bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and genomic characterization of hypervirulent Klebsiella pneumoniae (hvKp) infections via passive surveillance in Southern California, 2020–2022
Authors: Kamau Edwin , Ranson Elizabeth L. , Tsan Allison T. , Bergmann-Leitner Elke S. , Garner Omai B. , Yang Shangxin
Published: October 2022

Hypervirulent Klebsiella pneumoniae (hvKp) is more invasive and virulent than classical K. pneumoniae, and requires specialized treatment. To raise clinical awareness, this study determined the prevalence, clinical characteristics, and genomic epidemiology of hvKp infections in Southern California (SoCal) by conducting a passive surveillance in a single large academic medical center. We report here that hvKp infections were more common than expected, accounting for 2.6% of invasive K. pneumoniae infections, and presented with a wide disease spectrum, occasionally mimicking tumors, even co-infecting a COVID-19 patient. Most infections were community acquired with no recent international travel, suggesting hvKp strains are circulating in the community. Genomic analysis revealed genetic diversity, with the K1-ST23 lineage predominating but not clonal, and multiple sequence types of K2 including a SoCal unique K2-ST66 sublineage that had been unrecognized. Our findings highlight the urgency of heightened awareness of hvKp infection in the US, the need for rapid diagnosis of hvKp, and the necessity of implementing robust surveillance programs for hvKp at the institutional or local level.
A methyltransferase LaeA regulates ganoderic acid biosynthesis in Ganoderma lingzhi
Authors: Luo Qin , Li Na , Xu Jun-Wei
Published: October 2022

The methyltransferase LaeA is a global regulator involved in the biosynthesis of secondary metabolites by ascomycete fungi. However, little is known of its regulatory role in basidiomycete fungi. In this study, the laeA gene was identified in the basidiomycete Ganoderma lingzhi and its function in regulating the biosynthesis of anti-tumor ganoderic acids was evaluated. A laeA deletion (ΔlaeA) Ganoderma strain exhibited significantly reduced concentration of ganoderic acids. qRT-PCR analysis further revealed that the transcription levels of genes involved in the biosynthesis of ganoderic acids were drastically lower in the ΔlaeA strain. Moreover, deletion of laeA resulted in decreased accumulation of intermediates and abundances of asexual spores in liquid static culture of G. lingzhi. In contrast, constitutive overexpression of laeA resulted in increased concentration of ganoderic acids. These results demonstrate an essential role of LaeA in the regulation of ganoderic acid biosynthesis in Ganoderma.
Untargeted stable isotope-resolved metabolomics to assess the effect of PI3Kβ inhibition on metabolic pathway activities in a PTEN null breast cancer cell line
Authors: Lackner Marcel , Neef Sylvia K. , Winter Stefan , Beer-Hammer Sandra , Nürnberg Bernd , Schwab Matthias , Hofmann Ute , Haag Mathias
Published: October 2022

The combination of high-resolution LC-MS untargeted metabolomics with stable isotope-resolved tracing is a promising approach for the global exploration of metabolic pathway activities. In our established workflow we combine targeted isotopologue feature extraction with the non-targeted X13CMS routine. Metabolites, detected by X13CMS as differentially labeled between two biological conditions are subsequently integrated into the original targeted library. This strategy enables monitoring of changes in known pathways as well as the discovery of hitherto unknown metabolic alterations. Here, we demonstrate this workflow in a PTEN (phosphatase and tensin homolog) null breast cancer cell line (MDA-MB-468) exploring metabolic pathway activities in the absence and presence of the selective PI3Kβ inhibitor AZD8186. Cells were fed with [U-13C] glucose and treated for 1, 3, 6, and 24 h with 0.5 µM AZD8186 or vehicle, extracted by an optimized sample preparation protocol and analyzed by LC-QTOF-MS. Untargeted differential tracing of labels revealed 286 isotope-enriched features that were significantly altered between control and treatment conditions, of which 19 features could be attributed to known compounds from targeted pathways. Other 11 features were unambiguously identified based on data-dependent MS/MS spectra and reference substances. Notably, only a minority of the significantly altered features (11 and 16, respectively) were identified when preprocessing of the same data set (treatment vs. control in 24 h unlabeled samples) was performed with tools commonly used for label-free (i.e. w/o isotopic tracer) non-targeted metabolomics experiments (Profinder´s batch recursive feature extraction and XCMS). The structurally identified metabolites were integrated into the existing targeted isotopologue feature extraction workflow to enable natural abundance correction, evaluation of assay performance and assessment of drug-induced changes in pathway activities. Label incorporation was highly reproducible for the majority of isotopologues in technical replicates with a RSD below 10%. Furthermore, inter-day repeatability of a second label experiment showed strong correlation (Pearson R2 > 0.99) between tracer incorporation on different days. Finally, we could identify prominent pathway activity alterations upon PI3Kβ inhibition. Besides pathways in central metabolism, known to be changed our workflow revealed additional pathways, like pyrimidine metabolism or hexosamine pathway. All pathways identified represent key metabolic processes associated with cancer metabolism and therapy.
Learning multi-agent cooperation
Authors: Rivera Corban , Staley Edward , Llorens Ashley
Published: October 2022

