bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ED50 and ED95 of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy: a prospective, double-blinded trial
Authors: Xu Zhongling , Lang Yantao , Xu Xiaolei , Deng Linjuan , Song Hengya , Yin Dekun 
Published: November 2023

AbstractBackgroundThis study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy.Methods54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon’s up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions.ResultsThe ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05).ConclusionsIn this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively.Trial registrationChiCTR2200066663, 13/12/2022.
Patient perspective on task shifting from general practitioners to medical practice assistants – a quantitative survey in Germany
Authors: Kuschick Doreen , Dierks Marius Tibor , Grittner Ulrike , Heintze Christoph , Kümpel Lisa , Riens Burgi , Rost Liliana , Schmidt Konrad , Schulze Daniel , Toutaoui Kahina , Wolf Florian , Döpfmer Susanne 
Published: November 2023

Abstract
Introduction
Various developments result in increasing workloads in general practices. New models of care and a restructuring of the division of tasks could provide relief. One approach is to extend the delegation of medical tasks from general practitioners (GPs) to medical practice assistants (MPAs). So far, there has been a lack of information about specific situations in which patients are willing to be treated exclusively by MPAs.

Methods
In three German federal states, patients who visited a general practice were surveyed exploratively and cross-sectionally with a self-designed, paper-based questionnaire. The data were analysed descriptively and multivariate. A mixed binary logistic regression model was calculated to account for cluster effects at practice level (random intercept model). The dependent variable was patients' acceptance of task delegation.

Results
A total of 1861 questionnaires from 61 general practices were included in the analysis. Regarding the current problem/request, a total of 30% of respondents could imagine being treated only by MPAs. Regarding theoretical reasons for consultation, more than half of the patients agreed to be treated by MPAs. According to the regression model, MPAs were preferred when patients were younger (10-year OR = 0.84, 95%-CI [0.75, 0.93]) or had a less complicated issue (OR = 0.44, 95%-CI [0.26, 0.8]). For four current problems/requests (“acute complaints” OR = 0.27, 95%-CI [0.17, 0.45], “routine health check” OR = 0.48, 95%-CI [0.3, 0.79], “new problem” OR = 0.13, 95%-CI [0.06, 0.28], “known problem” OR = 0.16, 95%-CI [0.1, 0.27]) patients prefer to be treated by GPs instead of MPAs.

Discussion
For the first time, statements could be made on patients’ acceptance of task delegation in relation to current and theoretical reasons for treatment in general practices in Germany. The discrepancy in response behaviour on a theoretical and individual level could be explained by different contexts of questions and differences at practice level. Overall, patients seem to be open to increased delegation of medical tasks, depending on the reason for treatment. Selection and response biases should be considered in the interpretation.

Conclusion
The results are not completely opposed to an extension of task delegation. Further interventional studies could provide information on the possible effects of expansion of delegable tasks.
COVID 19 infection clinical features in pediatric patients in Southwestern Iran: a cross-sectional, multi-center study
Authors: Jamalidoust Marzieh , Jalil Mohsen , Ashkan Zahra , Sharifi Moslem , Hemmati Rouhollah , Dashti Anahita Sanaei , Kadivar Mohammad Rahim , Pouladfar Gholamreza , Amanati Ali , Hamzavi Seyeheh Sedigheh , Asaie Sadaf , Eskandari Maryam , Aliabadi Nasrin , Ziyaeyan Mazyar 
Published: November 2023

