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Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3β/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton's duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100 mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24 h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3β/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3β/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fetal electrocardiogram (FECG) contains crucial information about the fetus during pregnancy, making the extraction of FECG signal essential for monitoring fetal health. However, extracting FECG signal from abdominal electrocardiogram (AECG) poses several challenges: (1) FECG signal is often contaminated by noise, and (2) FECG signal is frequently overshadowed by high-amplitude maternal electrocardiogram (MECG). To address these issues and enhance the accuracy of signal extraction, this paper proposes an improved Cycle Generative Adversarial Networks (CycleGAN) with integrated contrastive learning for FECG signal extraction. The model introduces a dual-attention mechanism in the generator of the generative adversarial network, incorporating a multi-head self-attention (MSA) module and a channel-wise self-attention (CSA) module to enhance the quality of generated signals. Additionally, a contrastive triplet loss is integrated into the CycleGAN loss function, optimizing training to increase the similarity between the extracted FECG signal and the scalp fetal electrocardiogram. The proposed method is evaluated using the ADFECG dataset and the PCDB dataset both from the Physionet. In terms of signal extraction quality, Mean Squared Error is reduced to 0.036, Mean Absolute Error (MAE) to 0.009, and Pearson Correlation Coefficient reaches 0.924. When validating the model performance, Structural Similarity Index achieves 95.54%, Peak Signal-to-Noise Ratio (PSNR) reaches 38.87 dB, and R-squared (R 2 ) attains 95.12%. Furthermore, the positive predictive value (PPV), sensitivity (SEN) and F1-score for QRS wave cluster detection on the ADFECG dataset also reached 99.56%, 99.43% and 99.50%, respectively. On the PCDB dataset, the positive predictive value (PPV), sensitivity (SEN) and F1-score for QRS wave cluster detection also reached 98.24%, 98.60% and 98.42%, respectively. All of them are higher than other methods. Therefore, the proposed model has important applications in effective monitoring of fetal health during pregnancy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Frailty, an age-related state of reduced physiological reserve, is often associated with lower socio-economic position (SEP). This systematic review synthesised observational studies assessing (i) the association between SEP and frailty prevalence; (ii) how changes in frailty status over time vary by SEP; and (iii) whether the association between frailty and clinical outcomes is modified by SEP., Methods: We searched three electronic databases from 2001 to 2023. We included observational studies measuring early-, mid-, and late-life indicators of SEP (education, income, wealth, housing, occupation, and area-based measures of multiple deprivation) and frailty (assessed using any validated measure). Screening and extraction were performed in duplicate. Findings were synthesised using narrative synthesis., Results: We included 383 studies reporting findings from 265 independent samples/cohorts across 64 countries. Lower SEP was associated with higher frailty prevalence across all indicators (childhood deprivation 7/8 studies, education 227/248, occupation 28/32, housing 8/9, income 98/108, wealth 39/44 and area-based deprivation 32/34). Lower SEP was also associated with higher frailty incidence (27/30), with greater odds of transitioning towards a more severe frailty state (35/43), lower odds of frailty reversion (7/11), and (in some studies) with more rapid accumulation of deficits (7/15). The relationship between frailty and mortality was not modified by SEP., Interpretation: Preventative measures across multiple levels of individual and structural inequality are likely to be required to reduce the rising levels of frailty. Resourcing of interventions and services to support people living with frailty should be proportionate to needs in the population to avoid widening existing health inequalities., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD). There is a growing prevalence of UC, but current conventional drugs lack efficacy. Carthamin yellow (CY) is a flavonoid compound extracted from safflower that is widely used and has various pharmacological effects. In the present study, we established colitis models in mice via DSS and in Caco-2 cells via lipopolysaccharide (LPS). Our results showed that CY treatment attenuated the symptoms of colitis by decreasing colonic pathological damage and improving disease activity index (DAI) scores. Notably, we observed that CY treatment decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) by inhibiting the NLRP3/Caspase-1/IL-1β and MAPK/NF-κB signaling pathways. Moreover, we verified that treatment with CY obviously improved intestinal barrier function in both DSS-induced mice and LPS-stimulated Caco-2 cells. Ferroptosis-related markers were assessed. CY attenuated DSS-induced colitis by inhibiting ferroptosis, as assessed by Fe 2+ accumulation, total antioxidant capacity (T-AOC), and reactive oxygen species (ROS), 4-hydroxynonenal (4-HNE), and glutathione (GSH) levels. Additionally, there was an increase in superoxide dismutase (SOD) and catalase (CAT) activity, as well as alterations in ferroptosis-related protein and gene expression (ACSL4, GPX4, SLC7A11, TfR1, and FTH1). Further analyses revealed that CY could inhibit ferroptosis via the Nrf2/GPX4 axis in both in vivo and RSL3-induced Caco-2 cell models. Importantly, the antiferroptotic and protective effects of CY were nullified by Nrf2 knockout in vivo and by the use of ML385 in vitro. In conclusion, the effects of CY on UC are strongly associated with the Nrf2 pathway. CY might be a potential candidate for the treatment of UC. Therefore, our results provide an important reference for investigating the mechanisms of flavonoid compounds involved in preventing inflammatory diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate binocular visual deficits at low to high spatial frequencies in patients with intermittent exotropia (IXT) after surgical correction, using the binocular orientation combination task., Methods: Thirteen patients whose IXT has been aligned surgically (17 ± 4.8 years old; 7 females) and 13 normal individuals (21.8 ± 2.5 years old; 6 females) were recruited. All participants had normal or corrected-to-normal visual acuity. The IXT patients had undergone surgery at least one month prior to the study and achieved successful eye alignment post-surgery. We measured participants' balance points (BPs), defined as the interocular contrast ratio (nondominant eye/dominant eye) when both eyes contributed equally to binocular combination, using the binocular orientation combination task at three spatial frequencies (0.5, 4.0, and 8.0 cycles/degree). The absolute values of log10(BP) (i.e., |logBP|) and the area under of the |logBP| versus spatial frequency curve were used to quantify the extent of binocular imbalance., Results: Surgery aligned the eye position of patients with IXT, with a postoperative exodeviation of -4.92 ± 4.29 prism diopters at distance. Participants' |logBP| values showed significant differences between groups, F(1,24) = 9.175, P = 0.006, and across spatial frequencies, F(2,48) = 7.127, P = 0.002. However, the interaction between group and spatial frequency was not significant, F(2,48) = 0.379, P = 0.687., Conclusions: Patients whose IXT has been alighted surgically experience binocular imbalance across a wide range of spatial frequencies, with greater binocular imbalance occurring at high spatial frequencies than low spatial frequencies.

