bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proposed Confidence Ellipse Approach for Benefit-Risk Assessment in Clinical Trials
Authors: Zhang Yinuo , Zhang Xiaofang , Wang Peijing , Wu Yangfeng , Chow Shein-Chung 
Published: October 2024

Abstract

In clinical development, an independent data safety monitoring committee (IDMC) is often established to ensure the test treatment's integrity, quality, safety, and efficacy under investigation. In clinical trials, IDMC may recommend stopping the trial early due to safety, futility/efficacy, or both after reviewing observed data in the interim based on pre-specified stopping boundaries. In practice, the interim data is often too small to reach clinically meaningful differences with statistical significance (i.e., the observed clinically meaningful difference is reproducible and not purely by chance alone). To provide an overall assessment (or complete clinical picture) of the performance of the test treatment under investigation, the FDA (2023) published guidance on the benefit-risk assessment (BRA) framework to facilitate IDMC decision-making. Several methods have been studied in the literature following the FDA's recommended framework. However, these methods did not consider the uncertainties and heterogeneities. Alternatively, a BRA approach is proposed based on a confidence ellipse of primary safety and efficacy endpoints. The proposed confidence ellipse approach was evaluated both theoretically and via a clinical trial simulation. The results indicate that the proposed confidence ellipse provides consistent and stable metrics, particularly as sample sizes increase. The derived metrics of Benefit-Risk Difference (BRD) and Benefit-Risk Ratio (BRR) showed favorable performance across different scenarios and thresholds. Applied to the TESTING trial data, our method confirmed and extended the original finding that a reduced methylprednisolone dose offered a more favorable benefit-risk profile. Specifically, the confidence ellipse method highlighted that the reduced dose consistently provided a better balance between efficacy and safety, particularly under stricter criteria for clinical significance. This method validated the original conclusions and provided additional insights into how different dosing regimens perform across various clinical scenarios, potentially offering a more refined tool for optimizing treatment decisions in complex therapeutic contexts.
Improving clinical expertise in large language models using electronic medical records
Authors: Zhu Lifeng , Liu Jingping , Wang Jiacheng , Zhang Weiyan , Jiang Sihang , Yang Hai , Wang Chao , Ye Qi , Ruan Tong , Rui Xinkai , Chen Huajun 
Published: October 2024

Abstract

Electronic medical records (EMRs) are essential in clinical practice. Although current medical large language models (LLMs) excel in tasks like US Medical Licensing Examination, they struggle with real-world clinical applications due to insufficient large-scale EMR data in their training, hindering their clinical expertise. To address this limitation, we proposed EMR-LLM, an LLM for clinical practice using EMRs. Firstly, we continually pre-trained a general LLM on medical corpora to enhance its domain knowledge. Then, we designed three categories of instruction tasks using EMRs: structure understanding, numerical understanding, and downstream tasks. Finally, we introduced an ability-boosting instruction-tuning method, which mimics human learning, progressing from simple to complex tasks while introducing a data replay strategy to retain learned knowledge. Experimental results demonstrated that EMR-LLM outperformed strong competitors on six EMR tasks, nine medical benchmarks, and three open-domain benchmarks. Moreover, in discharge summary generation, EMR-LLM achieved performance levels close to those of expert clinicians.
Plant-Derived Recombinant Macromolecular PAP-IgG Fc as A Novel Prostate Cancer Vaccine Candidate Eliciting Robust Immune Responses
Authors: Kang Yangjoo , Kim Deuk-Su , Hwang Hyunjoo , Seo Young-Jin , Hinterdorfer Peter , Ko Kisung 
Published: October 2024

