: Marnis Huria , Syahputra Khairul , Kadarusman Kadarusman , Darmawan Jadmiko , Cartealy Imam Civi , Larashati Sekar , Kusuma Wahyu Endra , Hayuningtyas Erma Primanita , Iswanto Bambang , Asaf Ruzkiah , Muchlies Admi Athirah , Subangkit Arsad Tirta , Sularto Sularto , Indrawati Indrawati
Published: June 2024

The Fasin Rainbow fish, scientifically known as Melanotaenia fasinensis, is highly sought after by aquarium enthusiasts due to its vibrant colors and adaptability to artificial aquatic environments. This species is endemic to the karst landscape of the Bird’s Head region in Papua, Indonesia, and belongs to the Melanotaeniidae family. Discovered relatively recently in 2010, it has been designated as endangered by the International Union for Conservation of Nature (IUCN) in 2021. However, there is currently insufficient data regarding its phylogenetic positioning. To address this gap, our study employed next-generation sequencing to analyze the entire mitochondrial genome of M. fasinensis. The mitochondrial genome consists of 13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes, with a total length of 16,731 base pairs. The base composition of the mitogenome revealed percentages of 27.76% adenine (A), 27.34% thymine (T), 16.15% guanine (G), and 28.75% cytosine (C). Our phylogenetic analysis, based on nucleotide sequences mitogenome, indicated that M. fasinensis occupies a relatively basal position within the Melanotaenia genus. This study provides valuable molecular insights for further exploration of phylogeography and evolutionary history, not only for M. fasinensis but also for other members of the Melanotaenia genus.
Predictive Failure Mode Identification in Reinforced Concrete Flat Slabs Using Advanced Ensemble Neural Networks
Authors: Barkhordari Mohammad Sadegh , Fattahi Hadi , Armaghani Danial Jahed , Khan Naseer Muhammad , Afrazi Mohammad , Asteris Panagiotis G.
Published: June 2024

Reinforced concrete (RC) flat slabs without transverse reinforcement are commonly used in RC buildings. Despite their appeal and widespread use, these slabs are susceptible to brittle shear failure. While most previous research has focused on estimating the punching shear strength (PSS) of RC flat slabs, accurately identifying their failure modes is crucial for effective design and reinforcement. This paper presents an analysis of ensemble neural network and ensemble deep neural network models, including bagging neural network (BaggingNN), model averaging (MA), separate stacking (SS), and integrated stacking (IS) algorithms, to develop a predictive model for failure mode identification. The results of this new model are compared with those of earlier studies. To evaluate how variables such as concrete strength and reinforcement ratio impact the failure modes of RC flat slabs, the model's prediction process is examined using the SHapley Additive exPlanation (SHAP) method. Findings indicate that the SI algorithm outperformed the BaggingNN, MA, and SS algorithms, and also surpassed models from previous research.
Analysis of the impact of the COVID-19 pandemic lockdown on the spatiotemporal variations in water quality in three wetland areas in Oran, western Algeria
Authors: BENDIB Abdelhalim , BOUTRID Mohamed Lamine
Published: June 2024

In arid regions, water is a scarce and invaluable resource. Moreover, with urban expansions and socioeconomic changes, its quality has become a matter of significance and an indicator of environmental preservation. The objective of this study was to shed light on the impact of the COVID-19 pandemic on three wetlands in Oran, western Algeria (Lake of Dayet Oum Rhalez (DORh), Lake of Dhayat Morasli (DMo), and Lake of Sidi Chahmi (SCh)). Three parameters, namely, the chlorophyll-a concentration (Chl-a), trophic state index (TSI), and Secchi depth (SD), were selected and calculated for the period from 2019–2022. The results showed that, except for DORh, the Chl-a concentration decreased from 41.73 µg/l to 21.01 µg/l for DMo and from 42.82 µg/l to 23.08 µg/l for SCh between 2019 and 2021. The TSI decreased from 5.67 to 5.32 for DORh, from 5.95 to 5.36 for DMo, and from 5.32 to 4.12 for SCh. These results are also validated by the SD values, with an improvement in water transparency from 1.16 m to 2.61 m for DORh, from 1.31 m to 2.75 m for DMo, and from 1.4 m to 2.07 m for SCh. This reduction in biological activity justifies the impact of the applied lockdown on the improvement of water quality. Additionally, despite this improvement, the overall health of the three studied wetlands remains concerning (eutrophic ecological characteristics), and water quality is often mediocre. This study, in its entirety, can contribute to better decision-making and targeted actions for the preservation of these ecosystems.
Incorporating Mobility on Demand into Public Transit in Suburban Areas: A Comparative Evaluation of Cost-Effectiveness
Authors: Cai Mingming , Ashour Lamis Abu , Shen Qing , Chen Cynthia
Published: June 2024

