bluuebunny/crossref_metadata_2025 huggingface dataset:
ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma
Authors: Fan Yugeng , Yan Dujuan , Ma Lijun , Liu Xiaoxi , Luo Guoqiang , Hu Yan , Kou Xin
Published: January 2024

Despite numerous reports indicating the significant impact of RNA modification on malignant glioblastoma (GBM) cell behaviors such as proliferation, invasion and therapy efficacy, its specific involvement in glioblastoma (GBM) angiogenesis is remains unclear and is currently under investigation. In this study, we aimed to investigate the relevance between RNA modification regulators and GBM angiogenesis. Our study employed bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), differential expression analysis, and Kaplan–Meier survival analysis, to identify regulators of angiogenesis-associated RNA modification (RM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to identify the enrichment of angiogenesis associated signatures in ALKBH5-high expression GBMs. We also utilized Western blot to verify the upregulation of ALKBH5 in clinical GBM samples. By a series of in vitro and in vivo assays, including plasmid transfection, wound healing, transwell invasion test, tube formation, RT-qPCR, ELISA assays and xenograft mice model, we validated the angiogenesis regulation ability of ALKBH5 in GBM. The N6-methyladenosine (m6A) modification “erase” ALKBH5 emerged as a candidate regulator associated with angiogenesis, demonstrating elevated expression and robust prognostic predictive ability in GBM patients. We also revealed enrichment of vasculature development biological process in GBMs with high ALKBH5 expression. Subsequently, we validated the elevated the expression of ALKBH5 in clinical GBM and paired adjacent tissues through western blot. Additionally, we knocked down the expression of ALKBH5 using sh-RNAs in U87 GBM cells to access the angiogenesis induction ability in U87 cells. In vitro experiments, Human Umbilical Vein Endothelial Cells (HUVECs) were used to perform wound healing, transwell migration and tube formation analysis, results indicated that ALKBH5 knock-down of U87 cells could decrease the pro-angiogenesis ability of U87 GBM cells. Further validation of our bioinformatic findings confirmed that ALKBH5 knockdown impaired VEGFA secretion in both in vitro and in vivo settings in U87 cells. These results comprehensively affirm the crucial role of ALKBH5 in regulating GBM-induced angiogenesis, both in vitro and in vivo. ALKBH5 not only emerges as a promising prognostic factor for GBM patients, but also plays a pivotal role in sustaining GBM progression by promoting angiogenesis.
Integrated guidance and control design by active disturbance rejection method for high-velocity target interceptor with DCS thruster
Authors: Chitsaz Ali , Naghash Abolghasem , Saberi Farhad Fani
Published: January 2024

The present paper proposes a novel integrated guidance and control (IGC) method for engaging with high-speed targets such as ballistic projectiles. considering an extreme short period of terminal engagement due to high relative velocity between target and interceptor, it is particularly important for IGC law to show desirable performance in the presence of various uncertainties (e.g. variation in aerodynamic coefficients) and disturbances (e.g. target maneuver and drag). This article extends the ICG law for mismatched and feedback form equations based on the Active Disturbance Rejection Control (ADRC) method using the back-stepping technique and the Reduced-order Extended State Observer (RESO). The primary consideration is the application of thrusters on the center of mass as the Divert Control System (DCS), along with the daisy-chain technique for control allocation between the fins and thruster commands. Contrary to previous research, the filter and angle measurement error are modeled for the seeker as a crucial parameter to highlight the significance of the thruster. The simulation results indicate the efficiency of the developed method for near-miss or hit-to-kill engagement with tactical ballistic targets. It is shown that the thruster plays a significant role in high-altitude engagements, specifically in the presence of non-ideal seeker. Finally, using the Monte Carlo simulation, it is proved that adding inner loops to the developed technique will not remove the IGC’s advantage over the conventional approach and Non-singular Terminal Sliding Mode (NTSM) guidance law.
In vitro influence of PEG functionalized ZnO–CuO nanocomposites on bacterial growth
Authors: Jayanetti Madara , Thambiliyagodage Charitha , Liyanaarachchi Heshan , Ekanayake Geethma , Mendis Amavin , Usgodaarachchi Leshan
Published: January 2024