Abstract

Prostatic acid phosphatase (PAP) is a specific protein that is highly expressed in prostate cancer. In this study, we constructed two recombinant PAP fusion genes: PAP fused to the immunoglobulin G (IgG) Fc fragment (designated PAP-Fc) and PAP-Fc fused to the endoplasmic reticulum retention sequence KDEL (designated PAP-FcK). Transgenic Nicotiana tabacum plants expressing these recombinant macromolecular proteins (MPs) were generated using Agrobacterium-mediated transformation, and the presence of both genes was confirmed through genomic PCR. Western blot analysis validated the expression of PAP-Fc and PAP-FcK MPs, which were successfully purified via protein A affinity chromatography. Size-exclusion high-performance liquid chromatography revealed dimeric peaks for PAP-Fc (PAP-FcP) and PAP-FcK (PAP-FcKP). Bio-transmission electron microscopy demonstrated 'Y'-shaped protein particles resembling antibody structures. Moreover, PAP-FcP and PAP-FcKP exhibited a high association rate with human FcγR and FcRn. Vaccination of mice with both PAP-FcP and PAP-FcKP resulted in increased total IgG against PAP and enhanced activation of CD4+ T cells, comparable to mice immunized with PAP, which served as a positive control. These findings indicate that both plant-derived MPs can effectively induce adaptive immunity, positioning them as promising candidates for prostate cancer vaccines. Overall, plants expressing PAP-Fc and PAP-FcK represent a viable production system for antigenic macromolecule-based prostate cancer vaccines.
Contrasting recovery of metagenome‑assembled genomes and derived microbial communities from lizard fecal and cloacal samples
Authors: Hernández Mauricio , Langa Jorge , Aizpurua Ostaizka , Navarro-Noya Yendi E. , Alberdi Antton 
Published: October 2024

Abstract

Genome-resolved metagenomics, based on shotgun sequencing, has become a powerful strategy for investigating animal-associated microbiomes, due its heightened capability for delivering detailed taxonomic, phylogenetic, and functional insights compared to amplicon sequencing-based approaches. While genome-resolved metagenomics holds promise across various non-lethal sample types, their effectiveness in yielding high-quality metagenome-assembled genomes (MAGs) remains largely unexplored. Our investigation of fecal and cloacal microbiota of the mesquite lizards (Sceloporus grammicus) using genome-resolved metagenomics revealed that fecal samples contributed 97% of the 127 reconstructed bacterial genomes, whereas only 3% were recovered from cloacal swabs, which were largely enriched with host DNA. Taxonomic, phylogenetic and functional alpha microbial diversity was greater in fecal samples than in cloacal swabs. We also observed significant differences in microbial community composition between sampling methods, and higher inter-individual variation in cloacal swabs. Bacteroides, Phocaeicola and Parabacteroides (all Bacteroidota) were more abundant in the feces, whereas Hafnia and Salmonella (both Pseudomonadota) increased in the cloaca. Functional analyses showed that metabolic capacities of the microbiota to degrade polysaccharides, sugars and nitrogen compounds were enriched in fecal samples, likely reflecting the role of the microbiota in nutrient metabolism. Overall, our results indicate that fecal samples outperform cloacal swabs in characterizing microbial assemblages within lizards using genome-resolved metagenomics.
Development and performance analysis of a novel triple-anode plasma torch with annular powder feeding for high-efficiency powder processing
Authors: Fan Ying , Yu Deping , Qiu Jier , Xiao Yu , Qu Yun , Gao Zhengjiang , Zhang Fei , Zhang Jian 
Published: October 2024

Abstract

Direct current (DC) plasma torches play a pivotal role in the field of material processing, with their performance largely determined by the characteristics of the plasma jet. However, conventional DC plasma torches produce a plasma jet that has a small high-temperature region and a high velocity, which limits their powder processing rate. This paper introduces a novel triple-anode plasma torch (TAPT) equipped with annular powder feeding to address these challenges. Comprehensive investigation into the plasma jet characteristics of the TAPT was carried out through a combination of experimental measurements and numerical simulations. Results show that the TAPT produces an optimal plasma jet for powder processing, marked by a large high-temperature region, low velocity, and high uniformity. The plasma jet's peak temperature reaches over 20,000 K, with a 4,000 K region of 150 mm in length and 33 mm in diameter, and minimal regions exceeding a velocity of 80 m/s. The annular powder feeding of the TAPT guarantees a stable plasma jet for effective material processing, with the arc voltage exhibiting a small standard deviation of just 1.08 V. Furthermore, the TAPT’s efficacy in powder processing was exemplified by spheroidization trials involving aluminum oxide powder, which yielded an impressive energy efficiency of approximately 4.35 kWh/kg. Overall, the TAPT shows considerable potential in the field of powder processing, specifically in raising the efficiency of powder spheroidization processes.
Magnetic carbon bead-based concentration method for SARS-CoV-2 detection in wastewater
Authors: Angga Made Sandhyana , Raya Sunayana , Hirai Soichiro , Haramoto Eiji 
Published: October 2024