Background: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP., Methods: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP., Results: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014)., Conclusions: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ying Deng et al.)

A comparative study was performed to investigate the physicochemical properties and protective effects of hydrochloric acid-resistant dextrin (H-RD), citric acid-resistant dextrin (C-RD) and tartaric acid-resistant dextrin (T-RD) on the metabolic disorders and intestinal microbiota for type 2 diabetes mellitus (T2DM) mice. T-RD had the minimum molecular weight, with the highest short chain (DP 6-12) proportion and resistant starch content. After 4-week intervention with the three resistant dextrins, the body weight and fasting blood glucose of T2DM mice were improved significantly, accompanied by the reduction of serum indexes (TG, TC, LDL-C, ALT, AST, CRE, BUN, FINS, and GSP), but the serum HDL-C and liver glycogen levels increased. Among the three RDs intervention groups, T-RD showed the most significant improvement, followed by C-RD and finally H-RD. The 16 s rDNA results indicated that oral administration of resistant dextrins favored the proliferation of specific gut microbiota, including Faecalibaculum, Parabacteroides and Dubosiella, and reduced the ratio of Firmicutes/Bacteroidota, which is beneficial for reducing insulin resistance. Herein, the findings supported that the resistant dextrins exhibited a remission effect on T2DM, providing a basis for the development of functional food adjuvants for T2DM treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To assess the efficacy of early rehabilitation program for VV-ECMO patients and observe the influence on the respiratory and skeletal muscles., Design: A cohort study., Setting: The study was conducted with VVECMO patients in a comprehensive ICU with 32 beds., Main Outcome Measures: Ultrasound measurements were performed on each patients on day 1, 4, 7, 10, and 14, including diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), intercostal muscle thickening fraction (ICMTF), thickness of the rectus femoris (RF), thickness of vastus intermedius (VI), and rectus femoris cross-sectional area (RF-CSA). Data on basic characteristics, results of ultrasound measurements, patients outcomes and adverse events were collected., Results: 22 patients received usual rehabilitation measures were set as the control group and 23 patients underwent early rehabilitation program were set as the study group. There were no differences in diaphragmatic excursion, diaphragmatic thickening fraction, intercostal muscle thickening fraction, thickness of rectus femoris, thickness of vastus intermedius, rectus femoris cross-sectional area between two groups on day 1 after VV-ECMO treatment (P > 0.05). The variation of diaphragmatic thickening fraction and intercostal muscle thickening fraction decreased on the day 7 and 14 after treatment (P < 0.05). The variation of vastus intermedius thickness and rectus femoris cross-sectional area in the study group was less compared with those in the control group on day 4, 7, 10 and 14. The ECMO duration in the study group was shorter than that in the control group (12.00 [10.00-16.25] days vs. 8.00 [6.00-12.25] days, P = 0.002), but there was no difference in the duration of mechanical ventilation., Conclusion: Early rehabilitation program can ameliorate muscle atrophy. We recommend implementation of our rehabilitation program in VV-ECMO patients. This program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively and perhaps improve quality of life for patients in the future., Implications for Clinical Practice: Early rehabilitation program put higher demands bedside nurses. It requires them to observe conditions of VVECMO patients closely, assess the feasibility of rehabilitation promptly, and monitor for any adverse reactions. Ultrasound measurement is a noninvasive and useful tool to assess muscle atrophy in ICU patients. Early rehabilitation program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yubiao Gai reports financial support was provided by Health Commission of Shandong Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: While there are various health literacy scales that exist, none of health literacy scale suitable for pregnant women with gestational diabetes mellitus (GDM). To address this gap, this study aimed to develop GDM health literacy scale and evaluate its psychometric properties., Methods: Based on the Delphi expert consultation, we developed the initial GDM health literacy scale. Item analysis was taken using a sample (n = 299) recruited in China to form formal scale. Additional participants (n = 395) completed survey to assess the internal consistency reliability, test-retest reliability, content validity, construct validity and criterion correlation validity of scale., Results: The scale performed well in terms of internal consistency reliability, content validity, construct validity and criterion correlation validity. Test-retest reliability indicated that the instrument was effective at measuring health literacy of GDM over time., Conclusion: The scale is a reliable and valid measure of six domains of health literacy for GDM., Practice Implications: The scale can be used to effectively evaluate the level of health literacy of pregnant women with GDM. The information can provide targeted health support for pregnant women with GDM to improve their health literacy and self-management ability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: In trials, subgroup analyses are used to examine whether treatment effects differ by important patient characteristics. However, which subgroups are most commonly reported has not been comprehensively described., Design and Settings: Using a set of trials identified from the US clinical trials register (ClinicalTrials.gov), we describe every reported subgroup for a range of conditions and drug classes., Methods: We obtained trial characteristics from ClinicalTrials.gov via the Aggregate Analysis of ClinicalTrials.gov database. We subsequently obtained all corresponding PubMed-indexed papers and screened these for subgroup reporting. Tables and text for reported subgroups were extracted and standardised using Medical Subject Headings and WHO Anatomical Therapeutic Chemical codes. Via logistic and Poisson regression models we identified independent predictors of result reporting (any vs none) and subgroup reporting (any vs none and counts). We then summarised subgroup reporting by index condition and presented all subgroups for all trials via a web-based interactive heatmap (https://ihwph-hehta.shinyapps.io/subgroup&#95;reporting&#95;app/)., Results: Among 2235 eligible trials, 23% (524 trials) reported subgroups. Follow-up time (OR, 95%CI: 1.13, 1.04-1.24), enrolment (per 10-fold increment, 3.48, 2.25-5.47), trial starting year (1.07, 1.03-1.11) and specific index conditions (eg, hypercholesterolaemia, hypertension, taking asthma as the reference, OR ranged from 0.15 to 10.44), predicted reporting, sponsoring source and number of arms did not. Results were similar on modelling any result reporting (except number of arms, 1.42, 1.15-1.74) and the total number of subgroups. Age (51%), gender (45%), racial group (28%) were the most frequently reported subgroups. Characteristics related to the index condition (severity/duration/types etc) were frequently reported (eg, 69% of myocardial infarction trials reported on its severity/duration/types). However, reporting on comorbidity/frailty (five trials) and mental health (four trials) was rare., Conclusion: Other than age, sex, race ethnicity or geographic location and characteristics related to the index condition, information on variation in treatment effects is sparse., Prospero Registration Number: CRD42018048202., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases., (© 2024. The Author(s).)

