bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence and Its Challenges To Elections In Indonesia: A Legal Analysis
Authors: Armiwulan Hesti , Rahman Rofi Aulia , Prabowo Valentino Nathanael , Hajdú József
Published: August 2024

The improper utilization of AI technology poses difficulties to democracy, particularly the growing threat of unjust elections, exemplified by the deployment of bot accounts and deep fakes during electoral processes. Hence, it is crucial to build a strong and comprehensive framework to regulate the utilization of AI technology in Indonesia's political process. This article analyzes four main topics: (a) the advancement of AI technology and its connection to elections; (b) the influence of AI technology on election principles; (c) the pressing need for regulating AI in elections; and (d) the possibilities and difficulties of regulating AI technology within Indonesia's legal framework. The paper employs doctrinal legal research to examine the necessity of regulating AI technology in the context of conducting elections, taking into account the constitutional framework, established principles, and democratic election norms. The result shows that irresponsible use of AI technology remains a menace to democratic election ideals, and Indonesia must establish adequate legal mechanisms to tackle the problems stemming from the improper use of AI technology in the political process. The regulation of AI technology can be initiated by introducing a bill specifically focused on artificial intelligence (AI). This process should also involve the synchronization and harmonization of election rules, including election laws, laws governing the election of governors, regents, and mayors, laws concerning political parties, and other implementing regulations such as those established by the General Election Commission and the Election Supervisory Board.
Optimal design of observation holes on strainers for groundwater measurements
Authors: Assuncao Milton , Cesana Pierluigi , Fukumoto Yasuhide , Hocking Graeme , Vynnycky Michael , O'Kiely Doireann
Published: August 2024

A common method for determining the direction and speed of groundwater is using cylindrical “strainers”, which are bored into the ground to depths up to 50 metres. The strainer has an array of “observation holes” which allow water through and a heater at the centre which heats the water as it passes. Measurements of the temperature distribution are made via an array of sensors placed around the heater, and then used to infer information about the direction and speed of groundwater flow. In this report, we investigate two different strainer designs: one with circular holes and the other with slit-shaped holes. A combination of analysis and computational fluid dynamics is used to better understand the momentum and heat transfer associated with the two designs; even probability theory is used shed light on why the strainer with slit-shaped holes has historically been found to give inaccurate results in 20% of experiments.
Analisis Konflik dan Masalah Sosial di Papua
Authors: Robert Hendrik  , Endah Ratna Sonya
Published: August 2024

Papua adalah salah satu provinsi yang terletak paling ujung di bagian timur wilayah Indonesia. Wilayah Papua memiliki kekayaan sumber daya alam, iklim yang baik, dan keanekaragaman hayati. Kondisi kekayaan alam Papua ini seolah berbanding terbalik, bila kita berbicara tentang kondisi sosial di wilayah itu pada beberapa dekade terakhir. Sejak tahun 1963 ketika Indonesia mengambil alih Papua menjadi bagian dari wilayah negara Indonesia, banyak sejumlah konflik terjadi yang kemudian berdampak pada kehidupan sosial dan politik di Papua. Konflik tersebut terkait isu kemerdekaan, diskriminasi, dan pelanggaran Hak Asasi Manusia (HAM). Masalah sosial lainnya yang ditemukan di Papua yakni kesenjangan sosial, dimana mencakup ekonomi, pendidikan, kesehatan, wilayah, dan eksploitasi sumber daya alam. Penelitian ini menggunakan pendekatan deskriptif kualitatif dimana objek penelitian ini adalah provinsi Papua. Penelitian ini bertujuan untuk menganalisis penyebab konflik dan masalah sosial yang terjadi di Papua. Hasil penelitian ini adalah komitmen dan kerjasama yang kuat antara pemerintah, masyarakat Papua, kelompok etnis non Papua dengan pendekatan yang komprehensif dan holistik yang berkelanjutan. Keterbukaan dialog untuk mendengar aspirasi masyarakat dalam menyelesaikan konflik dan permasalahan sosial adalah bentuk keadilan dan perhatian. Implementasi kebijakan pemerintah dengan memperhatikan prinsip HAM secara inklusi sosial akan menjaga keutuhan integrasi dan persatuan masyarakat.
Analisis Strategi Penerjemahan Idiom Pada Novel “I Rise” Karya Marie Arnold
Authors: Sandi Firda Anny Kurnia , Diah Maya Andina
Published: August 2024