Abstract

Wastewater surveillance for pathogens is important to monitor disease trends within communities and maintain public health; thus, a quick and reliable protocol is needed to quantify pathogens present in wastewater. In this study, a method using a commercially available magnetic carbon bead-based kit, i.e., the Carbon Prep (C.prep) method (Life Magnetics), was employed to detect and quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as bacteriophage Phi6 and pepper mild mottle virus (PMMoV) in wastewater samples. The performance of this method was evaluated by modifying several steps and comparing it with the polyethylene glycol (PEG) precipitation method to demonstrate its applicability to virus detection in wastewater. The protocol of the C.prep method, based on the manufacturer’s instructions, could not detect SARS-CoV-2 RNA, while the optimized protocol could detect it in the tested samples at concentrations that were not significantly different from those obtained using the PEG precipitation method. However, the optimized C.prep method performed more poorly in recovering Phi6 and detecting PMMoV than the PEG precipitation method. The results of this study indicated that the full workflow of the C.prep method was not sufficient to detect the target viruses and that an additional RNA extraction step was needed to remove inhibitors in wastewater.
In-silico inhibitory Activities of Tribulusamide D Against Cannabinoid Receptor (CB1)
Authors: MOHAMMED Isiaka , KOMOLAFE Tomilayo Modupe , OSANYINBI Adetoro Ajibike , EBIEKPI Alison Michael , ADEKUNLE Olawale Kabir , OLADOSU Ibrahim Adebayo 
Published: October 2024

Abstract

Many women experience the effect of excess endocannabinoid production in the body by noticing some changes such as anxiety, the effect on learning and memory, reproduction and sex, metabolism, growth, and development. Others take cannabinoids as drugs. Cannabinoids are known to have anti-depressant properties but are also inhibitors of sexual urges. Research has shown that cannabinoids reduce dopamine levels, hence the need to inhibit the activities of cannabinoid receptors found all over the body, especially the brain. This research focuses on in-silico inhibition of cannabinoid receptors which serve as a precursor to the metabolism of cannabinoids. A Cannabinoid Receptor (CB1) PDB was downloaded (7V3Z) from https://www.rcsb.org. The protein was prepared, the sitemap identified and the receptor grid generated too. Tribulusamide D (TD) is a natural product isolated from Tribullus terrestris and has been confirmed to have anti-inflammatory activities. TD was drawn using the 2-D sketcher and copied to the 3-D workspace of the maestro Schrodinger suite. The native ligand, 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol was used as the reference drug (since it acts as an agonist to the receptor) and was prepared using ligprep module. The prepared protein and ligands were docked using the ligand docking module of the Maestro Schrodinger suite. The docking of the ligands with CB1 shows that Tribulusamide D has a better docking score with a higher negative value than the reference drug and hence could enhance sexual urge when the desire is inhibited by excess cannabi. In-vivo and in-vitro research is recommended to confirm the inhibitory activities of Tribulusamide D against CB1 as predicted by this study.
Performance Evaluation and Optimization of Graphene Nanosheet FET
Authors: Abdul-kadir Firas Natheer , Mohammad Khalid khaleel , Abdulqader Hussein Ali AL , Smaani Billel 
Published: October 2024

