bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Barriers and Facilitators for the Potential Implementation of the Decision Tool-Functional Independence in Primary Care
Authors: Molenaar E. A.L.M. , Barten J. A. , Bleijenberg N. , Wit de N. J. , Veenhof C.
Published: November 2024

Background
The aging population presents challenges for healthcare, particularly in maintaining the functional independence of older adults. The Decision Support Tool for Functional Independence was developed to identify declines in functional independence and promote collaboration between healthcare professionals. This study examines the barriers and facilitators to implementing the tool in primary care.
Methods
Thirteen healthcare professionals and two focus groups with older adults participated in this study, which was guided by the Consolidated Framework for Implementation Research. Thematic analysis, both deductive and inductive, was used to identify and analyze the barriers and facilitators to implementation.
Results
Key facilitators included the tool’s potential to enhance collaboration, support informed decision-making, and address societal pressures related to aging. However, four main barriers emerged: limited applicability in certain contexts, time constraints, issues of ownership among stakeholders, and challenges in preventive outreach.
Conclusions
The diversity and complexity of factors influencing the implementation of the Decision Support Tool for Functional Independence highlight the need for multifaceted, tailored strategies. Future research should focus on developing customized approaches to overcome identified barriers, exploring adaptations for a broader audience, and determining the appropriate healthcare professionals for the tool’s practical application. The potential of the tool to foster professional collaboration and alleviate societal challenges emphasizes its relevance in primary care.
Brazil’s experiment to expand its medical workforce through private and public schools. Impacts and consequences of the balance of regulatory and market forces in resource- scarce settings
Authors: Scheffer Mário , Mosquera Paola , Cassenote Alex , McPake Barbara , Russo Giuliano
Published: November 2024

Background. There is a global shortage of doctors, and governments worldwide are concerned with expanding national medical workforces to improve services. Since 2013 the Government of Brazil has introduced legislation to liberalise the medical education market and implement quotas to improve its supply of physicians – the Mais Médicos (More Doctors) Legislation (MML). Such experience provides an insight for the global debate on the role of the private sector in medical education.
Methods. We draw from the analysis of unique medical demography datasets to assess the impact of those policies on number and distribution of doctors and medical students, composition of the workforce, and quality of training. To analyze the increasing trend of students and physicians, interrupted time-series analysis was conducted using segmented linear regression, comparing two time periods considering the MML as the start of the intervention.
Findings. Within the context of Brazil’s population and economic growth over the last decades, we find that since 2003 Brazil has almost doubled its medical workforce to 2.77 per 1,000 population, with the largest increase recorded after the 2013 legislation. Our analysis shows such growth has benefited poorer, remote states, although the bulk of new doctors and students are still located in the country’s richer regions. The diversity of medical students increased significantly since the More Doctors Legislation, with more female (61.4% in 2023 as opposed to 55.5% in 2013), and mixed-race enrolments (25.5% and 19.4%). However, medical students are still predominantly white (68.7% and 71.6%), and from fee-paying secondary schools (68.1% and 75.8%).
Conclusions. We conclude that Brazil’s policy approach has delivered a substantial overhaul of its medical workforce through a combination of public and private sector policies and discuss the implications for similar countries. Private schools can be critical for expansion; but the data from Brazil suggest the private sector does little to address inequalities and cast doubt on the quality of the training offered.
Hip Abduction Angle and the Risk of Avascular Necrosis (AVN) After Closed Reduction (CR) in Developmental Dysplasia of the Hip (DDH)
Authors: Yasin Mohamad Samih , Abukhalaf Bashar , Khateeb Dana Q. , Badayneh Reham , Mufleh Nadine , Twal Basil , AlSamhori Jehad Feras , Aldowekat Osama , Samarah Omar Q. , AbuHassan Freih O.
Published: November 2024

Objectives
Developmental dysplasia of the hip (DDH) is a prevalent pediatric orthopedic condition with a prevalence of 5–13 per 1000 live births worldwide. Early detection and management are paramount to mitigate long-term complications such as osteoarthritis and avascular necrosis of the hip (AVN). While various interventions exist, closed reduction (CR) and spica casting play pivotal roles in restoring normal hip anatomy. Given that AVN is a significant concern after CR, we aimed to investigate the correlation between the hip abduction angle in the spica and the risk of AVN.
Methods
This retrospective cohort study was conducted at Jordan University Hospital from 2016–2022. A total of 74 patients, aged up to 20 months, underwent CR, which was followed by CT scans with a minimum 12-month follow-up. CT scans were used for calculating the hip abduction angle, and X-rays were used for determining the Salter classification of AVN.
Results
The mean age at the time of CR was 7.29 ± 2.71 months. Fifty-one percent of the patients had bilateral DDH, and 7.6% had a positive personal or family history of DDH. The mean right and left abduction angles were 60.37° ± 8.03° and 59.53° ± 7.12°, respectively. The mean right and left International Hip Dysplasia Institute (IHDI) scores were 3.13 ± 0.7 and 3.38 ± 0.67, respectively. The mean right and left Salter AVN indices were 0.48 ± 1.13 and 0.55 ± 1.29, respectively. There were statistically significant relationships between right and left Salter (r = 0.793, p < 0.001), between right and left abduction angles (r = 0.335, p = 0.043), between right and left IHDI grades (r = 0.336, p = 0.039), between left IHDI grades and left Salter (r = 0.261, p = 0.047), and between left Salter and age (r = 0.264, p = 0.047). Neither the right nor the left abduction angle was associated with increased right or left Salter AVN grade, as indicated by the p values.
Conclusions
If a patient develops AVN on one side, the other side is also likely to be affected; however, the degree of abduction in CR does not correlate with the AVN rate. There was a correlation between the degree of abduction and the degree of subluxation/dislocation. Additionally, age at reduction is correlated with the risk of AVN.
Computational Approaches to Identification and Characterization of Masitinib as Potential Treatment for Alzheimer's Disease through Molecular Docking and Two-sample Mendelian Randomization
Authors: Li Xindi , Liu Tingwei , Cammann Davis , Cummings Jeffrey L. , Xu Lingyun , Chen Jingchun
Published: November 2024