Polyethyleneglycol-coated biocompatible CuO–ZnO nanocomposites were fabricated hydrothermally varying Zn:Cu ratios as 1:1, 2:1, and 1:2, and their antibacterial activity was determined through the well diffusion method against the Gram-negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and the Gram-positive Staphylococcus aureus. The minimum inhibitory concentration and the minimum bactericidal concentration values of the synthesized samples were determined. Subsequently, the time synergy kill assay was performed to elucidate the nature of the overall inhibitory effect against the aforementioned bacterial species. The mean zone of inhibition values for all four samples are presented. The inhibitory effect increased with increasing concentration of the nanocomposite (20, 40 and 60 mg/ml) on all the bacterial species except for S. aureus. According to the MBC/MIC ratio, ZnO was found to be bacteriostatic for E. coli and P. aeruginosa, and bactericidal for S. aureus and K. pneumoniae. Zn:Cu 2:1 was bactericidal on all bacterial species. A bacteriostatic effect was observed on E. coli and P. aeruginosa in the presence of Zn:Cu 1:1 whereas, it showed a bactericidal effect on S. aureus and K. pneumoniae. Zn:Cu 1:2 exhibited a bacteriostatic effect on E. coli while a bactericidal effect was observed for E. coli, P. aeruginosa, and K. pneumoniae. The metal oxide nanocomposites were found to be more sensitive towards the Gram-positive strain than the Gram-negative strains. Further, all the nanocomposites possess anti-oxidant activity as shown by the DPPH assay.
A DFT study on CH3NH3MnBr3: a novel multiferroic organic–inorganic hybrid perovskite
Authors: Peng Kai , Zhang Ming , Wang Chao , Ma Linhao , Liu Yuqing , Zhao Junjie , Wang Ruzhi
Published: January 2024

Nowadays, ferroelectric organic–inorganic hybrid perovskite represents a crucial issue since it exhibits a huge potential to enhance solar cell efficiency significantly.
A lightweight smart contracts framework for blockchain‐based secure communication in smart grid applications
Authors: Faheem Muhammad , Kuusniemi Heidi , Eltahawy Bahaa , Bhutta Muhammad Shoaib , Raza Basit
Published: January 2024

Energy is a crucial need in today's world for powering homes, businesses, transportation, and industrial processes. Fossil fuels, such as oil, coal, and natural gas, have been the primary sources of energy for decades. However, there is growing recognition of the negative environmental impact of fossil fuels and the need to transition to cleaner and more sustainable sources of energy. Distributed Energy Resources , such as wind and solar offer several benefits including, reducing energy costs, increasing resiliency, and decreasing carbon emissions. However, the integration of () into the grid requires advanced communication and secure control strategies to ensure a stable and reliable grid operations. In this regard, a blockchain‐based industrial wireless sensor network can provide secure and resilience data transmission to facilitate intelligent integration, monitoring, and control of in the smart grid. In this research, a smart contracts framework in Solana called Advanced Solana Blockchain () is proposed for in the smart grid. The proposed scheme enables resilient and secure real‐time control and monitoring of in smart grids. The performance evaluations and security analysis illustrated that this scheme is secure, reliable, and suitable in terms of lightweight data sharing between in smart grids.
Pre‐insertion resistors temperature prediction based on improved WOA‐SVR
Authors: Dai Honghe , Mo Site , Wang Haoxin , Yin Nan , Fan Songhai , Li Bixiong
Published: January 2024

The pre‐insertion resistors (PIR) within high‐voltage circuit breakers are critical components and warm up by generating Joule heat when an electric current flows through them. Elevated temperature can lead to temporary closure failure and, in severe cases, the rupture of PIR. To accurately predict the temperature of PIR, this study combines finite element simulation techniques with Support Vector Regression (SVR) optimized by an Improved Whale Optimization Algorithm (IWOA) approach. The IWOA includes Tent mapping, a convergence factor based on the sigmoid function, and the Ornstein–Uhlenbeck variation strategy. The IWOA‐SVR model is compared with the SSA‐SVR and WOA‐SVR. The results reveal that the prediction accuracies of the IWOA‐SVR model were 90.2% and 81.5% (above 100°C) in the ± 3°C temperature deviation range and 96.3% and 93.4% (above 100°C) in the ± 4°C temperature deviation range, surpassing the performance of the comparative models. This research demonstrates that the method proposed can realize the online monitoring of the temperature of the PIR, which can effectively prevent thermal faults PIR and provide a basis for the opening and closing of the circuit breaker within a short period.
Purification, Molecular Docking and Cytotoxicity Evaluation of Bioactive Pentacyclic Polyhydroxylated Triterpenoids from Salvia urmiensis
Authors: Farimani Mahdi Moridi , Abbas-Mohammadi Mahdi , Ghorbannia-Dellavar Samira , Nejad-Ebrahimi Samad , Hamburger Matthias
Published: January 2024

Triterpenoids, as one of the largest classes of naturally occurring secondary metabolites in higher plants, are of interest due to their high structural diversity and wide range of biological activities. In addition to several promising pharmacological activities such as antimicrobial, antiviral, antioxidant, anti-inflammatory and hepatoprotective effects, a large number of triterpenoids have revealed high potential for cancer therapy through their strong cytotoxicity on cancer cell lines and, also, low toxicity in normal cells. So, this study was aimed at discovering novel and potentially bioactive triterpenoids from the Salvia urmiensis species. For this, an ethyl acetate fraction of the acetone extract of the aerial parts of the plant was chromatographed to yield five novel polyhydroxylated triterpenoids (1–5). Their structure was elucidated by extensive spectroscopic methods including 1D (1H, 13C, DEPT-Q) and 2D NMR (COSY, HSQC,
HMBC, NOESY) experiments, as well as HRESIMS analysis. Cytotoxic activity of the purified compounds was also investigated by MTT assay against the MCF-7 cancer cell line. Furthermore, a molecular docking analysis was applied to evaluate the inhibition potential of the ligands against the nuclear factor kappa B (NF-κB) protein, which promotes tumor metastasis or affects gene expression in cancer disease. The 1β,11β,22α-trihydroxy-olean-12-ene-3-one (compound 4) indicated the best activity in both in vitro and in silico assays, with an IC50 value of 32 µM and a docking score value of − 3.976 kcal/mol, respectively.
Antiproliferative and Antitelomerase Effects of Silymarin on Human Colorectal and Hepatocellular Carcinoma Cells
Authors: Rahimi Daruosh , Sharifi Roya , Jaberie Hajar , Naghibalhossaini Fakhraddin
Published: January 2024

