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Shusheng Lin,1,2,* Yi Cao,3,* Ke Zhu,1,2,4,* Caini Yang,1,2 Xiangping Zhu,2 Honghua Zhang,1,2 Rui Zhang1,2 1Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Emergency Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Guangdong TCRCure Biopharma Technology Co., Ltd, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Zhang; Honghua Zhang, Email zhangr95@mail.sysu.edu.cn; zhanghh68@mail.sysu.edu.cnBackground: The complex tumor microenvironment of hepatocellular carcinoma (HCC) has led to a low response to immune checkpoints inhibitors (ICIs) and a poor prognosis. PD-L1, as one of the indications for ICIs, is rich in glycosylation modifications, which result in untimely ICIs. Our study constructed a prognostic model based on N-linked glycosylation related genes for predicting the prognosis and the response to ICIs.Methods: The list of N-linked glycosylation related genes is from the AmiGO2 database. The patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled. The Cox regression was performed to develop a prognostic model and patients were divided into a low- and high-risk subgroups. The role of signature in HCC was well investigated by prognostic analysis, gene set enrichment analysis, and immune infiltration analysis. 21 recurrent HCC patients who received postoperative adjuvant ICIs were recruited to evaluate the relationship between immunotherapy response and the signature. In vitro studies were conducted to investigate the oncogenic effects of DDOST, STT3A and TMEM165 in HCC.Results: 59 N-linked glycosylation related differentially expressed genes were screened from HCC and normal tissues in the TCGA cohort. The prognostic model was developed with DDOST, STT3A and TMEM165. The risk score could be an independent prognostic factor. Patients in the high-risk subgroup showed a worse prognosis than patients in the low-risk one. ssGSEA showed that patients in the low-risk subgroup tended to be in the immune-activated state, with higher levels of B cell and macrophage cell infiltrations and lower levels of regulatory T cell (Treg) infiltrations in both TCGC and GEO cohorts. Immunohistochemistry studies showed that DDOST, STT3A and TMEM165 are highly expressed in tumor tissues and patients with a high-risk score correlated with poor progression free survival and worse immunotherapeutic response. Furthermore, the proliferation of HCC cells was reduced after the knockdown of DDOST, as well as upon the knockdown of STT3A and TMEM165.Conclusion: In this study, we establish that the risk model based on N-linked glycosylation related genes could efficiently predict the prognosis and tumor microenvironment immune state of HCC patients, and the risk score could serve as a novel indicator of immunotherapy.Keywords: N-linked glycosylation, prognostic signature, HCC, immune infiltration, immunotherapy

Sheng-Shing Lin,1,2 Chiu-Lin Tsai,3 Ching-Yeh Tu,3 Ching-Liang Hsieh2,4,5 1Graduate Institute of Chinese Medicine, College of Chinese Medicine, China Medical University, 2Department of Chinese Medicine, China Medical University Hospital, 3Division of Chinese Medicine, Department of Pharmacy, China Medical University Hospital, 4Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, 5Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung, Taiwan Background: Traditional Chinese medicine (TCM) and Western medicine are both popular in Taiwan. Approximately 14.1% of Taiwanese residents use Western drugs and Chinese herbs concurrently; therefore, drug–herb interaction is critical to patient safety. This paper presents a new procedure for reducing the risk of drug interactions.Methods: Hospital computer systems are modified to ensure that drug–herb interactions are automatically detected when a TCM practitioner is writing a prescription. A pop-up reminder appears, warning of interactions, and the practitioner may adjust doses, delete herbs, or leave the prescription unchanged. A pharmacist will receive interaction information through the system and provide health education to the patient.Results: During the 2011–2013 study period, 256 patients received 891 herbal prescriptions with potential drug–herb interactions. Three of the 50 patients who concurrently used ginseng and antidiabetic drugs manifested hypoglycemia (fasting blood sugar level ≤70 mg/dL).Conclusion: Drug–herb interactions can cause adverse reactions. A computerized reminder system can enable TCM practitioners to reduce the risk of drug–herb interactions. In addition, health education for patients is crucial in avoiding adverse reaction by the interactions. Keywords: Traditional Chinese medicine, Western medicine, adverse reaction

