bluuebunny/crossref_metadata_2025 huggingface dataset:
Grim-19 deficiency promotes decidual macrophage autophagy in recurrent spontaneous abortion
Authors: Yang Yang , Liu Haoran , Zhao Yue , Geng Chen , Chao Lan , Hao Aijun
Published: October 2022

Dysregulation of decidual macrophages leads to the occurrence of recurrent spontaneous abortion (RSA). However, the role of macrophages in RSA occurrence remains unclear. In this study, we found that the expression of Grim-19 was decreased, and the expression of autophagy related proteins Beclin1, LC3B II/I and BNIP3 was markedly upregulated in decidual macrophages of RSA patients compared with the normal pregnancy group. Furthermore, we demonstrated that downregulation of GRIM-19 increased the expression of autophagy related proteins Beclin1, LC3B II/I, BNIP3 and the proinflammatory cytokines IL1B, IL6 and TNFa in uterine mononuclear cells of GRIM-19+/- mice. The proportion of CD45+CD11b+F4/80+LC3B+ cells in GRIM-19+/- mouse uteri was significantly higher than that in WT mouse uteri. In addition, we confirmed that inhibition of Grim-19 by siRNA enhanced the expression of autophagy related proteins in RAW264.7 cells and THP-1 cells. More importantly, downregulation of Grim-19 in RAW264.7 cells promoted the release of proinflammatory cytokines and promoted phagocytic activity, which could be reversed by autophagy blockade. For THP-1-derived macrophages, the results of RNA-seq suggested that Grim-19 mainly modulates immune and inflammatory-related pathways, leading to cytokine production, and thus contributing to inflammation. Therefore, our data reveal that Grim-19 deficiency influences macrophage function, characterized by enhanced proinflammatory cytokines and phagocytic activity, and this might be regulated by autophagy. This may represent a novel mechanism for the occurrence of RSA.
The spoke wheel color Doppler blood flow signal is a specific sign of papillary thyroid carcinoma
Authors: Xue Nianyu , Li Ping , Deng Huadong , Yi Jing , Xie Yu , Zhang Shengmin
Published: October 2022

Background

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Grayscale ultrasound (US) is the main method used to diagnose benign and malignant thyroid nodules, While color doppler blood flow imaging(CDFI) is not widely recognized when diagnosing thyroid cancer.

Methods

This study used a retrospective analysis. The study included 36 spoked wheel blood flow nodules detected by CDFI in 37,372 patients in five hospitals from January 2020 to June 2021. All thyroid nodules were examined histologically after ultrasound-guided fine needle biopsy or following surgical resection. The value of color doppler in diagnosing papillary thyroid carcinoma was evaluated based on pathological results.

Results

Among 36 thyroid nodules, only 6 were highly suspected of being malignant on grayscale ultrasound (classified as 5, according to ACR TI-RADS). However, these 36 thyroid nodules showed spoke wheel blood flow signal distribution on CDFI. If the spoke wheel blood flow signal is used to diagnose papillary thyroid cancer, then the diagnostic accuracy of this group of papillary thyroid cancers can reach 100%, which is significantly higher than the accuracy of grayscale ultrasound diagnosis, and the difference is statistically significant (p<0.05).

Conclusions

The results of this study found that spoke wheel blood flow sign on CDFI can be used to diagnose PTC. PTC with spoke wheel blood flow have benign characteristics on gray-scale ultrasound, which is easy to be misdiagnosed.
Integrated analysis of potential gene crosstalk between non-alcoholic fatty liver disease and diabetic nephropathy
Authors: Yan Qianqian , Zhao Zihao , Liu Dongwei , Li Jia , Pan Shaokang , Duan Jiayu , Dong Jiancheng , Liu Zhangsuo
Published: October 2022

Background

Growing evidence indicates that non-alcoholic fatty liver disease (NAFLD) is related to the occurrence and development of diabetic nephropathy (DN). This bioinformatics study aimed to explore optimal crosstalk genes and related pathways between NAFLD and DN.

Methods

Gene expression profiles were downloaded from Gene Expression Omnibus. CIBERSORT algorithm was employed to analyze the similarity of infiltrating immunocytes between the two diseases. Protein–protein interaction (PPI) co-expression network and functional enrichment analysis were conducted based on the identification of common differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm were implemented to initially screen crosstalk genes. Machine learning models, including support vector machine, random forest model, and generalized linear model, were utilized to further identify the optimal crosstalk genes between DN and NAFLD. An integrated network containing crosstalk genes, transcription factors, and associated pathways was developed.

Results

Four gene expression datasets, including GSE66676 and GSE48452 for NAFLD and GSE30122 and GSE1009 for DN, were involved in this study. There were 80 common DEGs between the two diseases in total. The PPI network built with the 80 common genes included 77 nodes and 83 edges. Ten optimal crosstalk genes were selected by LASSO regression and Boruta algorithm, including CD36, WIPI1, CBX7, FCN1, SLC35D2, CP, ZDHHC3, PTPN3, LPL, and SPP1. Among these genes, LPL and SPP1 were the most significant according to NAFLD-transcription factor network. Five hundred twenty-nine nodes and 1,113 edges comprised the PPI network of activated pathway-gene. In addition, 14 common pathways of these two diseases were recognized using Gene Ontology (GO) analysis; among them, regulation of the lipid metabolic process is closely related to both two diseases.