Penelitian ini bertujuan untuk menganalisis idiom, menjelaskan strategi penerjemahan, serta mengetahui strategi penerjemahan idiom yang banyak digunakan dalam menerjemahkan idiom pada novel “I Rise” karya Marie Arnold. Masalah yang dihadapi oleh penulis adalah idiom tidak dapat diterjemahkan secara harfiah maka diperlukan strategi penerjemahan yang tepat untuk menerjemahkannya. Metode penelitian yang digunakan adalah metode penelitian deksriptif kualitatif. Ditemukan data sebanyak 30 idiom dalam novel. Penelitian ini menggunakan novel karya Marie Arnold yang bejudul “I Rise”. Hasil penelitian menunjukkan bahwa berdasarkan empat strategi penerjemahan teori Baker, ditemukan bahwa 30 idiom yang ditemukan pada novel “I Rise” terdapat tiga strategi yang digunakan, yaitu; 1). Strategi penerjemahan idiom similar meaning and form sebanyak 6 idiom; 2). Strategi penerjemahan idiom similar meaning but dissimilar form sebanyak 13 idiom; 3). Strategi penerjemahan parafrase sebanyak 11 idiom. Strategi penerjemahan yang paling banyak digunakan adalah strategi penerjemahan idiom similar meaning but dissimilar form.
Ultrasound-assisted laser therapy for selective removal of melanoma cells
Authors: Subramanian Karthikesh Madhumithra , Martinez-Rivera Noraida , Rosa-Molinar Eduardo , Wang Xueding , Yang Xinmai
Published: August 2024

The current study explores the potential of ultrasound-assisted laser therapy (USaLT) to selectively destroy melanoma cells. The technology was tested on an ex vivo melanoma model, which was established by growing melanoma cells in chicken breast tissue. Ultrasound-only and laser-only treatments were used as control groups. USaLT was able to effectively destroy melanoma cells and selectively remove 66.41% of melanoma cells in the ex vivo tumor model when an ultrasound peak negative pressure of 2 MPa was concurrently applied with a laser fluence of 28 mJ/cm2 at 532 nm optical wavelength for 5 min. The therapeutic efficiency was further improved with the use of a higher laser fluence, and the treatment depth was improved to 3.5 mm with the use of 1,064 nm laser light at a fluence of 150 mJ/cm2. None of the laser-only and ultrasound-only treatments were able to remove any melanoma cells. The treatment outcome was validated with histological analyses and photoacoustic imaging. This study opens the possibility of USaLT for melanoma that is currently treated by laser therapy, but at a much lower laser fluence level, hence improving the safety potential of laser therapy.
Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems
Authors: Morley Elliot J. , Brockett Claire L. , Verbruggen Stefaan W.
Published: August 2024

Cell-based therapies represent the current frontier of biomedical innovations, with the technologies required underpinning treatments as broad as CAR-T cell therapies, stem cell treatments, genetic therapies and mRNA manufacture. A key bottleneck in the manufacturing process for each of these lies in the expansion of cells within a bioreactor vessel, requiring by far the greatest share of time for what are often time-critical therapies. While various designs, culture feeding and mixing methods are employed in these bioreactors, a common concern among manufacturers and researchers lies in whether shear stresses generated by culture media flow will damage cells and inhibit expansion. This study develops an analytical tool to link macro-scale measures of flow to risk of cell death using relationships with eddy size and dissipation rates, from eddies generated off flat surfaces. This analytical tool was then employed using computational fluid dynamics (CFD) to replicate a range of generic bioreactor geometries and flow conditions. We found that no combination of flow condition or design parameter was predicted by the tool to cause cell death within eddies, indicating negligible risk of cell death due to eddy formation within cell culture systems. While this requires experimental validation, and does not apply when cells are expanded using microcarriers, this tool nonetheless provides reassurance and accessible prediction of bioreactor design parameters that could result in cell death. Finally, our findings show that bioreactor design can be tailored such that the shear stress stimulation of cells can be selectively altered through small changes in flow rate.
Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment
Authors: Li Zhong-Bin , Chen Dan-Dan , Jia Yun-Fei , He Qing-Juan , Cui Li , Du Feng-Xia , Kang Yao-Jie , Feng Xin , He Mengwen , Jin Xue-Yuan , Chen Jing , Wang Yudong , Ji Dong , Lau George , Wu Shu-Gao
Published: August 2024

Background

About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV.

Methods

In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed.

Results

Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV.