Advances in reinforcement learning (RL) have resulted in recent breakthroughs in the application of artificial intelligence (AI) across many different domains. An emerging landscape of development environments is making powerful RL techniques more accessible for a growing community of researchers. However, most existing frameworks do not directly address the problem of learning in complex operating environments, such as dense urban settings or defense-related scenarios, that incorporate distributed, heterogeneous teams of agents. To help enable AI research for this important class of applications, we introduce the AI Arena: a scalable framework with flexible abstractions for associating agents with policies and policies with learning algorithms. Our results highlight the strengths of our approach, illustrate the importance of curriculum design, and measure the impact of multi-agent learning paradigms on the emergence of cooperation.
Computing the partition dimension of certain families of Toeplitz graph
Authors: Luo Ricai , Khalil Adnan , Ahmad Ali , Azeem Muhammad , Ibragimov Gafurjan , Nadeem Muhammad Faisal
Published: October 2022

LetG= (V(G),E(G)) be a graph with no loops, numerous edges, and only one component, which is made up of the vertex setV(G) and the edge setE(G). The distanced(u, v) between two verticesu, vthat belong to the vertex set ofHis the shortest path between them. Ak-ordered partition of vertices is defined as β = {β1, β2, …, βk}. If all distancesd(v, βk) are finite for all verticesv∈V, then thek-tuple (d(v, β1),d(v, β2), …,d(v, βk)) represents vertexvin terms of β, and is represented byr(v|β). If every vertex has a different presentation, thek-partition β is a resolving partition. The partition dimension of G, indicated bypd(G), is the minimalkfor which there is a resolvingk-partition ofV(G). The partition dimension of Toeplitz graphs formed by two and three generators is constant, as shown in the following paper. The resolving set allows obtaining a unique representation for computer structures. In particular, they are used in pharmaceutical research for discovering patterns common to a variety of drugs. The above definitions are based on the hypothesis of chemical graph theory and it is a customary depiction of chemical compounds in form of graph structures, where the node and edge represent the atom and bond types, respectively.
Effects of short-term spinal cord stimulation on patients with prolonged disorder of consciousness: A pilot study
Authors: Zhuang Yutong , Yang Yi , Xu Long , Chen Xueling , Geng Xiaoli , Zhao Jizong , He Jianghong
Published: October 2022

Background

Spinal cord stimulation (SCS) can improve the level of awareness of prolonged disorder of consciousness (pDOC), but its application is restricted due to damage of invasive operation. Short-term spinal cord stimulation (st-SCS) in a minimally invasive manner will better balance the benefits and risks.

Objectives

This study focuses on the safety and efficacy of st-SCS for pDOC and reveals the modulation characteristics of different frequencies of SCS.

Methods

31 patients received 2-week st-SCS treatment and 3-months follow-up. All patients were divided into two types of frequency treatment groups of 5 Hz and 70 Hz according to the postoperative electroencephalography (EEG) test. The efficacy was assessed based on the revised coma recovery scale (CRS-R).