Feline calicivirus (FCV) is one of the few members of the Caliciviridae family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (14) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.IMPORTANCEResearch on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism., Competing Interests: The authors declare no conflict of interest.

This study addresses the critical need for rapid and online measurement of liquid concentrations in industrial applications. Although the thermal lens effect (TLE) is extensively explored in laser systems for determining thermal lens focal lengths, its application in quantifying solution concentrations remains underexplored. This research explores the relationship between various liquid concentrations and the interference fringes induced by the TLE. A novel approach is introduced, utilizing TLE to measure solution concentrations, with integration of image processing and discrete Fourier transform (DFT) techniques for feature extraction from interference rings. Further, machine learning, specifically backpropagation artificial neural network (BP-ANN), is employed to model concentration measurement. The model demonstrates high accuracy, evidenced by low root mean square error (RMSE) values of 3.055 and 5.396 for the training and test sets, respectively. This enables precise, real-time determination of soy sauce concentration, offering significant implications for industrial testing, environmental monitoring, and other related fields.

Purpose: The study investigates the value of the BRAF V600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features., Methods: The study selected 176 patients with BRAF V600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAF V600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAF V600E mutation. The results were verified using a nomogram model., Results: The analysis results indicate that the BRAF V600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAF V600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (<4.14 pmol/L) were independent risk factors for BRAF V600E mutation. While considering all these factors in the nomogram, the Concordance index (C-index) remained high at 0.764. This suggests that the model has a good predictive effect., Conclusion: Ultrasound features including nodule size, taller-than-wide shape ≥1, ill-defined margins, irregular shape, higher TT4 levels, and lower FT3 levels were associated with papillary thyroid cancer aggressiveness and BRAF V600E mutation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment., (© 2024 The Authors. Journal of Evidence‐Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population. The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function. A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m 2 , and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g. The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis. Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney function., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aims to evaluate the morphological features of gubernacular tract (GT) for erupting permanent mandibular canines at different ages from 5 to 9 years old with a three-dimensional (3D) measurement method., Methods: The cone-beam CT images of 50 patients were divided into five age groups. The 3D models of the GT for mandibular canines were reconstructed and analysed. The characteristics of the GT, including length, diameter, ellipticity, tortuosity, superficial area, volume, and the angle between the canine and GT, were evaluated using a centreline fitting algorithm., Results: Among the 100 GTs that were examined, the length of the GT for mandibular canines decreased between the ages of 5 and 9 years, while the diameter increased until the age of 7 years. Additionally, the ellipticity and tortuosity of the GT decreased as age advanced. The superficial area and volume exhibited a trend of initially increasing and then decreasing. The morphological variations of the GT displayed heterogeneous changes during different periods., Conclusions: The 3D measurement method effectively portrayed the morphological attributes of the GT for mandibular canines. The morphological characteristics of the GT during the eruption process exhibited significant variations. The variations in morphological changes may indicate different stages of mandibular canine eruption., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: The purpose of this study was to provide an evidence map for explaining research trends and gaps. Four databases and CPGs-related websites were searched up to March 2022. Basic information, methodological quality, reporting quality of CPGs, and similar stroke recommendations were extracted. The methodological and reporting quality of stroke CPGs were evaluated using the AGREE II instrument and the RIGHT checklist. The bubble plot format of the evidence map helped visualize the overall quality. Data management and analysis were performed using Excel 2013 and SPSS 22.0 software. A total of 12 CPGs, published between 1997 and 2020 were included for in-depth analysis. The identified CPGs had a mixed quality and scored poorly in the developmental rigor and applicability domains by AGREE II. According to the RIGHT checklist, field four (clarity of expression) showed the highest (79.2%), and field three (rigor of formulation) secured the lowest (28%) reporting rates. The stroke rehabilitation recommendations primarily focused on organizational management, timing and intensity, rehabilitation and nutritional management of dysphagia, return to work, communication, speech, and language function. This would promote improvement in developing trustworthy CPGs for stroke rehabilitation., Competing Interests: Author Disclosures: The authors declare they have no conflict of interest in competing interest or financial benefits. And all the data is available., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

L-ergothioneine is widely distributed among various microbes to regulate their physiology and pathogenicity within complex environments. One of the key steps in the ergothioneine-biosynthesis pathway, the C-S bond cleavage reaction, uses the pyridoxal 5'-phosphate dependent C-S lyase to produce the final product L-ergothioneine. Here, we present the crystallographic structure of the ergothioneine-biosynthesis C-S lyase EgtE from Mycobacterium smegmatis (MsEgtE) represents the first published structure of ergothioneine-biosynthesis C-S lyases in bacteria and shows the effects of active site residues on the enzymatic reaction. The MsEgtE and the previously reported ergothioneine-biosynthesis C-S lyase Egt2 from Neurospora crassa (NcEgt2) fold similarly. However, discrepancies arise in terms of substrate recognition, as observed through sequence and structure comparison of MsEgtE and NcEgt2. The structural-based sequence alignment of the ergothioneine-biosynthesis C-S lyase from fungi and bacteria shows clear distinctions among the recognized substrate residues, but Arg348 is critical and an extremely conserved residue for substrate recognition. The α14 helix is exclusively found in the bacteria EgtE, which represent the most significant difference between bacteria EgtE and fungi Egt2, possibly resulting from the convergent evolution of bacteria and fungi., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the context of training specialist nurses and nursing education, a game-based mobile app was used as a simulation to teach intensive critical care specialist nurses the knowledge and skills of extracorporeal membrane oxygenation (ECMO) pipeline preflushing., Objective: This study aimed to evaluate the impact of a game-based mobile app on improving ECMO pipeline preflushing skills in intensive critical care specialist nurses., Methods: A total of 86 intensive critical care specialist nurses who were learning ECMO for the first time were included in this study. The nurses were divided into 2 groups: a control group (n=43) and an experimental group (n=43). Participants in the experimental group used a game-based mobile app for simulation exercises; the control group received no additional intervention. All participants took a theoretical test and a skill operation test at the beginning of the study and 1 week later. The differences in scores between the 2 groups were compared, and the learning curve of the experimental group was observed., Results: The final theoretical test scores (88.44 and 85.02) and skill operation test scores (89.42 and 86.33) of the experimental group and control group, respectively, were significantly higher than those of the initial tests (theoretical test scores: 75.88 and 74.42; skill operation test scores: 75.44 and 75.93; all P<.001). The scores of the final theoretical test (88.44) and the final skill operation test (89.42) in the experimental group were higher than the scores of the control group (85.02; P<.001 and 86.33; P<.001, respectively). Learning curve analysis showed that the experimental group needed an average of 17 operations to master the skill., Conclusions: This study suggests that a game-based mobile app may be more effective for intensive critical care specialist nurses in ECMO pipeline preflushing education than traditional Chinese lecture-practice education., (© Zihan Wang, Ruting Gu, Jingyuan Wang, Yubiao Gai, Hui Lin, Yan Zhang, Qianqian Li, Tong Sun, Lili Wei. Originally published in JMIR Serious Games (https://games.jmir.org).)