Conclusions

High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.
Teaching dynamics to enhance critical thinking and knowledge socialization in the mathematics classroom
Authors: Dominguez Angeles
Published: August 2024

Building the future of education together means that, as educators, we need to promote innovation and educational strategies in our classroom to foster the development of skills such as critical thinking and argumentation. Moreover, we should encourage using technology as an efficient and effective tool to solve complex problems. Mathematics is a cornerstone in the education of engineering students. However, students’ mathematic classroom experiences have only presented them with a rigid and pure side to the discipline. Active learning strategies foster the development of competencies such as critical thinking and argumentation while generating knowledge socialization and learning democratization. The active learning dynamics were conducted in first-year undergraduate calculus course for engineering and are based on collaborative learning, model-eliciting activities, and the use of technology. Students reported that being actively involved and interacting with classmates and tools made them enjoy the class, broaden their view of mathematics, and connect with contexts from other disciplines. Moreover, these dynamics favor different types of formative assessment for students, self- and peer-assessment, and for teachers about the students learning and the design of the activity. Based on educational research, the design of the dynamics is innovative in the combination of implementations used to potentiate the benefits of a student-centered learning environment and the socialization of knowledge.
Exploration of predictive risk factors for diabetic foot in patients with diabetes in Beijing: analysis of 5-year follow-up data of patients with diabetes mellitus in a single center in Beijing
Authors: Su Guanming , Yuan Xiaoyong , Yuan Geheng , Sun Yalan , Zhang Donghui , Liu Wei , Zhang Junqing , Guo Xiaohui
Published: August 2024

Background

Large-scale prospective cohort studies on diabetic foot ulcers risk factor screening in China are limited. Therefore, this prospective cohort study aimed to explore the predictive risk factors for diabetic foot ulcers to provide clinicians with concise and effective clinical indicators for identifying a high-risk diabetic foot and guiding the prevention of diabetic foot ulcers.

Methods

Patients with diabetes who visited the Department of Endocrinology of Peking University First Hospital from October 2017 to December 2018 were selected as research participants by convenience sampling. A total of 968 patients were included. After enrollment, a dedicated person collected and recorded all baseline data. A dedicated telephone follow-up was conducted every 12–24 months to evaluate whether the endpoint event had occurred. All patients were followed up for an average of 61 (57–71) months, with 95% of them followed up for more than 60 months. According to the occurrence of endpoint events, they were divided into the DFU and non-DFU groups. The data between the two groups were analyzed using independent-sample t-test, Wilcoxon rank sum test, and chi square test. We used univariate and multivariate logistic regression analysis to analyze the factors that affected the occurrence of diabetic foot ulcers.

Results and conclusions

After the 5-year follow-up, the incidence of diabetic foot was 25.83%. Multivariate logistic regression analysis revealed that body mass index (odds ratio: 1.046; 95% confidence interval: 1.001–1.093), abnormal pinprick sensation (odds ratio: 4.138; 95% confidence interval: 1.292–13.255), history of fungal foot infection (odds ratio: 2.287; 95% confidence interval: 1.517–3.448), abnormal 128-Hz tuning fork test (odds ratio: 2.628; 95% confidence interval: 1.098–6.294), and HbA1c≥ 8% (odds ratio: 1.522; 95% confidence interval: 1.014–2.284) were independent predictors of diabetic foot. Our study highlights clinically relevant indicators that may help to prevent the occurrence of diabetic foot and guide timely interventions.
Woodland expansion and upland management strategy dilemmas for biodiversity and carbon storage in the Cairngorms national park
Authors: Valette Michel , Newey Scott , Schreckenberg Kate , Dawson Terence P.
Published: August 2024

Nature-based solutions are increasingly advocated to mitigate climate change and biodiversity loss, while improving ecosystem resilience and providing additional ecosystem services. In Scotland, woodland expansion and restoration of degraded peatlands are expected to play a major role in meeting net-zero emissions by 2045 and have prompted debates about the impact of increased woodland cover and prescribed fire on the biodiversity and ecosystem services provided by upland landscapes. In alignment with national policy, the Cairngorms National Park, the UK’s largest national park, has committed to an ambitious programme of woodland expansion and peatland restoration in a landscape dominated by heather moorlands that is predominantly managed through prescribed burning for game management. Using the Native Woodland Model and the InVest modelling platform, we assessed the effects of five land cover and land use change scenarios, with different levels of prescribed fire regulation and woodland expansion, to evaluate their benefits and costs on biodiversity and carbon sequestration. Results show that changing the extent and management of habitats will result in different carbon sequestration pathways, as well as biodiversity winners and losers. The scenario presenting greater benefits for the conservation of biodiversity also has lower above-ground carbon sequestration potential and a larger negative impact on red grouse habitats, thus being less profitable to sporting estates. Hence, trade-offs will be necessary to achieve optimal carbon sequestration and biodiversity gains, with a potential role played by the continuation of prescribed fires and traditional moorland management practices as well as complementary grants and support measures based on biodiversity benefits rather than carbon sequestration. The results from this study could support discussions regarding future management of the uplands, trade-offs between loss of carbon in soils, carbon sequestration in woodlands and conservation of biodiversity, as well as stakeholders likely to be affected.
Using a new fish indicator-based index with scoring and evaluation criteria to assess the ecological status in a disturbed subtropical river of China
Authors: Wang Sai , Gao Yu-Jia , Wu Dong-Hai , Xu De-Lin , Wang Tuan-Tuan , Fan Shi-Di , Wu En-Ni , Song Yong-Duo , Zhang Hong-Jin , Fu Guo-Ping , Chen Zhong-Bing , Mo Ling , Zhang Yang , Ma Zhuo-Luo
Published: August 2024