Silymarin, a widely-used hepatoprotective agent, has shown antitumor properties in both in vitro and animal studies. Currently, there is limited knowledge regarding silymarinʼs antitelomerase effects on human colorectal cancer and hepatocyte carcinoma cells. In this study, we investigated the antiproliferative and antitelomerase effects of silymarin on four human colorectal cancer and HepG2 hepatocyte carcinoma cell lines. The cell viability and telomerase activity were assessed using MTT and the telomerase repeat amplification protocol assay, respectively. We also investigated the effects of silymarin on the expression of human telomerase reverse transcriptase and its promoter methylation in HepG2 cells by real-time RT-PCR and methylation-specific PCR, respectively. Silymarin treatment inhibited cell proliferation and telomerase activity in all cancer cells. After 24 h of treatment, silymarin exhibited IC50 values ranging from 19 – 56.3 µg/mL against these
cancer cells. A 30-min treatment with silymarin at the IC50 concentration effectively inhibited telomerase activity in cell-free extracts of both colorectal cancer and hepatocyte carcinoma cells. Treatment of HepG2 cells with 10 and 30 µg/mL of silymarin for 48 h resulted in a decrease in human telomerase reverse transcriptase expression to 75 and 35% of the level observed in the untreated control (p < 0.01), respectively. Treatment with silymarin (10, 30, and 60 µg/mL) for 48 h did not affect human telomerase reverse transcriptase promoter methylation in HepG2 cells. In conclusion, our findings suggest that silymarin inhibits cancer cell growth by directly inhibiting telomerase activity and downregulating its human telomerase reverse transcriptase catalytic subunit. However, silymarin did not affect human telomerase reverse transcriptase promoter methylation at the concentrations of 10 – 60 µg/mL used in this study.
Affinin, Isolated from Heliopsis longipes, Induces an Antihypertensive Effect That Involves CB1 Cannabinoid Receptors and TRPA1 and TRPV1 Channel Activation
Authors: Luz-Martínez Beatriz A. , Marrero-Morfa Dailenys , Luna-Vázquez Francisco J. , Rojas-Molina Alejandra , Ibarra-Alvarado César
Published: January 2024

In previous studies, we demonstrated that the ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels. However, it has not yet been demonstrated whether the EEH and affinin are capable of lowering high blood pressure. Therefore, the aim of the present study was to determine the effect of the oral administration of the EEH and affinin on the systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats and to explore the participation of cannabinoid receptors and transient receptor potential channels in the mechanism of action of this alkamide. Our results showed that the ethanolic extract of H. longipes and affinin significantly lowered systolic blood pressure
and induced an improvement in endothelial function, which is associated with increased serum nitric oxide levels. Inhibition of cannabinoid type 1 receptors by rimonabant (3 mg/kg), transient receptor potential ankyrin 1 channels by HC-030031 (8 mg/kg), and transient receptor potential vanilloid 1 channels by capsazepine (5 mg/kg) significantly decreased the antihypertensive effect induced by affinin, suggesting that the blood pressure-lowering effect of this alkamide involves activation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels.
Exploring strengths and weaknesses in health services research culture and capacity
Authors: Stormon Nicole , Lawrenson Peter , Rahmann Ann , Eames Sally , Gavin Nicole
Published: January 2024

Objective Fostering a research culture and enhancing research capacity within the workforce is essential for any health service aiming to provide evidence-based care. This study aims to explore the research culture and capacity in a community health service setting and provide a comparison to previous published research in other health service settings. Methods Participants were invited to complete a survey consisting of demographics and the Research Capacity and Culture (RCC) tool. Median and interquartile ranges were calculated for each RCC item and compared to three Australian and one international comparison. Results A total of 73 staff members from Metro North Community and Oral Health service participated. The team-level scores for the RCC were overall the lowest. Comparison to previously published research using the RCC indicated marginally higher scores for individual-level items in our study across all domains. Individual-level items were very weak to weakly correlated with the team and organisation-level RCC items. Strong to very strong correlations were found between a majority of the team and organisation-level items. Conclusions Team-level scores were substantially lower when compared to individual and organisational levels. The item ‘team leaders that support research’ was positively correlated with various organisation-level items, indicating that if the respondent perceived the team leader as a low supporter of research the respondent perceived several organisation items also poorly. As an important stakeholder in enabling research in a health service, organisations should investigate the challenges experienced by team leaders in facilitating research and the support or training they may need.
Yield and nutritional quality of intercropped forages for organic production in a hot-summer Mediterranean oak grassland ecosystem
Authors: Plaza Javier , Criado Marco , Morales-Corts M. Remedios , Pérez-Sánchez Rodrigo , Gómez-Sánchez M. Ángeles , Vázquez-de-Aldana Beatriz , Zabalgogeazcoa Iñigo , Palacios Carlos
Published: January 2024