Traditional fixed-route transit services are inefficient in low-density areas due to limited and dispersed service demand. Many transit agencies look for effective alternatives to provide adequate transportation services in these areas, especially by leveraging mobile ICT-enabled new mobility services. This study evaluates the cost-effectiveness of transit incorporating mobility-on-demand (TIMOD) compared to fixed-route bus transit, driving, and commercial ride-hailing services in suburban areas. It extends a comprehensive analytical framework to evaluate the cost-effectiveness of TIMOD and other alternatives from a societal perspective by considering transportation externalities. The analysis accounts for travelers’ monetary and time costs, service providers’ operating costs, and external costs to society. Using real-world data from a TIMOD program, Metro Flex, in the Seattle region and estimates based on simulation, the study compares the economic cost of TIMOD trips with counterfactuals by other travel modes within two separate suburban case areas. The results indicate that, in our study areas, TIMOD trips have a total generalized cost for travelers that is higher than driving but lower than fixed-route transit trips and ride-hailing trips, owing to its on-demand nature coupled with subsidized fare. Compared to TNCs, TIMOD’s more common shared rides contribute to its lower external costs by reducing vehicle miles traveled per person. Adding service operation, TIMOD in the suburban areas becomes less cost-effective due to high operating costs. However, the disparity is slight in comparison to fixed-route transit. Our findings also show that areas with higher population densities result in lower operation costs per rider of TIMOD. Riders living in higher income areas with lower population densities and more limited transit services benefit more from TIMOD services with a higher reduction in travelers’ generalized cost compared to fixed-route transit. The study highlights the potential benefits and tradeoffs of providing TIMOD services in suburban areas, shedding light on the conditions under which such services are economically competitive.
Real-Time IoT Solutions for Automating Occupational Safety in 3rd World Industries
Authors: Gharami Kanchon , Islam Mazharul , Barai Anirban , Rahman Md. Asifur , Shovan S.M. , Sri Md. Azmain Yakin
Published: June 2024

Occupational safety and health is an essential part of the work setting and so with effective monitoring measures it has the potential to significantly enhance workers' quality of life, decrease the financial consequences of workplace incidents, and boost efficiency. However, ensuring occupational safety and health in 3rd world industries is a challenging task due to lack of regular monitoring, proper emergency response system, and awareness. Integration of Internet of Things (IoT) technology can offer new opportunities for monitoring and management of occupational safety and health risks. To this end, this paper presents an affordable IoT-based real-time occupational safety and health monitoring system that is suitable for garment industries. The proposed monitoring and emergency alert system has the capability to detect potential hazardous conditions by analyzing data gathered from five interlinked modules that continuously monitor the work environment through various sensors. To assess the effectiveness of the proposed IoT system, this study conducted individual module tests in appropriate settings and compared their performance with standard equipment readily available on the market.
Absorption, Metabolism, and Excretion of Oral [14C] Radiolabeled Donafenib: An Open-Label, Phase I, Single-Dose Study in Humans
Authors: Ma Sheng , Yi Ling , Bian Yicong , Lv Binhua , Zhang Cong , Zhang Hua , Miao Liyan
Published: June 2024

Donafenib, a deuterated derivative of Sorafenib, exhibited significant efficacy and improved safety for the treatment of hepatocellular carcinoma (HCC) in clinical trials. In this study, the absorption, metabolism, and excretion of donafenib were investigated in six healthy Chinese male volunteers after administration of a single oral dose of 300 mg of [14C]donafenib (120 µCi). Mean recovery of total radioactivity was 97.31% of the dose. A total of 6 metabolites were identified in plasma, urine and feces. The parent drug was the major radioactive component detected in the plasma and feces, accounting for 67.52% of total radioactivity and 83.17% of the dose, respectively. M2, the N-oxidation metabolite was a major metabolite in human plasma. Overall, donafenib was excreted mainly by feces through liver metabolism and less by kidney. The metabolic pathways of donafenib identified were similar to those of sorafenib, but metabolite profiles in plasma, urine and feces were quantitatively different, and especially the amide hydrolysis metabolite M6 in sorafenib was not detectable in donafenib. The difference of metabolic characteristics between donafenib and sorafenib, due to the deuterium isotope effect, may partially explain the better safety and efficacy of donafenib as the treatment of advanced HCC.
Variational Bayesian Inference for Modelswith Nuisance Parameters and an Intractable Likelihood
Authors: Tseng Yu-Hsiu , Tran Minh-Ngoc , Kohn Robert
Published: June 2024