Retroviruses in nondividing cells and yeast retrotransposons must transit the nuclear membrane in order for integration to occur. Mutations in a bipartite basic motif in the carboxyl-terminal domain of the Ty3 integrase (IN) protein were previously shown to block transposition at a step subsequent to 3'-end processing of Ty3 extrachromosomal DNA. In this work, the Ty3 IN was shown to be sufficient to target green fluorescent protein to the nucleolus. Mutations in the bipartite basic motif abrogated this localization. The region containing the motif was shown to be sufficient for nuclear but not subnuclear localization of a heterologous protein. Viruslike particles (VLPs) from cells expressing a Ty3 element defective for nuclear localization were inactive in an in vitro integration assay, suggesting that nuclear entry is required to form active VLPs or that this motif is required for post-nuclear entry steps. Ty3 inserts at transcription initiation sites of genomic tRNA genes and plasmid-borne 5S and U6 RNA genes transcribed by RNA polymerase III. In situ hybridization with Ty3- and Ty3 long terminal repeat-specific probes showed that these elements which are associated with tRNA genes do not colocalize with the ribosomal DNA (rDNA). However, a PCR assay of cells undergoing transposition showed that Ty3 insertion does occur into the 5S genes, which, in yeast, are interspersed with the rDNA and therefore, like Ty3 IN, associated with the nucleolus.

We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H(2)O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter.

Spontaneous cell fusion can occur in cocultured stem cells. We examined whether telomerase activity change and cell fusion occurred in mesenchymal stem cell (MSC) and nucleus pulposus cell (NPC) coculture. MSCs and NPCs were labeled with PKH26 and PKH67 dyes and cocultured at a 50:50 ratio. An equal number of MSCs or NPCs were used as the control. After 14 days, cells were evaluated by cell growth, telomerase activity, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and histologic observation. Cell fusion was confirmed by microscopic observation and fluorescence-activated cell sorter (FACS) analysis. The results suggested cell growth rate and telomerase activity were higher in cocultured cells than in NPCs cultured alone. The mRNA expression levels of the Type II collagen and aggrecan were elevated in cocultured cells. Immunohistochemical analysis revealed positive staining for Type II collagen and keratan sulfate in NPCs cultured alone and in a proportion of cocultured cells. Histologic observation revealed binucleated cocultured cells expressed both PKH dyes in the same location and slide focus. The FACS analysis revealed 42% of cocultured cells were double-stained. Cocultured cells partially maintained the NPC phenotype. The partially maintained phenotype of the NPCs may be attributable to spontaneous cell fusion in association with increased telomerase activity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent technological advancements in total ankle arthroplasty (TAA) have included the introduction of the mobile bearing concept. This bearing has several advantages, but researchers have questioned whether or not increased mobility sacrifices joint stability or durability of the implant. The present study evaluated the kinematics of this type of prosthesis implanted in patients. MATERIALS AND METHODS: Fluoroscopy and 3D-to-2D registration techniques were used to determine the in vivo kinematics for 20 TAA subjects performing two activities: gait and step-up. The motion of the prostheses was described in terms of clinical rotations and as rotation about the helical (screw) axis. Then, the anterior-posterior translation and axial rotation of the mobile bearing insert were determined. RESULTS: Among the clinical rotations, the dorsi-/plantarflexion was the most dominant, revealing the greatest pattern change and the largest magnitude. During gait, the orientation of the prosthetic components changed smoothly from plantarflexion to dorsiflexion. The average range of this motion was 9.2 degrees. For step-up activity, the range was 8.0 degrees. However, between 33% and 66% of stance phase, the talar component's orientation changed from dorsiflexion to plantarflexion. The average absolute range of anterior-posterior translation of the mobile bearing insert was 1.5 mm and 2.3 mm for gait and step-up, respectively. CONCLUSION: These measured translations were relatively small and may suggest that the rotational portion of the motion was more dominant than translational and provided sufficient mobility. [ABSTRACT FROM AUTHOR]

Purpose: Reproductive factors are often evaluated in epidemiologic interview studies as risk factors for diseases in women. Similarly, childhood social class has been implicated in the etiology of several diseases. Nevertheless, questions related to these factors have not been thoroughly evaluated for test-retest reliability. This research measured the test-retest reliability of reproductive and childhood social class variables, and determined whether reliability differed by case-control status, age, educational level, time between interviews, and interviewer-rated quality of the interview.Methods: Subjects were participants in a population-based case-control in-person interview study of Hodgkin's disease in northern California women. Twenty-four cases and 22 controls were reinterviewed by telephone between 1992 and 1995, with an average interval of 8 months between interviews. Reliability was assessed using kappa or intraclass correlation coefficients; mean reliability coefficients and 95% confidence intervals (CIs) were estimated using the bootstrap method.Results: Reliability was excellent for all variables (reliability coefficients between 0.76 and 0.96) and did not differ by case-control status (mean reliability = 0.82 for cases and 0.84 for controls), age (mean reliability = 0.85 for age < 40 and 0.82 for age > or = 40), time between interviews (mean reliability = 0.75 for 0-5 months, 0.88 for 6-11 months, and 0.87 for 1 year or more), or interviewer-rated quality of the validity of the original responses (mean reliability = 0.93 for "not too confident" and 0.83 for "confident"). However, reliability was consistently lower among less educated women (mean reliability = 0.56 for high school or less and 0.88 for more than high school), a finding consistent with results of prior studies.Conclusions: These results indicate that questions about reproductive experience and childhood social class posed in in-person interviews can be answered reliably. However, inclusion of subjects at lower socioeconomic status may result in lower reliability for some interview responses. [ABSTRACT FROM AUTHOR]