Context Forage cultivation plays a pivotal role in sustaining ruminants in resource-limited ecosystems such as the hot-summer Mediterranean agroforestry systems of the Iberian Peninsula comprising oak trees (Quercus spp.) and grassland species. Intercropping techniques can enhance forage yields and nutritional quality. Aims This study assessed the yield and nutritional quality of organic forage mixtures in an Iberian oak grassland ecosystem. Methods Six forage associations were assessed over two growing seasons: vetch (Vicia sativa L.)–triticale (Triticum × Secale), vetch–rye (Secale cereale), vetch–oat (Avena sativa), pea (Pisum sativum L.)–triticale, pea–rye, and pea–oat. The data were analysed using a multivariate procedure. Key results Differences in forage composition influenced nutritional quality but not yield. Vetch-based associations exhibited higher crude protein, calcium, phosphorus, potassium, zinc, magnesium, manganese and sulfur contents, along with lower proportions of neutral-detergent fibre and ether extract. The vetch–oat mixture emerged as the highest quality association. Interannual variations in precipitation and temperature caused differences in forage yield, with greater values observed in 2020 than in 2019. Forage associations also had significantly higher nutritional quality in 2020 (increased protein and mineral content, and decreased neutral detergent fibre and lignin). Conclusions All forages demonstrated satisfactory performance and quality, even in the drier conditions of 2019, suggesting high resilience and adaptability to hot-summer Mediterranean oak grassland ecosystems. Implications The findings of this study are relevant for organic farmers in resource-limited ecosystems. This information empowers them to select the most suitable forage species based on the specific agroclimatic conditions of each growing season.
The provision of sexual and reproductive health information and services to travellers: an exploratory survey of Australian travel medicine clinicians
Authors: Warzywoda Sarah , Fowler James A. , Debattista Joe , Mills Deborah J. , Furuya-Kanamori Luis , Durham Jo , Lau Colleen L. , Mullens Amy B. , Istiko Satrio Nindyo , Santaolaya Carlos , Malhotra Juhi , Dean Judith A.
Published: January 2024

Background International travel can increase the risk of exposure to infectious diseases including sexually transmissible infections (STI). Pre-travel medical consultation provides an opportunity for travel-related health risk assessments and advice. This study explored how travel medicine clinicians integrate sexual and reproductive health (SRH) services into clinical practice. Methods A convenience sample of travel medicine clinicians completed a cross-sectional survey online or via hard-copy disseminated at an annual national Australian travel medicine conference. Results Of the 67 respondents, most (n, 51; 76.1%) had a postgraduate qualification relevant to travel medicine and 55.2% (n, 37) had worked in travel medicine for over 10 years. Only 22.4% (n, 15) reported conducting a SRH history/STI risk assessment for all travel patients. STI testing pre-departure was conducted on patient request (48, 71.6%), if symptomatic (32, 47.8%) or based on risk history (28, 41.8%). SRH information pre-departure was most frequently provided if prompted by patient questions (n, 42; 62.7%), or based on the patient’s history (n, 37; 55.2%). Over half the sample (n, 40; 59.7%) expressed interest in further training in SRH. Conclusion Providing and engaging with additional training may assist travel medicine clinicians to take a more proactive approach to SRH consultations and STI testing. Additional research is needed to explore models of care that will allow comprehensive SRH and STI services to be integrated into standard pre- and post-travel care.
Lived experiences with pre-exposure prophylaxis uptake and adherence among transgender women in Thailand: a qualitative study
Authors: Janamnuaysook Rena , Guo Yan , Yu Yeon Jung , Phanuphak Nittaya , Kawichai Surinda , MacDonell Karen , Jupimai Thidarat , Rongkavilit Chokechai , Wang Bo
Published: January 2024