Conclusions

This study offers hints that NAFLD and DN have a common pathogenesis, and LPL and SPP1 are the most relevant crosstalk genes. Based on the common pathways and optimal crosstalk genes, our proposal carried out further research to disclose the etiology and pathology between the two diseases.
Lipoprotein profiles of fat distribution and its association with insulin sensitivity
Authors: Wei Dongmei , Marrachelli Vannina González , Melgarejo Jesus D. , Liao Chia-Te , Janssens Stefan , Verhamme Peter , Vanassche Thomas , Van Aelst Lucas , Monleon Daniel , Redón Josep , Zhang Zhen-Yu
Published: October 2022

Background

Fat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated.

Methods

In 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. Statistical methods included multivariable-adjusted linear regression analysis, logistic regression analysis, and mediation analysis.

Results

The prevalence of WHR obesity was 54.6%, approximately 3 times of BMI-determined obesity (19.1%). Individuals with WHR obesity had significantly higher metabolic complications, such as hypertension (57.1%), dyslipidemia (61.8%), and insulin resistance (14.2%). WHR and WHR obesity were positively associated with total very-low-density lipoprotein (VLDL) particle concentration, remnant cholesterol, and triglycerides, but were negatively associated with VLDL particle size (P ≤ 0.027), independent of body mass index and other covariates. WHR was inversely associated with total high-density lipoprotein (HDL) particle concentration, whereas WHR obesity was inversely associated with HDL cholesterol (P ≤ 0.039). Neither WHR nor WHR obesity was associated with the concentration of total low-density lipoprotein (LDL) particles, LDL particle size, and LDL cholesterol (P ≥ 0.089). In the mediation analysis, insulin sensitivity significantly mediated the effect of WHR on total VLDL particle concentration (mediation percentage: 37.0%), remnant cholesterol (47.7%), and HDL cholesterol (41.1%). Individuals with WHR obesity were at increased cardiovascular risk, regardless of LDL cholesterol (P ≤0.028). In WHR obesity, higher total VLDL particle concent36ration and remnant cholesterol, and lower HDL cholesterol were associated with an increased cardiovascular risk (P≤ 0.002).

Conclusions

Upper-body fat deposition was independently associated with an unfavorable lipoprotein profile, and insulin sensitivity significantly mediated this association. LDL cholesterol might underestimate lipid abnormality for people with upper-body obesity and lowering VLDL particles and remnant cholesterol might potentially reduce the residual cardiovascular risk.
Perirenalfat thickness is associated with bone turnover markers and bone mineral density in postmenopausal women with type 2 diabetes mellitus
Authors: Wang Wei , Huang Rong , Tang Ping Tai , Tu Mei , Guo Xiu Li
Published: October 2022

Objectives

Emerging evidence demonstrated that perirenal fat may modulate bone metabolism through several pathological pathways. This study was aimed to assess the associations between perirenal fat thickness (PrFT) and bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) and further explore the correlation between PrFT and osteoporosis.

Methods

In this cross-sectional study, a total of 626 participants with complete data were enrolled in this study. Demographic and anthropometric information was collected. Biochemical parameters and BTMs were determined. PrFT and BMD were measured by computed tomography and dual-energy x-ray absorptiometry, respectively. Correlation analysis and regression models were used to assess the associations between PrFT and BTMs and BMD. The multiple binomial logistic regression model was used to estimate the independent variables of PrFT for osteoporosis.

Results

Overall, the prevalence of osteoporosis was 38.7%. PrFT was negatively correlated with β-cross-linked C-telopeptide of type I collagen (β-CTX) (r = -0.216,< 0.001), L1–L4 BMD (r = -0.351, < 0.001), and T-score (r = -0.396, < 0.001). PrFT also remained significantly correlated with β-CTX (β = -0.291, P< 0.001), L1–L4 BMD (β = -0.109, P= 0.027), and L1–L4 T-score (β = -0.149, P= 0.001) after adjustment for other confounding factors. Furthermore, PrFT was also independently associated with osteoporosis after adjustment for other confounding factors; the OR (95% CI) was 1.13 (1.04–1.23). PrFT also seems to have a relatively good identifying value for osteoporosis. The area under the curve (AUC) value of PrFT in identifying osteoporosis was 0.766 (95% CI: 0.705–0.826, P < 0.001). The optimal cutoff value of PrFT was 15.2 mm (sensitivity: 72.5%, specificity: 79.8%).

Conclusions

PrFT was significantly associated with β-CTX, BMD, and osteoporosis. These findings indicate that perirenal fat may play an important role in bone metabolism.