Rivers are constantly disturbed by anthropogenic stressors. Developing robust biotic indicators to assess river environments across large spatial scales is important. In the subtropical Liuxi River of China, 34 native fish indicators, including 4 genera and 30 species, were selected from 108 fish species by linear discriminant analysis. These indicators were grouped into 19 ecological items and assigned evaluation scores according to the roles they played in the food web (e.g., keystoneness and trophic level) and their positive feedback on the environment (e.g., requirements for feeding, spawning/nursing, and migrating). Three formulae for calculating the index of fish indicators (IFI) were developed based on the scoring of each indicator and weighted by relative abundance (individual number, i.e., IFIN) and relative biomass (wet weight, i.e., IFIB). Spearman correlation analysis showed that IFIB, which had positive (P< 0.05) correlations with elevation (m), dissolved oxygen (mg/L), flow velocity (cm/s), Shannon-Wiener diversity, benthic index of biotic integrity, exhibited a more powerful explanation of biodiversity and environmental factors than IFIN and unweighted IFI. Therefore, IFIB was most suitable for constructing a scoring system to evaluate ecological status (e.g., water and habitat quality). These results suggested that fish indicator-based scoring and evaluation system was effectively in not only assessing the site- or region-specific ecological status bot also reflecting the fluvial biodiversity and food web integrity. Further application and promotion of this indicator-based evaluation method may improve field investigation efficiency and contribute greatly to the conservation and management of river ecosystems.
Exploration of large-scale vegetation transition in wet ecosystems: a comparison of conifer seedling abundance across burned vs. unburned forest-peatland ecotones in Western Patagonia
Authors: Zaret Kyla , Holz Andrés
Published: August 2024

Altered fire regimes, combined with a warmer and drier climate, have been eroding the resilience of temperate rainforests and peatlands worldwide and leading to alternative post-fire vegetation communities. Chronic anthropogenic burning of temperate rainforests at the forest-peatland ecotone in western Patagonia appears to have shifted vegetation communities in poorly-drained sites from forests dominated by the threatened conifer, Pilgerodendron uviferum, to peat-accumulating wetlands covered by Sphagnum mosses. We collected and modeled post-reburn field data using ordinations and hierarchical Bayesian regressions to examine mechanisms through which P. uviferum forests may recover following fire or become locked into alternative development pathways by comparing biophysical factors of a reburned ecotone to those of an unburned (control) ecotone. We found that, (1) the significantly higher densities of P. uviferum trees and seedlings in the forested patches at both the reburned and control sites were associated with significantly lower seasonal water tables, lower cover of Sphagnum mosses and higher cover of other mosses (i.e., not in the Sphagnum or Dicranaloma genera); (2) despite abrupt boundaries in vegetation at both sites, successive fires homogenized the environment at the reburned site; and (3) the distinct life forms and individual species that characterized the understory plant communities across the ecotones affected seedling abundance by shaping microtopography and the substrates available for establishment. Together, our results suggest that fire can push edaphically wet P. uviferum-dominated sites towards a non-forested state by reducing the diversity of microsite structure and composition, thereby placing P. uviferum seedlings in direct competition with Sphagnum mosses and potentially limiting the availability of microsites that are protected from both seasonal inundation and seasonal drought. If wildfires continue under increasingly warmer and drier conditions, the forest-peatland ecotone of western Patagonia may be susceptible to large-scale transformation towards a non-forested state.
Physiological and biochemical changes of Picea abies (L.) during acute drought stress and their correlation with susceptibility to Ips typographus (L.) and I. duplicatus (Sahlberg)
Authors: Basile Sara , Stříbrská Barbora , Kalyniukova Alina , Hradecký Jaromír , Synek Jiří , Gershenzon Jonathan , Jirošová Anna
Published: August 2024

Introduction

In recent years, Norway spruce (Picea abies L.) forests in Central Europe have faced escalating threats from bark beetles, primarily Ips typographus (L.), and other species, such as I. duplicatus (Sahlberg). Outbreaks are partially attributed to weakened tree defense resulting from drought periods induced by climate change. This study examines Norway spruce’s physiological and metabolic reactions to acute drought stress during the growing season and evaluates its susceptibility to I. typographus and I. duplicatus.