Background Transgender women (TGW) are disproportionately affected by HIV, and HIV prevalence among TGW in Thailand has been increasing. Although oral daily pre-exposure prophylaxis (PrEP) is effective for HIV prevention, PrEP uptake and persistence among TGW have been low. This study aimed to provide a deeper understanding of TGW’s experiences with PrEP uptake and adherence, and to identify major barriers to PrEP use to inform intervention adaptation. Methods We interviewed 20 young TGW (six non-PrEP users, eight adherent, six non-adherent) and 10 health care providers from two HIV clinics in Bangkok, Thailand, in 2022. We focused on understanding challenges to PrEP use in this population using an interview guide based on a theoretical model of behaviour change and thematic content analysis. Results Thematic analysis identified major barriers to and facilitators of PrEP uptake and adherence. Barriers to PrEP initiation included low self-perceived HIV risk, concern about potential side-effects, patient burdens such as frequent HIV testing for prescription refills and social stigma against PrEP. Barriers to adherence included side-effects, inconvenient access to health services (especially during COVID-19 lockdowns), forgetfulness resulting from busy schedules and low self-perceived HIV risk. TGW also reported health care providers’ stigma against PrEP users deterred them from seeking further PrEP services. TGW identified major facilitators of PrEP initiation, including awareness about the benefits of PrEP, concern about risks of HIV and supportive social networks of PrEP users. As to PrEP regimens, most TGW participants reported a clear preference for long-lasting, injectable PrEP over daily oral PrEP. TGW and health care providers largely agreed on barriers and facilitators of PrEP use, but they differed in perceptions of HIV risk. Conclusions The results highlighted challenges and opportunities to improve the delivery of PrEP, as well as other sexually transmissable infection and mental health services, especially among TGW. Thus, there is an urgent need for developing effective intervention programs that could raise PrEP awareness and knowledge, reduce PrEP stigma, and improve PrEP delivery systems among TGW in Thailand.
Field-based generic empirical flame length–fireline intensity relationships for wildland surface fires
Authors: Rossa Carlos G. , Davim David A. , Sil Ângelo , Fernandes Paulo M.
Published: January 2024

Background Fireline intensity (If) quantifies the power of the fireline and is used for various purposes. If and flame length (Lf) are relatable to each other using an empirical power function, which has been considered fuel-specific. Aims The aim of this study was to develop generic Lf − If relationships based on a robust set of field head fires from the literature (n = 797) conducted worldwide in forest, shrubland and grassland. Methods Lf was determined from the base of the fuel bed for comparability across fires in different fuel heights, and the effect of vegetation type was examined. Key results Although If could be approximately described using the same function in forest and shrubland, fires in grassland required different fitted coefficients; we speculate that fuel particles’ surface area-to-mass ratio is the main fuel metric influencing flame structure. Conclusions Fuel-generic relationships for If are reasonably accurate and encompass the high end of surface fire If. Previous studies suggested their unviability, most likely because of limitations in the number of observations and data ranges, difficulty in objectively measuring Lf and variation in Lf definition. Implications The generic relationships presented in this work will be of interest for research and management purposes when specific models for If are non-existent.
Digital technologies to prevent falls in people living with dementia or mild cognitive impairment: a rapid systematic overview of systematic reviews
Authors: Eost-Telling Charlotte , Yang Yang , Norman Gill , Hall Alex , Hanratty Barbara , Knapp Martin , Robinson Louise , Todd Chris
Published: January 2024

Objective

Falls are a common cause of potentially preventable death, disability and loss of independence with an annual estimated cost of £4.4bn. People living with dementia (PlwD) or mild cognitive impairment (MCI) have an increased fall risk. This overview evaluates evidence for technologies aiming to reduce falls and fall risk for PlwD or MCI.

Methods

In October 2022, we searched five databases for evidence syntheses. We used standard methods to rapidly screen, extract data, assess risk of bias and overlap, and synthesise the evidence for each technology type.

Results

We included seven systematic reviews, incorporating 22 relevant primary studies with 1,412 unique participants. All reviews had critical flaws on AMSTAR-2: constituent primary studies were small, heterogeneous, mostly non-randomised and assessed as low or moderate quality. Technologies assessed were: wearable sensors, environmental sensor-based systems, exergaming, virtual reality systems. We found no evidence relating to apps. Review evidence for the direct impact on falls was available only from environmental sensors, and this was inconclusive. For wearables and virtual reality technologies there was evidence that technologies may differentiate PlwD who fell from those who did not; and for exergaming that balance may be improved.

Conclusions

The evidence for technology to reduce falls and falls risk for PlwD and MCI is methodologically weak, based on small numbers of participants and often indirect. There is a need for higher-quality RCTs to provide robust evidence for effectiveness of fall prevention technologies. Such technologies should be designed with input from users and consideration of the wider implementation context.
Effectiveness of low-density lipoprotein cholesterol reduction with lipid lowering therapy for secondary prevention amongst older individuals: a nationwide cohort study
Authors: Andersson Niklas W , Corn Giulia , Dohlmann Tine L , Melbye Mads , Wohlfahrt Jan , Lund Marie
Published: January 2024

Background

Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort.

Methods

Individuals aged ≥ 50 years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1 mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70 years old) using Cox regression.

Results

LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1 mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84–0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83–0.93; P-value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73–0.90) and younger (0.81, 95% CI 0.72–0.91) individuals.

