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Background: Nurses' competency in pain management is essential for effectively alleviating patients' acute pain, controlling chronic pain, and promoting patient recovery. However, reliable tools for evaluating these competencies across different clinical specialties and healthcare settings are lacking. This study aimed to develop and validate a Pain Management Competency Scale for Nurses (PMCSN) and to assess the pain management competencies of nurses in China through a nationwide survey., Methods: An item pool and a draft scale were developed through literature reviews, semi-structured interviews, and expert panel discussions. This was followed by refinement of the scale via Delphi expert consultations and a pilot test. To validate the scale, 342 nurses were conveniently sampled from six hospitals in Eastern and Central China. The validation process included item analysis, internal consistency reliability assessment, test-retest reliability (with 40 nurses retaking the questionnaire after a 14-day interval), content validity (evaluated by six experts using a 4-point Likert scale), and structural validity (assessed through exploratory and confirmatory factor analyses). The validated scale was then applied in a survey of 1,500 nurses from 15 hospitals across Eastern, Central, and Western China. Statistical analyses included descriptive statistics, analysis of variance (ANOVA), and t-tests., Results: The PMCSN comprised six primary dimensions-Pain Assessment and Monitoring, Pharmacological Pain Management, Non-Pharmacological Pain Management, Management of Analgesic Adverse Effects, Patient/Family Education, and Professional Development-and includes 52 tertiary items. The PMCSN scores ranged from 6 to 120, calculated by summing the standardized scores across the six dimensions, with higher scores indicating greater competency in pain management. The scale's Cronbach's α was 0.974 (dimension-specific values ranging from 0.863 to 0.935) and a test-retest reliability of 0.871. The content validity index (CVI) of the scale was 0.965. Exploratory factor analysis (EFA) showed that the six-factor model explained 67.50% of the variance. Confirmatory factor analysis (CFA) indicated good model fit, with average variance extracted (AVE) values ranging from 0.659 to 0.811 and composite reliability (CR) between 0.909 and 0.973, confirming good convergent validity. The square roots of the AVE values exceeded the inter-factor correlations, indicating good discriminant validity. In the nationwide survey, the average PMCSN score among 1,500 nurses was 101.27 ± 20.97. Nurses with higher education levels scored higher (F = 14.173, p < 0.01), as did those working in Eastern regions (F = 24.632, p < 0.01) and tertiary hospitals (T = -5.476, p < 0.01)., Conclusions: The PMCSN is a valid and reliable tool for assessing nurses' pain management competencies. It provides a standardized approach for evaluation and guides targeted interventions to improve competency. Regional and hospital-level disparities highlight the need for enhanced training in underdeveloped areas and collaboration between hospitals to promote balanced healthcare resources., Competing Interests: Declarations. Ethics approval and consent to participate: This study protocol was approved by the Ethics Committee of the Nursing College of Hangzhou Normal University (2022055). The study was conducted after obtaining written informed consent from the participants. It was also carried out in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Bloodstream infection (BSI) is a systemic infection that predisposes individuals to sepsis and multiple organ dysfunction syndrome. Early identification of infectious agents and determination of drug-resistant phenotypes can help patients with BSI receive timely, effective, and targeted treatment and improve their survival. This study was based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), Decision Tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), eXtreme Gradient Boosting (XGBoost), and Extremely Randomized Trees (ERT) models were constructed to classify carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP). Bacterial species were identified by MALDI-TOF MS in positive blood cultures isolated via the serum isolation gel method, and E. coli and K. pneumoniae in positive blood cultures were collected and placed into machine learning models to predict susceptibility to carbapenems. The aim of this study was to provide rapid detection of CREC and CRKP in blood cultures, to shorten the turnaround time for laboratory reporting, and to provide a basis for early clinical intervention and rational use of antibiotics., Results: The collected MALDI-TOF MS data of 640 E. coli and 444 K. pneumoniae were analysed by machine learning algorithms. The area under the receiver operating characteristic curve (AUROC) for the diagnosis of E. coli susceptibility to carbapenems by the DT, RF, GBM, XGBoost, and ERT models were 0.95, 1.00, 0.99, 0.99, and 1.00, respectively, and the accuracy in predicting 149 E. coli-positive blood cultures were 0.89, 0.92, 0.90, 0.92, and 0.86, respectively. The AUROC for the diagnosis of K. pneumoniae susceptibility to carbapenems by the DT, RF, GBM, XGBoost, and ERT models were 0.78, 0.95, 0.93, 0.90, and 0.95, respectively, and the accuracy in predicting 127 K. pneumoniae-positive blood cultures were 0.76, 0.86, 0.81, 0.80, and 0.76, respectively., Conclusions: Machine learning models constructed by MALDI-TOF MS were able to directly predict the susceptibility of E. coli and K. pneumoniae in positive blood cultures to carbapenems. This rapid identification of CREC and CRKP reduces detection time and contributes to early warning and response to potential antibiotic resistance problems in the clinic., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethical approval: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Identifying markers or genes crucial for growth traits in Zhongwei goats is pivotal for breeding. Pinpointing genetic factors linked to body size gain enhances breeding efficiency and economic value. In this study, we used the MGISEQ-T7 platform to re-sequence 240 Zhongwei goats (133 male; 107 female) belonging to 5 metrics of growth traits at different growth stages (40 days and 6 months, here in after referred to as 40d and 6 m), namely, Body Weight (BW), Body Height (BH), Body Length (BL), Chest Circumference (CC), Tube Circumference (TC) were examined. A Genome-wide association study (GWAS) was conducted to identify candidate genes associated with the five indicators of body conformation traits, thereby establishing a foundation for subsequent investigations into the biological functions of these genes., Results: A total of 19.89 Tb of raw data was generated with an average sequencing depth of about 20×. After quality control, 15,958,716 SNPs were available for the analysis. A total of 342 genome-wide significant SNPs were obtained. Among them, in the two physiological stages of 40d and 6 m, 147 and 32 SNPs were significantly associated with BW; 1 and 4 SNPs were significantly associated with BH; 19 and 6 SNPs were significantly associated with BL; 33 and 64 SNPs were significantly associated with CC, 34 and 2 SNPs were significantly associated with TC. These SNPs were annotated to 425 candidate genes. Finally, A total of 39 candidate genes are closely related to biological processes such as skeletal muscle development, skeletal formation, carcass quality, and embryonic development, where ADIPOQ, CCDD39, PTPRT, ZNF215, VRTN, ABCD4, DLST, ADAMTS2, ROBO1, AKAP13, AQPI, SOX2, and AHSG were identified as an important component of the genetic framework that may control somatic conformational traits in Zhongwei goats. which warrants further investigation and review. We verified the polymorphism of 11 SNPs by KASP, and found that Chr13&#95;g.11,700,438 A > G, Chr15&#95;g.37,120,328 A > G, Chr6&#95;g.7,209,383 C > T, Chr20&#95;g.51277932T > A, Chr19&#95;g.17,078,199 A > G, and Chr1&#95;g.79,943,276 C > T were significantly genotyped in verified populations (P < 0.001)., Conclution: It is the first GWAS study to analyze genomic data from 40d and 6 m of Zhongwei goats to understand the molecular genetic mechanisms of growth. Our research identified a series of SNPs and candidate genes associated with growth traits, which could assist us in developing the meat production trait in Zhongwei goats., Competing Interests: Declarations. Ethics approval and consent to participate: All samples were collected in accordance with the International Guiding Principles for Biomedical Research involving animals and approved by the Special Committee on Scientific Research and Academic Ethics of Inner Mongolia Agricultural University, responsible for the approval of Biomedical Research Ethics of Inner Mongolia Agricultural University [Approval No. (2020) 056]. No specific permissions were required for these activities, and no endangered or protected species were involved. These activities were performed under the informed consent from all owners. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear. Our study developed a risk model utilizing three PANoptosis-associated genes (Caspase 4 (CASP4), TLR3, and CASP5). This model demonstrated a high degree of precision in predicting the prognosis for patients with ccRCC. ccRCC patients in the high-risk group had the strongest immune cell activity, experiencing immune evasion, and might potentially derive advantages from treatment involving combined immune checkpoint inhibitors. CASP5 was highly expressed in ccRCC tissues by RT-qPCR, western blotting, and immunofluorescence. Stable CASP5 knockdown cell lines were constructed by lentivirus in vitro transfection technique. Reducing CASP5 level suppressed the growth, migration, and invasion of ccRCC cells, while encouraging cell apoptosis. In addition, the results of in vivo tumorigenesis experiments showed that down-regulating CASP5 expression inhibited the tumorigenic ability of 786-O cells. Together, the innovative risk model using PANoptosis-associated genes effectively forecasts the tumor microenvironment and survival rates for ccRCC, offering a novel approach to the early, precise diagnosis of ccRCC and the advancement of personalized treatment strategies., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of the Affiliated Central Hospital of Dalian University of Technology (Dalian Central Hospital) (No. YN2024-053-01). All the study subjects provided informed consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Laparoscopic radical gastrectomy has been reported to be associated with substantial trauma and pain. This study compared the impact of ultrasound-(US)-guided, bilateral, double-injection intertransverse process block (ITPB) on postoperative analgesia with subcostal transversus abdominis plane block (TAPB) in patients who were undergoing laparoscopic radical gastrectomy., Methods: Sixty-two patients who were undergoing laparoscopic radical gastrectomy surgery under general anesthesia were included. These patients were randomized to either the ITPB group or the TAPB group. Patients in the ITPB group received a double-shot US-guided bilateral ITPB at the thoracic level T6/7 and T9/10 level using ropivacaine (0.3%, 15 mL). Patients in the TAPB group received bilateral subcostal TAPB one injection per side using ropivacaine (0.3%, 30 mL). All patients used a BIS-guided combined intravenous and inhalation anesthesia. The primary outcome was defined as postoperative morphine-equivalent consumption during the first 24 h., Results: The study recruited 62 patients (31 in each group) for the analysis. A comparatively less postoperative opioid consumption was observed in the ITPB group compared with the subcostal TAPB group within the first 24 h postoperatively (mean [standard deviation-(SD)] morphine-equivalent dose): 27.8 (5.7) mg vs 31.2 (4.4) mg, P < 0.001. The ITPB group showed lower intraoperative opioid use, and statistical significantly lower scores at rest and coughing at 6, 24 h postoperatively. The time to first requiring rescue analgesia was longer in the ITPB group than the subcostal TAPB group (median [IQR]): 8.0 [8.0] vs 6.0 [6.0] h, P = 0.009. The patients in the ITPB group exhibited earlier independent movement, lower incidence of postoperative complications and higher levels of satisfaction (P = 0.021)., Conclusion: This study showed that the double-shot bilateral ITPB could reduce opioids consumption and achieve longer and better pain relief. Additionally, it promoted early postoperative activity and improved patient satisfaction., Trial Registration: ChiCTR2300072986. Registered 29 June 2023., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of Yancheng First People's Hospital (2023-k-089, 17/06/2023). All patients provided signed informed consent forms. The trial registration number was as follows: ChiCTR2300072986, date of registration: 29/06/2023. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Enhancer RNA (eRNA) has emerged as a key player in cancer biology, influencing various aspects of tumor development and progression. In this study, we investigated the role of eRNAs in kidney renal clear cell carcinoma (KIRC), the most common subtype of renal cell carcinoma. Leveraging high-throughput sequencing data and bioinformatics analysis, we identified differentially expressed eRNAs in KIRC and constructed eRNA-centric regulatory networks. Our findings revealed that up-regulated eRNAs in KIRC potentially regulate immune response and hypoxia pathways, while down-regulated eRNAs may impact ion transport, cell cycle, and metabolism. Furthermore, we developed a diagnostic prediction model based on eRNA expression profiles, demonstrating its effectiveness in KIRC diagnosis. Finally, we elucidated the regulatory mechanism of an eRNA (ENSR00000305834) on the expression of SLC15A2, a potential prognostic biomarker in KIRC, through bioinformatics analysis and in vitro validation experiments. In summary, Our study highlights the clinical significance of eRNAs in KIRC and underscores their potential as therapeutic targets., Competing Interests: Declarations. Ethics approval and consent to participate: The authors declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Backgrounds: Adapter proteins (APs) complex is a class of heterotetrameric complexes comprising of 4-subunits with important regulatory functions in eukaryotic cell membrane vesicle trafficking. Foxtail millet (Setaria italica L.) is a significant C 4 model plant for monocotyledon studies, and vesicle trafficking may plays a crucial role in various life activities related to growth and development. Despite this importance, studies on AP complexes in foxtail millet have been lacking., Results: This research conducted genome-wide identification and systematical analysis of AP complexes in foxtail millet. 33 SiAP complex genes were identified and classified into 7 groups, distributed unevenly across 9 chromosomes in foxtail millet. Among these genes, 11 segmental duplication pairs were found. Out of the 33 SiAP complex genes, 24 exhibited collinear relationships with Setaria viridis, while only one showed relationship with Arabidopsis thaliana. Gene structure and motif composition were investigated to understand the function and evolution of these SiAP complex genes. Furthermore, these promoter region of the SiAP complex genes contains 49 cis-elements that are associated with responses to light, hormones, abiotic stress, growth and development. The interaction network between the SiAP complexes was analyzed, and there were strong interactions among the SiAP complex proteins. Expression patterns of SiAP complex genes in different organs and developmental stages of foxtail millet were investigated. The majority of the SiAP complex genes exhibited expressed in multiple tissues, with some genes being predominantly expressed in specific tissues. Subsequently, we selected SiAP4M and SiAP2M for validation of subcellular localization. The signal of 35 S:: SiAP4M: GFP (Long) and 35 S:: SiAP4M: GFP (Short) fused proteins were primarily observed in the nucleus, while the signal of 35 S:: SiAP2M: GFP fused proteins was widely distributed on the cell membrane and vesicles., Conclusions: Overall, this study presents a comprehensive map of the SiAP complexes in foxtail millet. These findings not only administer to understanding the biological functions of AP complexes in foxtail millet growth and development but also offer insights for enhancing genetic breeding in this crop., Competing Interests: Declarations. Ethics approval and consent to participate: In this study, the Setaria italica varieties and tobacco were from the College of Agriculture, Shanxi Agricultural University. These plant materials do not include any wild species at risk of extinction. No specific permits were required for sample collection in this study. We complied with relevant institutional, national, and international guidelines and legislation for plant study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Asthma is a prevalent status attributing to lower respiratory tract chronic inflammation. Azithromycin (AZM) is known to be effective against asthma. Thus, this study delved into the mechanism of AZM repressing airway remodeling (AR) via the SAPK/JNK pathway in asthma., Methods: Simulated asthmatic AR mouse model was developed by induction with ovalbumin (OVA) and intervened with AZM or dexamethasone (DEX) and anisomycin (JNK activator). Pathological changes in mouse lung tissues and AR were assessed by HE and Masson staining. The numbers of inflammatory cells, macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) were detected by Diff-Quik staining. Inflammatory factor levels (IL-6, TNF-α, IL-4) in BALF, and Collagen I, Collagen III, SAPK/JNK and p-SAPK/JNK protein levels in lung tissues were measured by ELISA and Western blot., Results: The OVA-led asthmatic mouse model was successfully established. Relative to the OVA group, AZM and DEX treatment improved pulmonary smooth muscle thickening and bronchial epithelial fibrosis, reduced inflammatory cells, macrophages, eosinophils, neutrophils and lymphocytes in BALF, inhibited inflammatory factor TNF-α, IL-6, and IL-4 levels in BALF, and down-regulated Collagen I, Collagen III, and p-SAPK/JNK protein levels in lung tissues, with no prominent difference between the two regimens. JNK activator partially reversed the protective effect of AZM against OVA-induced asthma in mice., Conclusion: AZM alleviated airway inflammation by inhibiting the SAPK/JNK pathway, thereby repressing AR in asthmatic mice. This study provided partial theoretical basis for clarifying asthma pathogenesis and new ideas for treating asthma., Competing Interests: Declarations. Ethics approval and consent to participate: The study was authorized by the academic ethics committee of the Second Affiliated Hospital Zhejiang University School of Medicine (Approval number: 2023081). All procedures were strictly implemented by the Guide for the Care and Use of Laboratory Animals. All the laboratory procedures were used to minimize the pain of mice. Consent for publication: Not applicable. Disclosure: The authors report there are no competing interests to declare. Submission declaration and verification: The work described has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The Hezuo (HZ) pig, a famous indigenous breed in China, is characterized by precocious puberty compared with foreign-introduced pig breeds. Sexual maturation is a complex physiological process, and in recent years, circular RNAs (circRNAs), a new class of noncoding RNAs with endogenous regulatory functions, have been shown to play important roles in regulating sexual maturation. However, the dynamic expression and regulatory mechanism of circRNAs during sexual maturation in HZ pigs remain unclear. In this study, we performed RNA sequencing and bioinformatics analysis to reveal circRNA expression patterns in the testes of HZ boars at 30 days (sexual immaturity; Ha) and 120 days (sexual maturity; Hb), with Landrace (LC) boars of the same age (La and Lb) as controls. Subsequently, an abundant circ&#95;005678 (circPAN3) transcribed from the PAN3 gene, was functionally investigated by RT-qPCR, Western Blot, CCK-8, and flow cytometry., Results: We identified 31,134 circRNAs in 12 samples, and 2,562, 2,401, 749, and 831 differentially expressed (DE) circRNAs were identified in the Ha-vs-Hb, La-vs-Lb, Ha-vs-La, and Hb-vs-Lb groups, respectively. The results of functional enrichment analyses indicated that these source genes of the DE circRNAs were involved mainly in testicular development and spermatogenesis. Furthermore, we constructed a circRNA-miRNA-mRNA interaction network and functionally analyzed the target genes. GO functional annotation of the target genes suggested that they were mainly involved in biological processes such as gland development, cell proliferation, and reproduction. KEGG pathway analysis further revealed that these genes were enriched mainly in signaling pathways involved in testicular development and spermatogenesis, including the PI3K-Akt and MAPK signaling pathways. Cellular assays revealed that circPAN3 promoted proliferation and inhibited apoptosis in immature Sertoli cells, whereas opposite changes were observed by circPAN3 knockdown., Conclusions: This study revealed the dynamic expression profiles and regulatory mechanisms of circRNAs during sexual maturation in HZ pigs. Further functional studies demonstrated that circPAN3 promoted the proliferation and inhibited the apoptosis of immature Sertoli cells, suggesting that circPAN3 may be closely related to the characteristics of precocious puberty in HZ boars. These findings provide a new perspective for exploring the regulatory mechanism of circRNAs in precocious puberty in HZ pigs., Competing Interests: Declarations. Ethics approval and consent to participate: All animals used in the present study were approved by the Animal Ethics Committee of Gansu Agricultural University (Approval No. 2006 − 398). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The aim of this study was to compare the effectiveness of two different vitrification methods and slow freezing in terms of the recovery of endocrine function, follicular morphology and proliferation, apoptosis of stromal cells, and angiogenesis after heterotopic transplantation of human ovarian tissue., Methods: Ovarian tissue from young women aged 29 to 40 was subjected to two vitrification methods and one slow freezing method. The thawed ovarian tissue was then transplanted into nude mice and divided into three groups (VF1 group, VF2 group, SF group) according to the different freezing methods. Ovarian tissue samples were collected at 4 and 6 weeks post-transplantation. The recovery of ovarian function was evaluated by observing the estrous cycle and measuring estradiol levels using Elisa. Histological evaluation was performed to assess the integrity of ovarian follicles. TUNEL assay was used to detect stromal cell apoptosis, and immunohistochemistry was conducted to evaluate follicular proliferation and tissue angiogenesis., Results: After heterotopic transplantation, mice in the experimental groups exhibited restoration of the estrous cycle. Hormone levels showed an increasing trend in the vitrification groups. At 6 weeks post-transplantation, the VF2 group had significantly higher hormone levels compared to the VF1 group and the slow freezing (SF) group (P < 0.05). At 4 weeks post-transplantation, the proportion of normal follicles was higher in the VF2 group compared to the other two groups (P > 0.05), and at 6 weeks post-transplantation, the VF2 group was significantly higher than the SF group (P < 0.05) and slightly higher than the VF1 group. Immunohistochemistry analysis indicated a higher proportion of proliferating follicles in the vitrification groups compared to the slow freezing group (P > 0.05). CD31 expression was established in all groups at 4 and 6 weeks post-transplantation, with better results in the slow freezing group compared to the vitrification group. TUNEL analysis showed that stromal cell apoptosis was higher in the SF group compared to the vitrification group at 4 weeks post-transplantation (P < 0.05), while there was no significant statistical difference among the groups at 6 weeks post-transplantation., Conclusions: Vitrification showed better results than slow freezing, with the VF2 group performing slightly better than the VF1 group. Considering the lower economic and time costs associated with vitrification, it may be more suitable for ovarian tissue cryopreservation in major research centers in the future., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Board of Peking University Shenzhen Hospital. Consent for publication: Our manuscript does not contain any individual person’s data in any form. However, three attenders provided written consents for the publication of the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hallux valgus (HV) is a multiplanar deformity and surgical treatment is often guided by two-dimensional radiographic parameters. This study assessed the reliability and accuracy of the AIR classification(The first metatarsal head's lateral edge can be delineated as angular (type A), round (type R), or intermediate (type I) through visual inspection or circle measurements on weight-bearing radiographs.)commonly used in clinical settings to categorize the shape of the lateral edge of the first metatarsal head, against measurements from weight-bearing computed tomography (WBCT)., Methods: This retrospective study evaluated 18 patients, including 31 feet affected by HV. Two surgeons independently categorized the first metatarsal head's lateral edge by both visual inspection and circle measurement. Additionally, two separate surgeons evaluated the α angle relative to the floor in WBCT scans. The reliability of the measurements was assessed using intraclass correlation coefficients (ICC) and weighted kappa statistics., Results: While the first surgeon demonstrated perfect intra-observer reliability for both visual inspection and circular measurements (kappa values of 1.000 and 0.857, respectively), the second surgeon showed high and perfect reliability (kappa values of 0.759 and 1.000, respectively) for the same assessments. While the interobserver reliability for visual inspection was moderate (kappa values of 0.407 and 0.455, respectively), it was little to low for circular measurements (kappa values of 0.173 and 0.232, respectively). The interobserver reliability for the α angle assessment relative to the floor on WBCT scans was perfect (ICC = 0.968)., Conclusion: The AIR classification may not provide a reliable estimate of first metatarsal pronation, so clinicians should be cautious and recognize these limitations in their diagnostic applications. Between the two AIR classifications, the visual inspection measurement seems to be more reliable according to kappa value. If allowed, it may be better to additionally include a 3D assessment method such as WBCT, in the preoperative evaluation., Level of Evidence: IV, case series., Competing Interests: Declarations. Ethics approval and consent to participate.: The study received approval from the Ethics Committee of the Beijing Jishuitan Hospital, Capital Medical University. All methods were conducted in accordance with relevant guidelines and regulations. The procedures adhered to the principles outlined in the Helsinki Declaration. Because this was a retrospective review, informed consent was waived with agreement of the Ethics Committee. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