Abstract

Graphene Nanosheet Field Effect Transistor (GNSFET) is constructed for the first time (using grapheme material) and simulated by Silvaco TCAD Tools it can be considered as a novelty work in Nanosheet FET design. This paper study and explore the effects of the device dimensions’ variation for 2-nanosheets GNSFET device. The variation in dimension of the gate length (Lg = 14,16 and 18) nm, gate width (Wg = 12,14 and 16) nm, and gate height (Hg = 6,7 and 8) nm are to be considered for the evaluation and optimization of the designed GNSFET performances. In addition, the performances and characteristics of the 2-nanosheets GNSFET device have been compared with that of 3- Nanosheets GNSFET device. Several nanosheet performance factors have been taken into consideration throughout the optimization process, including the following: on-current (ION), off-current (IOFF), ION/IOFF ratio, Sub threshold Swing (SS), Drain Induced Barrier Lowering (DIBL) and Trans conductance (gm). ION/IOFF ratio which represents the device switching capability is improved to 1.77e+10 at Lg=14 nm, Wg=14 nm and Hg=7 nm. The Sub Threshold Swing (SS) in this paper approaches the ideal value of 60 mV/dec which insure the device's improved gate control. The value of SS= 61.23 mV/dec at Lg = 18 nm, Wg=14 nm and Hg=7nm was obtained. The value of DIBL is between 1.28 mV/V and 31.05 mV/V. Finally, the resulted value of gm is 71.36 µS at Lg=14 nm, Wg=14 nm and Hg=7 nm.
The proposal and application of the "Suture Formula" make single port laparoscopic myomectomy simpler and more efficient: a retrospective cohort study
Authors: Wu Yihan , Jia Qiucheng , Tang Huimin , Chen Wanying , Yu Yi , Wei Weiwei , Tang Bin , Chen Jiming 
Published: October 2024

Abstract

Background: Single-port laparoscopic surgery offers unique minimally invasive and cosmetic results and facilitates the patient's postoperative recovery.In transumbilical single-port laparoscopic myomectomy, suturing of the uterine wound is a critical intraoperative step.Due to the difficulty of operating with a single hole, it takes longer to suture the uterine wound, which somewhat increases the potential risk and limits the development of this procedure.This study describes the technique of the "suture formula" and compares it with the traditional randomized suture pattern.
Materials and Methods:The author's team summarized the uterine incision selection and suture pattern in single-port laparoscopic myomectomy, conceptualizing the steps of uterine incision selection and suture closure to reduce unnecessary intraoperative backstitching and thread winding operations.In this study, we retrospectively analyzed 91 patients who underwent transumbilical single-port laparoscopic myomectomy and compared the intraoperative and postoperative indices between the two groups.
Results:Surgical time, intraoperative bleeding, and hemoglobin drop were lower in the "suture mode" group than in the traditional randomized suture group (p<0.05).There was no statistically significant difference between the "suture formula" group and the traditional randomized suture group in terms of the number of days of postoperative hospitalization, the time to the first postoperative anal evacuation, the VAS score at 12h postoperatively, the VAS score at 24h postoperatively, and the postoperative complications (P > 0.05).Suture pattern (Beta: -19, P=0.043), number of leiomyosarcomas (Beta: 43, P=0.002), maximum diameter of the tumor (Beta: 6.2, P=0.032), and BMI (Beta: 4.0, P=0.018) were the factors influencing the duration of surgery.Suture pattern (Beta: -46, p=0.011), and maximum tumor diameter (Beta: 13, p=0.027) were the factors influencing intraoperative bleeding.
Conclusion:The "Suture Formula" technique conceptualizes the selection of the uterine incision and the suture steps, which reduces the difficulty of the operation and ensures the hemostatic effect while reducing the unnecessary inverted needle and thread wrapping during the operation, thus shortening the operation time and improving the efficiency of the operation.The use of the "suture formula" does not increase the risk of surgery or the incidence of surgical complications compared with conventional single-port laparoscopic myomectomy.This suture pattern provides a new breakthrough in single-port laparoscopic myomectomy.
medicX-KE: A Knowledge Graph for Pharmacists’ Drug Information Needs
Authors: Farrugia Lizzy , Azzopardi Lilian M. , Debattista Jeremy , Abela Charlie 
Published: October 2024

Abstract

The contribution of pharmacists to patient care is evolving from the traditional role of dispensing medicine to that of providing pharmaceutical services within a multidisciplinary healthcare context. An important component for this transformation towards a holistic patient-centric approach is the availability of relevant and up-to-date information about medicinal products that leverages a robust data collection mechanism. Over the past decade, Knowledge Graphs (KGs) have rev-olutionised the organisation and utilisation of vast biomedical data. Powered by Artificial Intelligence (AI) and advanced inferencing techniques, KGs unlock the potential to derive valuable insights, discover hidden relationships, and enable data-driven decision making. In this paper, we present the medicX-KE knowledge graph that is tailored to the Maltese pharmaceutical landscape. The KG serves as a centralised repository, integrating data from several authoritative sources, including DrugBank and the British National Formulary (BNF). We present a specific use case for our KG that relies on information related to medicine provided by the Malta Medicines Authority (MMA). In addition, we conducted interviews with six pharmacists to understand their needs and to obtain feedback on the suitability of the KG. We describe data acquisition, mappings, ontology design, construction, and evaluation of medicX-KE, and discuss the challenges faced and potential future enhancements.
Deriving water quality index using site-specific water quality parameter guidelines for real-time water quality stations
Authors: Rahman Shibly , Khan Amir Ali , Brake Kyla , Tobin Annette 
Published: October 2024