Results

The results showed a significant increase in CRS-R scores after treatment (Z = −3.668, p < 0.001) without significant adverse effects. Univariate analysis showed that the minimally conscious state minus (MCS–) benefits most from treatment. Furthermore, two frequency have a difference in the time-point of the CRS-R score increase. 5 Hz mainly showed a significant increase in CRS-R score at 2 weeks of treatment (p = 0.027), and 70 Hz additionally showed a delayed effect of a continued significant increase at 1 week after treatment (p = 0.004).

Conclusion

st-SCS was safe and effective in improving patients with pDOC levels of consciousness, and was most effective for MCS–. Both 5 Hz and 70 Hz st-SCS can promote consciousness recovery, with 70 Hz showing a delayed effect in particular.
Single- and dual-task gait performance and their diagnostic value in early-stage Parkinson's disease
Authors: Zhang Xiaodan , Fan Weinv , Yu Hu , Li Li , Chen Zhaoying , Guan Qiongfeng
Published: October 2022

Background

Gait parameters are considered potential diagnostic markers of Parkinson's disease (PD). We aimed to 1) assess the gait impairment in early-stage PD and its related factors in the single-task (ST) and dual-task (DT) walking tests and 2) evaluate and compare the diagnostic value of gait parameters for early-stage PD under ST and DT conditions.

Methods

A total of 97 early-stage PD patients and 41 healthy controls (HC) were enrolled at Hwa Mei hospital. Gait parameters were gathered and compared between the two groups in the ST and DT walking test, controlling for covariates. Utilizing the receiver operating characteristic curve, diagnostic parameters were investigated.

Results

In the ST walking test, significantly altered gait patterns could be observed in early-stage PD patients in all domains of gait, except for asymmetry (P < 0.05). Compared to the ST walking test, the early-stage PD group performed poorly in the DT walking test in the pace, rhythm, variability and postural control domain (P < 0.05). Older, heavier subjects, as well as those with lower height, lower level of education and lower gait velocity, were found to have a poorer gait performance (P < 0.05). Stride length (AUC = 0.823, sensitivity, 68.0%; specificity, 85.4%; P < 0.001) and heel strike angle (AUC = 0.796, sensitivity, 71.1%; specificity, 80.5%; P < 0.001) could distinguish early-stage PD patients from HCs with moderate accuracy, independent of covariates. The diagnostic accuracy of gait parameters under ST conditions were statistically noninferior to those under DT conditions(P>0.05). Combining all gait parameters with diagnostic values under ST and DT walking test, the predictive power significantly increased with an AUC of 0.924 (sensitivity, 85.4%; specificity, 92.7%; P < 0.001).

Conclusion

Gait patterns altered in patients with early-stage PD but the gait symmetry remained preserved. Stride length and heel strike angle were the two most prominent gait parameters of altered gait in early-stage of PD that could serve as diagnostic markers of early-stage PD. Our findings are helpful to understand the gait pattern of early-stage PD and its related factors and can be conducive to the development of new diagnostic tools for early-stage PD.
Diagnostic model optimization method for ADHD based on brain network analysis of resting-state fMRI images and transfer learning neural network
Authors: Meng Xiaojing , Zhuo Wenjie , Ge Peng , Zou Bin , Zhu Yao , Liu Weidong , Li Xuzhou
Published: October 2022

Introduction: Attention deficit and hyperactivity disorder (ADHD) is a common inherited disease of the nervous system whose cause(s) and pathogenesis remain unclear. Currently, the diagnosis of ADHD is mainly based on clinical experience and guidelines that have laid out some diagnostic standards. Our study aimed to apply a learning-based classification method to assist the ADHD diagnosis based on high-dimensional resting-state fMRI.

Methods: Our study selected the ADHD-200 Peking dataset of resting-state fMRI, which has an ADHD patient (n = 142) group and a typically developing control (TDC) healthy control (n = 102) group. We first used Pearson and partial correlation coefficients to perform functional connectivity (FC) analysis between ROIs. Then, the Pearson and partial correlation coefficient matrices were concatenated into a dual-channel feature to build a dual data channel as input to the transfer learning neural network (TLNN) architecture. Finally, we transferred the pretrained model from the auxiliary domain to our target domain and fine-tuned it.