As a significant fruit and timber tree species among conifers, Pinus koraiensis remains it evergreen status throughout the harsh winters of the north, a testament to its intricate and prolonged evolutionary adaptation. This study delves into the annual trends of physiological indicators, gene expression levels, and metabolite accumulation to dissect the seasonal adaptability of P. koraiensis needles. Chlorophyll content reaches its zenith primarily between July and September, whereas carotenoids persist until spring. Additionally, notable seasonal variations are observed in the levels of soluble sugar and protein. Transcriptome data is categorized into four distinct stages: spring (S2), summer (S3-S4), autumn (S5), and winter (S6-S1). The differential expression of transcription factor genes, including bHLH, MYB-related, AP2/ERF, C3H, and NAC, provides insights into the needles' seasonal adaptations. Analysis of chlorophyll and carotenoid metabolism, sugar metabolism, and the MAPK signaling pathway identifies PSY5 (Cluster-50735.3), AMY13 (Cluster-37114.0), pgm1 (Cluster-46022.0), and MEKK1-1 (Cluster-33069.0) may as potential key genes involved in sustaining the needle's evergreen nature and cold resistance. Ultimately, a comprehensive annual adaptability map for P. koraiensis is proposed, enhancing understanding of its responses to seasonal variations., Competing Interests: Declarations. Ethics approval and consent to participate: The experiments did not involve endangered or protected species. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Chronic Kidney Disease (CKD) is a common severe complication after radical nephrectomy in patients with renal cancer. The timely and accurate prediction of the long-term progression of renal function post-surgery is crucial for early intervention and ultimately improving patient survival rates., Objective: This study aimed to establish a machine learning model to predict the likelihood of long-term renal dysfunction progression after surgery by analyzing patients' general information in depth., Methods: We retrospectively collected data of eligible patients from the Affiliated Hospital of Qingdao University. The primary outcome was upgrading of the Chronic Kidney Disease stage between pre- and 3-year post-surgery. We constructed seven different machine-learning models based on Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (Lightgbm), Gaussian Naive Bayes (GaussianNB), and K-Nearest Neighbors (KNN). The performance of all predictive models was evaluated using the area under the receiver operating characteristic curve (AUC), precision-recall curves, confusion matrices, and calibration curves., Results: Among 360 patients with renal cancer who underwent radical nephrectomy included in this study, 185 (51.3%) experienced an upgrade in Chronic Kidney Disease stage 3-year post-surgery. Eleven predictive variables were selected for further construction of the machine learning models. The logistic regression model provided the most accurate prediction, with the highest AUC (0.8154) and an accuracy of 0.787., Competing Interests: Declarations. Ethics approval and consent to participate: As this publication is a report that contains no identifiable content to the patient, this publication was exempt from ethical approval by the Human Research Protection Program (HRPP) and its Institutional Review Board (IRB) at the Ethics Committee of the affiliated hospital of Qingdao University. Consent for publication: N/A. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated., Methods: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive genomics, transcriptomics, and deep phenotyping analysis approach on 137 individuals affected by MRXSL. Genomic structural information was correlated with transcriptomic and quantitative phenotypic analysis using Human Phenotype Ontology (HPO) semantic similarity scores., Results: Duplication sizes in the cohort ranging from 64.6 kb to 16.5 Mb were classified into four categories comprising of tandem duplications (48%), terminal duplications (22%), inverted triplications (20%), and other CGRs (10%). Most of the terminal duplication structures consist of translocations (65%) followed by recombinant chromosomes (23%). Notably, 65% of de novo events occurred in the Terminal duplication group in contrast with 17% observed in Tandem duplications. RNA-seq data from lymphoblastoid cell lines indicated that the MECP2 transcript quantity in MECP2 triplications is statistically different from all duplications, but not between other classes of genomic structures. We also observed a significant (p < 0.05) correlation (Pearson R = 0.6, Spearman p = 0.63) between the log-transformed MECP2 RNA levels and MECP2 protein levels, demonstrating that genomic aberrations spanning MECP2 lead to altered MECP2 RNA and MECP2 protein levels. Genotype-phenotype analyses indicated a gradual worsening of phenotypic features, including overall survival, developmental levels, microcephaly, epilepsy, and genitourinary/eye abnormalities in the following order: Tandem duplications, Other complex duplications, Terminal duplications/Translocations, and Triplications encompassing MECP2., Conclusion: In aggregate, this combined analysis uncovers an interplay between MECP2 dosage, genomic rearrangement structure and phenotypic traits. Whereas the level of MECP2 is a key determinant of the phenotype, the DNA rearrangement structure can contribute to clinical severity and disease expression variability. Employing this type of analytical approach will advance our understanding of the impact of genomic rearrangements on genomic disorders and may help guide more targeted therapeutic approaches., Competing Interests: Declarations. Ethics approval and consent to participate: This study is approved by Baylor College of Medicine (BCM) and Pacific Northwest Research Institute (PNRI). For patients who were evaluated at TCH-BBC Rett Center, clinical information was obtained by retrospective chart review using H-46044 protocol approved by Baylor College of Medicine’s (BCM) Institutional Review Board (IRB). We used BCM IRB approved H-32407 and H-47281/PNRI WIRB #20202158 protocols to clinically examine patients on a research basis. For genomic studies, participants were consented according to the IRB at BCM approved protocols: H-29697, H-20268, H-18122, and H-26667 or H-47281/Pacific Northwest Research Institute WIRB #20202158. The research was conducted in compliance with the principles of Helsinki Declaration. Consent for publication: All subjects gave consent for participation into our study and publication of genomic and clinical information. Competing interests: BCM and Miraca Holdings have formed a joint venture with shared ownership and governance of BG, which performs clinical microarray analysis (CMA), clinical ES (cES), and clinical biochemical studies. J.R.L. serves on the Scientific Advisory Board of the BG. J.R.L. has stock ownership in 23andMe, is a paid consultant for Genomics International, and is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, genomic disorders and bacterial genomic fingerprinting. D.P. and M.B.R. provide consulting service for Ionis Pharmaceuticals. The remaining authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Cancer navigation programs aim to support, educate, and empower patients and families, addressing barriers to diagnostics, treatment, and care. Navigators engage with people to ensure timely access to services and resources. While promising for older people with cancer, these programs are scarce in Europe, and research on their effectiveness and implementation is limited. We describe the protocol of the EU NAVIGATE randomized controlled trial, aimed to evaluate (1) effectiveness and cost-effectiveness of NavCare-EU, an intervention that aims to support older people with cancer throughout their illness trajectory, spanning the continuum of supportive, palliative, and end-of-life care, and (2) the intervention's implementation processes and feasibility of its integration into different health care systems in Europe, contextual barriers and facilitators for effective and sustainable implementation, and mechanisms involved in reaching the outcomes., Methods: We will conduct a multisite pragmatic fast-track randomized controlled trial with embedded convergent mixed-method process evaluation in Belgium, Ireland, Italy, Netherlands, Poland, and Portugal. The study targets people with cancer and declining health, 70 years or older, and their close family caregivers. The trial compares the NavCare-EU intervention plus standard care with standard care alone. We will perform a baseline measurement prior to randomization and follow-up measurements at 12 weeks, 24 weeks, and 48 weeks in intervention and control group, and an additional measurement at 72 weeks in the control group. Primary outcomes, measured at 24 weeks are (1) the older person's global health status/quality of life, a 2-item subscale from EORTC-QLQ-C30 (revised) measuring health-related quality of life, (2) level of social support measured with Medical Outcomes Study Social Support Survey (MOS-SSS scale). The study will include at least 246 older persons with completed global health status/quality of life at 24 weeks., Discussion: The EU NAVIGATE trial will cross-nationally test the effectiveness and cost-effectiveness of a navigation intervention for older people with cancer and their family caregivers, and its implementation in different health care systems in Europe. As continuity and access to health, social, and community care is a priority for patients and caregivers, the trial is timely and critically needed., Trial Registration: Clinicaltrials.gov: identifier NCT06110312 (2023/10/31)., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval from the relevant ethics committees were obtained in all participating countries. Belgium: Commissie Medische Ethiek, 09/08/2023; Ireland: SJH/TUH Joint Research Ethics Committee, 14/11/2023; Italy: Comitato Etico Territoriale Lombardia 4, Istituto Tumori, 31/07/2023; the Netherlands: METC Amsterdam UMC, 22/08/2023; Portugal: Ethics Committee of the Faculty of Medicine of the University of Coimbra and Ethics Committee of the Portuguese Institute of Oncology of Coimbra Francisco Gentil, 25/09/2023; Poland: Komisja Bioetyczna, Uniwersytetu Jagiellońskiego, 14/06/2023. If all eligibility criteria are met, the researcher or research assistant will obtain informed consent from both the older person and the close family caregiver (if there is one). Patients and caregivers will be given the time to consider participation and will be assured that they are free to withdraw their participation without any effect on their care. Written consent will be obtained without any coercion of study participants. The research team will provide all participants with full disclosure about the nature and goal of the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S. boulardii affects the small intestine remains unclear. Here, we aimed to explore the effects of S. boulardii on the small intestine and the underlying mechanisms in mice with loperamide-induced constipation. While S. boulardii administration did not fully reverse the alterations in loperamide-induced defecation parameters, it altered the small intestinal floral composition toward a community conducive to alleviate constipation. Moreover, S. boulardii up-regulated the expression of tyrosine-protein kinase Kit (c-Kit), aquaporin 3 (AQP3), interleukin (IL)-10, myosin light chain kinase (MLCK), and phosphorylated myosin light chain 20 (P-MLC20), while concurrently down-regulating the expression levels of inducible nitric oxide synthase (iNOS), p65, and IL-17 A. These alterations indicate a discernible effect of small intestinal water reabsorption, inflammatory factor levels, and smooth muscle contraction. Saccharomyces boulardii also positively regulated small intestinal metabolite levels, such as fructose 6-phosphate, dihomo-alpha-linolenic acid, and 3-(4-hydroxyphenyl) lactate, and participated in metabolic pathways such as arginine biosynthesis, linoleic acid metabolism, and protein digestion and absorption. While not fully reversing defecation changes, Saccharomyces boulardii alters intestinal flora, up-regulates key proteins affecting water reabsorption and inflammation, and positively influences metabolic pathways. Our study provides serves as a basis for further studies on the application of S. boulardii in the treatment of intestinal disorders., Competing Interests: Declarations. Ethics approval and consent to participate: All experimental protocols were approved by the Animal Ethics Committee of People’s Liberation Army General Hospital, Beijing, China (2022-X18-71). Patient consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Primary ovarian insufficiency (POI) is a disorder characterized by the premature decline in ovarian function, leading to significant fertility and health impacts on women under 40. The unclear etiology of POI hinders the development of effective treatments, highlighting the need for novel therapeutic targets., Methods: This study employed genome-wide association analysis (GWAS) integrated with expression quantitative trait loci (eQTL) data from the GTEx and eQTLGen databases. Mendelian randomization (MR) and colocalization analyses were conducted to investigate causal relationships between genetic variants and POI and to identify potential therapeutic targets., Results: We identified 431 genes with available index cis-eQTL signals, of which four (HM13, FANCE, RAB2A, and MLLT10) were significantly associated with POI. Colocalization analysis revealed strong evidence for FANCE and RAB2A, indicating their potential as therapeutic targets. Subsequent druggability assessments identified FANCE and RAB2A as promising candidates for POI treatment, supported by their involvement in DNA repair and autophagy regulation, respectively., Conclusions: Our study establishes a causal link between specific genes and POI, highlighting FANCE and RAB2A as potential drug targets. These findings provide a foundation for future research and therapeutic development, aiming to improve outcomes for women with POI. Validation in further trials is necessary to confirm these potential targets., (© 2024. The Author(s).)