Background
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by declines in cognitive and functional abilities. Masitinib has demonstrated potential in AD clinical trials, but its precise mechanism of action in the context of AD remains unclear. Advancing computational techniques is one approach to identifying novel and repurposable agents that may be treatment candidates for AD.
Methods
In this study, we first collected disease-target genes for AD and drug-target genes for masitinib from extensive studies and databases. We identified overlapping genes as candidates and performed molecular docking to determine their binding affinity with masitinib. Following this, two-sample Mendelian randomization (MR) was used to evaluate the causal relationship between the brain expression of candidate genes, and AD or cognitive function (CF) in European ancestry (EUR). Genetic colocalization was then used to test for the presence of shared causal variants.
Results
Two candidate genes, epidermal growth factor receptor (EGFR) and tyrosine-protein kinase FYN (FYN), were identified as potential drug targets, showing strong binding affinities with masitinib (EGFR: -12.4 kcal/mol; FYN: -7.8 kcal/mol). MR analysis found that higher EGFR expression in the cortex had a significant causal effect on AD liability [P = 1.56 × 10−8, odds ratio (OR) = 1.09] and cognitive function [P = 1.34 × 10−3, OR = 0.98]. We replicated this observation in an independent Finnish population AD cohort [P = 0.018, OR = 1.05]. Sensitivity analyses did not show evidence of heterogeneity or horizontal pleiotropy. Colocalization analysis identified a known AD-risk variant in the EGFR gene, rs74504435, as the shared causal variant.
Conclusion
Our findings demonstrate that the therapeutic effects of masitinib on AD are closely associated with its inhibition of EGFR expression in the brain.
Predictors of physical fitness in rural and urban elderly in West Sumatra during the pandemic mobility restriction period
Authors: Syandra Dwita Ghina , Ilmiawati Cimi , Afriwardi Afriwardi
Published: November 2024

Objective
During the COVID-19 pandemic, the Indonesian government implemented large-scale mobility restrictions, which may have affected sunlight exposure and physical fitness levels in the elderly. Given that macro- and micronutrients are well-established determinants of physical fitness, this study aimed to investigate the predictors of physical fitness among elderly individuals residing in both rural and urban areas.
Methods
This study employed a cross-sectional design, recruiting elderly participants from both rural (n = 35) and urban (n = 35) areas in West Sumatra, Indonesia. Nutritional intake was estimated using a Food Frequency Questionnaire, while serum 25(OH)D levels were measured via enzyme-linked immunosorbent assay. Physical activity was assessed using the Global Physical Activity Questionnaire, and physical fitness was evaluated through the six-minute walk test. Logistic regression analysis was conducted to identify predictors of physical fitness.
Results
The physical fitness level of elderly living in the rural area was mostly good (21/35), while in the urban area was mostly poor (24/35). Predictors of physical fitness for the rural elderly were protein intake (OR = 1.25; CI = 1.02–1.53; p = 0.035) and serum 25(OH)D level (OR = 1.12; CI = 1.00-1.26; p = 0.048), while the predictors in urban elderly were fat (OR = 1.31; CI = 1.01–1.69; p = 0.044) and vitamin C (OR = 1.09; CI = 1.01–1.17; p = 0.028) intake.
Conclusion
During the COVID-19 pandemic, the physical fitness levels in elderly living in rural and urban areas are different and predicted by serum 25(OH)D levels and distinct nutritional factors.
Analyzing the Upper Mass Boundary of Main Sequence Stars
Authors: Gonfa Diriba
Published: November 2024

This study analyzes the upper mass boundary of stars on the main sequence, examining the various factors that influence their formation and evolution. The maximum mass of a star is not a fixed value; it fluctuates based on conditions such as stellar winds, metallicity, and the characteristics of the molecular cloud from which the star originates. For decades, the astrophysical community has debated the existence of a maximum mass limit, with estimates typically ranging from 120 to 300 solar masses, contingent upon environmental factors and initial conditions. The formation of massive stars initiates with the gravitational collapse of gas clumps in giant molecular clouds, leading to protostar formation. This phase is characterized by non-homologous collapse, significantly influenced by magnetic fields and accretion dynamics. As material accretes onto the protostar, radiation-driven winds sculpt the surrounding environment, culminating in supernova events. This research reviews several formation mechanisms, including monolithic collapse, competitive accretion, and stellar mergers, each dependent on the initial properties of the interstellar medium (ISM). By analyzing recent simulations and observational data, this work aims to enhance our understanding of the parameters governing massive star formation and their implications for the initial mass function (IMF). Ultimately, this study highlights the complexities of high-mass stars and their vital role in the evolution of the universe.
Dating of mortars from Kastelli hill, Chania based on their physicochemical analyses
Authors: MARAVELAKİ PAGONA-NONİ , Andreadaki-Vlazaki Maria
Published: November 2024