A primary challenge in Bayesian analysis lies in computing the posterior distributionof model parameters, a task that becomes more challenging for models with a largenumber of parameters or when the likelihood is intractable; as seen in Bayesian Lassoand state-space models. Often, the focus of the analysis is on a subset of the parameters,with the remainder regarded as nuisance parameters, which are either not of inferen-tial interest or are introduced to simplify computational processes. This complexitynecessitates more refined computational methods. Variational Bayesian inference (VB) has emerged as a powerful solution, enhancing computational efficiency by recastinginference as an optimization problem within a family of tractable distributions. How-ever, common VB techniques sometimes fall short, especially for models with nuisanceparameters or intractable likelihoods. To overcome these limitations, we introduce a uni-fied VB framework, termed Hybrid Variational Bayes (HVB), designed to achieve moreprecise Bayesian inference in such scenarios. This framework innovatively leverages ahybrid variational structure between the parameters of interest and nuisance parame-ters. A significant contribution of this work is the development of two robust gradientapproaches that effectively reduce variance, enhancing reliability in gradient-based op-timization algorithms for approximating complex posterior distributions. Furthermore,we link our strategy to Fisher’s identity, providing deeper theoretical insights. We alsoestablish a method to treat the stochastic element of likelihood estimation as a nuisanceparameter in models with intractable likelihoods due to complexity or computationaldemands. Through theoretical exploration and a series of illustrative examples, ourapproach demonstrates notable improvements over traditional VB methods.
Association of MnSOD, CAT, and GPx1 gene polymorphism with risk of diabetic nephropathy in South Indian patients – A case control study
Authors: Begum Farhana , Lakshamanan Karpagavel
Published: June 2024

Purpose:
Diabetic nephropathy (DN) is a remarkable complication of type 2 diabetes mellitus (T2DM), mediated by oxidative stress playing a key role. The antioxidants gene polymorphism (MnSOD, CAT, GPx1) have been interconnected to T2DM and DN. The role of these genes in the pathogenesis of DN among T2DM individuals in the South Indian population is investigated in this study. It clarifies the importance of early manifestation and reliable genetic indicators modulating the mechanism of oxidative stress in DN.
Methods:
The voluntary participants were divided and grouped as Group 1: Control, Group 2: T2DM without DN, and Group 3: T2DM with DN (n = 100 in each group). The levels of blood glucose, HbA1c, renal profile, plasma SOD, CAT, GPx1, MDA, and TAS were assessed. MnSOD, CAT, and GPx1 were genotyped via Tetra-arms PCR.
Results:
All the genotypic models of GPx1 depicts a significant role in the progression of T2DM patients with nephropathy (Co-dominant [OR: 2.134; 95%CI (1.202–3.788), p < 0.01], dominant [OR: 2.015; 95%CI (1.117–3.634), p = 0.02], and recessive model [OR: 2.215; 95%CI (1.235–3.972), p = 0.008]) but is not associated with T2DM without DN individuals; while MnSOD and CAT genotypes are not associated with the development of the disease. This data suggest that genotypes of GPx1 are at higher risk of developing DN in T2DM individuals. Moreover, MnSOD and GPx1 genotypes show significant difference in the antioxidant parameters compared to CAT genotypes.
Conclusion:
In contradiction to earlier studies, our study have demonstrated that compared to MnSOD and CAT genotypes, GPx1 genotypes can be considered as a influential component for higher susceptibility and risk of DN in T2DM patients among South Indian population.
Large Language Model Understands Chinese Better with Mega Tokenization
Authors: Lu Xinyu , Wang Qizhen , Liu Xian
Published: June 2024