As an essential micronutrient, copper is crucial in aquatic organisms' growth and development. Numerous studies have consistently reported that excessive intake of copper can have harmful effects on organisms. However, there are limited studies on the impact of copper on the intestine of the swamp eel (Monopterus albus). This study aimed to investigate the changes of intestinal histopathology, tight junction complex, immune response, and microbiota in swamp eel treated with 0 mg/L Cu 2+ , 0.05 mg/L Cu 2+ , and 0.10 mg/L Cu 2+ for 56 d. Intestinal histopathology showed major changes such as the increased number of erythrocytes and goblet cells in the lamina propria, and separation of the lamina propria. The expression of genes involved in tight junction complex (ZO-1, Claudin-3, Claudin-12 and Claudin-15) was significantly changed. In addition, copper exposure significantly increased the mRNA levels of TLR3, TLR7, TLR8, NF-κB, I-κB, TNF-α and IL-8, especially in 0.10 mg/L Cu 2+ group. In contrast, the relative expression level of anti-inflammatory cytokine TGF-β was significantly decreased after exposure to copper. Analysis of the intestinal microbiome showed the intestinal microbiota of swamp eels in the control and copper exposure groups were dominated by Firmicutes and Proteobacteria at the phylum level. Notably, copper exposure changed the diversity of the intestinal microbiota and decreased the relative abundance of Firmicutes and Proteobacteria in the intestine of swamp eel. Collectively, this study demonstrates that chronic copper exposure induces intestinal pathologic changes and inflammatory response, disrupts the intestinal microbial diversity and microbiota composition, and decreases intestinal barrier function in swamp eel, which enhances our understanding of copper-induced intestinal toxicity in fish., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-β1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin's anti-fibrotic properties. Elevated levels of TGF-β1 ( p < 0.01) and alpha-smooth muscle actin (α-SMA) ( p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-β1-induced fibrosis by inhibiting SMAD phosphorylation ( p < 0.01) through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) ( p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) ( p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Wound healing is a dynamic and complex process in which the microenvironment at the wound site plays an important role. As a common material for wound healing, dressings accelerate wound healing and prevent external wound infections. Hydrogels have become a hot topic in wound-dressing research because of their high water content, good biocompatibility, and adjustable physical and chemical properties. Intelligent hydrogel dressings have attracted considerable attention because of their excellent environmental responsiveness. As smart polymer hydrogels, thermosensitive hydrogels can respond to small temperature changes in the environment, and their special properties make them superior to other hydrogels. This review mainly focuses on the research progress in thermosensitive intelligent hydrogel dressings for wound healing. Polymers suitable for hydrogel formation and the appropriate molecular design of the hydrogel network to achieve thermosensitive hydrogel properties are discussed, followed by the application of thermosensitive hydrogels as wound dressings. We also discuss the future perspectives of thermosensitive hydrogels as wound dressings and provide systematic theoretical support for wound healing., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: The COVID-19 pandemic posed a detrimental impact on the conduct of non-COVID-19 related clinical trials, raising concerns about the completeness of these studies and waste of resources. While several measures and strategies have been suggested to address these issues, a thorough and timely summarisation is still lacking. Therefore, our aim is to conduct a scoping review to summarise the negative effects of COVID-19 on non-COVID-19 clinical trials, outline the effective measures for mitigating these impacts, and provide insights for future pandemics., Methods and Analysis: This scoping review will be conducted in line with the Joanna Briggs Institute's scoping review methodological framework, and the results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Relevant articles will be searched in PubMed, Embase and the Cochrane Library from 1 December 2019 to 1 July 2023. We will also screen the reference lists of the included studies manually to identify more potentially relevant articles. Articles focusing on the adverse impacts of COVID-19 on non-COVID-19 clinical trials and effective measures for mitigating them will be included. Two investigators will perform study selection and data extraction independently. A narrative summary as well as a descriptive analysis of the basic characteristics and key results of the included studies will be performed., Ethics and Dissemination: Ethical approval is not required, as this scoping review will be completed based only on published literature. The findings of this scoping review will be disseminated through a peer-reviewed publication and/or conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Randomized controlled trials are the gold-standard for determining therapeutic efficacy, but are often unrepresentative of real-world settings. Statistical transportation methods (hereafter transportation) can partially account for these differences, improving trial applicability without breaking randomization. We transported treatment effects from two heart failure (HF) trials to a HF registry., Study Design and Setting: Individual-patient-level data from two trials (Carvedilol or Metoprolol European Trial (COMET), comparing carvedilol and metoprolol, and digitalis investigation group trial (DIG), comparing digoxin and placebo) and a Scottish HF registry were obtained. The primary end point for both trials was all-cause mortality; composite outcomes were all-cause mortality or hospitalization for COMET and HF-related death or hospitalization for DIG. We performed transportation using regression-based and inverse odds of sampling weights (IOSW) approaches., Results: Registry patients were older, had poorer renal function and received higher-doses of loop-diuretics than trial participants. For each trial, point estimates were similar for the original and IOSW (e.g., DIG composite outcome: OR 0.75 (0.69, 0.82) vs. 0.73 (0.64, 0.83)). Treatment effect estimates were also similar when examining high-risk (0.64 (0.46, 0.89)) and low-risk registry patients (0.73 (0.61, 0.86)). Similar results were obtained using regression-based transportation., Conclusion: Regression-based or IOSW approaches can be used to transport trial effect estimates to patients administrative/registry data, with only moderate reductions in precision., Competing Interests: Declaration of competing interest J.G.F.C. is supported by a British Heart Foundation Centre of Research Excellence award RE/18/6/34217; he has received personal honoraria for advisory boards and lectures from Abbott, Amgen, Astra-Zeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, Novartis, Medtronic, Myokardia, NI Medical, Pharmacosmos, Idorsia, Respicardia, Servier, Torrent, Vifor, and Viscardia; nonfinancial support from Boehringer-Ingelheim and Boston Scientific; and research funding for his institution from Bayer, Bristol Myers Squibb, Medtronic, and Vifor. All other authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The combination of mRNA and lncRNA profiles for establishing an integrated mRNA-lncRNA prognostic signature has remained unexplored in cholangiocarcinoma (CCA) patients. We utilized a training dataset of 36 samples from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 30 samples from Gene Expression Omnibus. Two mRNAs (CFHR3 and PIWIL4) and 2 lncRNAs (AC007285.1 and AC134682.1) were identified to construct the integrated signature through a univariate Cox regression (P-value = 1.35E-02) and a multivariable Cox analysis (P-value = 3.07E-02). Kaplan-Meier curve showed that patients with low risk scores had notably prolonged overall survival than those with high risk scores (P-value = 4.61E-03). Subsequently, the signature was validated in GSE107943 cohort with an area under the curve of 0.750 at 1-year and 0.729 at 3-year. The signature was not only independent from diverse clinical features (P-value = 3.07E-02), but also surpassed other clinical characteristics as prognostic biomarkers with area under the curve of 0.781 at 3-year. Moreover, the weighted gene co-expression network analysis and gene enrichment analyses found that the integrated signature were associated with metabolic-related biological process and lipid metabolism pathway, which has been implicated in the pathogenesis of CCA. Taken together, we developed an integrated mRNA-lncRNA signature that had an independent prognostic value in the risk stratification of patients with CCA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost-effectiveness of non-pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research., (© 2023 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Background: N6-methyladenosine (m6A) has a critical role in the development and progression of cancer. However, the genetic and epigenetic patterns, as well as tumor microenvironment (TME) infiltration characteristics of m6A regulators in colorectal cancer (CRC) remain largely unknown., Methods: Molecular patterns of m6A modifications of 24 m6A regulators in CRC samples were evaluated using data from The Cancer Genome Atlas (TCGA). Mutations, copy number variations (CNVs), DNA methylation, and chromatin accessibility were examined to investigate the underlying mechanisms of the aberrant expression of m6A regulators. Correlations between m6A-related genes and TME cell-infiltrating characteristics were evaluated using Tumor Immune Estimation Resource (TIMER)., Results: The m6A regulators were frequently dysregulated in CRC, with two downregulated and 16 upregulated. All the m6A regulators had mutations (frequency ranging from 0.9% to 7%), with active mutations tending to occur in RBM15 and inactive mutations in ZC3H13 . Only five m6A regulators had CNV frequency greater than 1%: YTHDC2 (2.4%), YTHDF1 (7.0%), YTHDF3 (1.9%), VIRMA (1.7%), and ZC3H13 (3.0%). The copy numbers of these five genes were positively correlated with their expression levels. The m6A regulators frequently showed imbalanced methylation in CRC, with hypomethylation of YTHDF2 , IGF2BP3 , FTO , and hypermethylation of HNRNPC , METTL3 , and WTAP . Most m6A regulators had high chromatin accessibility, which was positively correlated with their gene expression. IGF2BP1 was identified as an independent prognostic factor for overall survival. Moreover, the expression of most m6A regulators was positively correlated with the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells., Conclusions: Aberrant expression of m6A regulators is associated with mutation, CNV, and chromatin accessibility, owing to both genetic and epigenetic modifications. The TME infiltration characterization of m6A regulators could guide the development of more effective immunotherapy strategies in CRC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-186/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