The study of mortars plays a crucial role in determining the chronology of construction phases. According to the database of mortars analysed from historical monuments in Crete and other areas of Greece, significant differences in mortar composition are observed across historical periods. In the present study, 14 mortars from Kastelli Hill and Katre Street in Chania, originating from the fortified wall and neighboring buildings, are analysed. The physico-chemical and mineralogical analysis aims at clarifying the nature of mortars, their manufacturing technology, and, in particular, to compare different construction phases. In addition, comparing historically identified mortars with those under study reveals similarities and differences across construction phases. The indicators considered include the trace elements of aggregates and binder, the characteristics of aggregate grain size, the type of binder (hydraulic or aerial), and the presence of pozzolanic additives. The comparisons indicated that the mortars from the wall were manufactured during the early Roman period, since they are successfully compared with the mortars of buildings identified at that time.
First identification of Sarcocystis arctica in captive cheetahs (Acinonyx jubatus) in China with annotations on closely related species in carnivore intermediate hosts
Authors: Liao Zhe , Zhu Niuping , Yang Yurong , Jäkel Thomas , Hu Junjie
Published: November 2024

Background Sarcocystis
spp. are cyst-forming, intracellular protozoan parasites that are transmitted between hosts linked through a predator-prey relationship. There was only one previous report describing cysts of Sarcocystis in the musculature of cheetahs (Acinonyx jubatus), and the species was designated to be S. felis because of morphological similarity to this species. However, no nucleotide sequences of genetic markers for the parasite in cheetahs are presently provided to serve as references.
Methods
Light microscopy (LM) and transmission electron microscopy (TEM) were used to morphologically characterize the sarcocysts isolated from muscular tissues of cheetahs died in zoos in Zhengzhou city, China. Meanwhile, four marker genes (nuclear 18S rRNA, 28S rRNA, ITS-1, and mitochondrial cox1) of the sarcocysts were amplified, sequenced and analyzed.
Results
Only one type of sarcocyst was observed in two out of six cheetahs. Under LM, the sarcocyst wall was striated and 1.4–2.3 µm thick. Ultrastructurally, the wall had irregular-shaped, small villous protrusions resembling wall type 9c, similar to those of S. arctica, S. caninum and S. felis. Molecularly, the samples shared their highest identity values with those of S. arctica and S. caninum: 99.9–100% and 99.8–100% (18S rRNA), 99.5% and 99.3–99.5% (28S rRNA), 95.9–97.5% and 96.3–97.3% (ITS-1), and 99.6% and 99.2–99.7% (cox1), respectively. Compared to ITS-1 of S. felis, identities ranged between 87.5% and 88.9%. Phylogenetic reconstruction revealed the newly-sequenced Sarcocystis clustered with S. arctica and S. caninum, whereby S. felis (ITS-1) and S. canis (ITS-1, 18s rRNA, cox1) were sister species.
Conclusions
We regard the Sarcocystis samples to represent S. arctica, which is the first record of a Sarcocystis species believed specific for canids as intermediate hosts to infect a feline host. The occurrence of S. arctica in a feline carnivore suggests a broader intermediate host range for this Sarcocystis species for which predatory birds are likely definitive hosts. Furthermore, our study supports the notion that S. caninum is conspecific with S. arctica.
Oriented Object Detection in Optical Remote Sensing Images using Deep Learning: A Survey
Authors: Wang Kun , Wang Zi , Li Zhang , Su Ang , Teng Xichao , Pan Erting , Liu Minhao , Yu Qifeng
Published: November 2024

Oriented object detection is one of the most fundamental and challenging tasks in remote sensing, aiming to locate and classify objects with arbitrary orientations.Recent advancements in deep learning have significantly enhanced the capabilities of oriented object detection.Given the rapid development of this field, this paper presents a comprehensive survey of recent advances in oriented object detection.To be specific, we begin by tracing the technical evolution from horizontal object detection to oriented object detection and higlighting the specific challenges, including feature misalignment, spatial misalignment, and oriented bounding box (OBB) regression problems.Subsequently, we further categorize existing methods into detection framework, OBB regression, and feature representations, and providing an in-depth discussion on how these approaches address the above challenges.In addition, we cover several publicly available datasets and performance evaluation protocols.Furthermore, we provide a comprehensive comparison and analysis of state-of-the-art methods.Toward the end of this paper, we identify several future directions for oriented object detection.
How Long-term Care Insurance Coverage of Dementia would Impact Healthcare Utilization and Expenditure of People with Disability and Dementia: A Triple Difference Analysis.
Authors: He Qianyu , Zhou Yujing , Ye Bei , Chan Wing Kit , Liao Jing
Published: November 2024