The rapid evolution of natural language processing has seen significant advancements in language models, particularly for languages with simpler orthographies. However, challenges persist in accurately processing and understanding languages with complex morphological structures, such as Chinese, due to the limitations of traditional tokenization methods. Introducing mega tokenization, which involves significantly larger tokens, represents a novel and transformative approach that enhances semantic preservation and contextual coherence in sophisticated character sequences. The study compares the performance of an adapted language model with mega tokenization against a standard model, demonstrating substantial improvements across tasks such as machine translation, text summarisation, and question answering. Through rigorous evaluation and statistical analysis, the adapted model shows superior performance metrics, indicating the effectiveness of mega tokenization in addressing the unique challenges posed by the Chinese language. The implications of this approach extend to various applications, underscoring its potential to revolutionise language processing in multilingual and high-stakes environments. Future research directions are proposed to further optimise and expand the applicability of mega tokenization across diverse linguistic contexts.
Curved Nanomagnets: An Experimental Archetype for Skyrmion Stabilization
Authors: Dugato Danian A. , Jalil Wesley , Cardias Ramon , Albuquerque Marcelo , Costa Marcio , Garcia Flavio
Published: June 2024

In the fields of nanomagnetism and spintronics, the controlled stabilization of mag- netic skyrmions is a topic of great interest for potential applications in data storage and innovative computing systems. This study delves into the intriguing phenomenon of skyrmions on a hexagonal array of curved nanomagnets. Through a combination of atomistic calculation, micromagnetic simulations, and experimental observations, we thoroughly explore the intricate interplay between magnetic parameters, curvature, and interfacial Dzyaloshinskii-Moriya interaction (iDMI) in the formation of these topolog- ically non-trivial magnetic structures. We have observed the spontaneous formation of isolated skyrmions (<150 nm) on a curved nanomagnet matrix of symmetric Pt/Co/Pt multilayer without the necessity of applied fields. Our research sheds light on the pro- found impact of geometric curvature on iDMI, offering invaluable insights for engi- neering and controlling skyrmionic configurations. This work advances nanomagnetism knowledge and sets the stage for designing skyrmion-based technologies.
Živimo, mičemo se i jesmo među tehnologijama
Authors: Salihu Astrit
Published: June 2024

Bez da bi iscrpili projekt postfenomenologije u filozofiji tehnologije, koja ima više empirijski karakter u mišljenju odnosa s tehnologijom, pokušat ćemo iznaći neke općenite pretpostavke za drugačije promišljanje odnosa čovjek – svijet, koje bi također mogle jasnije ocrtati novi hipertehnološki kontekst aktualnosti. To je kontekst u kojemu se može misliti postheideggerovski ili postfenomenologijski, odnosno u kojemu se misli svijet bez »darova bitka« kroz sistemski i praktični konstruktivizam, koji bi »svijet života« ili »bitak-u-svijetu« iz gole čistine ili zastrašujuće otvorenosti nadopunili tehnološkim i umjetnim. Ovo nadopunjavanje ne podrazumijeva misliti tehnološko i umjetno samo kao nešto puko dopunsko u konstelaciji čovjek – svijet, naprotiv, tek se mišljenjem tehnološkog i umjetnog može uistinu misliti ujedno čovjek i svijet. Ako bi se postfenomenologija mogla identificirati kao »kritički dijalog« s fenomenološkom tradicijom, onda su mišljenja Dona Ihdea i Petera Sloterdijka najviše utjecala na to da iz takvog dijaloga iznikne drugačije poimanje odnosa čovjeka i svijeta, te tako izokrenuli predodžbe o nekoj autoreferencijalnosti čovjeka – svijeta unutar klasične fenomenologije.
YÜRÜTMENİN DURDURULMASI KARARI VERİLMESİNİN ŞARTLARININ DEĞERLENDİRİLMESİ VE KARARIN UYGULANMASINA İLİŞKİN REFORM ÖNERİLERİ
Authors: Baydemir Elif
Published: June 2024