In recent years, food safety caused by foodborne pathogens and spoilage bacteria has become a major public health problem worldwide. Bacteriocins are a kind of antibacterial peptide synthesized by microbial ribosomes, and are widely used as food preservatives. However, when used individually bacteriocins may have limitations such as high cost of isolation and purification, narrow inhibitory spectrum, easy degradation by enzymes, and vulnerability to complex food environments. Numerous studies have demonstrated that co-treatment with bacteriocins and a variety of chemical substances can have synergistic antibacterial effects on spoilage microorganisms and foodborne pathogens, effectively prolonging the shelf life of food and ensuring food safety. Therefore, this paper systematically summarizes the synergistic bacteriostatic strategies of bacteriocins in combination with chemical substances such as essential oils, plant extracts, and organic acids. The impacts of bacteriocins when used individually and in combination with other chemical substances on different food substrates are clarified, and bacteriocin-chemical substance compositions that enhance antibacterial effectiveness and reduce the potential negative effects of chemical preservatives are highlighted and discussed. Combined treatments involving bacteriocins and different kinds of chemical substances are expected to be a promising new antibacterial method and to become widely used in both the food industry and biological medicine.

In plant cells, a large pool of iron (Fe) is contained in the nucleolus, as well as in chloroplasts and mitochondria. A central determinant for intracellular distribution of Fe is nicotianamine (NA) generated by NICOTIANAMINE SYNTHASE (NAS). Here, we used Arabidopsis thaliana plants with disrupted NAS genes to study the accumulation of nucleolar iron and understand its role in nucleolar functions and more specifically in rRNA gene expression. We found that nas124 triple mutant plants, which contained lower quantities of the iron ligand NA, also contained less iron in the nucleolus. This was concurrent with the expression of normally silenced rRNA genes from nucleolar organizer regions 2 (NOR2). Notably, in nas234 triple mutant plants, which also contained lower quantities of NA, nucleolar iron and rDNA expression were not affected. In contrast, in both nas124 and nas234, specific RNA modifications were differentially regulated in a genotype dependent manner. Taken together, our results highlight the impact of specific NAS activities in RNA gene expression. We discuss the interplay between NA and nucleolar iron with rDNA functional organization and RNA methylation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Excessive copper can induce many adverse effects although it's an essential trace element in organisms. The effects of copper on the lipid metabolism have aroused increasing attention. This study investigated the liver lipid metabolism in swamp eel (Monopterus albus, M. albus) chronically exposed to 0, 10, 50, and 100 μg/L Cu 2+ for 56 days. The results showed that copper increased the contents of triglyceride (TG), total cholesterol (T-CHO), non-esterified fatty acids (NEFA), and lipid droplets. Transcriptomic analysis found 1901 differentially expressed genes (DEGs) and 140 differential alternative splicing (DAS) genes in the 50 μg/L Cu 2+ group, and 1787 DEGs and 184 DAS genes in the 100 μg/L Cu 2+ group, respectively, which were enriched in peroxisome proliferator-activated receptor (PPAR), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and other signaling pathways. The expression levels of key genes related to PPAR and AMPK signaling pathways were significantly down-regulated after chronic exposure to Cu 2+ . Meanwhile, metabolomics analysis showed that 52 and 110 differentially expressed metabolites (DEMs) were identified, which were mainly enriched in glycerophospholipids metabolism and steroid synthesis. Moreover, combined analysis of transcriptome and metabolome showed that glycerophospholipid metabolism co-enriched 19 down-regulated DEGs and 4 down-regulated DEMs. Taken together, our results suggested that chronic waterborne copper exposure promoted lipid synthesis, disrupted the metabolic homeostasis of glycerophospholipid, and led to excessive hepatic lipid deposition in M. albus. The combined omics approach enhanced our understanding of copper pollution to lipid metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Nurses are greatly affected by patient safety incidents, but little is known about the classifications of nurses' second victim experiences and their effects on job insecurity and turnover intention. This study aimed to identify the profiles of nurses' second victim experiences, including perceived support and distress, and explore the effects of the different experiences on nurses' job insecurity and turnover intention. A convenience sample of 2000 nurses, who were directly involved in patient safety incidents within a year at 25 hospitals in 13 provinces in China, was invited to participate. The online surveys included the Second Victim Experience and Support Tool-Chinese version, job insecurity scale, and turnover intention scale. Data were analyzed using regression and latent profile analysis to identify second-victim nurses' different experience predictors and examine the relationships among the factors. A total of 1298 valid questionnaires were obtained. Three profiles of second victim experiences were identified. Univariate analysis demonstrated that nurses' experience, education level, hospital type, specialty, working hours, credentials, clinical ladder, type of employment, income, training on adverse events, and the type of adverse event were statistically significant (p < 0.05) variables differentiating the three profiles. After controlling these significant variables, the multiple regression analysis showed that the higher the support and the lower the distress level of the second victim, the lower the job insecurity and turnover intention. This study highlights the significance of nurse' leader and organizational support. Nursing leaders should recognize nurses' second-victim experiences, provide the support nurses need, and help them reduce job insecurity and turnover intention., (© 2023 Wiley Periodicals LLC.)