Background
Despite dementia is becoming a major public health issue in China, only few long-term care pilot cities have incorporated dementia into the coverage of its insurance. This study examined the impact of long-term care insurance (LTCI) coverage for dementia on beneficiaries’ healthcare utilization and expenditure.
Methods
Utilizing data from 12 first-round LTCI pilot cities surveyed in the China Health and Retirement Longitudinal Study (2011–2018), we employed a quasi-experimental triple difference model to assess the impact of the LTCI policy that covered people with dementia (PwDs) on healthcare utilization and expenditure. We compared differences between PwDs in LTCI pilot cities with dementia coverage vs. those without, eligible vs. ineligible for LTCI, and before vs. after LTCI implementation. Robustness test and validity test were used to validate the results.
Results
Statistically significant increase in healthcare utilization, in terms of inpatient but not outpatient services, among PwDs in cities eligible for LTCI coverage was detected, which was 1.5 times higher (P < 0.001) than their counterparts in cities without. On the other hand, non-significant change in healthcare expenditure measured by out-of-pocket expenses was found. Consistent results showed in the robustness test, and the validity of triple-difference method was confirmed.
Conclusions
Our study showed that expanding LTCI coverage for PwDs may stimulate their essential inpatient services utilization, while control the associated expenses paid by them. These findings suggest LTCI policy should strengthen its coverage and insurance benefit standards to better meet the healthcare needs of PwDs.
User Voice Mining and Prediction: Topic Evolution and Prediction on E-commerce Using Hybrid BERTopic-LDA-RF Model
Authors: Wei Mengdi
Published: November 2024

This study addresses significant gaps in the analysis of user-generated content on e-commerce platforms, particularly regarding the limitations of traditional topic modeling methods like Latent Dirichlet Allocation (LDA). Existing methodologies often overlook the complexities of consumer sentiment and fail to capture the dynamic evolution of topics over time. To address these challenges, we propose the BERTopic-LDA-RF hybrid model, which combines the contextual strengths of BERTopic with LDA's topic refinement capabilities and integrates predictive analytics through Random Forests. Our findings demonstrate that this hybrid model significantly enhances topic coherence and the ability to track topic evolution, providing a nuanced understanding of shifting consumer preferences. Furthermore, the model's predictive capabilities empower businesses to anticipate future trends based on historical data, transforming it into a strategic asset for decision-making. This study contributes to both theoretical frameworks in NLP and practical applications in e-commerce, facilitating more informed and agile business strategies.
Single-Cell Transcriptome Atlas of the Canine Peri-implantitis Reveals stromal–immune cells interaction
Authors: Wang Ming , Liao Chunhui , Wu Daner , Geng Ningbo , Xia Yixin , Chen Yu , Peng Wei , Chen Songling
Published: November 2024

Background
Most current research has focused on the entire periodontal tissue, which restricts a comprehensive understanding of the heterogeneity between gingiva and bone tissues, and hinders the development of targeted host therapies for peri-implantitis. To uncover the pathogenic mechanisms of peri-implantitis, our study employed a tissue-specific approach to investigate the interactions between stromal and immune cells in gingiva and bone tissues separately, using single-cell sequencing techniques. This strategy aims to develop the insights of the pathogenesis of peri-implantitis, providing a scientific basis for the treatment of peri-implantitis.
Methods
Single-cell RNA sequencing transcriptomics profiling was conducted on samples from peri-implantitis-affected and healthy beagle dogs. Flow cytometry was utilized to further verify the identified subclusters and their involvement in peri-implantitis.
Results
In peri-implantitis, inflammation-associated cells increased, exhibiting distinct subclusters in gingival and bone tissues. In gingival tissues, IL6+ endothelial cells, IL18BP+ endothelial cells, and CXCL8+ fibroblasts played significant roles. APOD+ fibroblasts were predominantly found in bone tissues, while SFN+ fibroblasts were present in both tissues. Additionally, a unique ligand-receptor pair, C3 (APOD+ fibroblast) – C3AR1 (Monocyte/ Macrophage), was identified in bone tissue.
Conclusions
Stromal cells exert distinct regulatory influences on immune cells in gingival and bone tissues during peri-implantitis, offering new perspectives for studying the pathogenic mechanisms of the disease.
Lightweight 3D Human Pose Estimation and Visualization System Using Encoding-Decoding BlazePose+SYS
Authors: Liu Hui , Li HuLing , Aboduaini Yiliyasi , Tang Dandan , Wang Jiaqi , Sen Gan
Published: November 2024

Human pose estimation (HPE) is a fundamental problem in computer vision, aiming to obtain the spatial coordinates of human joints from images or videos. Despite significant progress, traditional methods often struggle with real-time performance due to their computational complexity. In this paper, we propose a lightweight 3D human pose estimation and visualization system based on the BlazePose+SYS model, which employs an encoding-decoding architecture. Our system can detect human key points and reconstruct 3D human poses in real-time, providing high-precision and real-time solutions for various applications such as action recognition, virtual reality, and sports training. By discarding the heatmap branch during inference, our model achieves lightweight performance suitable for mobile devices and edge computing environments. Experimental results on public datasets demonstrate the effectiveness and accuracy of our system in real-time human pose estimation tasks. This work contributes to advancing the field of HPE by providing a practical and efficient solution.
Numerical Modelling for Piles in Gypseous Collapsible Soils Subjected to Axial Load
Authors: Mohsen A. H. , Albusoda B. S. , Baker J. , Mashhour I. , I.M Hanna
Published: November 2024