Methodology

In order to induce drought stress, mature Norway spruces had their roots covered with a roof in April 2021, depriving them of water. Control trees were left with free access to natural rainwater. Over 5 months of the growing season, soil water potential, bark temperature, tree trunk circumference, and sap flow were monitored. Roofed trees and controls were sampled in July, August, and September and analyzed for non-structural carbohydrates and the two classes of defensive compounds, phenolics and terpenes. Furthermore, two different bioassays in tubes and boxes were performed using adult I. typographus and I. duplicatus beetles to assess host choice and acceptance.

Results

Roofed trees exhibited signs of stress as early as July, resulting in decreased tree trunk and a consequent increase in non-structural carbohydrate content. Defensive metabolites remained largely unaffected except for an increase in diterpenes in September. In bioassays, I. typographus preferred boring into the bark of roofed trees in August in tubes and in September in boxes. This increased tree acceptance correlated with increased levels of soluble carbohydrates in the phloem. I. typographus and I. duplicatus beetles showed higher mobility in boxes in August and September on roofed trees but not in July, even though bark surface temperatures were elevated in roof-covered trees during all three bioassay periods.

Conclusion

The study revealed rapid physiological responses of trees to acute drought stress, although not many changes were observed in defense traits. Despite the absence of natural bark beetle attacks, drought trees were more accepted by I. typographus than naturally watered trees. This response may indicate the beetles’ preference for trees with phloem of higher nutritional quality induced by the acute drought stress conditions.
Hub genes identification and validation of ferroptosis in SARS-CoV-2 induced ARDS: perspective from transcriptome analysis
Authors: Li Yutang , Tang Li , Wang Fang , Gao Chencheng , Yang Qi , Luo Liyu , Wei Jiahang , Tang Qiuyun , Qi Mingran
Published: August 2024

Introduction

Acute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment.

Method

To investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment.

Result

The analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators.

Discussion

This study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19.
High throughput long-read sequencing of circulating lymphocytes of the evolutionarily distant sea lamprey reveals diversity and common elements of the variable lymphocyte receptor B (VLRB) repertoire
Authors: Zia Amin , Orozco Ariel , Fang Irene S. Y. , Tang Aspen M. , Mendoza Viruega Ana Sofia , Dong Shilan , Leung Leslie Y. T. , Devraj Vijaya M. , Oludada Opeyemi E. , Ehrhardt Götz R. A.
Published: August 2024

The leucine-rich repeat-based variable lymphocyte receptor B (VLRB) antibody system of jawless vertebrates is capable of generating an antibody repertoire equal to or exceeding the diversity of antibody repertoires of jawed vertebrates. Unlike immunoglobulin-based immune repertoires, the VLRB repertoire diversity is characterized by variable lengths of VLRB encoding transcripts, rendering conventional immunoreceptor repertoire sequencing approaches unsuitable for VLRB repertoire sequencing. Here we demonstrate that long-read single-molecule real-time (SMRT) sequencing (PacBio) approaches permit the efficient large-scale assessment of the VLRB repertoire. We present a computational pipeline for sequence data processing and provide the first repertoire-based analysis of VLRB protein characteristics including properties of its subunits and regions of diversity within each structural leucine-rich repeat subunit. Our study provides a template to explore changes in the VLRB repertoire during immune responses and to establish large scale VLRB repertoire databases for computational approaches aimed at isolating monoclonal VLRB reagents for biomedical research and clinical applications.
ICU patients receiving remifentanil do not experience reduced duration of mechanical ventilation: a systematic review of randomized controlled trials and network meta-analyses based on Bayesian theories
Authors: Lu Fangjie , Qin Sirun , Liu Chang , Chen Xunxun , Dai Zhaoqiu , Li Cong
Published: August 2024

Background

The purpose of this network meta-analysis (NMA) was to evaluate the efficacy of intravenous opioid μ-receptor analgesics in shortening the duration of mechanical ventilation (MV) in ICU patients.

Methods

Randomized controlled trials comparing the efficacy of remifentanil, sufentanil, morphine, and fentanyl on the duration of MV in ICU patients were searched in Embase, Cochrane, Pubmed, and Web of Science electronic databases. The primary outcome was MV duration. The Bayesian random-effects framework was used to evaluate relative efficacy.