Background: Intensive Care Unit nurses are related to the medical quality and life outcome of critically ill patients. In the context of nurse shortage, it is of great significance to reduce the turnover intention of Intensive Care Unit nurses. Inclusive Leadership, organizational-based self-esteem and Interactional Justice are important factors affecting the turnover intention of Intensive Care Unit nurses. However, for the special group of Intensive Care Unit nurses, there are few studies that explore the associations between these factors. This study explores the effect of inclusive leadership on the turnover intention of Intensive Care Unit nurses and the potential mediation through organizational-based self-esteem and interactional justice., Method: A cross-sectional study design was used to investigate 460 Intensive Care Unit nurses in 4 general hospitals in northern China. The scales used in this study include the inclusive leadership scale, the organization-based self-esteem scale, the interactional justice scale and the turnover intention scale. SPSS 27.0 was used for descriptive analysis and Pearson correlation analysis. AMOS 25.0 was used to construct structural equation model and Bootstrap test., Results: The results showed that the turnover intention of Intensive Care Unit nurses was higher (2.05 ± 0.67). Inclusive leadership had a negative predictive effect on turnover intention (β=-0.27, P < 0.001), and organizational-based self-esteem and interactional justice played a chain mediating role in the relationship between them (β=-0.051, P < 0.05)., Conclusions: Inclusive leadership is significantly related to the turnover intention of Intensive Care Unit nurses, and organizational-based self-esteem and interactional justice play a chain mediating role between the two. When medical institutions and nursing managers intervene to reduce the turnover intention of Intensive Care Unit nurses, they should not only focus on inclusive leadership but also consider the impact of organizational-based self-esteem and interactional justice on turnover intention, in order to develop effective talent retention strategies., (© 2024. The Author(s).)