Clinical Trial Registration

http://www.chictr.org.cn/, identifier (ChiCTR2100052032).
Study on coal ash loaded nano iron filler to improve the efficient phosphorus removal of biological detention facility
Authors: Zhang Yuxuan , Gao Xueqin , Zhang Lulu , He Shunde
Published: October 2022

Bioretention cells are an important facility to solve the hydrological and non-point pollution problems in urban areas, especially phosphorus. In this paper, ceramsite composite was made from coal ash and modified by nano-iron through coprecipitation and reduction, which was used to remove the phosphorus in the water. The results of the characteristics of the ceramsite composite using scanning electron microscope showed that the surface of the ceramsite loaded with nano-iron became rougher and the iron nanoparticles were uniformly distributed on the surface, and there was no obvious agglomeration of nano-iron particles. The loading effect was good and the activity of the ceramsite was greatly improved. The results from the static and dynamic continuous experiments indicated that the modified ceramsite with nano-iron had a good removal effect on phosphorus, and the removal rate reached over 99%. The results of this study can provide a new way for the resource utilization of coal ash, and also inspires a new idea for the improvement of filler in bioretention facilities.
Statistical evaluation of the similarity of characteristics in springs of the California Desert, United States
Authors: Love Adam H. , Zdon Andy , Fraga Naomi S. , Cohen Brian , Palacios Mejia Maura , Maxwell Rachel , Parker Sophie S.
Published: October 2022

Desert ecosystems are an environment of climatic extremes, to which many forms of life have adapted. These systems are characterized by scarce water and often sparsely vegetated lands where ecological adaptation to arid conditions has its underpinnings in the universal dependency on water to support life. Understanding the ecohydrological similarity of springs in water-limited areas requires integration of multiple lines of evidence from diverse disciplines. A unique dataset of hydrological and ecological characteristics of Mojave and Sonoran Desert spring ecosystems in California has been developed, incorporating a wide range of spring conditions that enables a broad evaluation of similarity in ecohydrological characteristics across springs in the region. The lack of observed correlation between hydrologic and ecological parameters suggests that the springs in the California Desert each represent a somewhat unique ecosystem that has developed in relative isolation from the other springs. These results imply that because of the uniqueness of these desert ecosystems the idea of mitigation compensation or mitigation offset via replacement or substitution can never truly be achieved if/when these spring areas are impacted. Any ecosystem used as a replacement or substitution could not reasonably be expected to be similar in terms of the associated hydrologic and ecologic conditions to the ecosystem lost. While such offsets can represent a coarser view of replacements or substitution, the more specific conditions that support endemic and water-dependent biodiversity cannot be easily replaced or substituted.
Influencing factors and environmental effects of interactions between goethite and organic matter: A critical review
Authors: Yi Shuqi , Chen Xiaorui , Cao Xu , Yi Bing , He Wei
Published: October 2022

This paper reviews progresses in the interactions between goethite and organic matter (OM) and their environmental effects in recent decades. The interactions mainly include the effect of organic matter on the surface properties and the crystallization of goethite, molecular changes of OM caused by goethite, and their interaction mechanisms, which can be depicted by the commonly used Langmuir model, the charge distribution multi-site complexation model (CD-MUSIC model), ligand charge distribution model (LCD model), and natural organic matter charge distribution model (NOM-CD model). The influencing factors of the interactions are summarized with emphasis on the external, including pH, ionic strength, carbon dioxide (CO2), and the internal, including the structure of OM and iron species. The goethite—OM complexes caused by the interactions will affect migration and transformation of conventional heavy metals and emerging antibiotics. The complexes, as the carrier of carbon and iron, are also the critical parts of the carbon and iron cycles, which are associated with climate change. This review provides a basis for future mechanism studies of formation, transformation, and effects of goethite—OM complexes (particulate OM or carbon-contained minerals) in different environmental systems at a molecular level.
FunOrder 2.0 – a method for the fully automated curation of co-evolved genes in fungal biosynthetic gene clusters
Authors: Vignolle Gabriel A. , Mach Robert L. , Mach-Aigner Astrid R. , Zimmermann Christian
Published: October 2022

Coevolution is an important biological process that shapes interacting proteins – may it be physically interacting proteins or consecutive enzymes in a metabolic pathway, such as the biosynthetic pathways for secondary metabolites. Previously, we developed FunOrder, a semi-automated method for the detection of co-evolved genes, and demonstrated that FunOrder can be used to identify essential genes in biosynthetic gene clusters from different ascomycetes. A major drawback of this original method was the need for a manual assessment, which may create a user bias and prevents a high-throughput application. Here we present a fully automated version of this method termed FunOrder 2.0. In the improved version, we use several mathematical indices to determine the optimal number of clusters in the FunOrder output, and a subsequent k-means clustering based on the first three principal components of a principal component analysis of the FunOrder output to automatically detect co-evolved genes. Further, we replaced the BLAST tool with the DIAMOND tool as a prerequisite for using larger proteome databases. Potentially, FunOrder 2.0 may be used for the assessment of complete genomes, which has not been attempted yet. However, the introduced changes slightly decreased the sensitivity of this method, which is outweighed by enhanced overall speed and specificity.
The development of a physical therapy service to treat urinary incontinence: Results of a RE-AIM evaluation
Authors: Brosina de Leon Elisa , Cardoso Maria Natália , de Brito Elorides , dos Santos Maira Mendes , Almeida Fabio Araujo
Published: October 2022

Background

A conservative physiotherapy service development addressed to treat urinary incontinence for older women was studied using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework.