Results

In total 20 studies were included in this NMA involving 3,442 patients. Remifentanil was not associated with a reduction in the duration of MV compared with fentanyl (mean difference (MD) -0.16; 95% credible interval (CrI): −4.75 ~ 5.63) and morphine (MD 3.84; 95% CrI: −0.29 ~ 10.68). The secondary outcomes showed that, compared with remifentanil, sufentanil can prolong the duration of extubation. No regimen significantly shortened the ICU length of stay and improved the ICU mortality, efficacy, safety, and drug-related adverse events.

Conclusion

Among these analgesics, remifentanil did not appear to be associated with a reduction in MV duration. Clinicians should carefully titrate the analgesia of MV patients to prevent a potentially prolonged duration of MV due to excessive or inadequate analgesic therapy.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, CRD42021232604.
The role of artificial intelligence in disease prediction: using ensemble model to predict disease mellitus
Authors: Du Qinyuan , Wang Dongli , Zhang Yimin
Published: August 2024

The traditional complications of diabetes are well known and continue to pose a considerable burden to millions of people with diabetes mellitus (DM). With the continuous accumulation of medical data and technological advances, artificial intelligence has shown great potential and advantages in the prediction, diagnosis, and treatment of DM. When DM is diagnosed, some subjective factors and diagnostic methods of doctors will have an impact on the diagnostic results, so the use of artificial intelligence for fast and effective early prediction of DM patients can provide decision-making support to doctors and give more accurate treatment services to patients in time, which is of great clinical medical significance and practical significance. In this paper, an adaptive Stacking ensemble model is proposed based on the theory of “error-ambiguity decomposition,” which can adaptively select the base classifiers from the pre-selected models. The adaptive Stacking ensemble model proposed in this paper is compared with KNN, SVM, RF, LR, DT, GBDT, XGBoost, LightGBM, CatBoost, MLP and traditional Stacking ensemble models. The results showed that the adaptive Stacking ensemble model achieved the best performance in five evaluation metrics: accuracy, precision, recall, F1 value and AUC value, which were 0.7559, 0.7286, 0.8132, 0.7686 and 0.8436. The model can effectively predict DM patients and provide a reference value for the screening and diagnosis of clinical DM.
Causal relationship between gut microbiota and gynecological tumor: a two-sample Mendelian randomization study
Authors: Xiong Yajun , Zhang Xiaonan , Niu Xiaoya , Zhang Long , Sheng Yanbing , Xu Aiguo
Published: August 2024

Introduction

Previous research has established associations between alterations in gut microbiota composition and various gynecologic tumors. However, establishing a causal relationship between gut microbiota and these tumors remains necessary. This study employs a two-sample Mendelian randomization (MR) approach to investigate causality, aiming to identify pathogenic bacterial communities potentially involved in gynecologic tumor development.

Methods

Data from the MiBioGen consortium’s Genome-Wide Association Study (GWAS) on gut microbiota were used as the exposure variable. Four common gynecologic neoplasms, including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), were selected as outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with gut microbiota were chosen as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary MR analysis to assess the causal relationship. External validation An was conducted using an independent. Sensitivity analyses were performed to ensure robustness. Reverse MR analysis was also conducted to assess potential reverse causation.

Results

Combining discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower UF risk (OR: 0.882, 95% CI: 0.793-0.982, P = 0.022). Conversely, higher OC incidence is associated with increased relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019–1.732, P = 0.036). Sensitivity analyses confirmed these findings’ reliability. Reverse MR analysis showed no evidence of reverse causation between UF, OC, and Lachnospiraceae.

Discussion

This study establishes a causal relationship between Lachnospiraceae relative abundance and both UF and OC. These findings provide new insights into the potential role of gut microbiota in mechanisms underlying gynecological tumors development.
Seasonal environmental factors drive microbial community succession and flavor quality during acetic acid fermentation of Zhenjiang aromatic vinegar
Authors: Ye Xiaoting , Yu Yongjian , Liu Jiaxin , Zhu Yuanyuan , Yu Zhen , Liu Peng , Wang Yuqin , Wang Ke
Published: August 2024