Objective: Cancer is currently the most common cause of death in adult dogs. Like humans, dogs have a one-third chance of developing cancer in their lifetime. We used shallow whole-genome sequencing (sWGS) to analyze blood cell-free DNA (cfDNA) from four tumor-bearing dogs (one with benign and three with malignant tumors) and 38 healthy dogs., Results: Similar to the results observed in the healthy dogs, no copy number aberration (CNA) was detected in the dog with benign lipomas, and the distribution of cfDNA fragment size (FS) closely resembled that of the healthy dogs. However, among the three dogs diagnosed with malignant tumors, two dogs exhibited varying degrees and quantities of CNAs. Compared to the distribution of FS in the healthy dogs, the cancer dogs exhibited a noticeable shift towards shorter lengths. These findings indicated that CNA and FS profiles derived from sWGS data can be used for non-invasive cancer detection in dogs., (© 2024. The Author(s).)

Background: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation., Methods: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits., Results: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period., Conclusion: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses., Trial Registration: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021., (© 2024. The Author(s).)

Background: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear., Objective: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model., Methods: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method., Results: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions)., Conclusion: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions., (© 2024. The Author(s).)

Background: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive., Methods: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15., Results: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1., Conclusions: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling., (© 2024. The Author(s).)

Background: Our previous study demonstrated that β2-microglobulin (β2M) promoted ER + /HER2 - breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of β2M has not been investigated in ER - /HER2 + breast cancer. Here, we aimed to determine the role of β2M in ER - /HER2 + breast cancer., Methods: The interaction between β2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of β2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. β2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry., Results: HFE was found to be an interacting protein of β2M in ER - /HER2 + breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that β2M directly interacted with HFE. β2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. In addition to breast cancer cells BT474, endogenous β2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA-MB-231, and MCF-7. β2M activated the ERK signaling pathway by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments., Conclusions: β2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer., (© 2024. The Author(s).)

Background: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies., Methods: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics., Results: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China., Conclusions: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk., (© 2024. The Author(s).)

Cochlear implants can directly activate the auditory system's primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration., (© 2024. The Author(s).)