AbstractWith the SARS-CoV-2 pandemic, the impact of recent coronavirus, especially in children, cannot be ignored. In this study, we evaluated the SARS-CoV-2 infection rates and associated features in children less than 18 years of age in “Fars” and “Kohgiluyeh and Boyer Ahmad”, provinces, Iran. 5943 children who were suspected cases to SARS-CoV-2 infection were enrolled in this study. Demographic and clinical data of SARS-CoV-2 patients were collected from 16 February 2020 to 20 June 2021. Underlying conditions were considered in this study as well. Among 5943 patients suspected COVID 19 cases, 13.51% were confirmed by real-time PCR assay. The female/male ratio was 1:1.3 with a mean age of 5.71 years. 11.2% of confirmed patients were transferred and admitted in Pediatric ICU. COVID 19 was significantly higher in children with malignancy and diabetes rather than those with other underlying diseases. Children of all ages were susceptible to COVID 19, and there is no significant difference between both sexes. Most of the COVID 19 cases were in 10–18 years old group. Among a number of children with different underlying diseases, children with malignancy had the highest rate of SARS-CoV-2 infection, followed by those with diabetes.
Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data
Authors: Zou Yanzheng , Yue Ming , Jia Linna , Wang Yifan , Chen Hongbo , Zhang Amei , Xia Xueshan , Liu Wei , Yu Rongbin , Yang Sheng , Huang Peng 
Published: November 2023

Abstract
Background
Most existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model.

Methods
A total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison.

Results
During a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838–0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively).

Conclusions
Our longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.
Finite element analysis of the angle range in trans-inferior alveolar nerve implantation at the mandibular second molar
Authors: Wu Wenli , Song Liangyue , Liu Jinming , Du Lingyi , Zhang Yuhang , Chen Yingying , Tang Zichun , Shen Ming 
Published: November 2023

Abstract
Background
Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle.

Methods
Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height < 9 mm in the edentulous area were selected. The distances from the mandibular nerve canal to the buccal cortex, the lingual cortex and the alveolar ridge crest were measured by using a combination of software. The angular ranges of the buccal-lingual inclination of simulated trans-IAN implants were measured and three-dimensional finite element models were constructed in the mandibular second molar area according to the differences of the inclination angles. A vertical load (200N) was then applied to analyze the biomechanical conditions of the implant-bone interface during median occlusion.

Results
The distance at the second molar from the nerve canal to the buccal cortex, lingual cortex and alveolar crest were 6.861 ± 1.194 mm, 2.843 ± 0.933 mm and 7.944 ± 0.77 mm. Trans-IAN implantation was feasible in 73.33% of patients. The minimum angle and maximum angles of the buccal-lingual inclination of the simulated implant were 19.135 ± 6.721° and 39.282 ± 6.581°. When a vertical static load of 200N was applied, the tensile stress in cortical bone gradually increased with the increase of the implant tilt angle. When the inclination angle reached 30°, the tensile stress (105.9 MPa) exceeded the yield strength (104 MPa) of cortical bone. Compared with the conventional implants, the stress peak value of the vertical ultra-short implant in cortical bone was greater than the stress peak value of the conventional implants at 10°(79.81 MPa) and 20°(82.83 MPa) and was smaller than the stress of the implant at 30°(105.9 MPa) and 40°(107.8 MPa). Therefore, when the bone mass allows, conventional-length implants should be selected whenever possible, and an operative range of the trans-IAN implantation in the mandibular second molar could be retained with an inclination angle of < 30°.

Conclusions
The mandibular nerve canal at the mandibular second molar was obviously biased to the lingual side, which ensured sufficient bone mass at the buccal side. In most patients with severe mandibular atrophy, it was possible to maintain a safe distance from the nerve canal with conventional-length implants via the trans-IAN implantation technique.
Time to complete contemporary dental procedures – estimates from a cross-sectional survey of the dental team
Authors: Bannister Christian , Cope Anwen Louise , Karki Anup , Harper Paul , Peddle Sarah , Walters Brenda , Allen Michael , Chestnutt Ivor Gordon 
Published: November 2023

Abstract
Background
There are few contemporary studies on the time taken to complete dental procedures, those most heavily relied on in the United Kingdom date back to 1999.

Objectives
This work aimed to establish how long members of the dental team took to complete specific dental procedures, relevant to their scope of practice.

Methods
Data were collected via a purposive sample of 96 dentists, dental hygienists/therapists and dental nurses. Via an online survey, participants were asked to state the mean, minimum and maximum time they estimated that they took to complete individual dental procedures.