Piles installed in collapsible soils experience negative skin friction that develops along the pile’s shaft, which reduces the pile capacity and increases its settlement. The negative skin friction is developed due to inundation of the ground and indirect loading (surcharge). A 3-D numerical model was developed using the finite element technique and the commercial software “PLAXIS 3D” to simulate the case of piles embedded in gypseous collapsible soil, overlying dense sand deposits. The objective of this investigation is to examine the developed negative skin friction for a given pile under the effecting of the loading, and soil condition after conducting pile load test. And accordingly, to determine the location of the neutral plane. In this investigation, the pile’s tip was located at the interface of the dense sand deposit, or at 5D higher or lower the interface. Piles were subjected to surcharge load of 50, 100, or 400 kPa and the axial load of 50–100% of the allowable axial load on the pile. The results were presented in the form of the changing (reduction) in the value of negative skin friction as well as the variation in the neutral plane location The maximum drag load reduction was recorded along the pile embedded in the dense sand layer with a depth equal to five times the pile diameter and subjected to a surcharge of 400 kPa under an axial load of 100% of the allowable load.
Linking larval experiences of the crown-of-thorns sea star to early benthic success: carryover effects of freshening on metamorphosis and the early juvenile.
Authors: Clements Matthew , Byrne Maria
Published: November 2024

The environmental experiences of marine invertebrate larvae can affect their later life stage performance, subsequently influencing population regulation, as posited for the crown-of-thorns sea star (CoTS; Acanthasterspp.) by the terrestrial runoff hypothesis (TRH). The TRH proposes that eutrophic river runoff plumes boost larval phytoplankton food levels, enhancing metamorphic success to the juvenile to seed outbreaks. However, runoff plumes also freshen seawater which can be deleterious to sea star larvae. For settlement-ready brachiolaria larvae of CoTS, the impact of decreased salinity (17-34 ‰) across a range of exposure durations on survival and normal development were assessed. Salinity performance curves were generated to identify salinity levels with deleterious effects (tipping points, 50% normal development and survival). Decreasing salinity and prolonged exposure significantly reduced larval survival and morphology, with salinity ranges optimal for survival and normal morphology decreasing with exposure time. To examine carryover effects on metamorphosis and juvenile production, competent larvae exposed to salinities seen in runoff plumes (25-34 ‰) on the Great Barrier Reef (GBR) were induced to settle. Juvenile production was highest in slightly reduced (30 ‰) and control (34 ‰) salinity treatments, with faster transition to the juvenile under extended 30 ‰ exposures. However by 5-days post settlement juveniles produced by larvae that had experienced 30‰ were smaller indicating the presence of negative carry over traits that reduce juvenile quality. This highlights the need to consider metamorphic transitions when evaluating the TRH, particularly as climate change intensifies low-salinity events on the GBR.
Nano-sized heterogeneous photocatalyst Fe 3 O 4 @V/TiO 2 -catalyzed synthesis and antimicrobial evaluation of 2-substituted benzimidazoles
Authors: Bao Lijian , Chen Xiaodong , Li Yanli , Zhu Guangyuan , Wang Jingjun , Chen Mingyue , Bian Xingyu , Gu Qiang , Zhang Yumin , Lin Feng
Published: November 2024

The method for coating Fe3O4 with V-doped TiO2 was presented. On the base of characterizing composition, morphology and properties, the prepared nano-sized Fe3O4@V/TiO2 composites were used as a heterogeneous photocatalyst to catalyze the synthesis of 2-substituted benzimidazoles under light. The photocatalyst Fe3O4@V/TiO2 composites showed the enhanced photocatalytic activity compared to no V-doped Fe3O4@TiO2, being able to yield various 2-substituted benzimidazoles in moderate to good yield with recyclability and stability. A possible photocatalysis mechanism was investigated. It was evident that holes, singlet oxygen and ∙O2̄ radical played important roles in the synthesis of 2-substituted benzimidazole. Moreover, some of the obtained products were proved to have excellent antibacterial activity.
Efficacy and Safety of Vonoprazan as Treatment and Long-term Management of Peptic Ulcer: A Systematic Review and Meta-Analysis
Authors: Lanari Valeria Chiara , Govindarajan Karthikeyan , Iftikhar Munazza , Knapper Laura Grace , Khan Awais Ahmed , Rehman Muhammad Inhamur , Saddique Muhammad Nabeel
Published: November 2024