Yürütmenin durdurulması müessesesi, idarenin işlemlerinin yargısal denetiminin önemli bir aşamasıdır. Türk hukukunda İşlemin muhatabının, idarenin işlemine karşı hukuka aykırılık iddiasıyla yargı denetimine başvurması kural olarak işlemin icrailiğini kendiliğinden durdurmamaktadır. Yürütmenin durdurulması tam da bu noktada karşımıza çıkan bir tür fren mekanizmasıdır. Hukuk devleti ilkesinin bir gereği olarak idarenin işlemlerindeki olası hukuka aykırılıklara yargılama sonuçlanıncaya dek geçici süre ile de olsa müdahale edilebilmesi bireyin idare karşısındaki güçsüz konumuna önemli bir güvence sistemi getirmektedir. Mevzuatta normatif düzeyde temellendirilen yürütmenin durdurulması kararının şartları hem düzenlenişi itibariyle hem de zaman içerisinde getirilen değişiklikler nedeniyle tartışmaya açıktır. Bu suretle akademik çalışmalar bakımından önem arz eden yürütmenin durdurulması kararı verilmesinin şartları ve kararın uygulanması bu çalışmanın odak noktasıdır. Çalışmada, öncelikle yürütmenin durdurulması kararının hukuki niteliği, işlevi ve dava konusu işleme etkisi açıklanacak, ardından yürütmenin durdurulması kararı verilmesi şartlarının tartışmalı noktaları değerlendirilecek, son olarak yürütmenin durdurulması kararının işlevselliğinin artırılmasına yönelik reform önerilerinin uygulanabilirliği, adli yargıda uygulanan ihtiyati tedbir kararı bağlamında tartışılacaktır.
A case of asthmatic granulomatosis
Authors: Avdeev S. N. , Gaynitdinova V. V. , Merzhoeva Z. M. , Nuralieva G. S. , Nikitina L. Yu. , Berikkhanov Z. G.-M.
Published: June 2024

Severe asthma (SA) is a pressing problem in respiratory diseases and accounts for 3–10% of all asthma cases. It is increasingly recognized that SA consists of multiple heterogeneous phenotypes and their histopathology, especially in the distal airways and interstitium, remains poorly understood. Transbronchial biopsy with video imaging and histologic examination allow the detection of various changes, including cases associated with granulomatous inflammation in addition to eosinophilic infiltrates. In the presented clinical case of a patient with severe eosinophilic bronchial asthma in the absence of autoimmune diseases, transbronchial biopsy with further histologic examination of the biopsy specimen revealed eosinophilic granuloma in the form of polyp-like masses in the lung tissue and walls of small bronchi. The cellular composition of the granuloma was represented by macrophage elements, a cluster of lymphocytes with an admixture of eosinophils, individual plasma cells, fibroblasts and capillary vessels with clusters of eosinophils. The treatment (baseline and anti-IL5 therapy), in addition to achieving complete control of asthma symptoms, reduction of nasal congestion, reduction of blood eosinophils, FENO, led to the disappearance of polyposis eosinophilic formation in the bronchial mucosa. Such pathology is described in the literature as “asthmatic granulomatosis” and is of interest for further studies.
Chronic adenoiditis and its effect on the reactivity of the bronchopulmonary system, the possibility of non-drug correction
Authors: Korkmazov A. M. , Solodovnik A. V. , Kornova N. V. , Krasheninnikova L. S.
Published: June 2024

Introduction. In pediatric otorhinolaryngological practice, chronic adenoiditis is one of the most common diseases and causes the search for additional and effective methods of treatment.

Aim. To evaluate the clinical effectiveness of the use of aqueous solutions treated with low-frequency ultrasound with high specific energy and monochromatic light radiation in the complex therapy of chronic adenoiditis in children.

Materials and methods. The number of participants in the study was 104 patients aged 4 to 15 years with a verified diagnosis of chronic adenoiditis and were divided into 3 groups depending on the treatment. A comparative analysis of the results obtained was carried out before the start of therapy (day 0) and on the 7th day after the treatment. The state of the nasopharynx was assessed using a flexible nasopharyngoscope, as well as the structure of the middle ear and auditory tube during acoustic impedancemetry.

Results. The use of a course of treatment of low-frequency ultrasonic cavitation in combination with photochromotherapy made it possible to relieve the signs of chronic adenoiditis in 62% of cases (p < 0.001), reduce the number of patients with grade III adenoid hypertrophy by 54% (p = 0.035), and reduce by 2 times (p = 0.05) number of relapses of chronic adenoiditis. In the group of children using low-frequency ultrasonic cavitation, the positive effect of treatment was 3.3 times [CI 0.75; 14.6] higher compared to the control group, and in combination with photochromotherapy it was 3.6 times [CI 0.85; 15.5]. The absence of adenotomy was assessed as a positive effect.