Background: Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis and treatment have yet to be studied in detail. In recent years, Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to be effective in treating various diseases. Current understanding of RSA treatment using WJ-MSCs is limited, and the exact mechanisms of WJ-MSCs action in RSA remains largely unclear. In this study, we explored the decidual deficiencies in RSA and the therapeutic potential of WJ-MSCs at single-cell resolution., Methods: Three mouse models were established: a normal pregnancy group, an RSA group, and a WJ-MSC treatment group. Decidual tissue samples were collected for single-cell RNA sequencing (scRNA-seq) and functional verification, including single-cell resolution in situ hybridization on tissues (SCRINSHOT) and immunofluorescence., Results: We generated a single-cell atlas of decidual tissues from normal pregnant, RSA, and WJ-MSC-treated mice and identified 14 cell clusters in the decidua on day 14. Among these cell populations, stromal cells were the most abundant cell clusters in the decidua, and we further identified three novel subclusters (Str&#95;0, Str&#95;1, and Str&#95;2). We also demonstrated that the IL17 and TNF signaling pathways were enriched for upregulated DEGs of stromal cells in RSA mice. Intriguingly, cell-cell communication analysis revealed that Str&#95;1 cell-related gene expression was greatly reduced in the RSA group and rescued in the WJ-MSC treatment group. Notably, the interaction between NK cells and other cells in the RSA group was attenuated, and the expression of Spp1 (identified as an endometrial toleration-related marker) was significantly reduced in the NK cells of the RSA group but could be restored by WJ-MSC treatment., Conclusion: Herein, we implemented scRNA-seq to systematically evaluate the cellular heterogeneity and transcriptional regulatory networks associated with RSA and its treatment with WJ-MSCs. These data revealed potential therapeutic targets of WJ-MSCs to remodel the decidual subpopulations in RSA and provided new insights into decidua-derived developmental defects at the maternal-foetal interface., (© 2024. The Author(s).)

Background: To evaluate the knowledge, attitude and practice of nurses regarding non-pharmacologic therapies for behavioral and psychological symptoms of dementia (BPSD)., Methods: This cross-sectional, questionnaire-based study enrolled nurses at Peking Union Medical College Hospital (Beijing, China) between September 2022 and October 2022. Correlations between knowledge, attitude and practice scores were evaluated by Pearson correlation analysis. Factors associated with knowledge, attitude and practice scores were identified by multivariable linear regression. Based on a cross-sectional questionnaire survey, this study designed a questionnaire according to the Guidelines for Diagnosis and Treatment of Dementia in China, and randomly selected nurses from Peking Union Medical College Hospital to fill in the questions through the Wen-Juan-Xing online platform from September 2022 to October 2022., Results: The analysis included 210 nurses (202 females). The average knowledge, attitude and practice scores were 11.06±2.61 (total score: 18), 53.51±5.81 (total score: 60) and 64.66 ± 10.35 (total score: 80) points, respectively. Knowledge score was positively correlated with attitude score (r = 0.416, P < 0.001) and practice score (r = 0.389, P < 0.001); attitude and practice scores were also positively correlated (r = 0.627, P < 0.001). Multivariable analysis demonstrated that age ≥ 40 years-old (vs. ≤30 years-old) was associated with higher knowledge score (β = 1.48, 95% confidence interval [95%CI] = 0.42-2.54, P = 0.006). Age ≥ 40 years-old (β = 1.43, 95%CI = 0.35-2.51, P = 0.010 vs. ≤30 years-old) and bachelor's degree or higher (β = 1.11, 95%CI = 0.12-2.10, P = 0.028 vs. college degree or lower) were associated with higher practice score., Conclusions: Older age and higher education level were associated with higher knowledge, attitude and/or practice scores. The findings of this study may help guide the development and implementation of education and training programs to improve the management of BPSD by nurses in China., (© 2024. The Author(s).)

Purpose: Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS)., Patients and Methods: In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation., Results: Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99))., Conclusion: A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk., (© 2024. The Author(s).)

Purpose: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities., Materials and Methods: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded., Results: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05)., Conclusion: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists., (© 2024. The Author(s).)

Background: Multi-population genomic prediction can rapidly expand the size of the reference population and improve genomic prediction ability. Machine learning (ML) algorithms have shown advantages in single-population genomic prediction of phenotypes. However, few studies have explored the effectiveness of ML methods for multi-population genomic prediction., Results: In this study, 3720 Yorkshire pigs from Austria and four breeding farms in China were used, and single-trait genomic best linear unbiased prediction (ST-GBLUP), multitrait GBLUP (MT-GBLUP), Bayesian Horseshoe (BayesHE), and three ML methods (support vector regression (SVR), kernel ridge regression (KRR) and AdaBoost.R2) were compared to explore the optimal method for joint genomic prediction of phenotypes of Chinese and Austrian pigs through 10 replicates of fivefold cross-validation. In this study, we tested the performance of different methods in two scenarios: (i) including only one Austrian population and one Chinese pig population that were genetically linked based on principal component analysis (PCA) (designated as the "two-population scenario") and (ii) adding reference populations that are unrelated based on PCA to the above two populations (designated as the "multi-population scenario"). Our results show that, the use of MT-GBLUP in the two-population scenario resulted in an improvement of 7.1% in predictive ability compared to ST-GBLUP, while the use of SVR and KKR yielded improvements in predictive ability of 4.5 and 5.3%, respectively, compared to MT-GBLUP. SVR and KRR also yielded lower mean square errors (MSE) in most population and trait combinations. In the multi-population scenario, improvements in predictive ability of 29.7, 24.4 and 11.1% were obtained compared to ST-GBLUP when using, respectively, SVR, KRR, and AdaBoost.R2. However, compared to MT-GBLUP, the potential of ML methods to improve predictive ability was not demonstrated., Conclusions: Our study demonstrates that ML algorithms can achieve better prediction performance than multitrait GBLUP models in multi-population genomic prediction of phenotypes when the populations have similar genetic backgrounds; however, when reference populations that are unrelated based on PCA are added, the ML methods did not show a benefit. When the number of populations increased, only MT-GBLUP improved predictive ability in both validation populations, while the other methods showed improvement in only one population., (© 2024. The Author(s).)

Objective: This scoping review aims to explore published literature testing Virtual Reality (VR) interventions for improving upper limb motor performance in children and adolescents with Developmental Coordination Disorder (DCD). Our primary focus was on the types of VR systems used and the measurement tools employed within the International Classification of Functioning, Disability and Health Children and Youth Version (ICF-CY) domains in these studies., Methods: A comprehensive search of six electronic databases up to 11th January 2024 was conducted using predefined terms. Inclusion and exclusion criteria were applied to determine study eligibility, with two authors independently assessing titles, abstracts, and full-text articles., Results: Out of 788 potential studies, 14 met the eligibility criteria. Studies predominantly utilized non-immersive VR (nVR) systems, for example, commercial platforms such as Nintendo Wii. Most interventions targeted general motor coordination or balance, with only four studies specifically focusing on upper limb motor performance. The Movement Assessment Battery for Children-2 was the predominant assessment tool. However, the use of game scores and trial durations raised concerns about the accuracy of assessments. The majority of studies reported no significant improvement in upper limb motor performance following VR interventions, though some noted improvements in specific tasks or overall outcomes., Conclusion: The findings suggest that, while nVR interventions are being explored for paediatric motor rehabilitation, their impact on enhancing upper limb motor performance in children with DCD is unclear. The variability in intervention designs, outcome measures, and the predominant focus on general motor skills rather than specific upper limb improvements highlight the need for more targeted research in this area., Impact: This review underscores the importance of developing precise and clinically relevant measurement tools in a broader range of VR technologies to optimize the use of VR in therapy for children with DCD. Future research should aim for more rigorous study designs and emerging immersive technologies to maximize therapeutic benefits., (© 2024. The Author(s).)