Results
The mean time taken to complete procedures common to both dentists and dental hygienists/therapists ranged from 3.7 to 4 min respectively for clinical note reading prior to seeing patients to 30.1 and 28 min to undertake root surface debridement. There were no significant differences between the time taken by dentists and dental hygienists/therapists to treat adult patients. However, in all but one procedure, dental hygienists/therapists reported taking longer (p = 0.04) to treat child patients.

Conclusions
The data provided here represent an up to date assessment of the time taken to complete specific tasks by different members of the dental team. These data will be of value to service planners and commissioners interested in evolving a dental care system that employs a greater degree of skill-mix and preventively oriented care.
Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer
Authors: Wang Ganggang , Zhang Hao , Shen Xiaowei , Jin Wenzhi , Wang Xiaoliang , Zhou Zhijie 
Published: November 2023

AbstractTriple-negative breast Cancer (TNBC) is a highly malignant cancer with unclear pathogenesis. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) vitally influence tumor onset and progression. Thus, this research aimed to identify distinct subgroups of CAF using single-cell and TNBC-related information from the GEO and TCGA databases, respectively. The primary aim was to establish a novel predictive model based on the CAF features and their clinical relevance. Moreover, the CAFs were analyzed for their immune characteristics, response to immunotherapy, and sensitivity to different drugs. The developed predictive model demonstrated significant effectiveness in determining the prognosis of patients with TNBC, TME, and the immune landscape of the tumor. Of note, the expression of GPR34 was significantly higher in TNBC tissues compared to that in other breast cancer (non-TNBC) tissues, indicating that GPR34 plays a crucial role in the onset and progression of TNBC. In summary, this research has yielded a novel predictive model for TNBC that holds promise for the accurate prediction of prognosis and response to immunotherapy in patients with TNBC.
Role of arachidonic acid metabolism in intervertebral disc degeneration: identification of potential biomarkers and therapeutic targets via multi-omics analysis and artificial intelligence strategies
Authors: Tan Jianye , Shi Meiling , Li Bin , Liu Yuan , Luo Shengzhong , Cheng Xigao 
Published: November 2023

Abstract
Background
Intervertebral disc degeneration (IVDD) is widely recognized as the primary etiological factor underlying low back pain, often necessitating surgical intervention as the sole recourse in severe cases. The metabolic pathway of arachidonic acid (AA), a pivotal regulator of inflammatory responses, influences the development and progression of IVDD.

Methods
Initially, a comparative analysis was conducted to investigate the relationship between AA expression patterns and different stages of IVDD using single-cell sequencing (scRNA-seq) data. Additionally, three machine learning methods (LASSO, random forest, and support vector machine recursive feature elimination) were employed to identify hub genes associated with IVDD. Subsequently, a novel artificial intelligence prediction model was developed for IVDD based on an artificial neural network algorithm and validated using an independent dataset. The identified hub genes were further subjected to functional enrichment, immune infiltration, and Connectivity Map analysis. Moreover, external validation was performed using flow cytometry and real-time reverse transcription polymerase chain reaction analysis.

Results
Both scRNA-seq and bulk RNA-seq data revealed a positive correlation between the severity of IVDD and the AA metabolic pathway. They also revealed increased AA metabolic activity in macrophages and neutrophils, as well as enhanced intercellular communication with nucleus pulposus cells. Utilizing advanced machine learning algorithms, five hub genes (AKR1C3, ALOX5, CYP2B6, EPHX2, and PLB1) were identified, and an incipient diagnostic model was developed with an AUC of 0.961 in the training cohort and 0.72 in the validation cohort. An in-depth exploration of the functionality of these hub genes revealed their notable association with inflammatory responses and immune cell infiltration. Lastly, AH6809 was found to delay IVDD by inhibiting AKR1C3.