Design

We conducted a pragmatic case study design based on RE-AIM.

Settings/participants

Included women ≥ 60 years of age, with self-reported UI symptoms.

Results

A total of 34 older women were enrolled in the service with a mean age of 61.53 years. There was a significant improvement in the strength of the pelvic floor muscles, power, endurance, and fast contraction capacity after the intervention, however, it was observed a high dropout rate. Program implementation was supported by Physical Therapy teams who engaged in care coordination. The program has been maintained for over 4 years.

Conclusion

Our findings demonstrate that UI patients would benefit from physiotherapy treatment and that this intervention is feasible. This RE-AIM evaluation provides lessons learned and strategies for future adoption, implementation, and maintenance of a Physical Therapy pelvic service.
Clinical, logistic, and geographic factors in ensuring adequate access to implant removals: A cross-sectional survey of public facilities and GIS modeling of geographic access in two districts of Senegal
Authors: Brunie Aurélie , Parker Caleb , Ndiaye Salif , Sarr Aw Fatou Ndiaté Rachel , Keyes Emily B. , Lebetkin Elena , Dioh Etienne , MacCarthy James , Ndiaye Marème Mady Dia
Published: October 2022

Introduction

Ensuring adequate access to contraceptive implant removal services requires an understanding of potential clinical, logistical, and geographic challenges.

Methods

We conducted a cross-sectional survey of 39 public health facilities in two districts of Senegal. To assess facility readiness, we reported the proportion of facilities meeting all minimum conditions for regular and difficult implant removals. We then describe characteristics of referral networks. Geographic access modeling was conducted in a geographic information system to estimate the proportion of women of reproductive age living within specific travel times of facilities ready for regular and difficult removals.

Results

72% of facilities met all conditions for regular removals, and 8% for difficult removals. In both cases, the main gaps related to equipment availability (79% of facilities had the minimum equipment for regular removals and 8% for difficult removals). 72% of facilities organized in three referral networks sent clients to other facilities for cases they could not manage. Of 11 receiving or single-network facilities, seven were ready for regular removals and one for difficult removals. Altogether, 36% of women in Dakar Centre and 99% of women in Kolda lived within two hours of a facility that was equipped to handle regular removals, compared to 15% and 69%, respectively, for difficult removals.

Conclusion

Data such as those provided in this assessment are important to provide a realistic picture of the state of readiness of the health system and its ability to meet the inevitable demand for implant removals. Referral networks should be considered as an emerging strategy to avail sufficient capacity at the systems level, including for managing difficult removals. However, careful thought should be given to the location of facilities that are ready to receive cases in order to target upgrades.
A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
Authors: Yuan Ying-Shi , Jin Xin , Chen Lu , Liao Jia-Min , Zhang Yang , Yu Ke-Wei , Li Wei-Kang , Cao Shun-Wang , Huang Xian-Zhang , Kang Chun-Min
Published: October 2022

Background

Glioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis.

Methods

A necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features.

Results

Three necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis.

Conclusions

Our necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.
Cardio-sarcopenia: A syndrome of concern in aging
Authors: Loh De Rong , Tan Ru-San , Lim Wee Shiong , Koh Angela S.
Published: October 2022

Cardiac alterations in structure and function, namely, the left ventricle, have been intensely studied for decades, in association with aging. In recent times, there has been keen interest in describing myocardial changes that accompany skeletal muscle changes in older adults. Initially described as a cardio-sarcopenia syndrome where alterations in myocardial structure were observed particularly among older adults with skeletal muscle sarcopenia, investigations into this syndrome have spurred a fresh level of interest in the cardiac-skeletal muscle axis. The purpose of this perspective is to summarize the background for this “syndrome of concern,” review the body of work generated by various human aging cohorts, and to explore future directions and opportunities for understanding this syndrome.
Metagenomic insights into the rumen epithelial integrity responses to the vitamin B1 supplement under high-concentrate diets treatments
Authors: Ma Peng , Sun Chaoqun , Liu Minze , You Hongnan , Shen Yao , Kang Yajie , Sun Yuqin , Yang Zhengang , Ma Pengyun , Yang Liang , Xue Fuguang
Published: October 2022