Conclusion. The data obtained showed that the inclusion of non-drug methods of physical influence (low-frequency ultrasonic cavitation both in monotherapy and in combination with photochromotherapy) in complex treatment can reduce the number of surgical interventions on the organs of the lymphopharyngeal ring – the pharyngeal tonsil.
Potential role of short-chain fatty acids in irritable bowel syndrome in overweight and obese individuals
Authors: Fedorin M. M. , Livzan M. A. , Gaus O. V. , Pashkova E. V.
Published: June 2024

Due to increasing prevalence of functional diseases of the colon in obese patients, the mechanisms by which the intestinal microbiota affects the development of symptoms of irritable bowel syndrome (IBS) in the setting of metabolic activity of adipose tissue should be investigated. The quantitative and qualitative changes in the pool of synthesized short-chain fatty acids, which have a multidirectional impact on the colonic motility is one of the key mechanisms by which the intestinal microbiota affects the occurrence and features of the course of irritable bowel syndrome. But as regards the issue of whether individual short-chain fatty acids have an impact on the severity of abdominal pain and characteristics of colonic motility dysfunction, it remains a subject of discussions. The study of the mechanisms of impact of short-chain fatty acids on the development and progression of obesity deserves special attention. Increased serum and faecal short-chain fatty acid levels in obese patients can either be a result of changes in the intestinal microflora composition associated with special eating habits and lifestyle, or have an independent effect on the development of obesity in individuals due to intestinal microflora composition disorders that have been already developed. Due to special features of the course of irritable bowel syndrome associated with overweight and obesity, studying the intestinal microbiota composition and the short-chain fatty acids produced by it in this cohort of IBS patients is of particular interest. This publication has been prepared to describe and systematize the possible mechanisms of impact of short-chain fatty acids on the development of abdominal pain and impaired colonic motility in IBS patients with overweight and obesity. The literature search was conducted in the databases Embase, PubMed and Google Scholar using the keywords “irritable bowel syndrome”, “obesity”, “short-chain fatty acids”, “gut microbiota”.
Chronic constipation: current options of pathogenetic therapy
Authors: Ardatskaya M. D. , Butorova L. I. , Anuchkin A. A. , Gaivoronsky I. N. , Pavlov A. I. , Patsenko O. Yu.
Published: June 2024

Symptoms of constipation such as derangements of the motor, secretory and/or evacuation functions of the colon are recorded occasionally or for a long period in at least 20% of the population in economically developed countries. QoL is significantly impaired in patients with chronic constipation. The frequency, time of bowel movement and stool consistency is, in large part, determined by the motor function of the colon. The primary approach to the treatment algorithm for chronic constipation (CC) is modification of a lifestyle and a diet rich in dietary fiber. If dietary measures provide poor efficacy, laxatives are prescribed to the patients. According to the current guidelines, therapeutic approaches to the treatment of CC should include the sequential administration of laxatives that increase the volume of contents and stimulate the motor function of the colon. According to the Russian Gastroenterological Association guidelines for the diagnosis and treatment of chronic diseases in adult patients, it is reasonable to use stimulant laxatives as second-line drugs. Contact laxatives, which increase intestinal peristalsis due to stimulation of nerve endings in the intestinal mucosa, have been shown to be more effective in treating chronic constipation than placebo. Among the drugs in this group, Bisacodyl®, a diphenylmethane derivative, and Regulax® Picosulfate, a sodium picosulfate derivative, are the most studied ones. These substances are hydrolyzed into bis-(p-hydroxyphenyl)-pyridyl-2-methane in the intestine, which, on contact with the receptors in colonic mucosa, stimulates propulsive activity and increases intestinal secretions. Regulax® Picosulfate is effective and safe in patients with acute and chronic constipation of various origin.
The effectiveness of long-term respiratory support in a patient after pneumonectomy
Authors: Mukatova I. Yu. , Serikova A. S. , Nuralieva G. S. , Avdeev S. N.
Published: June 2024