One of the most often studied associations in epidemiology is dietary fat and breast cancer risk. That migrants from low-risk countries increase their risk on immigrating to higher-risk countries suggests that some modifiable lifestyle or environmental factor is responsible for the development of breast cancer. Although early international correlational studies and experimental animals studies support dietary fat as a risk factor for breast cancer, more recent data from case-control studies and cohort studies have been equivocal, thus the analytical data do not support a strong positive association. The conflicting results from analytic studies may be due to methodologic issues associated with study design, dietary assessment tools, measurement error, improper statistical analyses, and a lack of heterogeneity in fat intake among the study population. Moreover, current dietary questionnaires may be inadequate in capturing true dietary intakes or capturing the risk with exposure during earlier periods of a woman's life. Although two large clinical trials investigating the fat/breast cancer relationships issue are underway, researchers are generally skeptical at their ability to detect an independent association between fat and breast cancer risk. Further epidemiologic studies using current methodology may not prove to be fruitful in generating definitive answers to shed light on this controversial issue. In addition, rather than concentrating on dietary fat, researchers should focus on diets that are not only low in saturated fat, but also high in fruit and vegetable consumption. Researchers should take advantage of advances in molecular and genetic technology for a different perspective in examining the issue. For example, markers of susceptibility to breast cancer that can detect women at higher risk for breast cancer may be helpful in clarifying the role of dietary fat. More comprehensive and multiple approaches to studying dietary factors and breast cancer are recommended. [ABSTRACT FROM AUTHOR]

Functional testing is recommended for risk stratification of medically treated patients with unstable angina. Exercise echocardiography is used in this situation, but its safety and prognostic value are not well defined. The objective of this study was to assess the incremental prognostic value of exercise echocardiography in 226 consecutive patients (128 men, age 59+/-13 years) with medically treated unstable angina, who underwent exercise echocardiography from 1991 to 1996. Clinical risk was designated as low in 108 patients, intermediate in 116, and high in 2 patients according to the unstable angina practice guidelines. There were no major complications from the stress tests. The exercise electrocardiogram was nondiagnostic in 57 patients (25%). Ischemia was identified by exercise electrocardiography in 33 patients and exercise echocardiography in 55 patients. Patients were followed for 29+/-18 months. After exclusion of 38 patients who underwent early revascularization, 28 patients had cardiac death, nonfatal infarction, and late (>3 months) revascularization. Ischemia at exercise echocardiography was associated with a 24-month event-free survival of 81%, compared to 95% with negative exercise echocardiography (p=0.02). A positive exercise electrocardiogram was associated with a 24-month event-free survival of 84%, compared to 93% with negative exercise electrocardiograms (p=0.08). In a Cox regression model, event-free survival was predicted by ischemia at exercise echocardiography (relative risk 2.8, confidence interval: 1.3 to 6.3, p=0.05), but not at exercise electrocardiography (relative risk 2.1, confidence interval 0.7 to 5.8, p=0.16). [ABSTRACT FROM AUTHOR]

Background: Despite widespread acceptance of echocardiography for diagnosis of infective endocarditis, few investigators have evaluated its utility as a risk-stratification tool to aid therapeutic decision-making. Methods: A decision tree and Markov analysis model were constructed using published and institutional data to estimate the cost-effectiveness of an echocardiographic risk-stratification strategy for infective endocarditis. The models compared surgery for high-risk patients based on clinical factors ("standard care") and surgery for high-risk patients based on echocardiographic findings ("echocardiography-guided"). Results: The cost per patient for standard care and echocardiography-guided strategies was $47,766 and $53,669, respectively. The expected quality-adjusted life years (QALY) for standard care and echocardiography-guided strategies were 5.86 years and 6.10 years, respectively. Compared with standard care, the echocardiography-guided strategy cost an additional $23,867 per QALY saved. In one-way sensitivity analyses, the incremental cost of this strategy remained <$50,000/QALY across a broad range of scenarios. Baseline stroke risk had the greatest effect on cost-effectiveness. For populations with stroke risk less than 3.65%, the echocardiography-guided strategy was not cost-attractive (ICER >$50,000/QALY). At stroke risk between 3.65% and 14%, the ICER for the echocardiography-guided strategy was attractive (<$50,000 /QALY). The echocardiography-guided strategy became economically dominant at any baseline stroke risk greater than 18.3%. Conclusion: Echo-guided risk stratification for early surgery in patients with large vegetations is a cost-attractive treatment strategy for IE, as it improves outcome for an incremental cost <$50,000/QALY. [ABSTRACT FROM AUTHOR]