Conclusions

This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70 years.
Optimal Regulatory Enforcement
Authors: Dari-Mattiacci Giuseppe , Raskolnikov Alex
Published: January 2024

Criminal law applies to everyone, but regulations constrain only those who choose to participate in a regulated activity. Firms considering such participation face three choices: comply with imperfectly enforced rules, violate them, or stay out of the activity altogether. Importantly, regulators not only punish violators but also reward firms with a strong record of compliance. We show that the presence of compliance-contingent rewards in a regime with optional participation unsettles several tenets of the traditional optimal deterrence model: (1) the maximal sanction may not be optimal, (2) it may be optimal to over-deter violations, (3) the probability and magnitude of sanctions may be complements rather than substitutes, (4) more frequent audits may have lower enforcement costs, and (5) the pursuit of a common enforcement objective of raising the rate of compliance may lead to lower welfare even if the overall deterrence level is too low. We illustrate the practical relevance of our findings and conclude that optimal regulatory enforcement is significantly more challenging than the basic deterrence model suggests. (JEL K10, K20, K42)
Advancements in bioinformatics and computational biology: 15th annual Polish Bioinformatic Society Symposium
Authors: Zyla Joanna , Tobiasz Joanna , Mika Justyna , Łabaj Paweł P , Gruca Aleksandra
Published: January 2024

The Polish Bioinformatic Society (PTBI) Symposium convenes annually at leading Polish Universities, and in 2023, the Silesian University of Technology hosted participants from all over the world. The 15th PTBI Symposium, spanning a 3-day duration and divided into four scientific sessions, gathered around 100 participants and centered on research related to machine learning in biomedicine, RNA structure algorithms, next-generation sequencing methods, and microbiome analysis but was not limited to only those topics. The meeting also recognized outstanding research conducted by young scientists by awarding the best poster and best talk. Finally, the awards for the best PhD, MSc, and BSc thesis in bioinformatics defended in Poland were given. This report summarizes the key highlights and outcomes of the meeting.
DIAgui: a Shiny application to process the output from DIA-NN
Authors: Gerault Marc-Antoine , Camoin Luc , Granjeaud Samuel
Published: January 2024

DIAgui is an R package to simplify the processing of the report file from the DIA-NN software thanks to a Shiny application. It returns the quantification of either the precursors, the peptides, the proteins, or the genes thanks to the MaxLFQ algorithm. In addition, the latest version provides the Top3 and iBAQ quantification and the number of peptides used for the quantification. In the end, DIAgui produces ready-to-interpret files from the results of DIA mass spectrometry analysis and provides visualization and statistical tools that can be used in a user-friendly way.

Availability and implementation

Code and documentation are available on GitHub at https://github.com/marseille-proteomique/DIAgui. The package is written in R and also uses C++ code. A vignette shows its use in an R command line workflow.
RespirAnalyzer: an R package for analyzing data from continuous monitoring of respiratory signals
Authors: Zhang Teng , Dong Xinzheng , Wang Dandan , Huang Chen , Zhang Xiaohua Douglas
Published: January 2024

Motivation

The analysis of data obtained from continuous monitoring of respiratory signals (CMRS) holds significant importance in improving patient care, optimizing sports performance, and advancing scientific understanding in the field of respiratory health.

Results

The R package RespirAnalyzer provides an analytic tool specifically for feature extraction, fractal and complexity analysis for CMRS data. The package covers a wide and comprehensive range of data analysis methods including obtaining inter-breath intervals (IBI) series, plotting time series, obtaining summary statistics of IBI series, conducting power spectral density, multifractal detrended fluctuation analysis (MFDFA) and multiscale sample entropy analysis, fitting the MFDFA results with the extended binomial multifractal model, displaying results using various plots, etc. This package has been developed from our work in directly analyzing CMRS data and is anticipated to assist fellow researchers in computing the related features of their CMRS data, enabling them to delve into the clinical significance inherent in these features.

Availability and implementation

The package for Windows is available from both Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/RespirAnalyzer/index.html and GitHub: https://github.com/dongxinzheng/RespirAnalyzer.
ClusterV-Web: a user-friendly tool for profiling HIV quasispecies and generating drug resistance reports from nanopore long-read data
Authors: Su Junhao , Li Shumin , Zheng Zhenxian , Lam Tak-Wah , Luo Ruibang
Published: January 2024

Third-generation long-read sequencing is an increasingly utilized technique for profiling human immunodeficiency virus (HIV) quasispecies and detecting drug resistance mutations due to its ability to cover the entire viral genome in individual reads. Recently, the ClusterV tool has demonstrated accurate detection of HIV quasispecies from Nanopore long-read sequencing data. However, the need for scripting skills and a computational environment may act as a barrier for many potential users. To address this issue, we have introduced ClusterV-Web, a user-friendly web-based application that enables easy configuration and execution of ClusterV, both remotely and locally. Our tool provides interactive tables and data visualizations to aid in the interpretation of results. This development is expected to democratize access to long-read sequencing data analysis, enabling a wider range of researchers and clinicians to efficiently profile HIV quasispecies and detect drug resistance mutations.