Objectives: Lymph node (LN) metastasis is a common cause of recurrence in oral cancer; however, the accuracy of distinguishing positive and negative LNs is not ideal. Here, we aimed to develop a deep learning model that can identify, locate, and distinguish LNs in contrast-enhanced CT (CECT) images with a higher accuracy., Methods: The preoperative CECT images and corresponding postoperative pathological diagnoses of 1466 patients with oral cancer from our hospital were retrospectively collected. In stage I, full-layer images (five common anatomical structures) were labeled; in stage II, negative and positive LNs were separately labeled. The stage I model was innovatively employed for stage II training to improve accuracy with the idea of transfer learning (TL). The Mask R-CNN instance segmentation framework was selected for model construction and training. The accuracy of the model was compared with that of human observers., Results: A total of 5412 images and 5601 images were labeled in stage I and II, respectively. The stage I model achieved an excellent segmentation effect in the test set (AP 50 -0.7249). The positive LN accuracy of the stage II TL model was similar to that of the radiologist and much higher than that of the surgeons and students (0.7042 vs. 0.7647 (p = 0.243), 0.4216 (p < 0.001), and 0.3629 (p < 0.001)). The clinical accuracy of the model was highest (0.8509 vs. 0.8000, 0.5500, 0.4500, and 0.6658 of the Radiology Department)., Conclusions: The model was constructed using a deep neural network and had high accuracy in LN localization and metastasis discrimination, which could contribute to accurate diagnosis and customized treatment planning., Key Points: • Lymph node metastasis is not well recognized with modern medical imaging tools. • Transfer learning can improve the accuracy of deep learning model prediction. • Deep learning can aid the accurate identification of lymph node metastasis., (© 2022. The Author(s).)

Objectives: To investigate the reliability and validity of Chinese version of the Pediatric Eye Questionnaire (PedEyeQ-CN) by testing ophthalmic patients in China., Methods: The PedEyeQ (standard English version) was translated by local researchers. Children were asked to complete the Child section, and their parents the Proxy and Parent sections. 160 children (32 normal controls, 77 with refractive error, 48 with strabismus/amblyopia, 3 with other eye conditions) aged 5-11 years old, and one parent of each child were recruited. Cronbach's α and intraclass correlation coefficient were calculated to examine the reliability and test-retest reliability; the score differences between controls and patients were compared to examine the validity., Results: The internal consistency (Cronbach's α ≥ 0.76) and test-retest reliability (r > 0.80) of PedEyeQ-CN were robust. Children with eye conditions had lower scores compared with children with normal vision (refractive error: 10 out of 13 domains, P ≤ 0.021; strabismus/amblyopia: all domains, P ≤ 0.015). Children with strabismus/amblyopia had lower scores compared with children with refractive error (two domains, P = 0.048, P = 0.001). Visual acuity was significantly correlated with functional vision (P = 0.005), but not significantly correlated with the eye-related quality of life (ER-QOL)., Conclusions: The PedEyeQ-CN is a valuable tool for assessing the functional vision and ER-QOL of Chinese children and help us increase our understanding about the impact of eye conditions on children and their families., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff., Competing Interests: Lujun Shen is an youth editorial board member for Journal of Interventional Medicine and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2023 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Objectives: This study aimed to evaluate the level of oxidative stress (OS) in human and rat chronic sialadenitis (CS) of the submandibular gland (SMG)., Method: We collected human SMG tissues and established a rat CS model using Wharton's duct partial ligation (PL). Morphological changes in the SMG were evaluated by HE, Sirius Red, AB/PAS, TUNEL and immunohistochemical (IHC) staining. Oxidative damage and antioxidant capacity were detected by ELISA, commercial assay kits and IHC staining to evaluate their expression levels and locations in the SMG., Results: Histopathological damage were observed in the human and rat CS. In rat PL group, the oxidative damage products (8-OHdG, AOPP, 8-iso-PGF2α and H 2 O 2 ) were significantly increased. For antioxidants, the PL group had markedly decreased T-AOC and CAT activity, but markedly increased SOD activity. 3-NT, 4-HNE and MDA expression changed during the process of CS, and antioxidant enzymes (CAT, SOD1, SOD2, GPX1 and GPX4) were mainly expressed in ducts., Conclusions: The oxidative-antioxidant imbalance of CS in human and rats was revealed, the different expression of oxidative damage during the process of CS was detected, and the different antioxidant reaction in acinar and ductal cells was demonstrated., (© 2021 Wiley Periodicals LLC.)