Although shrimp are a valuable protein source, shrimp aquaculture has numerous challenges from various infectious diseases and understanding molecular mechanisms of disease pathogenesis is crucial for disease management. In this study, a gene-to-gene correlation network generated from a transcriptomic database of the stomach of shrimp infected with acute hepatopancreatic necrosis disease (AHPND) was used to identify a new α-arrestin, termed arrestin domain containing-3 gene (LvARRDC3), with crucial roles in development of both AHPND and white spot disease (WSD). Double stranded RNA-mediated silencing or plasmid-mediated overexpression of LvARRDC3 gene significantly decreased expression of WSSV genes (IE1, VP28, and ICP11) and viral genome copy numbers. Nevertheless, in AHPND, silencing the LvARRDC3 gene increased the AHPND-associated plasmid and Pir toxins copy numbers, whereas overexpression of LvARRDC3 had the opposite effect. An in vitro pathogen binding assay with recombinant LvARRDC3 protein produced robust binding to WSSV virions and AHPND-causing V. parahaemolyticus. Moreover, based on immunofluorescence, LvARRDC3 was localized in the cytoplasm of Spodoptera frugiperda (Sf9) insect cells. Therefore, we inferred that LvARRDC3 has a role in pathogen internalization, making it a valuable target for addressing AHPND and WSD and also a biomarker for marker-associated shrimp breeding., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As the incidence and prevalence of Atrial Fibrillation (AF) proliferate worldwide, the condition has become the epicenter of a plethora of ECG diagnostic research. In recent diagnostic methodologies, Morse Continuous Wavelet Transform (MsCWT) is a feature extraction technique utilized to draw out distinctive attributes of ECG signals. In our study, we explore the employment of MsCWT in the classification of AF with ECG signals in a continuum., Results: We present a MsCWT image-based deep learning machine for AF differentiation. For the training, validation, and test sets, we achieved average accuracies of 97.94%, 97.84%, and 91.32%; and overall F1 scores of 97.13%, 96.86%, and 89.41% respectively. Moreover, AUC ROC curves of over 0.99 were obtained for all classes in the training and validation sets; and were over 0.9679 for the test set., Conclusions: Training deep learning machines for the classification of AF with MsCWT-based images demonstrated to yield favorable outcomes and achieved superior performance amongst studies utilizing the same dataset. Though minimal, the conversion of signals into wavelet form with MsCWT may drastically improve outcomes not only in future ECG signal studies; but all signal-based diagnostics., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing of interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Polymyxin B is a viable option for treating antibiotic-resistant infections; however, current data on its pharmacokinetics, particularly in patients with renal insufficiency, remain inconclusive and necessitates further investigation. To address this gap, we conducted an open-label, single-center, single-dose, parallel-group pharmacokinetic study. Participants received an intravenous dose of 0.75 mg/kg of polymyxin B and were categorized based on their renal function: those with normal function (creatinine clearance [CLcr] ≥ 90 mL/min), mild renal insufficiency (CLcr 60-89 mL/min), and end-stage kidney disease patients on intermittent hemodialysis (IHD) (CLcr < 10 mL/min). The pharmacokinetic parameters assessed included the area under the curve (AUC), maximum concentration (C max ), clearance rate (CL), volume of distribution (Vz), and half-life (t 1/2 ). Results indicated that subjects with mild renal insufficiency exhibited pharmacokinetic profiles similar to healthy individuals. Nevertheless, in patients undergoing long-term IHD, we observed significant differences: the AUC was 58% higher, C max was 29% lower, CL was 42% lower, Vz was 60% larger, and t 1/2 was extended by 10 h compared to healthy controls. Secondary outcomes revealed good tolerability of polymyxin B across all groups, with no serious adverse effects related to renal function. In summary, while kidney function may have a slight impact on the pharmacokinetic of polymyxin B, it does not compromise the drug's therapeutic effectiveness., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Mandibular full-arch distalization (MFD) is a popular approach, particularly in non-extraction cases. However, we still cannot confirm whether facial patterns affect the amount of limits. This study aimed to determine the anatomical MFD limits in patients with different facial patterns., Study Design: Using computed tomography (CT), the shortest distances from the mandibular second molar to the inner cortex of the mandibular lingual surface and from the lower central incisor to the inner cortex of the lingual mandibular symphysis were measured in 60 samples (30 patients). The available distalization space in both regions was compared between groups with different facial patterns., Results: The available space in symphysis was more critical than that in retromolar area: the shortest distances to the inner cortex of the lingual mandibular symphysis at root levels 8 mm apical to the cementoenamel junction of the incisor were 1.28, 1.60, and 3.48 mm in the high-, normal-, and low-angle groups, respectively., Conclusions: Facial patterns affected the MFD capacity, and the thickness of the lingual mandibular symphysis was the most critical anatomic limit encountered. Practitioners should always pay attention to the possible impacts from facial patterns, especially in the treatment of high-angle cases.