Subacute ruminal acidosis (SARA) becomes the most common nutritional metabolic disease in high-yielding dairy cows and later fatting beef cattle because of the increasing consumption of high-concentrate diets in modern feeding patterns. Our previous research found a certain piece of evidence that adding 180 mg thiamine/kg DMI could increase the rumen pH and regulate the structure of the rumen microbial community in vivo. However, there is still limited experimental data on the effects of SARA on thiamine status, the damage to the structure of rumen epithelial cells, and the underlying mechanism of the epithelium alterations. For this purpose, a total of 18 Angus bulls (average 22.0-months-old) with an average live weight of 567.6 ± 27.4 kg were randomly allocated into a control treatment (CON), a high-concentrate diet treatment (HC), and a high-concentrate diet with the vitamin B1 supplement treatment (HCB). All bulls were conducted with a 7-day adjustment period followed by a 60-day-long main feeding procedure. Results indicated that ADFI and ADG significantly decreased in the HC treatment compared with CON (P < 0.05), while significantly increased after the VB1 supplement (P < 0.05). Besides, ruminal acetate content was significantly downregulated while propionate was significantly upregulated under the HC treatment compared with CON (P < 0.05); however, these alterations showed a completely inverse regulatory effect on the VB1 supplement compared with HC (P < 0.05). These changes causatively induced a significant decrease in the A/P ratio in the HC treatment compared with CON and HCB treatments (P < 0.05). Bacterial communities in the HC treatment could be separated from those in CON through PCoA axes 1 and 2. Meanwhile, the VB1 supplement significantly altered the bacterial communities compared with the HC treatment, except for HCB-3. Furthermore, the HC treatment significantly upregulated the expression of JNK, Bax, Caspase-8, Caspase-3, Caspase-9, and Cyt-C compared with CON, while significantly downregulated the expression of Bcl-2. The VB1 supplement showed a complete converse gene expression compared with HC. In conclusion, the VB1 supplement could effectively attenuate the alterations that occurred when exposed to high-concentrate diets, and help promote production performance through increased fermentability.
Translocation pause of remdesivir-containing primer/template RNA duplex within SARS-CoV-2’s RNA polymerase complexes
Authors: Shi Yuanjun , Wang Jimin , Batista Victor S.
Published: October 2022

The mechanism of remdesivir incorporation into the RNA primer by the RNA-dependent RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains to be fully established at the molecular level. Here, we compare molecular dynamics (MD) simulations after incorporation of either remdesivir monophosphate (RMP) or adenosine monophosphate (AMP). We find that the Mg2+-pyrophosphate (PPi) binds more tightly to the polymerase when the added RMP is at the third primer position than in the AMP added complex. The increased affinity of Mg2+-PPi to the RMP-added primer/template (P/T) RNA duplex complex introduces a new hydrogen bond of a substituted cyano group in RMP with the K593 sidechain. The new interactions disrupt a switching mechanism of a hydrogen bond network that is essential for translocation of the P/T duplex product and for opening of a vacant NTP-binding site necessary for next primer extension. Furthermore, steric interactions between the sidechain of S861 and the 1′-cyano group of RMP at position i+3 hinders translocation of RMP to the i + 4 position, where i labels the insertion site. These findings are particularly valuable to guide the design of more effective inhibitors of SARS-CoV-2 RNA polymerase.
Autonomous maneuver decision-making method based on reinforcement learning and Monte Carlo tree search
Authors: Zhang Hongpeng , Zhou Huan , Wei Yujie , Huang Changqiang
Published: October 2022

Autonomous maneuver decision-making methods for air combat often rely on human knowledge, such as advantage functions, objective functions, or dense rewards in reinforcement learning, which limits the decision-making ability of unmanned combat aerial vehicle to the scope of human experience and result in slow progress in maneuver decision-making. Therefore, a maneuver decision-making method based on deep reinforcement learning and Monte Carlo tree search is proposed to investigate whether it is feasible for maneuver decision-making without human knowledge or advantage function. To this end, Monte Carlo tree search in continuous action space is proposed and neural networks-guided Monte Carlo tree search with self-play is utilized to improve the ability of air combat agents. It starts from random behaviors and generates samples consisting of states, actions, and results of air combat through self-play without using human knowledge. These samples are used to train the neural network, and the neural network with a greater winning rate is selected by simulations. Then, repeat the above process to gradually improve the maneuver decision-making ability. Simulations are conducted to verify the effectiveness of the proposed method, and the kinematic model of the missile is used in simulations instead of the missile engagement zone to test whether the maneuver decision-making method is effective or not. The simulation results of the fixed initial state and random initial state show that the proposed method is efficient and can meet the real-time requirement.
Exploration of sensory-motor tradeoff behavior in Parkinson’s disease
Authors: Sengupta Sonal , Medendorp W. Pieter , Selen Luc P. J. , Praamstra Peter
Published: October 2022