Kidney diseases pose a significant threat to human health due to their high prevalence and mortality rates. Worryingly, the clinical use of drugs for kidney diseases is associated with more side effects, so more effective and safer treatments are urgently needed. Oleanolic acid (OA) is a common pentacyclic triterpenoid that is widely available in nature and has been shown to have protective effects in kidney disease. However, comprehensive studies on its role in kidney diseases are still lacking. Therefore, this article first explores the botanical sources, pharmacokinetics, derivatives, and safety of OA, followed by a summary of the anti-inflammatory, immunomodulatory, anti-oxidative stress, autophagy-enhancing, and antifibrotic effects of OA and its analogues in renal diseases, and an analysis of the molecular mechanisms, aiming to provide further insights for the development of novel drugs for the treatment of kidney diseases., (© 2024. The Author(s).)

Background: Chronic kidney disease (CKD) is a common postoperative complication in patients who undergo radical nephrectomy for renal tumours. However, the factors influencing long-term renal function require further investigation., Objective: This study was designed to investigate the trends in renal function changes and risk factors for renal function deterioration in renal tumour patients after radical nephrectomy., Methods: We monitored changes in renal function before and after surgery for 3 years. The progression of renal function was determined by the progression and degradation of CKD stages. Univariate and multivariate logistic regression analyses were used to analyse the causes of renal function progression., Results: We analysed the data of 329 patients with renal tumours who underwent radical nephrectomies between January 2013 and December 2018. In this study, 43.7% of patients had postoperative acute kidney injury (AKI), and 48.3% had CKD at advanced stages. Further research revealed that patients' renal function stabilized 3 months after surgery. Additionally, renal function changes during these 3 months have a substantial impact on the progression of long-term renal function changes in patients., Conclusion: AKI may be an indicator of short-term postoperative changes in renal function. Renal function tests should be performed in patients with AKI after radical nephrectomy to monitor the progression of functional impairment, particularly within the first 3 months after radical nephrectomy., (© 2024. The Author(s).)

Background: Kidney cancer has become known as a metabolic disease. However, there is limited evidence linking metabolic syndrome (MetS) with kidney cancer risk. This study aimed to investigate the association between MetS and its components and the risk of kidney cancer., Methods: UK Biobank data was used in this study. MetS was defined as having three or more metabolic abnormalities, while pre-MetS was defined as the presence of one or two metabolic abnormalities. Hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk by MetS category were calculated using multivariable Cox proportional hazards models. Subgroup analyses were conducted for age, sex, BMI, smoking status and drinking status. The joint effects of MetS and genetic factors on kidney cancer risk were also analyzed., Results: This study included 355,678 participants without cancer at recruitment. During a median follow-up of 11 years, 1203 participants developed kidney cancer. Compared to the metabolically healthy group, participants with pre-MetS (HR= 1.36, 95% CI: 1.06-1.74) or MetS (HR= 1. 70, 95% CI: 1.30-2.23) had a significantly greater risk of kidney cancer. This risk increased with the increasing number of MetS components (P for trend < 0.001). The combination of hypertension, dyslipidemia and central obesity contributed to the highest risk of kidney cancer (HR= 3.03, 95% CI: 1.91-4.80). Compared with participants with non-MetS and low genetic risk, those with MetS and high genetic risk had the highest risk of kidney cancer (HR= 1. 74, 95% CI: 1.41-2.14)., Conclusions: Both pre-MetS and MetS status were positively associated with kidney cancer risk. The risk associated with kidney cancer varied by combinations of MetS components. These findings may offer novel perspectives on the aetiology of kidney cancer and assist in designing primary prevention strategies., (© 2024. The Author(s).)

Objective: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding., Methods: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics., Results: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049)., Conclusion: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk., (© 2024. The Author(s).)

Objective: This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method., Methods: A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach., Results: A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30-59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30-34 and 45-49 age groups (p < 0.05), while no significant differences were found among other age groups. 99.7% of the samples were tested qualified, and there was no significant difference in sampling failure rate among age groups. Analysis of demographic and social elements showed no significant impact on the rates of sample provision among groups in most of the social elements but the medical insurance and the monthly family-incomes., Conclusion: The findings demonstrate that online cervical cancer screening is reliable for self-registration, self-sampling, and self-ordering for specimen transportation. It is suitable for women of all ages needing to be screened, irrespective of social elements, and effectively facilitates screening for women with limited access to medical resources. Therefore, online screening holds promise as an effective approach to increase screening coverage., (© 2024. The Author(s).)

Background: NODAL signaling plays a critical role in embryonic patterning and heart development in vertebrates. Genetic variants resulting in perturbations of the TGF-β/NODAL signaling pathway have reproducibly been shown to cause laterality defects in humans. To further explore this association and improve genetic diagnosis, the study aims to identify and characterize a broader range of NODAL variants in a large number of individuals with laterality defects., Methods: We re-analyzed a cohort of 321 proband-only exomes of individuals with clinically diagnosed laterality congenital heart disease (CHD) using family-based, rare variant genomic analyses. To this cohort we added 12 affected subjects with known NODAL variants and CHD from institutional research and clinical cohorts to investigate an allelic series. For those with candidate contributory variants, variant allele confirmation and segregation analysis were studied by Sanger sequencing in available family members. Array comparative genomic hybridization and droplet digital PCR were utilized for copy number variants (CNV) validation and characterization. We performed Human Phenotype Ontology (HPO)-based quantitative phenotypic analyses to dissect allele-specific phenotypic differences., Results: Missense, nonsense, splice site, indels, and/or structural variants of NODAL were identified as potential causes of heterotaxy and other laterality defects in 33 CHD cases. We describe a recurrent complex indel variant for which the nucleic acid secondary structure predictions implicate secondary structure mutagenesis as a possible mechanism for formation. We identified two CNV deletion alleles spanning NODAL in two unrelated CHD cases. Furthermore, 17 CHD individuals were found (16/17 with known Hispanic ancestry) to have the c.778G > A:p.G260R NODAL missense variant which we propose reclassification from variant of uncertain significance (VUS) to likely pathogenic. Quantitative HPO-based analyses of the observed clinical phenotype for all cases with p.G260R variation, including heterozygous, homozygous, and compound heterozygous cases, reveal clustering of individuals with biallelic variation. This finding provides evidence for a genotypic-phenotypic correlation and an allele-specific gene dosage model., Conclusion: Our data further support a role for rare deleterious variants in NODAL as a cause for sporadic human laterality defects, expand the repertoire of observed anatomical complexity of potential cardiovascular anomalies, and implicate an allele specific gene dosage model., (© 2024. The Author(s).)

Background: The pig (Sus Scrofa) is one of the oldest domesticated livestock species that has undergone extensive improvement through modern breeding. European breeds have advantages in lean meat development and highly-productive body type, whereas Asian breeds possess extraordinary fat deposition and reproductive performance. Consequently, Eurasian breeds have been extensively used to develop modern commercial breeds for fast-growing and high prolificacy. However, limited by the sequencing technology, the genome architecture of some nascent developed breeds and the human-mediated impact on their genomes are still unknown., Results: Through whole-genome analysis of 178 individuals from an Asian locally developed pig breed, Beijing Black pig, and its two ancestors from two different continents, we found the pervasive inconsistent gene trees and species trees across the genome of Beijing Black pig, which suggests its introgressive hybrid origin. Interestingly, we discovered that this developed breed has more genetic relationships with European pigs and an unexpected introgression from Asian pigs to this breed, which indicated that human-mediated introgression could form the porcine genome architecture in a completely different type compared to native introgression. We identified 554 genomic regions occupied 63.30 Mb with signals of introgression from the Asian ancestry to Beijing Black pig, and the genes in these regions enriched in pathways associated with meat quality, fertility, and disease-resistant. Additionally, a proportion of 7.77% of genomic regions were recognized as regions that have been under selection. Moreover, combined with the results of a genome-wide association study for meat quality traits in the 1537 Beijing Black pig population, two important candidate genes related to meat quality traits were identified. DNAJC6 is related to intramuscular fat content and fat deposition, and RUFY4 is related to meat pH and tenderness., Conclusions: Our research provides insight for analyzing the origins of nascent developed breeds and genome-wide selection remaining in the developed breeds mediated by humans during modern breeding., (© 2024. The Author(s).)