A new species of the genus Boulenophrys is described from the coastal hills of eastern Fujian Province, China. The new taxon can be distinguished from all recognized congeners by a combination of discrete morphological character state differences and genetic divergences in the combined mitochondrial 16S + CO1 genes. We also provide a map showing the distribution pattern of Boulenophrys species in Fujian and a provincial-specific key, which will aid their conservation by helping the local authorities accurately identify species during field identifications and data collection efforts., Competing Interests: The authors have declared that no competing interests exist., (Shi-Shi Lin, Hong-Hui Chen, Yuan-Hang Li, Zhao-Ning Peng, Zhao-Chi Zeng, Jian Wang.)

As a model plant for bryophytes, Marchantia polymorpha offers insights into the role of RNA silencing in aiding early land plants navigate the challenges posed by high-temperature environments. Genomic analysis revealed unique ARGONAUTE1 ortholog gene (MpAGO1) in M. polymorpha, which is regulated by two species-specific microRNAs (miRNAs), miR11707.1 and miR11707.2. Comparative studies of small RNA profiles from M. polymorpha cellular and MpAGO1 immunoprecipitation (MpAGO1-IP) profiles at various temperatures, along with analyses of Arabidopsis AGO1 (AtAGO1), revealed that MpAGO1 has a low selectivity for a diverse range of small RNA species than AtAGO1. Protein structural comparisons revealed no discernible differences in the guide strand small RNA recognition middle domain, MID domain, of MpAGO1 and AtAGO1, suggesting the complexity of miRNA species specificity and necessitating further exploration. Small RNA profiling and size exclusion chromatography have pinpointed a subset of M. polymorpha miRNAs, notably miR11707, that remain in free form within the cell at 22°C but are loaded into MpAGO1 at 28°C to engage in RNA silencing. Investigations into the mir11707 gene editing (mir11707ge) mutants provided evidence of the regulation of miR11707 in MpAGO1. Notably, while MpAGO1 mRNA expression decreases at 28°C, the stability of the MpAGO1 protein and its associated miRNAs is essential for enhancing the RNA-inducing silencing complex (RISC) activity, revealing the importance of RNA silencing in enabling M. polymorpha to survive thermal stress. This study advances our understanding of RNA silencing in bryophytes and provides groundbreaking insights into the evolutionary resilience of land plants to climatic adversities., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objective: Radiomics models have demonstrated good performance for the diagnosis and evaluation of prostate cancer (PCa). However, there are currently no validated imaging models that can predict PCa or clinically significant prostate cancer (csPCa). Therefore, we aimed to identify the best such models for the prediction of PCa and csPCa., Methods: We performed a retrospective study of 942 patients with suspected PCa before they underwent prostate biopsy. MRI data were collected to manually segment suspicious regions of the tumor layer-by-layer. We then constructed models using the extracted imaging features. Finally, the clinical value of the models was evaluated., Results: A diffusion-weighted imaging (DWI) plus apparent diffusion coefficient (ADC) random-forest model and a T2-weighted imaging plus ADC and DWI multilayer perceptron model were the best models for the prediction of PCa and csPCa, respectively. Areas under the curve (AUCs) of 0.942 and 0.999, respectively, were obtained for a training set. Internal validation yielded AUCs of 0.894 and 0.605, and external validation yielded AUCs of 0.732 and 0.623., Conclusion: Models based on machine learning comprising radiomic features and clinical indicators showed good predictive efficiency for PCa and csPCa. These findings demonstrate the utility of radiomic models for clinical decision-making., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Imidacloprid and other neonicotinoid insecticides severely impact the performance and survival of honey bees and other pollinators. In the present study, we focused on the gene expression profile of newly emerged Apis mellifera queen bees after sublethal imidacloprid treatment during the larval stage. Royal jelly containing 1 ppb imidacloprid was provided to larvae for 3 consecutive days (2-4 days postemergence). Queen larvae treated with imidacloprid showed lower capping and emergence rates (35.5% and 24.22%, respectively) than did control larvae (61.68% and 52.95%, respectively), indicating a high failure rate of queen rearing associated with imidacloprid exposure during the larval stage. The molecular response to imidacloprid treatment was examined next. By comparing the gene expression profiles of imidacloprid-treated queen larvae and those of control queen larvae using DESeq2, we identified 215 differentially expressed genes, with 105 and 111 up- and downregulated genes, respectively. Gene Ontology results indicated that chitin binding- and calcium ion binding-related genes were upregulated, while phototransduction- and visual perception-related genes were downregulated. The high mortality rate and altered gene expression profiles suggest that treatment with even 1 ppb imidacloprid can severely impact queen bee survival. Environ Toxicol Chem 2024;43:2232-2242. © 2024 SETAC., (© 2024 SETAC.)