Background: Peptic ulcer disease (PUD) has a prevalence of 5-10% and an annual incidence of 0.1-0.3% worldwide. Etiology involves H. pylori infection (60-90%) and chronic use of NSAIDs (15-30%). Proton Pump Inhibitors (PPIs), alone or in combination with other drugs, currently represent the first line therapy for both H. pylori- and NSAID-related PUD. This review aims to assess the efficacy and safety of Vonoprazan, an orally available potassium-competitive acid blocker (P-CAB), for the treatment and management of PUD.
Methods: We performed a systematic literature search of randomized controlled trials and observational studies on PubMed (MEDLINE), Embase, and clinicaltrials.gov databases from inception to October 1, 2024. We pooled dichotomous outcomes as risk ratio and continuous outcomes as mean differences with 95% confidence intervals, using random-effects models. Heterogeneity was assessed using I² and X² statistics. Statistical significance was defined by a p-value <0.05. All analyses were performed with RevMan 5.4.
Results: This meta-analysis included 6 RCT involving 2656 patients, divided into three partially overlapping subgroups: ulcer healing (1108), recurrence (1263), and re-bleeding in high-risk patients (214). 1668 were males, mean age was 61.6 years, 60.74% were H. pylori-positive, 60.55% had a chronic use of NSAIDs. Vonoprazan was at least equal to PPIs in all efficacy outcomes, including healing rate (RR=0.98, 95% CI 0.95–1.01, I2=0%), 30-day re-bleeding in high-risk peptic ulcers (RR=0.67, 95% CI 0.29–1.58, I2=0%), and resolution of PUD-related symptoms. Vonoprazan caused an increased level of gastrin at 8 (mean difference to comparison 20mg: 283.34, 95% CI=122.89–443.79, I2=87%; 10mg: 222.81, 95% CI=177.42–268.21, I2=0%) and 24 weeks (20mg: 386.24, 95% CI=325.48–447.00, I2=0%; 10mg: 258.33, 95% CI=205.33–311.33, I2=0%).
Conclusion: Vonoprazan is a non-inferior alternative to PPIs in the treatment and management of PUD in terms of efficacy and safety.
Dynamic Syntax Interaction Framework with Multi-Layer Syntax Engagement for Large Language Models
Authors: Amizern Valentin , Greaves Jonathan , Gauthier Christian , Stern Emmanuel
Published: November 2024

The rapid expansion of artificial intelligence applications in language-based tasks has exposed limitations in syntactic comprehension, especially in handling intricate, multi-layered syntactical structures essential for complex language understanding. Addressing these gaps, the proposed Dynamic Syntax Interaction Framework introduces a novel, multi-layered approach to syntactic engagement, enabling language models to process complex linguistic constructs through a dynamic interaction with syntactic layers. By integrating advanced syntactic processing modules, adaptive attention mechanisms, and a continuous feedback loop, the framework substantially enhances language models' capacity for syntactic fidelity and contextual relevance across a range of tasks. Experimental outcomes demonstrate significant improvements in syntactic accuracy, contextual coherence, and language generation fluency, demonstrating the framework's impact on overcoming traditional barriers in language comprehension. The implications of this syntactically aware framework extend across automated language applications, from content generation and translation to tasks demanding high levels of linguistic precision, marking a critical advancement in artificial intelligence-driven language comprehension and generation.
Comparative analysis of the efficacy and safety of non-immunogenic staphylokinase and alteplase in bridging therapy of ischemic stroke
Authors: Kazakov S. D. , Plotnikov D. M. , Kanev A. F. , Kamenskih E. M. , Alifirova V. M.
Published: November 2024

Introduction. Bridging therapy is the main method of treating ischemic stroke (IS) due to proximal occlusion, the effectiveness of which depends on the speed of its implementation. It is possible to increase the speed of systemic thrombolytic therapy (STT) and reduce the delay before mechanical thrombectomy (MT) by using bolus forms of thrombolytic drugs.

Aim. To evaluate the efficacy and safety of using non-immunogenic staphylokinase compared to alteplase in bridging therapy of IS in real clinical practice of a regional stroke center (RSC).

Materials and methods. A retrospective study of the combined use of STT and MT for the treatment of IS due to proximal occlusion was conducted from the reperfusion therapy registry of the RSC of the Tomsk Regional Clinical Hospital from 2017 to 2023. The final analysis included 49 patients who received non-immunogenic staphylokinase and 26 patients who received alteplase.

Results. The time between the stages of bridging therapy was 92.0 [65.0–130.0] min in the non-immunogenic staphylokinase group and 35.0 [25.0–50.0] min in the alteplase group (p < 0.001). No intergroup differences were found in the incidence of symptomatic hemorrhagic transformation: 8.1% in the non-immunogenic staphylokinase group and 3.8% in the alteplase group (p = 0.476). Mortality in both groups did not differ significantly and was 30.6% and 26.9%, respectively. Favorable functional outcome was observed in 40.8% of patients in the non-immunogenic staphylokinase group and in 23.1% in the alteplase group (p = 0.151).

Conclusion. Comparable efficacy and safety of non-immunogenic staphylokinase and alteplase in the context of staged reperfusion therapy were revealed. The use of non-immunogenic staphylokinase is associated with a decrease in the time between the stages of bridging therapy.
Somatic and neurological comorbidities in COVID-19 with fatal outcome
Authors: Ignatieva O. I. , Sergachev A. V. , Pavelkina V. F. , Ignatiev V. N. , Erovichenkov A. A.
Published: November 2024

Introduction. Although the risk of emerging coronavirus infection may seem to have disappeared at first glance, SARS-COV-2 has complex and poorly understood effects on many organ systems, including the nervous system. Disease progression and unfavorable outcome COVID-19 are not only due to lung damage, elderly age, concomitant pathology: hypertension, diabetes mellitus, etc. have a significant impact.

