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Abstract Prefrontal cortical activity represents stimuli in working memory tasks in a low-dimensional manifold that transforms over the course of a trial. Such transformations reflect specific cognitive operations, so that, for example, the rotation of stimulus representations is thought to reduce interference by distractor stimuli. Here we show that rotations occur in the low-dimensional activity space of prefrontal neurons in naïve male monkeys (Macaca mulatta), while passively viewing familiar stimuli. Moreover, some aspects of these rotations remain remarkably unchanged after training to perform working memory tasks. Significant training effects are still present in population dynamics, which further distinguish correct and error trials during task execution. Our results reveal automatic functions of prefrontal neural circuits allow transformations that may aid cognitive flexibility.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Sucra jujuba Chu, 1979 (Lepidoptera: Geometridae) is a major insect pest in jujube plantation. In this study, we have sequenced the complete mitochondrial genome of S. jujuba. The circular genome was 15,557 bp in length and contained 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one AT-rich region (GenBank accession no. MZ507574). The nucleotide composition was significantly biased (A, T, C, and G were 41.85%, 39.65%, 10.97%, and 7.53%, respectively) with A + T contents of 81.50%. The Bayesian phylogenetic analysis of the concatenated nucleotide sequences of 13 PCGs from 30 species in the subfamily Ennominae and two outgroup species was performed. The results indicated that S. jujuba was closely related to Amraica recursaria in the subfamily Ennominae.

Abstract Background Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. Method All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. Result The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p

Abstract Background Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. Methods A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. Results 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. Conclusion The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Objective: Executive dysfunction is common in in individuals with intellectual disability (ID). This study examined the effects of the Special Olympics Unified Sports (UNS) soccer program on executive function (EF) and prefrontal cortex activation in ID adolescents. Methods: Functional near-infrared spectroscopy (fNIRS) was utilized to compare EF between a group participating in UNS soccer training (n = 18) and a control group (n = 26) in the flanker task, 2-back task, and dots–triangles task. Results: The results revealed that the soccer group performed significantly better in the dots-triangles and 2-back tasks than the control group. However, it is unclear whethersoccer training may improve activation of R-DLPFC during performance of the dotstriangles task. In the 2-back task, activation in the right frontopolar area (R-FPA) was lower in the soccer group when compared to the control group. Notably, no significant differences were observed in the flanker task Conclusion: In conclusion, UNS soccer training may positively affect working memory in adolescents with intellectual disabilities by improving activation of RFA, but whether it activates R-VLPFC is uncertain. These results indicate that the UNS soccer trainingprogram holds promise for enhancing executive function in adolescents with ID, and improving the quality of life in this population.

Extreme wildfires threaten human lives, air quality, and ecosystems. Meteorology plays a vital role in wildfire behaviors, and the links between wildfires and climate have been widely studied. However, it is not fully clear how fire-weather feedback affects short-term wildfire variability, which undermines our ability to mitigate fire disasters. Here, we show the primacy of synoptic-scale feedback in driving extreme fires in Mediterranean and monsoon climate regimes in the West Coast of the United States and Southeastern Asia. We found that radiative effects of smoke aerosols can modify near-surface wind, air dryness, and rainfall and thus worsen air pollution by enhancing fire emissions and weakening dispersion. The intricate interactions among wildfires, smoke, and weather form a positive feedback loop that substantially increases air pollution exposure.

Abstract Background Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. Methods We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. Results Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. Conclusions Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.

Abstract Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. Methods This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. Results A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P

Abstract Background Lip squamous cell carcinoma (LSCC) was one of the most common cancer types of head and neck tumors. This study aimed to find more predictors of the prognosis in postoperative LSCC patients. Methods A total of 147 LSCC patients between June 2012 and June 2018 were collected from two tertiary care institutions. There were 21 clinicopathological factors included and analyzed in our study. The univariate and multivariate Cox regression analyses were performed to find the independent prognostic factors for predicting progression-free survival (PFS) and overall survival (OS) in postoperative LSCC patients. The role of adjuvant radiotherapy in various subgroups was displayed by Kaplan–Meier plots. Results The 1-, 3-, and 5-year PFS of postoperative LSCC patients were 88.4%, 70.1%, and 57.8%, respectively. Similarly, the 1-, 3-, and 5-year OS of postoperative LSCC patients were 94.6%, 76.9%, and 69.4%, respectively. The results suggested that postoperative LSCC patients with age at diagnosis ≥ 70 years, grade with moderate or poor differentiate, the American Joint Committee on Cancer (AJCC) stage IV, higher systemic immune-inflammation index (SII), surgical margin

ABSTRACTObjective: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment.Methods: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment.Results: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance.Conclusion: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.

Background: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. Methods: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. Results: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. Conclusions: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.

Objectives To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. Background MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production – an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. Methods The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. Results ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. Conclusions This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

Abstract Background Apatinib is an oral small‐molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor‐2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. Methods This retrospective study included 100 human epidermal growth factor receptor‐2 (HER2)‐negative mBC patients who received low‐dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. Results The median follow‐up time for this study was 38.1 months. Among 100 patients with HER2‐negative mBC, 66 were hormone receptor (HR)‐positive/HER2‐negative and 34 were triple‐negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2–6.8 months) and 23.0 months (95% CI, 19.9–26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR‐positive /HER2‐negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety‐five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3–4. The most common Grades 3–4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Conclusion Low‐dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2‐negative mBC.

Background and aimsMost studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM).MethodsThe two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events.ResultsThere is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively.ConclusionChanges in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.