In this study, a new species of the genus Boulenophrys is described from northwestern Guangdong, within the Nanling Moutains. The new species can be distinguished from all known congeners by a combination of morphological characteristics and the mitochondrial genetic divergence. The new species is found to breed in winter season which was not common in most amphibian groups but also present in some Boulenophrys congeners. We further discuss the inadequate surveys for these species due to the oversight of such multi-seasonal breeding pattern.

In recent years, deep neural networks (DNNs) have demonstrated remarkable performance in pathology applications, potentially even outperforming expert pathologists due to their ability to learn subtle features from large datasets. One complication in preparing digital pathology datasets for DNN tasks is variation in tinctorial qualities. A common way to address this is to perform stain normalization on the images. In this study, we show that a well-trained DNN model trained on one batch of histological slides failed to generalize to another batch prepared at a different time from the same tissue blocks, even when stain normalization methods were applied. This study used sample data from a previously reported DNN that was able to identify patients with early stage non-small cell lung cancer (NSCLC) whose tumors did and did not metastasize, with high accuracy, based on training and then testing of digital images from H&E stained primary tumor tissue sections processed at the same time. In this study we obtained a new series of histologic slides from the adjacent recuts of same tissue blocks processed in the same lab but at a different time. We found that the DNN trained on the either batch of slides/images was unable to generalize and failed to predict progression in the other batch of slides/images (AUC cross-batch = 0.52 - 0.53 compared to AUC same-batch = 0.74 - 0.81). The failure to generalize did not improve even when the tinctorial difference correction were made through either traditional color-tuning or stain normalization with the help of a Cycle Generative Adversarial Network (CycleGAN) process. This highlights the need to develop an entirely new way to process and collect consistent microscopy images from histologic slides that can be used to both train and allow for the general application of predictive DNN algorithms.

Background: Physical exercise and exposure to air pollution have counteracting effects on individuals' health outcomes. Knowledge on individuals' real-time exercise behavior response to different pollution information sources remains inadequate., Objective: This study aims to examine the extent to which individuals avoid polluted air during exercise activities in response to different air pollution information sources., Methods: We used data on individuals' exercise behaviors captured by wearable and mobile devices in 83 Chinese cities over a 2-year time span. In our data set, 35.99% (5896/16,379) of individuals were female and 64% (10,483/16,379) were male, and their ages predominantly ranged from 18 to 50 years. We further augmented the exercise behavior data with air pollution information that included city-hourly level measures of the Air Quality Index and particulate matter 2.5 concentration (in µg/m 3 ), and weather data that include city-hourly level measures of air temperature (ºC), dew point (ºC), wind speed (m/s), and wind direction (degrees). We used a linear panel fixed effect model to estimate individuals' exercise-aversion behaviors (ie, running exercise distance at individual-hour, city-hour, or city-day levels) and conducted robustness checks using the endogenous treatment effect model and regression discontinuity method. We examined if alternative air pollution information sources could moderate (ie, substitute or complement) the role of mainstream air pollution indicators., Results: Our results show that individuals exhibit a reduction of running exercise behaviors by about 0.50 km (or 7.5%; P<.001) during instances of moderate to severe air pollution, and there is no evidence of reduced distances in instances of light air pollution. Furthermore, individuals' exercise-aversion behaviors in response to mainstream air pollution information are heightened by different alternative information sources, such as social connections and social media user-generated content about air pollution., Conclusions: Our results highlight the complementary role of different alternative information sources of air pollution in inducing individuals' aversion behaviors and the importance of using different information channels to increase public awareness beyond official air pollution alerts., (©Yang Yang, Khim-Yong Goh, Hock Hai Teo, Sharon Swee-Lin Tan. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 10.09.2024.)

Whole slide imaging provides a wide field-of-view (FOV) across cross-sections of biopsy or surgery samples, significantly facilitating pathological analysis and clinical diagnosis. Such high-quality images that enable detailed visualization of cellular and tissue structures are essential for effective patient care and treatment planning. To obtain such high-quality images for pathology applications, there is a need for scanners with high spatial bandwidth products, free from aberrations, and without the requirement for z-scanning. Here we report a whole slide imaging system based on angular ptychographic imaging with a closed-form solution (WSI-APIC), which offers efficient, tens-of-gigapixels, large-FOV, aberration-free imaging. WSI-APIC utilizes oblique incoherent illumination for initial high-level segmentation, thereby bypassing unnecessary scanning of the background regions and enhancing image acquisition efficiency. A GPU-accelerated APIC algorithm analytically reconstructs phase images with effective digital aberration corrections and improved optical resolutions. Moreover, an auto-stitching technique based on scale-invariant feature transform ensures the seamless concatenation of whole slide phase images. In our experiment, WSI-APIC achieved an optical resolution of 772 nm using a 10×/0.25 NA objective lens and captures 80-gigapixel aberration-free phase images for a standard 76.2 mm × 25.4 mm microscopic slide., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice., (© 2024. The Author(s).)