Objectives: Near viewing distance (VD) and longer viewing times are associated with myopia. This study aimed to identify the font size and viewing time that guarantee the appropriate VD and pixels per degree (PPD) for children's online learning., Design: This cross-sectional study comprised two experiments. In experiment A, participants read text in five font sizes on three backlit displays (a personal computer, a smartphone and a tablet), an E-ink display and paper for 5 min per font size. In experiment B, participants watched videos for 30 min on three backlit displays., Setting: The Peking University People's Hospital in Beijing (China) and the School of Ophthalmology and Optometry, Wenzhou Medical University (Zhejiang Province, China)., Participants: Thirty-five participants completed experiment A. Ten of them participated in experiment B., Primary and Secondary Outcome Measures: VDs were measured by Clouclip. The corresponding PPD was calculated., Results: In experiment A, font size and display type significantly affected VD (F (4840) =149.44, p<0.001, ES (Effect size)=0.77; F (4840) , p<0.001, ES=0.37). VDs were >33 cm for all five font sizes on the PC, the tablet and paper and for 18-pt on the smartphone and 16-pt on E-ink. PPD for 16-pt on the PC, 14-pt on the tablet and all five font sizes on the phone were >60. In experiment B, VD increased over the four previous 5 min periods but decreased slightly on tablets and PCs in the fifth 5 min period. PPD was >60., Conclusion: Children demonstrated different VDs and PPDs based on font size and display type. To ensure a 33 cm VD and 60 PPD, the minimum font size for online reading should be 18-pt on smartphones, 16-pt on PCs and E-ink, 10.5-pt on tablets and 9-pt on paper. More attention should be given to children's VD with continuous video viewing of more than 25 min., Trial Registration Number: ChiCTR2100049584., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Nutrient resorption is a key mechanism to conserve nutrients and overcome nutrient limitation in perennial plants. As an important afforested tree species in subtropical regions, Pinus massoniana grows well in nutrient-poor environments, however, the age-related pattern of nutrient acquisition strategy and the underlying mechanisms in P. massoniana plantations remain unclear., Methods: In this study, concentrations of nitrogen (N) and phosphorus (P) were measured in green and senesced needles, roots and soil samples collected from P. massoniana plantations with different stand ages (9-, 17-, 26-, 34- and 43-year-old) in south China. From these samples, nutrient resorption efficiency (RE) and stoichiometry were calculated., Results: Needle PRE significantly decreased with stand age, while there was no clear pattern of NRE along the stand development. Green needle N:P in older stands was significantly lower than in younger ones. Senesced needle C:P and N:P significantly decreased with stand age. Root and soil available P concentrations were significantly higher in older stands than in younger ones, and PRE was negatively correlated with soil available P concentration., Discussion: There was a shift from "conservative consumption" to "resource spending" P-use strategy, and P limitation decreased with stand development of P. massoniana plantations. The results provide information of changes in nutrients dynamics, which is relevant for the sustainable management of subtropical forest plantations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Jiao, Lopez C, Chen, Wei, Liu, Hu and Wang.)

Six swine coronaviruses (SCoVs), which include porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine hemagglutination encephalomyelitis virus (PHEV), porcine respiratory coronavirus (PRCV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV), have been reported as infecting and causing serious diseases in pigs. To investigate the genetic diversity and spatial distribution of SCoVs in clinically healthy pigs in China, we collected 6400 nasal swabs and 1245 serum samples from clinically healthy pigs at slaughterhouses in 13 provinces in 2017 and pooled them into 17 libraries by type and region for next-generation sequencing (NGS) and metavirome analyses. In total, we identified five species of SCoVs, including PEDV, PDCoV, PHEV, PRCV, and TGEV. Strikingly, PHEV was detected from all the samples in high abundance and its genome sequences accounted for 75.28% of all coronaviruses, while those belonging to TGEV (including PRCV), PEDV, and PDCoV were 20.4%, 2.66%, and 2.37%, respectively. The phylogenetic analysis showed that two lineages of PHEV have been circulating in pig populations in China. We also recognized two PRCVs which lack 672 nucleotides at the N-terminus of the S gene compared with that of TGEV. Together, we disclose preliminarily the genetic diversities of SCoVs in clinically healthy pigs in China and provide new insights into two SCoVs, PHEV and PRCV, that have been somewhat overlooked in previous studies in China.

Background: Atrial fibrillation (AF) is becoming increasingly common. Effective self-management during the "Blanking Period" is critical. The Information-Motivation-Behavioral skills (IMB) model can be used to study health behaviors in chronic disease patients, but it has not been studied in AF patients., Objective: The goal of this study was to explore the influencing factors and interaction pathways of self-management behavior in AF patients during the "Blanking Period" using the IMB model., Methods: From June to December 2021, a cross-sectional design was conducted. Patients with AF during the "Blanking Period" (N=220) were recruited. They filled out several quantitative questionnaires, including the Jessa Atrial Fibrillation Knowledge Questionnaire, the Confidence in Atrial Fibrillation Management Scale, the Perceived Social Support Scale, the All Aspects of Health Literacy Scale, and the Self-care Scale for Chronic Atrial Fibrillation Patients. Data were analyzed using correlation analysis, multiple regression analysis, and path analysis., Results: Total score of self-management behavior was (33.83 ± 10.66). AF knowledge (β = 0.252, P < 0.001), self-management confidence (β = 0.219, P < 0.001), social support (β = 0.291, P < 0.001), and health literacy (β = 0.262, P < 0.001) were all positively correlated with patients' self-management behavior, accounting for 66.50 percent of the total variance., Conclusions: During the "Blanking Period", the IMB model can be used to predict the factors that influence self-management behavior in AF patients. By using IMB model, interventions targeting patient-specific influencing factors could improve self-management behavior and quality of life in AF patients., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

MC-LR is one of the cyanotoxins produced by fresh water cyanobacteria. Previous studies showed that autophagy played an important role in MC-LR-induced reproduction toxicity. However, information on the toxicological mechanism is limited. In this study, MC-LR could induce autophagy and apoptosis in GCO cells in vitro. In GCO cells that had been exposed to MC-LR, the inhibitor of 3-MA effectively decreased cell viability and damaged cell ultrastructure. Oxidative stress was significantly increased in the 3-MA + MC-LR group, accompanied by significantly increased MDA content and decreased CAT activity and GST, SOD1, GPx, and GR expression levels (P < 0.05). Inflammation was more serious in the 3-MA + MC-LR group than that of MC-LR group, which was evidenced by increasing expression levels of TNFα, IL11, MyD88, TNFR1, TRAF2, JNK, CCL4, and CCL20 (P < 0.05). Interestingly, the significant decrease of Caspase-9, Caspase-7, and Bax expression and significant increase of Bcl-2 and Bcl-2/Bax ratio in 3-MA + MC-LR group compared to MC-LR group, suggesting that extent of apoptosis were reduced. Taken together, these results indicated that MC-LR induced autophagy and apoptosis in GCO cells, however, the inhibition of autophagy decreased the extent of apoptosis, induced more serious oxidative stress and inflammation, which eventually induced cell death. Our findings provided some information for exploring the toxicity of MC-LR, however, the role of autophagy require further study in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