Aim. To study the structure of mortality in a new coronavirus infection COVID-19, caused by delta strain of coronavirus SARS- CoV-2, taking into account the nature of concomitant therapeutic and neurological pathology, the degree of comorbidity, fatal complications, and sex and age characteristics.

Materials and methods. A postmortem analysis of pathological and anatomical conclusions of 209 patients with COVID-19 with comorbid somatic and neurological pathology who received inpatient treatment in covid hospitals of the Republic of Mordovia in 2021 was performed. The severity of the underlying disease, concomitant therapeutic and neurological pathology, and comorbidity were analysed. The coincidence of the final clinical and pathological diagnoses, fatal complications were assessed. The presented data allowed to identify the main factors of unfavourable outcome.

Results and discussion. In unfavourable outcome of the disease, concomitant pathology is represented by hypertension, ischemic heart disease, chronic heart failure, chronic cerebral ischemia. In women, cases of diabetes mellitus and atherosclerosis were more frequent, in men – hypertension and chronic heart failure.

Conclusions. New coronavirus COVID-19 infection associated with delta strain of SARS-COV-2 virus is characterised by severe and extremely severe course in elderly patients with comorbid somatic and neurological pathology.
Water, Sanitation, and Hygiene insecurity and infectious disease outbreaks among internally displaced populations in Gaza: Implications of conflict-driven displacement on public health
Authors: Zinszer Kate , Abuzerr Samer
Published: November 2024

This study aims to assess the impact of Water, Sanitation, and Hygiene (WaSH) insecurity on the health of displaced populations and identify key factors associated with the spread of infectious diseases. A mixed-methods approach was employed, including both quantitative and qualitative components. The quantitative component involved a cross-sectional survey of 1,500 displaced persons across five Gaza Strip governorates from 3 April to 6 August 2024. The sample size was calculated to ensure statistical significance and representativeness of the population. Data on the incidence of infectious diseases were collected and adjusted for the sample size. The qualitative component included in-depth interviews and focus group discussions with a subset of participants to gain insights into their experiences and coping strategies. The quantitative analysis revealed high incidence rates of various infectious diseases among the displaced population. Diarrhea and acute respiratory infections were the most prevalent, with incidence rates of 24.9 and 49.3%, respectively. Other significant findings included rates of skin rash (3.7%), scabies (2.5%), and acute viral hepatitis (5.6%). Qualitative data highlighted severe WaSH-related challenges, including inadequate access to clean water and sanitation facilities. Participants reported widespread health issues, psychological distress, and resource scarcity.
Statistical Approach to Determining Trends in Regional Development and Peculiarities of Population Behavior in the Context of Modern Challenges
Authors: Kremlev N. D.
Published: November 2024

The purpose of the study is to determine the trends of regional development and the peculiarities of population behavior in the context of modern challenges. The relevance of the study of the specific behavior of the population of the regions is associated with the problems of reflecting economic development trends which affect the actions and deeds of people and the quality of their lives. At the same time, liberal approaches to the definition of behavioral strategies of the population do not allow to objectively reflect the peculiarities of regional development. The methodology is used from the point of view of substantiating digital meters reflecting the processes of interaction of needs, consumption, production and behavior of the population, their impact on the peculiarities and trends of regional development.Methods: Rosstat methodology, including the balance method, a method of comparative assessments of regional development trends and analysis of the degree of satisfaction of the needs of the population.Results. The peculiarities of the formation of the population behavior of the subsidized border region, which is directly related to the living conditions and the degree of satisfaction of people’s needs, are revealed. The unpredictable behavior of the population was used to assess the relationship between needs and the production of goods that affect the characteristics and well-being of people. It is established that the population of the Kurgan region is in a constant state of stress due to management miscalculations in inter-budgetary relations, the imbalance of interests of employers with employees who artificially underestimate the value of labor and knowledge of employees. All this affects the deterioration of demographic and migration behavior of the population, the quality of life of people.Conclusion. Official statistics allow us to truthfully determine the trends of regional development and the peculiarities of population behavior in the face of modern challenges. The results obtained allowed us to reveal the actual problems of the development of the subsidized region, which affect the behavioral strategies of the population. Also, when developing state measures to ensure people’s savings, maintaining a balance of interests of the population and employers with government authorities in order to reduce the negative impact of unpredictable behavior of people on the future.
SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity
Authors: Liang Demao , Zhang Qiuli , Pang Yanhua , Yan Rili , Ke Yi
Published: November 2024

Background:

The abnormal expression of small G protein signaling modulator 2 (SGSM2)
is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2
in uveal melanoma (UVM) is unclear.

Objects:

To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental
validation.

Methods:

The expression of SGSM2 was detected in UVM cell lines through quantitative real--
time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship
between SGSM2 expression and clinical characteristics, as well as its prognostic significance
in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2
in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and
drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing
data.