Objective: Intra-Individual Cognitive Variability (IICV) is an emerging clinical tool that has shown promise in predicting cognitive decline and dementia incidence. The present study aims to assess the predictive validity of IICV in remote cognitive screening tests, using nationally representative data., Method: Two waves of cognitive and diagnostic data from the Health and Retirement Study (collected in 2010 and 2012) were utilized to investigate whether baseline IICV can predict cognitive decline and dementia pathology. Middle-aged and older adults who were cognitively intact and completed all cognitive tests at both baseline and follow-up were recruited in the study, resulting in a sample of 6,050 participants. With the coefficient of variation method, the IICV-dispersion was calculated based on cognitive screeners to predict follow-up mean cognitive performance, global cognition, suspected cognitive impairment, and self-reported dementia diagnosis., Results: After accounting for demographics, depressive symptoms, and baseline cognitive performance, the results provide support for the predictive validity of IICV. Specifically, the study demonstrated that IICV-dispersion significantly predicted cognitive and diagnostic outcomes in a concave pattern where the prediction was more sensitive toward the higher end of IICV. IICV explained about 0.2%-2.3% of the variance of outcomes variables., Conclusions: IICV retrieved from cognitive screening tests in telemedicine settings offers insight into future cognitive functioning and neurocognitive diagnostic status, which can be cost-effective and reduce the burden on both patients and health care providers, especially benefitting individuals with low socioeconomic status and rural residents. Potential avenues for future research were also discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Antibiotic beads can be used to treat surgical infections. In this study, polylactide-polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

The miR390-derived TAS3 trans-acting short-interfering RNAs (tasiRNAs) module represents a conserved RNA silencing pathway in the plant kingdom; however, its characterization in the bryophyte Marchantia polymorpha is limited. This study elucidated that MpDCL4 processes MpTAS3 double-stranded RNA (dsRNA) to generate tasiRNAs, primarily from the 5'- and 3'-ends of dsRNA. Notably, we discovered a novel tasiRNA, tasi78A, which can negatively regulate a cytochrome P450 gene, MpCYP78A101. Additionally, tasi78A was abundant in MpAGO1, and transient expression assays underscored the role of tasi78A in repressing MpCYP78A101. A microRNA, miR11700, also regulates MpCYP78A101 expression. This coordinate regulation suggests a role in modulating auxin signaling at apical notches of gemma, influencing the growth and sexual organ development of M. polymorpha and emphasizing the significance of RNA silencing in MpCYP78A101 regulation. However, phylogenetic analysis identified another paralog of the CYP78 family, Mp1g14150, which may have a redundant role with MpCYP78A101, explaining the absence of noticeable morphological changes in loss-of-function plants. Taken together, our findings provide new insights into the combined regulatory roles of miR390/MpTAS3/miR11700 in controlling MpCYP78A101 and expand our knowledge about the biogenesis and regulation of tasiRNAs in M. polymorpha., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Motor assessment has emerged as complementary evidence for the detection of late life cognitive disorders. Clinicians lack inexpensive, accurate, and portable tools for this purpose. To fill this void, the current study piloted measures from the Mizzou Point-of-care Assessment System a multimodal sensor platform. We examined the ability of these motor function measures to distinguish neurocognitive status and assessed their associations with cognitive performance. Data came from 42 older adults, including 16 with mild cognitive impairment (MCI). Participants performed dual task gait, pairing walking with serial subtraction by sevens, along with aa neuropsychological test battery. T -tests revealed that individuals with MCI demonstrated slower stride times ( d = .55) and shorter stride lengths ( d = .98) compared to healthy older adults. Results from hierarchical regression showed that stride time and stride length predicted cognitive performance across several domains, after controlling for cognitive status and demographics. Cognitive status moderated this relationship for global cognition and attention, wherein gait measures were significantly related to these outcomes for the cognitively normal group, but not the MCI group. Evidence from the current study provided preliminary support that MPASS measures demonstrate expected associations with cognitive performance and can distinguish amongst those with and without cognitive impairment.