Conclusions
This study offers comprehensive insights into potential biomarkers and small molecules associated with the early pathogenesis of IVDD. The identified biomarkers and the developed integrated diagnostic model hold great promise in predicting the onset of early IVDD. AH6809 was established as a therapeutic target for AKR1C3 in the treatment of IVDD, as evidenced by computer simulations and biological experiments.
Fluorescence-enhanced dual signal lateral flow immunoassay for flexible and ultrasensitive detection of monkeypox virus
Authors: Yang Xingsheng , Cheng Xiaodan , Wei Hongjuan , Tu Zhijie , Rong Zhen , Wang Chongwen , Wang Shengqi 
Published: November 2023

AbstractThe outbreak of the monkeypox virus (MPXV) worldwide in 2022 highlights the need for a rapid and low-cost MPXV detection tool for effectively monitoring and controlling monkeypox disease. In this study, we developed a flexible lateral flow immunoassay (LFIA) with strong colorimetric and enhanced fluorescence dual-signal output for the rapid, on-site, and highly sensitive detection of the MPXV antigen in different scenarios. A multilayered SiO2-Au core dual-quantum dot (QD) shell nanocomposite (named SiO2-Au/DQD), which consists of a large SiO2 core (~ 200 nm), one layer of density-controlled gold nanoparticles (AuNPs, 20 nm), and thousands of small QDs, was fabricated instead of a traditional colorimetric nanotag (i.e., AuNPs) and a fluorescent nanotag (QD nanobead) to simultaneously provide good stability, strong colorimetric ability and superior fluorescence intensity. With the dual-signal output LFIA, we achieved the specific screening of the MPXV antigen (A29L) in 15 min, with detection limits of 0.5 and 0.0021 ng/mL for the colorimetric and fluorometric modes, respectively. Moreover, the colorimetric mode of SiO2-Au/DQD-LFIA exhibits the same sensitivity as the traditional AuNP- LFIA, whereas the overall sensitivity of this method on the basis of the fluorescent signal can achieve 238- and 3.3-fold improvements in sensitivity for MPXV compared with the AuNP-based LFIA and ELISA methods, respectively, indicating the powerful performance and good versatility of the dual-signal method in the point-of-care testing of the MPXV.
Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis
Authors: Guo Jie , Miao Yuqing , Nie Fayi , Gao Fei , Li Hua , Wang Yuan , Liu Qi , Zhang Tingbin , Yang Xiaohang , Liu Li , Fan Haiming , Wang Qiang , Qiao Haifa 
Published: November 2023

AbstractSepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn2+-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.
Role of hypermethylated SLC5A8 in follicular thyroid cancer diagnosis and prognosis prediction
Authors: Yang Yan , Liao Chenjin , Yang Qian , Li Yuxia , Tang Yunxiang , Xu Bin 
Published: November 2023

Abstract
Objective
Thyroid cancer is one of the most frequently reported endocrine system malignancies. It is difficult to distinguish follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) during pathological diagnosis in patients without lymph nodes or distant metastases. Therefore, we conducted a retrospective study to investigate the significance of SLC5A8 methylation and expression in the diagnosis and prognosis of FTC.

Methods
We used 165 tissue samples, including FTC (n = 58), thyroid tumors of uncertain malignant potential (TT-UMP, n = 40), and FTA (n = 67), to explore the differences in SLC5A8 methylation and mRNA transcription in different pathological types. Survival analysis was conducted to evaluate the recurrence rate at a 5-year follow-up.

Results
The SLC5A8 methylation positive rate was higher in patients with thyroglobulin ≥ 40 μg/l and Chol ≥ 5.17 mmol/l, and it was higher in patients with FTC (n = 42, 72.4%) than those with FTA (n = 27, 40.3%) and TT-UMP (n = 23, 57.5%). The relative concentration of SLC5A8 mRNA was lower in patients with FTC than in those with FTA (p < 0.05). At 5-year follow-ups, patients who were SLC5A8 methylation-positive had a higher recurrence rate than those who were methylation-negative.

Conclusions
Our current study indicates that SLC5A8 gene methylation occurs more commonly in patients with FTC than in those with FTA. The differences in SLC5A8 methylation and expression among FTA, FTC, and TT-UMP provide an important basis for further exploration of epigenetic changes in the occurrence, development, and prognosis of thyroid cancer. Our findings need to be further validated in larger populations with long-term follow-up in the future.