While slowness of movement is an obligatory characteristic of Parkinson’s disease (PD), there are conditions in which patients move uncharacteristically fast, attributed to deficient motor inhibition. Here we investigate deficient inhibition in an optimal sensory-motor integration framework, using a game in which subjects used a paddle to catch a virtual ball. Display of the ball was extinguished as soon as the catching movement started, segregating the task into a sensing and acting phase. We analyzed the behavior of 9 PD patients (ON medication) and 10 age-matched controls (HC). The switching times (between sensing and acting phase) were compared to the predicted optimal switching time, based on the individual estimates of sensory and motor uncertainties. The comparison showed that deviation from predicted optimal switching times were similar between groups. However, PD patients showed a weaker correlation between variability in switching time and sensory-motor uncertainty, indicating a reduced propensity to generate exploratory behavior for optimizing goal-directed movements. Analysis of the movement kinematics revealed that PD patients, compared to controls, used a lower peak velocity of the paddle and intercepted the ball with greater velocity. Adjusting the trial duration to the time for the paddle to stop moving, we found that PD patients spent a smaller proportion of the trial duration for observing the ball. Altogether, the results do not show the premature movement initiation and truncated sensory processing that we predicted to ensue from deficient inhibition in PD.
Effect of whole-hand water flow stimulation on the neural balance between excitation and inhibition in the primary somatosensory cortex
Authors: Le Cong Dat , Sato Daisuke , Ikarashi Koyuki , Fujimoto Tomomi , Ochi Genta , Yamashiro Koya
Published: October 2022

Sustained peripheral somatosensory stimulations, such as high-frequency repetitive somatosensory stimulation (HF-RSS) and vibrated stimulation, are effective in altering the balance between excitation and inhibition in the somatosensory cortex (S1) and motor cortex (M1). A recent study reported that whole-hand water flow (WF) stimulation induced neural disinhibition in the M1. Based on previous results, we hypothesized that whole-hand WF stimulation would lead to neural disinhibition in the S1 because there is a strong neural connection between M1 and S1 and aimed to examine whether whole-hand WF stimulation would change the neural balance between excitation and inhibition in the S1. Nineteen healthy volunteers were studied by measuring excitation and inhibition in the S1 before and after each of the four 15-min interventions. The excitation and inhibition in the S1 were assessed using somatosensory evoked potentials (SEPs) and paired-pulse inhibition (PPI) induced by single- and paired-pulse stimulations, respectively. The four interventions were as follows: control, whole-hand water immersion, whole-hand WF, and HF-RSS. The results showed no significant changes in SEPs and PPI following any intervention. However, changes in PPI with an interstimulus interval (ISI) of 30 ms were significantly correlated with the baseline value before whole-hand WF. Thus, the present findings indicated that the whole-hand WF stimulation had a greater decreased neural inhibition in participants with higher neural inhibition in the S1 at baseline. Considering previous results on M1, the present results possibly show that S1 has lower plasticity than M1 and that the duration (15 min) of each intervention may not have been enough to alter the balance of excitation and inhibition in the S1.
Modifying PCDH19 levels affects cortical interneuron migration
Authors: Pancho Anna , Mitsogiannis Manuela D. , Aerts Tania , Dalla Vecchia Marco , Ebert Lena K. , Geenen Lieve , Noterdaeme Lut , Vanlaer Ria , Stulens Anne , Hulpiau Paco , Staes Katrien , Van Roy Frans , Dedecker Peter , Schermer Bernhard , Seuntjens Eve
Published: October 2022

PCDH19 is a transmembrane protein and member of the protocadherin family. It is encoded by the X-chromosome and more than 200 mutations have been linked to the neurodevelopmental PCDH-clustering epilepsy (PCDH19-CE) syndrome. A disturbed cell-cell contact that arises when random X-inactivation creates mosaic absence of PCDH19 has been proposed to cause the syndrome. Several studies have shown roles for PCDH19 in neuronal proliferation, migration, and synapse function, yet most of them have focused on cortical and hippocampal neurons. As epilepsy can also be caused by impaired interneuron migration, we studied the role of PCDH19 in cortical interneurons during embryogenesis. We show that cortical interneuron migration is affected by altering PCDH19 dosage by means of overexpression in brain slices and medial ganglionic eminence (MGE) explants. We also detect subtle defects when PCDH19 expression was reduced in MGE explants, suggesting that the dosage of PCDH19 is important for proper interneuron migration. We confirm this finding in vivo by showing a mild reduction in interneuron migration in heterozygote, but not in homozygote PCDH19 knockout animals. In addition, we provide evidence that subdomains of PCDH19 have a different impact on cell survival and interneuron migration. Intriguingly, we also observed domain-dependent differences in migration of the non-targeted cell population in explants, demonstrating a non-cell-autonomous effect of PCDH19 dosage changes. Overall, our findings suggest new roles for the extracellular and cytoplasmic domains of PCDH19 and support that cortical interneuron migration is dependent on balanced PCDH19 dosage.
Systematic review and meta-analysis of multiparametric MRI clear cell likelihood scores for classification of small renal masses
Authors: Tian Jun , Teng Feixiang , Xu Hongtao , Zhang Dongliang , Chi Yinxiu , Zhang Hu
Published: October 2022

Purpose

To systematically assess the multiparametric MRI clear cell likelihood score (ccLS) algorithm for the classification of small renal masses (SRM).