Background: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera., Purpose: We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice., Methods: We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin-eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells., Results: SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α)., (© 2024. The Author(s).)

The morbidity of gestational diabetes mellitus (GDM) is increasing and is associated with adverse perinatal outcomes and long-term maternal and infant health. The exact mechanism underlying changes in plasma free fatty acid (FFA) profiles in patients with GDM is unknown. However, it is believed that changes in diet and lipid metabolism may play a role. Fatty acids contain many specific FFAs, and the type of FFA has different impacts on physiological processes; hence, determining changes in FFAs in individual plasma is essential. Alterations in FFA concentration or profile may facilitate insulin resistance. Additionally, some FFAs show potential to predict GDM in early pregnancy and are strongly associated with the growth and development of the fetus and occurrence of macrosomia. Here, we aimed to review changes in FFAs in women with GDM and discuss the relationship of FFAs with GDM incidence and adverse outcomes., (© 2024. The Author(s).)

Background: Photoperiod, or the length of the day, has a significant impact on the flowering and sex differentiation of photoperiod-sensitive crops. The "miben" pumpkin (the main type of Cucurbita moschata Duch.) is well-known for its high yield and strong disease resistance. However, its cultivation has been limited due to its sensitivity to photoperiod. This sensitivity imposes challenges on its widespread cultivation and may result in suboptimal yields in regions with specific daylength conditions. As a consequence, efforts are being made to explore potential strategies or breeding techniques to enhance its adaptability to a broader range of photoperiods, thus unlocking its full cultivation potential and further promoting its valuable traits in agriculture., Results: This study aimed to identify photoperiod-insensitive germplasm exhibiting no difference in sex differentiation under different day-length conditions. The investigation involved a phenotypic analysis of photoperiod-sensitive (PPS) and photoperiod-insensitive (PPIS) pumpkin materials exposed to different day lengths, including long days (LDs) and short days (SDs). The results revealed that female flower differentiation was significantly inhibited in PPS&#95;LD, while no differences were observed in the other three groups (PPS&#95;SD, PPIS&#95;LD, and PPIS&#95;SD). Transcriptome analysis was carried out for these four groups to explore the main-effect genes of sex differentiation responsive to photoperiod. The main-effect gene subclusters were identified based on the principal component and hierarchical cluster analyses. Further, functional annotations and enrichment analysis revealed significant upregulation of photoreceptors (CmCRY1, F-box/kelch-repeat protein), circadian rhythm-related genes (CmGI, CmPRR9, etc.), and CONSTANS (CO) in PPS&#95;LD. Conversely, a significant downregulation was observed in most Nuclear Factor Y (NF-Y) transcription factors. Regarding the gibberellic acid (GA) signal transduction pathway, positive regulators of GA signaling (CmSCL3, CmSCL13, and so forth) displayed higher expression levels, while the negative regulators of GA signaling, CmGAI, exhibited lower expression levels in PPS&#95;LD. Notably, this effect was not observed in the synthetic pathway genes. Furthermore, genes associated with ethylene synthesis and signal transduction (CmACO3, CmACO1, CmERF118, CmERF118-like1,2, CmWIN1-like, and CmRAP2-7-like) showed significant downregulation., Conclusions: This study offered a crucial theoretical and genetic basis for understanding how photoperiod influences the mechanism of female flower differentiation in pumpkins., (© 2024. The Author(s).)

Background: Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges., Methods: We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity., Results: Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86-5.23) and PFS (HR = 4.28; 95% CI, 3.34-5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01-1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes., Conclusions: Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC., Prospero Registration Number: CRD42023412465., (© 2024. The Author(s).)

Background: Population-level vaccine efficacy is a critical component of understanding COVID-19 risk, informing public health policy, and mitigating disease impacts. Unlike individual-level clinical trials, population-level analysis characterizes how well vaccines worked in the face of real-world challenges like emerging variants, differing mobility patterns, and policy changes., Methods: In this study, we analyze the association between time-dependent vaccination rates and COVID-19 health outcomes for 48 U.S. states. We primarily focus on case-hospitalization risk (CHR) as the outcome of interest, using it as a population-level proxy for disease burden on healthcare systems. Performing the analysis using Generalized Additive Models (GAMs) allowed us to incorporate real-world nonlinearities and control for critical dynamic (time-changing) and static (temporally constant) factors. Dynamic factors include testing rates, activity-related engagement levels in the population, underlying population immunity, and policy. Static factors incorporate comorbidities, social vulnerability, race, and state healthcare expenditures. We used SARS-CoV-2 genomic surveillance data to model the different COVID-19 variant-driven waves separately, and evaluate if there is a changing role of the potential drivers of health outcomes across waves., Results: Our study revealed a strong and statistically significant negative association between vaccine uptake and COVID-19 CHR across each variant wave, with boosters providing additional protection during the Omicron wave. Higher underlying population immunity is shown to be associated with reduced COVID-19 CHR. Additionally, more stringent government policies are generally associated with decreased CHR. However, the impact of activity-related engagement levels on COVID-19 health outcomes varied across different waves. Regarding static variables, the social vulnerability index consistently exhibits positive associations with CHR, while Medicaid spending per person consistently shows a negative association. However, the impacts of other static factors vary in magnitude and significance across different waves., Conclusions: This study concludes that despite the emergence of new variants, vaccines remain highly correlated with reduced COVID-19 harm. Therefore, given the ongoing threat posed by COVID-19, vaccines remain a critical line of defense for protecting the public and reducing the burden on healthcare systems., (© 2024. The Author(s).)

Background: Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. The factors contributing to the severity of illness caused by M. pneumoniae infection are still under investigation. We aimed to evaluate the sensitivity of common M. pneumoniae detection methods, as well as to analyze the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniae pneumonia in Wuhan., Results: Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via quantitative polymerase chain reaction (qPCR). Furthermore, we found that while serological testing is not highly sensitive in detecting M. pneumoniae infection, but it may serve as an indicator for predicting severe cases. We successfully identified the adhesin P1 (P1) genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniae isolates was 96% (48/50) and all mutations were A2063G in domain V of 23S rRNA gene. There was no significant difference between the upper respiratory microbiome of patients with mild and severe symptoms., Conclusions: During the period of this study, the main circulating M. pneumoniae was P1-type 1, with a resistance rate of 96%. Key findings include the efficacy of qPCR in detecting M. pneumoniae, the potential of IgM titers exceeding 1:160 as indicators for illness severity, and the lack of a direct correlation between disease severity and genotypic characteristics or respiratory microenvironment. This study is the first to characterize the epidemic and genomic features of M. pneumoniae in Wuhan after the COVID-19 outbreak in 2020, which provides a scientific data basis for monitoring and infection prevention and control of M. pneumoniae in the post-pandemic era., (© 2024. The Author(s).)

Background: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation., Methods: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed., Results: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death)., Conclusions: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients., (© 2024. The Author(s).)

Background: Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear., Methods: The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB)., Results: TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils., Conclusion: TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies., (© 2023. The Author(s).)

Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H 2 O 2 in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO 2 ) and β-lapachone as donors of H 2 O 2 and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO 2 and β-lapachone could significantly self-generated sufficient H 2 O 2 , which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca 2+ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H 2 O 2 , but also efficiently activates ferroptosis and initiates Ca 2+ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H 2 O 2 ., (© 2023. The Author(s).)