Results: Based on the Pearson correlation coefficient, FC between ROIs was detected in 22 brain regions, including the fusiform gyrus, superior frontal gyrus, posterior superior temporal sulcus, inferior parietal lobule, anterior cingulate cortex, and parahippocampal gyrus. Based on the partial correlation coefficient, we found FC in the salient network, default network, sensory-motor network, dorsal attention network, and cerebellum network. With the TLNN architecture, we solved the problem of insufficient training data and improved the sensitivity of the classification method. When the VGG model (fine-tuned transfer strategy, 1,024 fully connected layers) was applied, the accuracy of TLNN classification ultimately reached 82%.

Conclusion: Our study suggests that completing the training of the target domain by transferring the prior knowledge of the auxiliary domain is effective in solving the classification problem of small sample datasets. Based on prior knowledge of FC analysis, TLNN classification may assist ADHD diagnosis in a new way.
Recent advances in nutritional composition, phytochemistry, bioactive, and potential applications of Syzygium aromaticum L. (Myrtaceae)
Authors: Xue Qing , Xiang Zedong , Wang Shengguang , Cong Zhufeng , Gao Peng , Liu Xiaonan
Published: October 2022

Syzygium aromaticum is an aromatic plant native to Indonesia, and introduced to tropical regions worldwide. As an ingredient in perfumes, lotions, and food preservation, it is widely used in the food and cosmetic industries. Also, it is used to treat toothache, ulcers, type 2 diabetes, etc. A variety of nutrients such as amino acids, proteins, fatty acids, and vitamins are found in S. aromaticum. In addition to eugenol, isoeugenol, eugenol acetate, β-caryophyllene and α-humulene are the main chemical constituents. The chemical constituents of S. aromaticum exhibit a wide range of bioactivities, such as antioxidant, antitumor, hypoglycemic, immunomodulatory, analgesic, neuroprotective, anti-obesity, antiulcer, etc. This review aims to comprehend the information on its taxonomy and botany, nutritional composition, chemical composition, bioactivities and their mechanisms, toxicity, and potential applications. This review will be a comprehensive scientific resource for those interested in pursuing further research to explore its value in food.
Yeast mannoproteins are expected to be a novel potential functional food for attenuation of obesity and modulation of gut microbiota
Authors: Li Xiang , Wu Junsong , Kang Yijun , Chen Dan , Chen Guijie , Zeng Xiaoxiong , Wang Jialian
Published: October 2022

The yeast mannoproteins (MPs), a major component of yeast cell walls with large exploration potentiality, have been attracting increasing attention due to their beneficial effects. However, the information about the anti-obesogenic activity of MPs is still limited. Thus, the effects of MPs on the high-fat diet (HFD)-induced obesity and dysbiosis of gut microbiota were investigated in this work. The results showed that MPs could significantly attenuate the HFD-induced higher body weight, fat accumulation, liver steatosis, and damage. Simultaneously, the inflammation in HFD-induced mice was also ameliorated by MPs. The pyrosequencing analysis showed that intervention by MPs could lead to an obvious change in the structure of gut microbiota. Furthermore, the prevention of obesity by MPs is highly linked to the promotion of Parabacteroides distasonis (increased from 0.39 ± 0.12% to 2.10 ± 0.20%) and inhibition of Lactobacillus (decreased from 19.99 ± 3.94% to 2.68 ± 0.77%). Moreover, the increased level of acetate (increased from 3.28 ± 0.22 mmol/g to 7.84 ± 0.96 mmol/g) and activation of G protein-coupled receptors (GPRs) by MPs may also contribute to the prevention of obesity. Thus, our preliminary findings revealed that MPs from yeast could be explored as potential prebiotics to modulate the gut microbiota and prevent HFD-induced obesity.
Influence of traditional processing and genotypes on the antioxidant and antihyperglycaemic activities of yellow-fleshed cassava
Authors: Kareem Babajide , Irondi Emmanuel Anyachukwu , Alamu Emmanuel Oladeji , Ajani Emmanuel Oladipo , Abass Adebayo , Adesokan Michael , Parkes Elizabeth , Maziya-Dixon Busie
Published: October 2022