ABSTRACT
The Newfoundland and Labrador Real-Time Water Quality (RTWQ) monitoring program operates a network of surface water monitoring stations, measuring physical water quality parameters in near-real-time. The network generates vast amounts of data which are too complex for many stakeholders to interpret. While the CCME Water Quality Index (WQI) has been a valuable tool to simplify and summarize ambient quality of water, its use in RTWQ is virtually non-existent. This is largely due to the lack of alignment between the limited number of parameters from real-time networks, and availability of aquatic Water Quality Guidelines. This paper is the first attempt to outline a method of utilizing real-time water quality data to generate site specific water quality guidelines using Background Concentration method. Using these guidelines, we compute weekly WQI scores for select monitoring stations and examine how score is influenced by stage and precipitation. The influence of each parameter on the RTWQ WQI score is also plotted. Comparison is made between the Canadian Environmental Sustainability Indicator (CESI) WQI and RTWQ WQI yearly scores. The paper also discusses the challenges and benefits of using this methodology as well as the sensitivity of WQI scoring at stations with various anthropogenic influences.
Environmental monitoring of heavy metal content in the hydrographic network of a large city river
Authors: Popovych Vasyl , Kopylov Viktor 
Published: October 2024

ABSTRACT

Samples of edaphotopes were taken from a depth of 0–15 cm for analyses in this study. It was found that the water in the areas of the Hnidavske swamp and Teremniv ponds was the most polluted. The level of Zn (0.01 mg/dm3) exceeded the maximum permissible concentration (MPC) at site 5 (Lypnyany village, outside the city of Lutsk, the content was 0.015 mg/dm3) and Hnidavske marsh (0.019 mg/dm3). At all study sites, Cr (0.001 mg/dm3) ranging from 0.002 to 0.005 mg/dm3, Co (0.005 mg/dm3) from 0.008 to 0.01 mg/dm3, and Ni (0.01 mg/dm3) from 0.02 to 0.036 mg/dm3 were also found to exceed the MPC. However, Cd levels (0.005 mg/dm3) did not exceed the MPC and was within the normal range at all study sites (0.0016–0.003 mg/dm3).
Anchored Chitosan-Functionalized Magnetite Nanoparticles for Crystal Violet Decolorization from Aqueous Samples
Authors: Bandari Mahsa , Galangash Mohsen Mohammadi , Shariati Shahab , Ghavidast Atefeh 
Published: October 2024

Introduction:
In this research, 3-(triethoxysilyl)propyl isocyanate (TESPIC) functionalized
chitosan was successfully synthesized to fabricate silica-coated magnetite nanoparticles
(Fe3O4@SiO2-CS MNPs).

Method:
The synthesized MNPs were characterized using XRD, FT-IR, SEM, and TEM instruments
and were utilized for the decolorization of Crystal Violet cationic dye (CV). The affecting
variables controlling CV removal efficiency were investigated using the Taguchi fractional factorial
design method (L16 array).

Result:
Under the optimized removal conditions (adsorbent amount = 0.12 g (4.8 g L-1), pH = 4,
ionic strength = 0.05 mol L-1 NaCl, and 30 min stirring), 98.2% of the CV dye was eliminated.
The kinetic and equilibrium adsorption isotherms were explained by the pseudo-second-order kinetic
(R2 = 0.999) and Freundlich isotherm models, respectively. MATLAB’s fmincon function
as an efficient solution was applied in order to compare the Redlich-Peterson three-parametric
isotherm model with two-parametric models. Moreover, the Fe3O4@SiO2-CS-TESPIC MNPs
showed recyclability and reusability for subsequent runs

Conclusion:
The findings confirmed that these functional MNPs can be considered as proper adsorbents
for the removal of CV dye from the aqueous solutions