This study investigated the impact of seasonal environmental factors on microorganisms and flavor compounds during acetic acid fermentation (AAF) of Zhenjiang aromatic vinegar (ZAV). Environmental factors were monitored throughout the fermentation process, which spanned multiple seasons. Methods such as headspace solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), high performance liquid chromatography (HPLC), and high-throughput sequencing were employed to examine how these environmental factors influenced the flavor profile and microbial community of ZAV. The findings suggested that ZAV brewed in autumn had the strongest flavor and sweetness. The key microorganisms responsible for the flavor of ZAV included Lactobacillus acetotolerans, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, Acetobacter pasteurianus. Moreover, correlation analysis showed that room temperature had a significant impact on the composition of the microbial community, along with other key seasonal environmental factors like total acid, pH, reducing sugar, and humidity. These results provide a theoretical foundation for regulating core microorganisms and environmental factors during fermentation, enhancing ZAV quality.
Interplay between immune cells and metabolites in epilepsy: insights from a Mendelian randomization analysis
Authors: Wang Kai , Yang Jinwei , Xu Wenhao , Wang Lei , Wang Yu
Published: August 2024

Background

Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy.

Methods

We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1,400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results.

Results

MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI, −0.008, −30.6%, p = 0.049) of the effect of DN (CD4−CD8−) AC on epilepsy. 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI, 0.668, 10.6%, p = 0.026) and X-12544 levels (95%CI, −15.1, −0.856%, p = 0.028) contributed 5.63 and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy.

Conclusion

This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives.
The involvement of effector memory CD4+ T cells in mediating the impact of genus Oscillibacter gut microbiota on Alzheimer’s disease: a Mendelian randomization study
Authors: Zhang Huachang , Wang Yudong , Zhao Hui , Wang Wei , Han Fabin
Published: August 2024

Objective

This study aimed to investigate the causal relationship between gut microbiota characteristics (207 taxa and 205 pathways) and Alzheimer’s disease and determine and quantify the role of immune cells as potential mediators.

Methods

Gut microbiota characteristics (207 taxa and 205 pathways) were obtained from the NHGRI-EBI GWAS Catalog project, while Alzheimer’s disease data and 731 immune cell characteristics were obtained from the IEU Open GWAS project. Two-sample Mendelian randomization (MR) was conducted to determine whether gut microbiota characteristics (207 taxa and 205 pathways) were causally related to Alzheimer’s disease. Furthermore, two-step MR was employed to quantify the proportion of the effect of immune cell characteristics mediated by gut microbiota characteristics (207 taxa and 205 pathways) on Alzheimer’s disease.

Results

A total of 17 immune cell characteristics were identified as potential mediators for 13 gut microbiota influencing Alzheimer’s disease, with Effector Memory CD4+ T-cell Absolute Count accounted for 8.99% of the causal relationship between genus Oscillibacter and Alzheimer’s disease.

Conclusion

In summary, our research confirms a causal relationship between gut microbiota and Alzheimer’s disease, with immune cells contributing to a significant portion of the effect. However, the full mediators of gut microbiota’s impact on Alzheimer’s disease remain unclear. Further investigation is warranted to explore additional potential risk factors acting as mediators.
The arrangements of the microvasculature and surrounding glial cells are linked to blood–brain barrier formation in the cerebral cortex
Authors: Shigemoto-Mogami Yukari , Nakayama-Kitamura Kimiko , Sato Kaoru
Published: August 2024

The blood–brain barrier (BBB) blocks harmful substances from entering the brain and dictates the central nervous system (CNS)-specific pharmacokinetics. Recent studies have shown that perivascular astrocytes and microglia also control BBB functions, however, information about the formation of BBB glial architecture remains scarce. We investigated the time course of the formation of BBB glial architecture in the rat brain cerebral cortex using Evans blue (EB) and tissue fixable biotin (Sulfo-NHS Biotin). The extent of the leakage into the brain parenchyma showed that the BBB was not formed at postnatal Day 4 (P4). The BBB gradually strengthened and reached a plateau at P15. We then investigated the changes in the configurations of blood vessels, astrocytes, and microglia with age by 3D image reconstruction of the immunohistochemical data. The endfeet of astrocytes covered the blood vessels, and the coverage rate rapidly increased after birth and reached a plateau at P15. Interestingly, microglia were also in contact with the capillaries, and the coverage rate was highest at P15 and stabilized at P30. It was also clarified that the microglial morphology changed from the amoeboid type to the ramified type, while the areas of the respective contact sites became smaller during P4 and P15. These results suggest that the perivascular glial architecture formation of the rat BBB occurs from P4 to P15 because the paracellular transport and the arrangements of perivascular glial cells at P15 are totally the same as those of P30. In addition, the contact style of perivascular microglia dramatically changed during P4-P15.
Exploring the biological basis of acupuncture treatment for traumatic brain injury: a review of evidence from animal models
Authors: Wu Minmin , Song Wenjing , Teng Lili , Li Jinting , Liu Jiayu , Ma Hanwen , Zhang Ge , Zhang Jiongliang , Chen Qiuxin
Published: August 2024