Yellow-fleshed cassava root (YFCR) is processed into traditional products that may influence its bioactivities. In this study, the antioxidant and anti-hyperglycaemic activities of three traditional products (lafun, fufu and gari) from five genotypes (IITA-TMS-IBA070337, 182961, 182962, 182986, 183044) of YFCR were evaluated. The YFCR genotypes were grown at the International Institute of Tropical Agriculture (IITA) research field, Ibadan. The bioactive constituents (total carotenoids, total phenolics, tannins and total flavonoids), antioxidant [2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS•+) and 1,1-diphenyl-2- picrylhydrazyl radical (DPPH•) scavenging capacities, and reducing power], and starch-digesting enzymes (α-amylase and α-glucosidase) inhibitory activities of the products were determined using standard laboratory methods. The glucose response of the products was assessed in human subjects. The concentrations of the bioactive constituents of the products from different genotypes varied significantly (p < 0.05). The ABTS•+ and DPPH• scavenging capacities and the reducing power of the products also differed significantly (p < 0.05), such that the lafun from IITA-TMS-IBA182962, IITA-TMS-IBA070337 and IITA-TMS-IBA070337 had the strongest ABTS•+ and DPPH• scavenging capacities, and reducing power, respectively. The α-amylase and α-glucosidase inhibitory activities of the three products differed significantly (p < 0.05), with the lafun from IITA-TMS-IBA070337 and IITA-TMS-IBA07033 having the strongest α-amylase and α-glucosidase inhibitory activity, respectively. Also, the lafun from IITA-TMS-182986 had the least glucose response, while the fufu from IITA-TMS-IBA070337 had the highest glucose response. Overall, the lafun from different genotypes of YFCR had the most potent antioxidant and starch-digesting enzymes inhibitory activities and the least glucose responses. Hence, lafun may be a promising dietary intervention targeting oxidative stress, hyperglycaemia, and their resultant type 2 diabetes.
Performance effects of internal pre- and per-cooling across different exercise and environmental conditions: A systematic review
Authors: Roriz Maria , Brito Pedro , Teixeira Filipe J. , Brito João , Teixeira Vitor Hugo
Published: October 2022

Exercise in a hot and humid environment may endanger athlete’s health and affect physical performance. This systematic review aimed to examine whether internal administration of ice, cold beverages or menthol solutions may be beneficial for physical performance when exercising in different environmental conditions and sports backgrounds. A systematic search was performed in PubMed, Web of Science, Scopus and SPORTDiscus databases, from inception to April 2022, to identify studies meeting the following inclusion criteria: healthy male and female physically active individuals or athletes (aged ≥18 years); an intervention consisting in the internal administration (i.e., ingestion or mouth rinse) of ice slush, ice slurry or crushed ice and/or cold beverages and/or menthol solutions before and/or during exercise; a randomized crossover design with a control or placebo condition; the report of at least one physical performance outcome; and to be written in English. Our search retrieved 2,714 articles in total; after selection, 43 studies were considered, including 472 participants, 408 men and 64 women, aged 18-42 years, with a VO2max ranging from 46.2 to 67.2 mL⋅kg–1⋅min–1. Average ambient temperature and relative humidity during the exercise tasks were 32.4 ± 3.5°C (ranging from 22°C to 38°C) and 50.8 ± 13.4% (varying from 20.0% to 80.0%), respectively. Across the 43 studies, 7 exclusively included a menthol solution mouth rinse, 30 exclusively involved ice slurry/ice slush/crushed ice/cold beverages intake, and 6 examined both the effect of thermal and non-thermal internal techniques in the same protocol. Rinsing a menthol solution (0.01%) improved physical performance during continuous endurance exercise in the heat. Conversely, the ingestion of ice or cold beverages did not seem to consistently increase performance, being more likely to improve performance in continuous endurance trials, especially when consumed during exercises. Co-administration of menthol with or within ice beverages seems to exert a synergistic effect by improving physical performance. Even in environmental conditions that are not extreme, internal cooling strategies may have an ergogenic effect. Further studies exploring both intermittent and outdoor exercise protocols, involving elite male and female athletes and performed under not extreme environmental conditions are warranted.

Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268197], identifier [CRD42021268197].
Two-step artificial intelligence system for endoscopic gastric biopsy improves the diagnostic accuracy of pathologists
Authors: Zhu Yan , Yuan Wei , Xie Chun-Mei , Xu Wei , Wang Jia-Ping , Feng Li , Wu Hui-Li , Lu Pin-Xiang , Geng Zi-Han , Lv Chuan-Feng , Li Quan-Lin , Hou Ying-Yong , Chen Wei-Feng , Zhou Ping-Hong
Published: October 2022

Background

Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS).

Methods

The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance.

Results

The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00).

Conclusions

The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.
A novel amino acid metabolism-related gene risk signature for predicting prognosis in clear cell renal cell carcinoma
Authors: Su Jiaqi , Tian Xi , Zhang Zihao , Xu Wenhao , Anwaier Aihetaimujiang , Ye Shiqi , Zhu Shuxuan , Wang Yue , Shi Guohai , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei
Published: October 2022

Background

Renal cancer is one of the most lethal cancers because of its atypical symptoms and metastatic potential. The metabolism of amino acids and their derivatives is essential for cancer cell survival and proliferation. Thus, the construction of the amino acid metabolism-related risk signature might enhance the accuracy of the prognostic model and shed light on the treatments of renal cancers.

Methods

RNA expression and clinical data were downloaded from Santa Cruz (UCSC) Xena, GEO, and ArrayExpress databases. The “DESeq2” package identified the differentially expressed genes. Univariate COX analysis selected prognostic genes related to the metabolism of amino acids. Patients were divided into two clusters using the “ConsensusClusterPlus” package, and the CIBERSORT, ESTIMATE methods were explored to assess the immune infiltrations. The LASSO regression analysis constructed a risk model which was evaluated the prediction accuracy in two independent cohorts. The genomic alterations and drug sensitivity of 18-LASSO-genes were assessed. The differentially expressed genes between two clusters were used to perform functional enrichment analysis and weighted gene co-expression network analysis (WGCNA). Furthermore, external validation of TMEM72 expression was conducted in the FUSCC cohort containing 33 ccRCC patients.

Results

The amino acid metabolism-related genes had significant correlations with prognosis. The patients in Cluster A demonstrated better survival, lower Treg cell proportion, higher ESTIMATE scores, and higher cuproptosis-related gene expressions. Amino acid metabolism-related genes with prognostic values were used to construct a risk model and patients in the low risk group were associated with improved outcomes. The Area Under Curve of the risk model was 0.801, 0.777, and 0.767 at the first, second, and third year respectively. The external validation cohort confirmed the stable prognostic value of the risk model. WGCNA identified four gene modules correlated with immune cell infiltrations and cuproptosis. We found that TMEM72 was downregulated in tumors by using TCGA, GEO datasets (p<0.001) and the FUSCC cohort (p=0.002).

Conclusion

Our study firstly constructed an 18 amino acid metabolism related signature to predict the prognosis in clear cell renal cell carcinoma. We also identified four potential gene modules potentially correlated with cuproptosis and identified TMEM72 downregulation in ccRCC which deserved further studies.
Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy
Authors: Si Yishimei , Xu Jinjing , Meng Linghan , Wu Yuanqing , Qi Jianwei
Published: October 2022