Availability and implementation

ClusterV-Web is freely available and open source, with detailed documentation accessible at http://www.bio8.cs.hku.hk/ClusterVW/. The standalone Docker image and source code are also available at https://github.com/HKU-BAL/ClusterV-Web.
HIVseqDB: a portable resource for NGS and sample metadata integration for HIV-1 drug resistance analysis
Authors: Ssekagiri Alfred , Jjingo Daudi , Bbosa Nicholas , Bugembe Daniel L , Kateete David P , Jordan I King , Kaleebu Pontiano , Ssemwanga Deogratius
Published: January 2024

Human immunodeficiency virus (HIV) remains a public health threat, with drug resistance being a major concern in HIV treatment. Next-generation sequencing (NGS) is a powerful tool for identifying low-abundance drug resistance mutations (LA-DRMs) that conventional Sanger sequencing cannot reliably detect. To fully understand the significance of LA-DRMs, it is necessary to integrate NGS data with clinical and demographic data. However, freely available tools for NGS-based HIV-1 drug resistance analysis do not integrate these data. This poses a challenge in interpretation of the impact of LA-DRMs, mainly for resource-limited settings due to the shortage of bioinformatics expertise. To address this challenge, we present HIVseqDB, a portable, secure, and user-friendly resource for integrating NGS data with associated clinical and demographic data for analysis of HIV drug resistance. HIVseqDB currently supports uploading of NGS data and associated sample data, HIV-1 drug resistance data analysis, browsing of uploaded data, and browsing and visualizing of analysis results. Each function of HIVseqDB corresponds to an individual Django application. This ensures efficient incorporation of additional features with minimal effort. HIVseqDB can be deployed on various computing environments, such as on-premises high-performance computing facilities and cloud-based platforms.

Availability and implementation

HIVseqDB is available at https://github.com/AlfredUg/HIVseqDB. A deployed instance of HIVseqDB is available at https://hivseqdb.org.
Predicting axillary metastasis in breast cancer using lymphatic contrast-enhanced ultrasound-guided fine-needle aspiration of one lymph node
Authors: Zhuang Lingling , Liu Jun , Xu Xiaoxiao , Sun Xing , Li Fan , Shi Qiusheng , Zhang Weituo , Du Lianfang , Jin Lifang
Published: January 2024

Objectives

Fine-needle aspiration (FNA) is a microinvasive method to diagnose lymph nodes. This study aims to determine the capability of lymphatic contrast-enhanced ultrasound (LCEUS)-guided FNA in predicting the axillary metastasis with the target of one lymph node (LN) in patients with breast cancer.

Methods

LCEUS was prospectively performed in 105 patients with breast cancer. The most suspicious LN was targeted based on the characters of LCEUS. FNA was performed in the LN, followed by localization using a guide wire. The detection of lymph cells and/or tumour cells was recognized as a puncture success. Cytologic diagnosis was compared with histologic diagnosis of wire-marked LN for diagnosing accuracy and compared with histologic diagnosis of axillary LNs for predicting accuracy.

Results

LCEUS-guided FNA was performed in all 105 female patients who underwent axillary dissection. The puncture success rates were 74.3%, 91.4%, and 97.1% for three sequential groups (P = .010). In diagnosing LN metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 89.7%, 100%, and 95.7%, respectively. In predicting axillary metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 81.4%, 100%, and 91.3%, respectively.

Conclusions

The microinvasive LCEUS-guided FNA of one lymph node can be an accurate method and may help predict axillary metastasis in patients with breast cancer.

Advances in knowledge

This study presented that LCEUS combined with FNA would be practical in clinic. The characters of LCEUS could indicate the suspicious LNs and promote the accuracy in predicting axillary metastasis.
Mal-positioned nasogastric feeding tubes: are medical students safe to identify them?
Authors: Chew Cindy , O’Dwyer Patrick J , Young David , Banziger Carina , Hope Sarah , Rodolfo Sana , Obaro Anu E
Published: January 2024

Objectives

Nasogastric tube (NGT) placement is listed against Clinical Imaging in the upcoming Medical Licensing Assessment—compulsory for every graduating UK medical student from 2025. This study aims to establish the ability of medical students to correctly identify the position of an NGT on Chest X-ray (CXR) and to evaluate a learning tool to improve student outcome in this area.

Methods

Fourth-year (MB4) and fifth-year (MB5) medical students were invited to view 20 CXRs with 14 correctly sited and 6 mal-positioned NGT. MB5 students (Intervention) were exposed to an online interactive learning tool, with MB4 students kept as control. One week later, both groups of students were invited to view 20 more CXRs for NGT placement.

Results

Only 12 (4.8%) of 249 MB5 students and 5 (3.1%) of 161 MB4 students correctly identified all the NGTs on CXRs. The number of students misidentifying 1 or more mal-positioned NGT as “safe to feed” was 129 (51.8%) for MB5 and 76 (47.2%) for MB4 students. This improved significantly (P < .001) following exposure to the learning tool with 58% scoring all CXRs correctly, while 28% scored 1 or more mal-positioned NGT incorrectly. Students struggled to determine if the NGT tip had adequately passed into the stomach. However, they failed to identify an NG tube in the lung (“never event”) in just one out of 1,108 opportunities.

Conclusion

Medical students’ ability to determine if the NGT was in the stomach remains suboptimal despite exposure to over 60 CXRs. Feeding NGT should be formally reported before use.