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder characterized by significant motor difficulties that affect daily life. Current assessment methods primarily focus on behavioral analysis, lacking in neuroscientific metrics for a comprehensive evaluation. This study introduced an electroencephalography-based motor imagery brain-computer interface classification system for evaluating children with DCD. A key of this system was the implementation of entropy-based data screening, which markedly enhanced classification performance. Notably, using mu band power in a support vector machine achieved an accuracy rate of 79.0%. These findings pave the way for developing a tool that could assist professionals in identifying children potentially affected by DCD.

Background: Fear tactics were used in the pandemic of Coronavirus Disease 2019., Purpose: We tested how messaging style, fear vs. hope, and differences in age and political affiliation related to intentions to engage in preventive behaviors during Coronavirus Disease 2019., Methods: Participants (N = 606) aged 18 to 94 were randomly assigned to receive health messages that emphasized the dangers of the virus (fear messages) or the ability of health behaviors to mitigate the impact of the virus (hope messages). The primary outcome was health behavior intentions., Discussion: Hope messaging rather than fear messaging promoted health behavior intentions with no moderation by age or political affiliation. Older and Democratic-identified adults had higher health behavior intentions. Health behaviors were mediated by death anxiety and perceived credibility of the messages., Conclusion: Tailored hope messaging may improve health behaviors by increasing the credibility of messages., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To construct a simple term small-for-gestational-age (SGA) neonate prediction model that is clinically practical., Methods: This analysis was based on the Born in Guangzhou Cohort Study (BIGCS). Mothers who had a singleton pregnancy, delivered a term neonate, and had an ultrasonography within 30 + 0 to 32 + 6 weeks of gestation were included. Term SGA was defined with customized population percentiles. Prediction models were constructed with backward selection logistic regression in a four-step approach, where model 1 contained fetal biometrics only, models 2 and 3 included maternal features and a time factor (weeks between ultrasonography and delivery), respectively; and model 4 contained all features mentioned. The prediction performance of individual models was evaluated based on area under the curve (AUC) and a calibration test was performed., Results: The prevalence of SGA in the study population of 21 346 women was 11.5%. With a complete-case analysis approach, data of 19 954 women were used for model construction and validation. The AUC of the four models were 0.781, 0.793, 0.823, and 0.834, respectively, and all were well-calibrated. Model 3 consisted of fetal biometrics and corrected for time to delivery was chosen as the final model to build risk prediction graphs for clinical use., Conclusion: A prediction model derived from fetal biometrics in early third trimester is satisfactory to predict SGA., (© 2023 International Federation of Gynecology and Obstetrics.)

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU., (© 2024 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Immunodominant membrane protein (IMP) is a prevalent membrane protein in phytoplasma and has been confirmed to be an F-actin-binding protein. However, the intricate molecular mechanisms that govern the function of IMP require further elucidation. In this study, the X-ray crystallographic structure of IMP was determined and insights into its interaction with plant actin are provided. A comparative analysis with other proteins demonstrates that IMP shares structural homology with talin rod domain-containing protein 1 (TLNRD1), which also functions as an F-actin-binding protein. Subsequent molecular-docking studies of IMP and F-actin reveal that they possess complementary surfaces, suggesting a stable interaction. The low potential energy and high confidence score of the IMP-F-actin binding model indicate stable binding. Additionally, by employing immunoprecipitation and mass spectrometry, it was discovered that IMP serves as an interaction partner for the phytoplasmal effector causing phyllody 1 (PHYL1). It was then shown that both IMP and PHYL1 are highly expressed in the S2 stage of peanut witches' broom phytoplasma-infected Catharanthus roseus. The association between IMP and PHYL1 is substantiated through in vivo immunoprecipitation, an in vitro cross-linking assay and molecular-docking analysis. Collectively, these findings expand the current understanding of IMP interactions and enhance the comprehension of the interaction of IMP with plant F-actin. They also unveil a novel interaction pathway that may influence phytoplasma pathogenicity and host plant responses related to PHYL1. This discovery could pave the way for the development of new strategies to overcome phytoplasma-related plant diseases., (open access.)

Background and Objectives: Ageism is oftentimes sugarcoated within humor. Paper birthday cards are 1 delivery approach in which ageist messages are perpetuated and reinforced through humor., Research Design and Methods: A convenience sample of birthday cards (k = 227), all indicating a decade of age, were acquired from 7 national retail stores in Colorado Springs, CO. The decades sampled ranged from 21 to 100. With a predeveloped codebook, 3 raters coded the decade birthday cards on various variables, including age group, ageist tone, and humor., Results: Birthday cards intended for age 30-60 contained significantly more ageist messages compared to cards intended for age 21 and age 70-100, which did not show a significant difference from each other. Additionally, birthday cards with humor showed more ageist messages than cards without humor. Characteristics of decade birthday cards were also explored., Discussion and Implications: Consumers need to learn to evaluate these ageist messages in birthday cards to reduce the perpetuation of damaging stereotypes., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)