Traumatic brain injury (TBI) occurs when external physical forces impact the brain, potentially causing long-term issues such as post-traumatic stress disorders and cognitive and physical dysfunctions. The diverse nature of TBI pathology and treatment has led to a rapid acceleration in research on its biological mechanisms over the past decade. This surge presents challenges in assessing, managing, and predicting outcomes for TBI cases. Despite the development and testing of various therapeutic strategies aimed at mitigating neurological decline after TBI, a definitive cure for these conditions remains elusive. Recently, a growing focus has been on preclinical research investigating acupuncture as a potential treatment method for TBI sequelae. Acupuncture, being a cost-effective non-pharmacological therapy, has demonstrated promise in improving functional outcomes after brain injury. However, the precise mechanisms underlying the anticipated improvements induced by acupuncture remain poorly understood. In this study, we examined current evidence from animal studies regarding acupuncture’s efficacy in improving functional outcomes post-TBI. We also proposed potential biological mechanisms, such as glial cells (microglia astrocytes), autophagy, and apoptosis. This information will deepen our understanding of the underlying mechanisms through which acupuncture exerts its most beneficial effects post-TBI, assisting in forming new clinical strategies to maximize benefits for these patients.
H7N7 viral infection elicits pronounced, sex-specific neuroinflammatory responses in vitro
Authors: Gabele Lea , Bochow Isabell , Rieke Nele , Sieben Christian , Michaelsen-Preusse Kristin , Hosseini Shirin , Korte Martin
Published: August 2024

Influenza A virus (IAV) infection can increase the risk of neuroinflammation, and subsequent neurodegenerative diseases. Certain IAV strains, such as avian H7N7 subtype, possess neurotropic properties, enabling them to directly invade the brain parenchyma and infect neurons and glia cells. Host sex significantly influences the severity of IAV infections. Studies indicate that females of the reproductive age exhibit stronger innate and adaptive immune responses to IAVs compared to males. This heightened immune response correlates with increased morbidity and mortality, and potential neuronal damage in females. Understanding the sex-specific neurotropism of IAV and associated mechanisms leading to adverse neurological outcomes is essential. Our study reveals that primary hippocampal cultures from female mice show heightened interferon-β and pro-inflammatory chemokine secretion following neurotropic IAV infection. We observed sex-specific differences in microglia activation: both sexes showed a transition into a hyper-ramified state, but only male-derived microglia exhibited an increase in amoeboid-shaped cells. These disparities extended to alterations in neuronal morphology. Neurons derived from female mice displayed increased spine density within 24 h post-infection, while no significant change was observed in male cultures. This aligns with sex-specific differences in microglial synaptic pruning. Data suggest that amoeboid-shaped microglia preferentially target postsynaptic terminals, potentially reducing neuronal hyperexcitability. Conversely, hyper-ramified microglia may focus on presynaptic terminals, potentially limiting viral spread. In conclusion, our findings underscore the utility of primary hippocampal cultures, incorporating microglia, as an effective model to study sex-specific, virus-induced effects on brain-resident cells.
Data-driven and equation-free methods for neurological disorders: analysis and control of the striatum network
Authors: Spiliotis Konstantinos , Köhling Rüdiger , Just Wolfram , Starke Jens
Published: August 2024

The striatum as part of the basal ganglia is central to both motor, and cognitive functions. Here, we propose a large-scale biophysical network for this part of the brain, using modified Hodgkin-Huxley dynamics to model neurons, and a connectivity informed by a detailed human atlas. The model shows different spatio-temporal activity patterns corresponding to lower (presumably normal) and increased cortico-striatal activation (as found in, e.g., obsessive-compulsive disorder), depending on the intensity of the cortical inputs. By applying equation-free methods, we are able to perform a macroscopic network analysis directly from microscale simulations. We identify the mean synaptic activity as the macroscopic variable of the system, which shows similarity with local field potentials. The equation-free approach results in a numerical bifurcation and stability analysis of the macroscopic dynamics of the striatal network. The different macroscopic states can be assigned to normal/healthy and pathological conditions, as known from neurological disorders. Finally, guided by the equation-free bifurcation analysis, we propose a therapeutic close loop control scheme for the striatal network.
Therapeutic approaches targeting seizure networks
Authors: Langbein Jenna , Boddeti Ujwal , Kreinbrink Matthew , Khan Ziam , Rampalli Ihika , Bachani Muzna , Ksendzovsky Alexander
Published: August 2024

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50% of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.