Advances in knowledge

This is the first attempt at quantifying graduating medical students’, and by inference junior doctors’, competence in safely identifying misplaced nasogastric feeding tubes. An online, experiential learning resource significantly improved their ability.
Deep learning for acute rib fracture detection in CT data: a systematic review and meta-analysis
Authors: Lopez-Melia Manel , Magnin Virginie , Marchand-Maillet Stéphane , Grabherr Silke
Published: January 2024

Objectives

To review studies on deep learning (DL) models for classification, detection, and segmentation of rib fractures in CT data, to determine their risk of bias (ROB), and to analyse the performance of acute rib fracture detection models.

Methods

Research articles written in English were retrieved from PubMed, Embase, and Web of Science in April 2023. A study was only included if a DL model was used to classify, detect, or segment rib fractures, and only if the model was trained with CT data from humans. For the ROB assessment, the Quality Assessment of Diagnostic Accuracy Studies tool was used. The performance of acute rib fracture detection models was meta-analysed with forest plots.

Results

A total of 27 studies were selected. About 75% of the studies have ROB by not reporting the patient selection criteria, including control patients or using 5-mm slice thickness CT scans. The sensitivity, precision, and F1-score of the subgroup of low ROB studies were 89.60% (95%CI, 86.31%-92.90%), 84.89% (95%CI, 81.59%-88.18%), and 86.66% (95%CI, 84.62%-88.71%), respectively. The ROB subgroup differences test for the F1-score led to a p-value below 0.1.

Conclusion

ROB in studies mostly stems from an inappropriate patient and data selection. The studies with low ROB have better F1-score in acute rib fracture detection using DL models.

Advances in knowledge

This systematic review will be a reference to the taxonomy of the current status of rib fracture detection with DL models, and upcoming studies will benefit from our data extraction, our ROB assessment, and our meta-analysis.
Imaging spectrum and complications of otogenic infections: insights into delayed diagnosis
Authors: Lo Eugene Sean , Kwok Hoi Ming , Pan Nin Yuan
Published: January 2024

Skull base osteomyelitis (SBO) is a late manifestation of complicated otogenic infections that presents a diagnostic challenge. Delayed or missed diagnoses lead to high morbidity and mortality and can be attributed to non-specific symptoms, subtle early radiologic findings, radiologic mimicry of nasopharyngeal carcinoma (NPC), and under-recognition from clinician and radiologists. This pictorial review aims to emphasize on early imaging recognition and distinction between SBO and NPC.
Changes in lumbar muscle diffusion tensor indices with age
Authors: Weedall Andrew D , Dallaway Alexander , Hattersley John , Diokno Michael , Hutchinson Charles E , Wilson Adrian J , Wayte Sarah C
Published: January 2024

Objective

To investigate differences in diffusion tensor imaging (DTI) parameters and proton density fat fraction (PDFF) in the spinal muscles of younger and older adult males.

Methods

Twelve younger (19-30 years) and 12 older (61-81years) healthy, physically active male participants underwent T1W, T2W, Dixon and DTI of the lumbar spine. The eigenvalues (λ1, λ2, and λ3), fractional anisotropy (FA), and mean diffusivity (MD) from the DTI together with the PDFF were determined in the multifidus, medial and lateral erector spinae (ESmed, ESlat), and quadratus lumborum (QL) muscles. A two-way ANOVA was used to investigate differences with age and muscle and t-tests for differences in individual muscles with age.

Results

The ANOVA gave significant differences with age for all DTI parameters and the PDFF (P < .01) and with muscle (P < .01) for all DTI parameters except for λ1 and for the PDFF. The mean of the eigenvalues and MD were lower and the FA higher in the older age group with differences reaching statistical significance for all DTI measures for ESlat and QL (P < .01) but only in ESmed for λ3 and MD (P < .05).

Conclusions

Differences in DTI parameters of muscle with age result from changes in both in the intra- and extra-cellular space and cannot be uniquely explained in terms of fibre length and diameter.

Advances in knowledge

Previous studies looking at age have used small groups with uneven age spacing. Our study uses two well defined and separated age groups.
Legacies of salient environmental experiences—insights from chemosensation
Authors: Dias Brian G
Published: January 2024

Evidence for parental environments profoundly influencing the physiology, biology, and neurobiology of future generations has been accumulating in the literature. Recent efforts to understand this phenomenon and its underlying mechanisms have sought to use species like rodents and insects to model multi-generational legacies of parental experiences like stress and nutritional exposures. From these studies, we have come to appreciate that parental exposure to salient environmental experiences impacts the cadence of brain development, hormonal responses to stress, and the expression of genes that govern cellular responses to stress in offspring. Recent studies using chemosensory exposure have emerged as a powerful tool to shed new light on how future generations come to be influenced by environments to which parents are exposed. With a specific focus on studies that have leveraged such use of salient chemosensory experiences, this review synthesizes our current understanding of the concept, causes, and consequences of the inheritance of chemosensory legacies by future generations and how this field of inquiry informs the larger picture of how parental experiences can influence offspring biology.