Respiratory support for chronic respiratory failure in the last stages is widely used, most often in patients with end-stage COPD. It has been proven that the development of chronic hypercapnic respiratory failure is associated with an increasing in exacerbations, increased hospitalization rates, and an acceleration of the time before subsequent decompensation. Also hypercapnia is

a determining factor in mortality. Effective treatment method of hypercapnic insufficiency is non-invasive ventilation. Long-term non-invasive ventilation improves daytime hypercapnia, quality of life, increases the period until the next severe exacerbation and survival of patients with COPD. Patients with COPD have different phenotypes and various comorbid diseases, which which may be challenging while choosing method of respiratory support and assessing the effectiveness of this treatment method. There is lack of data on long-term non-invasive respiratory support for patients with COPD after pneumonectomy in chronic period. Most of publications dedicated for early post-operative period after pneumonectomy. The purpose of this publication is to present a case of successful long-term non-invasive ventilation combined with oxygen therapy in a patient with COPD and bronchiectasis of a single lung. Stages of management of hypoxemic and subsequently developed hypercapnic chronic respiratory failure are reflected. We demonstrate experience of successful long-term ambulatory non-invasive ventilation in a patient with chronic hypercapnic respiratory failure as a result of COPD and pneumonectomy was demonstrated. Observation study showed feasibility of combined respiratory support in outpatient settings for patient with COPD of a single lung and a history of pneumonectomy.
Helicobacter pylori infection and dermatological diseases
Authors: Dudukchyan D. A. , Sarkisyan D. K. , Andreev D. N.
Published: June 2024

Helicobacter pylori (H. Pylori), microaerophilic spiral-shaped Gram-negative bacteria which colonize the gastric mucosa of human population, is the leading causal factor in the development of a whole range of diseases of the gastroduodenal region (chronic gastritis, gastric and duodenal ulcer disease, MALT lymphoma and gastric adenocarcinoma). Since the discovery of H. pylori infection and the identification of its leading role in the development of a range of gastroenterological diseases, researchers have begun to actively study the potential trigger significance of this pathogen in the development of extragastric pathology. At the epidemiological level, H. pylori infection has been shown to be frequently associated with skin diseases such as rosacea, acne, chronic urticaria and psoriasis, although the clinical significance of these associations remains clouded. In fact, recent meta-analytic studies (2019–2024) demonstrate an increased risk of developing the above diseases in H. pylori-infected individuals with odds ratios ranging from 1.19 to 3.00. On the other hand, not all studies have showed that eradication therapy of this microorganism helps reduce the clinical severity of symptoms of skin diseases, which is hypothetically explained only by the trigger role of infection within the complex pathogenesis. In a modern light, such associations can be viewed in terms of pathogenetic findings through the implementation of the syndrome of increased epithelial permeability (SIEP). The chronic gastritis caused by H. pylori infection is believed to lead to increased permeability of the epithelial lining of the stomach, as well as the walls of the mucosal vessels and a higher exposure of bacterial and nutritional antigens in the systemic circulation, which can induce both local release of inflammatory mediators in tissues and systemic immunological reactions (autoimmune and inflammatory processes, formation of molecular mimicry-induced immune complexes and cross-reactive antibodies).
Pollutant removal efficiency of bare and planted rain gardens with diverse planting mixtures
Authors: Kumar Sandeep , Singh Krishna Kumar
Published: June 2024

This study examines the influence of planting mixture variations on the quality of the percolated water of the rain garden with and without plants. Six planting mixtures in experimental rain gardens have been used. It has been noted that pollutant removal efficiency of RG can exhibit variations based on specific parameters. Notably, RG6, utilizing a planting mix of 75% topsoil and 25% compost, demonstrated the highest performance. These results draw attention to the critical role of the specific planting mixtures in influencing the performance of vital parameters related to pollutant removal. The observation shows that RG5 exhibits exceptional removal efficiency in pH, Total Suspended Solids (TSS), Biological Oxygen Demand (BOD), and Chemical Oxygen Demand (COD), and RG6 performs best in electrical conductivity (EC), Total Dissolved Solids (TDS), Total Nitrogen (TN), and Total Phosphorus (TP) removal. In particular, when analyzing pollutant removal on a surface with Madagascar periwinkle plants, RG6 emerges as the most effective, achieving an impressive efficiency of approximately 49%. For the bare surface, pollutant removal efficiency is 40%. The study outcome will be useful in deciding the composition of the planting mixture, which will keep the rain garden to improve quality and quantitatively hydrological performance, lowering urban flooding magnitude.