Methods

We conducted an electronic literature search on Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar to identify relevant articles from 2017 up to June 30, 2022. We included studies reporting the diagnostic performance of the ccLS for characterization of solid SRM. The bivariate model and hierarchical summary receiver operating characteristic (HSROC) model were used to pool sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR). The quality evaluation was performed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

A total of 6 studies with 825 renal masses (785 patients) were included in the current meta-analysis. The pooled sensitivity and specificity for cT1a renal masses were 0.80 (95% CI 0.75–0.85) and 0.74 (95% CI 0.65–0.81) at the threshold of ccLS ≥4, the pooled LR+, LR−, and DOR were 3.04 (95% CI 2.34-3.95), 0.27 (95% CI 0.22–0.33), and 11.4 (95% CI 8.2-15.9), respectively. The area under the HSROC curve was 0.84 (95% CI 0.81–0.87). For all cT1 renal masses, the pooled sensitivity and specificity were 0.80 (95% CI 0.74–0.85) and 0.76 (95% CI 0.67–0.83).

Conclusions

The ccLS had moderate to high accuracy for identifying ccRCC from other RCC subtypes and with a moderate inter-reader agreement. However, its diagnostic performance remain needs multi-center, large cohort studies to validate in the future.
Application of ultrasonography in neonatal lung disease: An updated review
Authors: Wang Jin , Wei Hongjuan , Chen Hui , Wan Ke , Mao Ruifeng , Xiao Peng , Chang Xin
Published: October 2022

Lung disease is often life-threatening for both preterm and term newborns. Therefore, an accurate and rapid diagnosis of lung diseases in newborns is crucial, as management strategies differ with different etiologies. To reduce the risk of radiation exposure derived from the conventionally used chest x-ray as well as computed tomography scans, lung ultrasonography (LUS) has been introduced in clinical practice to identify and differentiate neonatal lung diseases because of its radiation-free characteristic, convenience, high accuracy, and low cost. In recent years, it has been proved that LUS exhibits high sensitivity and specificity for identifying various neonatal lung diseases. Here, we offer an updated review of the applications of LUS in neonatal lung diseases based on the reports published in recent years (2017 to present).
Association between serum folate concentrations and blood lead levels in adolescents: A cross-sectional study
Authors: He Huan , Zhang Zhan , Li Min
Published: October 2022

As a heavy metal, lead is a common toxic agent. Its accumulation in the body is harmful to physical health, particularly in children and adolescents. Studies have reported that folate may play a protective role in lead exposure. An association between serum folate concentrations (SFC) and blood lead levels (BLL) has been documented in adults, but studies in adolescents are limited. This study investigated the relationship between SFC and BLL in American adolescents. This cross-sectional study collected relevant data on both SFC and BLL of 5,195 adolescents in the NHANES database from 2007 to 2018. Multivariable linear regressions and smooth curve fittings were adopted to evaluate the correlation between BLL and SFC. After adjusting potential confounders, we found negative relationships between BLL and SFC [β = −0.0041 (−0.0063, −0.0019)], and the associations were significant in non-Hispanic Whites, Mexican Americans, and other races but not significant in non-Hispanic blacks (P = 0.139). Furthermore, the negative trends were significant in adolescents aged 16–19 years and females aged 12–15 years but insignificant in males aged 12–15 years (P = 0.172). Therefore, these findings provide a basis for future research on the mechanism of folate in regulating blood lead levels.
Comparison of short-term recovery in children with obstructive sleep apnea undergoing tonsillotomy vs. tonsillectomy
Authors: Dang Yanwei , Li Yujie , Zhang Junbo , Huang Wei , Dong Yuke , Shen Xiao , Han Wei , Li Tao
Published: October 2022

Objectives

To compare the pain levels, degrees of pharyngeal swelling, and weight loss after tonsillectomy vs. tonsillotomy in children clinically diagnosed with obstructive sleep apnea (OSA) over the first seven postoperative days, and to determine which procedure was associated with better recovery in the early postoperative period.

Methods

Between April 2021 and December 2021, 121 children with OSA (80 males and 41 females), ranging from 3 to 12 years of age with an average age of 6.7 years, were prospectively enrolled in this study conducted at Zhengzhou Central Hospital Affiliated to Zhengzhou University. The patients were randomly divided into two groups: a tonsillotomy group with 63 cases (40 males and 23 females) and a tonsillectomy group with 58 cases (40 males and 18 females). The patients' pain levels [as indicated by Parents' Postoperative Pain Measure (PPPM) scores] and degrees of pharyngeal swelling were recorded for seven days postoperatively, and the patients' body weights were recorded on postoperative day seven.