Results:

SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2
in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress-
free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally,
SGSM2 expression was identified as an independent prognostic factor in UVM patients (p <
0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway,
natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study
revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint
genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression
and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in
UVM patients.

Conclusion:

SGSM2 may not only serve as an important indicator for prognostic assessment.
Still, it may also be a key target for the development of new therapeutic approaches, providing
new perspectives on the treatment of UVM patients.
Stimuli-Responsive Nano/Biomaterials for Smart Drug Delivery in Cardiovascular Diseases: Promises, Challenges and Outlooks
Authors: Vosoughi Pegah , Naghib Seyed Morteza , Mozafari M. R.
Published: November 2024

Cardiovascular Diseases (CVDs) are responsible for the highest number of
deaths and disabilities globally. Although numerous therapeutic options exist for treating
CVDs, most traditional strategies have proven ineffective in halting or significantly
slowing disease progression, often leading to unfavorable side effects. Using nanocarriers
represents an innovative strategy for treating CVD, enabling the personalized delivery
of medications to precise locations within the cardiovascular system. Despite significant
advancements in pharmacological treatments, challenges persist in effectively administering
drugs to the CV system. Employing nanocarriers represents an innovative
strategy for treating CVD, enabling the tailored administration of medications to precise
locations within the cardiovascular system. Various studies have determined the future
outlook of nanomedicines for clinical applications as nanocarrier design continues to improve,
leading to enhanced drug delivery and treatment outcomes. The article focuses on
the delivery systems of drugs that are effective strategies for treating cardiovascular diseases.
This manuscript also seeks to explore new possibilities for how the emerging concept
of nanotherapeutics could revolutionize our traditional diagnostic and treatment
methods in the coming years.
C-Reactive Protein Biosensor for Diagnosing Infections Caused by Orthopedic Trauma
Authors: Liu Xiancui , Wang Cunhua , Fu Honglong , Li Xudong , Gopinath Subash C.B. , Subramaniam Sreeramanan
Published: November 2024

Introduction:

Infections linked to orthopedic trauma are common complications
that place a significant strain on the healthcare system. Immediate identification of
the infection and its severity is essential for providing effective treatment.

Method:

C-reactive Protein (CRP) is a commonly used inflammatory marker in orthopedic
surgery and has proven to be a valuable biomarker for diagnosing and monitoring infections.
Specifically, CRP aids in the early identification of postoperative infections.
This research work has focused on developing a highly sensitive CRP biosensor using
iron oxide nanomaterial-modified dielectric sensors.

Result:

Gold Urchin (GU)-conjugated aptamers and antibodies were used as probes and
attached to the electrode via amine linkers. The aptamer-GU-antibody-modified electrode
detected CRP at concentrations as low as 1 pg/mL, with an R2 value of 0.9942. Furthermore,
CRP-spiked serum exhibited an increase in current response at all concentrations
of CRP, indicating selective detection of CRP. Additionally, control experiments
using complementary sequences of the aptamer, relevant proteins, and non-immune antibodies
did not enhance the current responses, confirming the specific identification of
CRP.

Conclusion:

The sensing strategy has enabled the detection of CRP at its lowest levels,
facilitating the identification of infections during orthopedic surgery and subsequent
treatment.
The Mechanism of Action of Exosomes Derived from Glioblastoma Cells
Authors: Beylerli Ozal , Gareev Ilgiz , Ilyasova Tatiana , Musaev Elmar , Chekhonin Vladimir
Published: November 2024

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor characterized
by rapid growth, invasive behavior, and resistance to conventional therapies, such
as surgery, radiotherapy, and chemotherapy. Despite these interventions, patient survival
remains poor due to the tumor’s ability to recur and adapt to treatments. The function of
GBM-derived exosomes (GBM-exosomes) as essential mediators in tumor growth has
drawn attention in recent years. These small extracellular vesicles are involved in the
transfer of a variety of molecules, including cytokines, miRNAs, proteins, and DNA, facilitating
intercellular communication that promotes GBM cell proliferation, angiogenesis,
immune evasion, and resistance to therapies. This review aims to provide an in-
-depth examination of the mechanisms through which GBM-exosomes contribute to these
pathological processes, as well as to discuss the current methodologies for isolating
and characterizing GBM exosomes. Additionally, we explore the potential of exosomes
as biomarkers for diagnosis and prognosis and as novel therapeutic targets in the fight
against GBM. By improving our understanding of GBM-exosomes, we can pave the
way for the development of more effective, personalized treatment strategies that may
improve patient outcomes and quality of life.
A Comprehensive Review on the Synthesis of Mangiferin Derivatives and their Multiple Biological Activities
Authors: Turkar Milendra Kumar , Sahu Rishika , Jain Deepti
Published: November 2024

Mangiferin always draws the attention of traditional as well as modern medicinal chemists because of
its ease of chemical derivatization and diverse biological activities, including anticancer, anti-inflammatory,
neuroprotective, antidiabetic, analgesic, antimalarial, anticonvulsant, laxative, cardiotonic, hemopoietic, antioxidant,
antimicrobial, antipsychotic, anticoagulant, and antihypertensive properties. This review focuses on a
detailed and updated overview of the synthesis of mangiferin derivatives and their diverse biological activities,
with examples from both patented and non-patented literature.