X-linked inhibitor of apoptosis protein (XIAP) -associated factor 1 (XAF1) is an interferon-stimulated gene which exhibits pro-apoptosis effect. In this study, XAF1 was characterized from grass carp Ctenopharyngodon idella and its expression pattern and function were analyzed. The open reading frame (orf) of XAF1 is 789 nucleotides (nt) encoding 262 amino acids. SMART online search results showed that a C2H2-type and six C2HC-type zinc-fingers were found in XAF1, however, the XAF1 of grass carp showed high sequence identity to zebrafish (71%), low sequence identity to tetrapods (21-22%). Rt-qPCR results showed that XAF1 was constitutively expressed in all tested organs/tissues with highest expression in blood. An inductive expression of XAF1 at mRNA level was observed in peripheral blood leucocytes (PBLs) and C. idellus kidney cells (CIKs) after treatment with C. idellus recombinant interferon-γ (rIFNg). Overexpressing XAF1 in CIKs exhibited resistance against grass carp reovirus (GCRV) and more sensitivity to cisplatin. These results implied a functional homologue of XAF1 in evolution, however the mechanism may require further investigation., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The main aim of this study was to curate a COI barcode library of Chironomidae from the Tibetan Plateau (TP) as an essential supplement to the public database. Another aim is to evaluate the current status of the public database of Chironomidae in aspects of taxonomic coverage, geographic representation, barcode quality, and efficiency for molecular identification, the Tibetan Plateau, China. In this study, 512 individuals of Chironomidae from the TP were identified based on morphological taxonomy and barcode analysis. The metadata of public records of Chironomidae were downloaded from the BOLD, and the quality of the public barcodes was ranked using the BAGS program. The reliability of the public library for molecular identification was evaluated with the newly curated library using the BLAST method. The newly curated library comprised 159 barcode species of 54 genera, of which 58.4% of species were likely new to science. There were great gaps in the taxonomic coverage and geographic representation in the public database, and only 29.18% of barcodes were identified at the species level. The quality of the public database was of concern, with only 20% of species being determined as concordant between BINs and morphological species. The accuracy of molecular identification using the public database was poor, and about 50% of matched barcodes could be correctly identified at the species level at the identity threshold of 97%. Based on these data, some recommendations are included here for improving barcoding studies on Chironomidae. The species richness of Chironomidae from the TP is much higher than ever recorded. Barcodes from more taxonomic groups and geographic regions are urgently needed to fill the great gap in the current public database of Chironomidae. Users should take caution when public databases are adopted as reference libraries for the taxonomic assignment., Competing Interests: All authors declare that they have no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Coastal reclamation by seawall embankments and the spread of invasive C 4 perennial grass Spartina alterniflora have recently become more prevalent in eastern China's coastal wetlands. While trace metals (TMs), carbon, and nitrogen dynamics concerning reclamation have extensively been explored across China's coastal wetlands, to date, the impact of reclamation by coastal embankment and exotic plant invasion on TMs' pollution dynamics in coastal marshes remains largely unexplored. We compared TMs Cr, Cu, Pb, and Zn cumulation in coastal embankment-reclaimed versus unreclaimed S. alterniflora and Phragmites australis saltmarshes in eastern China coastal wetlands. In both S. alterniflora and P. australis marshes, coastal embankment reclamation spurred an increase in Cr, Cu, Pb, and Zn concentrations by 31.66%, 53.85%, 32.14%, 33.96% and by 59.18%, 87.50%, 55.55%, 36.84%, respectively, in both marsh types. Reclamation also reduced plant biomass, soil moisture, and soil salinity in both plants' marshes. Our findings suggest that the impact of coastal embankment reclamation and replacement of native saltmarshes by invasive S. alterniflora had a synergistic effect on TM accumulation in the P. australis marshes, as corroborated by bioaccumulation and translocation factors. Reclamation by coastal embankments and invasive alien plants could significantly impair the physico-chemical properties of native plant saltmarsh and essentially weaken the accumulation of Cr, Cu, Pb, and Zn potential of the coastal saltmarshes. Our findings provide policymakers with an enhanced knowledge of the relationship between reclamation, plant invasiveness, and TM pollution dynamics in coastal wetlands, providing a baseline for attaining future goals and strategies related to the tradeoffs of various wetland reclamation types.

Antibody-secreting B cells have long been considered the central element of gut homeostasis; however, tumor-associated B cells in human colorectal cancer (CRC) have not been well characterized. Here, we show that the clonotype, phenotype, and immunoglobulin subclasses of tumor-infiltrating B cells have changed compared to adjacent normal tissue B cells. Remarkably, the tumor-associated B cell immunoglobulin signature alteration can also be detected in the plasma of patients with CRC, suggesting that a distinct B cell response was also evoked in CRC. We compared the altered plasma immunoglobulin signature with the existing method of CRC diagnosis. Our diagnostic model exhibits improved sensitivity compared to the traditional biomarkers, CEA and CA19-9. These findings disclose the altered B cell immunoglobulin signature in human CRC and highlight the potential of using the plasma immunoglobulin signature as a non-invasive method for the assessment of CRC., Competing Interests: The authors declare no competing interests., (© 2023.)

Aim: Incorporating mobile applications into traditional clinical teaching methods to assess the impact of game-based mobile applications on the practical knowledge and skill levels of venous blood specimen collection among nursing students. Background: Although game-based mobile applications are recognized as teaching aids that replicate clinical practice in a safe environment, their impact and effectiveness are relatively unknown in the education of nursing students. Design: In September 2021, a single-blind randomized controlled trial was conducted in a university-affiliated hospital in China. Methods: One hundred five nursing students were randomly divided into the control group ( n  = 53) and the experimental group ( n  = 52). All participants received the same theoretical and operational training. For the next 7 days, the experimental group used a game-based mobile application, and the control group practiced venous blood specimen collection using traditional teaching methods. We observed the before-and-after comparison of the skill performance and learning curve of both groups of participants. Results: The final skill performance scores of the nursing students in the experimental group were higher than that of the nursing students in the control group ( P  < 0.001). Analysis of the learning curve showed that to master the skills, the experimental and control groups needed an average of 8 and 10 repetitions, respectively. Conclusion: This mobile application has a positive learning effect on nursing students' venous blood specimen collection skills in the short term. It should be applied to the training of clinical nursing skills.