Results

In the tonsillotomy group, the PPPM scores were the highest on the day of surgery and on the first postoperative day; the patients' pain levels gradually decreased.The PPPM scores in the tonsillectomy group were higher than those in the tonsillotomy group from the day of surgery to the seventh postoperative day (p < 0.05). The degree of pharyngeal swelling was lower in the tonsillotomy group than in the tonsillectomy group. Weight loss was lower in the tonsillotomy group than in tonsillectomy group on the 7th day after surgery (p < 0.05). On the fifth, sixth, and seventh postoperative days, compared with preschool children, school-age children who had undergone tonsillotomy experienced more pain relief than those who had undergone tonsillectomy (p < 0.05).

Conclusion

Children with OSA experienced less pain, less pharyngeal swelling, and less weight loss with tonsillotomy than with tonsillectomy. On the fifth, sixth, and seventh postoperative days, compared with preschool children, tonsillotomy in school-age children is more advantageous in school-age children.
The bone-protective mechanisms of active components from TCM drugs in rheumatoid arthritis treatment
Authors: Lu Qingyi , Xu Jie , Jiang Haixu , Wei Qiuzhu , Huang Runyue , Huang Guangrui
Published: October 2022

Rheumatoid arthritis (RA) is an autoimmune disease whose hallmarks are synovial inflammation and irreversible bone destruction. Bone resorption resulting from osteoclasts involves the whole immune and bone systems. Breakdown of bone remodeling is attributed to overactive immune cells that produce large quantities of cytokines, upregulated differentiation of osteoclasts with enhanced resorptive activities, suppressed differentiation of osteoblasts, invading fibroblasts and microbiota dysbiosis. Despite the mitigation of inflammation, the existing treatment in Western medicine fails to prevent bone loss during disease progression. Traditional Chinese medicine (TCM) has been used for thousands of years in RA treatment, showing great efficacy in bone preservation. The complex components from the decoctions and prescriptions exhibit various pharmacological activities. This review summarizes the research progress that has been made in terms of the bone-protective effect of some representative compounds from TCM drugs and proposes the substantial mechanisms involved in bone metabolism to provide some clues for future studies. These active components systemically suppress bone destruction via inhibiting joint inflammation, osteoclast differentiation, and fibroblast proliferation. Neutrophil, gut microenvironment and microRNA has been proposed as future focus.
Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent
Authors: Guo Sha-Sha , Wang Zhen-Guo
Published: October 2022

Salvia miltiorrhiza Bunge (Lamiaceae) is a perennial herb widely found in China since ancient times with a high economic and medicinal value. Salvianolic acid B (Sal-B) is an important natural product derived from Salvia miltiorrhiza and this review summarizes the anticancer activity of Sal-B. Sal-B inhibits tumor growth and metastasis by targeting multiple cell signaling pathways. This review aims to review experimental studies to describe the possible anticancer mechanisms of Sal-B and confirm its potential as a therapeutic drug.
GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS
Authors: Yang Zheng , Lv Yuhuan , Yu Meng , Mei Mei , Xiang Linyu , Zhao Subei , Li Rong
Published: October 2022

Background: GLP-1 receptor agonists (GLP-1RA) have demonstrated cardiovascular benefits, but the relationship between GLP-1RA and tumors is controversial. Recently, clinical trials reported higher rates of malignancy with semaglutide than control group. As real-world evidence of GLP-1RA-associated tumor risk is very limited, we explored the association of GLP-1RA and all types of neoplasms by mining the FDA Adverse Event Reporting System (FAERS) database.

Methods: The FAERS data from the first quarter (Q1) of 2004 to the second quarter (Q2) of 2020 in the AERSMine were extracted to conduct disproportionality analysis, which was used by the proportional reporting ratio (PRR) to assess the relationship between GLP-1RA and all types of neoplasms. Then, the details of disproportionate GLP-1RA-associated tumor cases from Q1 2004 to Q2 2021 in the FAERS Public Dashboard were collected to analyze demographic characteristics.

Results: A total of 8718 GLP-1RA-associated tumors were reported. Excluding cases with pre-existing tumors, other glucose-lowering drugs, and other GLP-1RA-related adverse events, diabetes cases with GLP-1RA as the main suspected drug were selected. GLP-1RA did not cause a disproportionate increase in all tumor cases (PRR 0.83) at the SOC level, and there was also no increase in most types of tumors associated with GLP-1RA at the HLGT/HLT levels. Significant signals were detected between GLP-1RA and certain tumors, including thyroid cancers [medullary thyroid cancer (PRR 27.43) and papillary thyroid cancer (PRR 8.68)], pancreatic neoplasms malignant (PRR 9.86), and islet cell neoplasms and APUDoma NEC (PRR 2.86). The combination of GLP-1RA with dipeptidyl-peptidase IV inhibitors (DPP4i) perhaps caused the increased reporting rate in some tumors.

Conclusion: Our study provided new real-world evidence for oncology safety information of GLP-1RA. Given the wide use of GLP-1RA, clinicians should be well informed about important potential adverse events. Our pharmacovigilance analysis also prompted clinicians to raise concerns about potential tumor-related adverse effects when combining GLP-1RA with DPP4i.