Nasopharyngeal carcinoma (NPC) is a type of head and neck tumor with noticeable regional and ethnic differences. It is associated with Epstein-Barr virus infection and has a tendency for local and distant metastasis. NPC is also highly sensitive to radiotherapy and chemotherapy. Over 70% of patients present with locoregionally advanced disease, and distant metastasis is the primary reason for treatment failure. A signal transducer and activator of transcription 3 (STAT3) promotes NPC oncogenesis through mechanisms within cancerous cells and their interactions with the tumor microenvironment, which is critical in the initiation, progression, and metastasis of NPC. Further, p-STAT3 is strongly associated with advanced NPC. Recent research on STAT3 has focused on its expression at the center of various oncogenic pathways. Here, we discuss the role of STAT3 in NPC and its potential therapeutic inhibitors and analogs for the treatment and control of NPC.
Identification of adenylate cyclase 2 methylation in bladder cancer with implications for prognosis and immunosuppressive microenvironment
Authors: Yang Jianfeng , Xu Jin , Gao Qian , Wu Fan , Han Wei , Yu Chao , Shi Youyang , Qiu Yunhua , Chen Yuanbiao , Zhou Xiqiu
Published: October 2022

Background

The incidence and mortality of bladder cancer (BCa) are increasing, while the existing diagnostic methods have limitations. Therefore, for early detection and response prediction, it is crucial to improve the prognosis and treatment strategies. However, with existing diagnostic methods, detecting BCa in the early stage is challenging. Hence, novel biomarkers are urgently needed to improve early diagnosis and treatment efficiency.

Methods

The gene expression profile and gene methylation profile dataset were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), differentially methylated genes (DMGs), and methylation-regulated differentially expressed genes (MeDEGs) were gradually identified. A cancer genome map was obtained using online gene expression profile interaction analysis, and survival implications were produced using Kaplan-Meier survival analysis. GSEA was employed to predict the marker pathways where DEGs were significantly involved. The study used bisulfite PCR amplification combined with bisulfite amplicon sequencing (BSAS) to screen for methylation analysis of multiple candidate regions of the adenylate cyclase 2 (ADCY2) based on the sequence design of specific gene regions and CpG islands.

Results

In this study, DEGs and DMGs with significantly up- or down-regulated expression were selected. The intersection method was used to screen the MeDEGs. The interaction network group in STRING was then visualized using Cytoscape, and the PPI network was constructed to identify the key genes. The key genes were then analyzed using functional enrichment. To compare the relationship between key genes and the prognosis of BCa patients, we further investigated ADCY2 and found that ADCY2 can be a potential clinical biomarker in BCa prognosis and immunotherapy response prediction. In human BCa 5637 and MGH1 cells, we developed and verified the effectiveness of ADCY2 primers using BSAS technology. The findings revealed that the expression of ADCY2 is highly regulated by the methylation of the promoter regions.

Conclusion

This study revealed that increased expression of ADCY2 was significantly correlated with increased tumor heterogeneity, predicting worse survival and immunotherapy response in BCa patients.
The potential of biology-guided radiation therapy in thoracic cancer: A preliminary treatment planning study
Authors: Seyedin Steven N. , Bassalow Rostem , Mawlawi Osama R. , Turner Lehendrick M. , Patel Roshal R. , Mazin Samuel R. , Oderinde Oluwaseyi M. , Voronenko Yevgen , Wages Cody A. , Olcott Peter D. , Chang Joe Y. , Balter Peter A. , Welsh James W.
Published: October 2022

Purpose

We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.

Methods

Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).

Results

For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT and IMPT.

Conclusions

BgRT has the potential to reduce the radiation dose to proximal critical structures but requires further detailed investigation.
The incidence risk of breast and gynecological cancer by antidepressant use: A systematic review and dose–response meta-analysis of epidemiological studies involving 160,727 patients
Authors: Zhuang Yanjia , Pang Xiaogang , Qi Yuchen , Zhang Tianshu , Cao Guimao , Xue Heming , Xu Yifan , Xie Shuoxin , Liu Yifan , Wang Yinuo , Li Yunxiao , Xiong Ying , Li Yuanyuan , Shen Hui
Published: October 2022

Background and objective

Antidepressants are widely prescribed to treat depression and anxiety disorders that may become chronic conditions among women. Epidemiological studies have yielded inconsistent results on the correlation between antidepressant use and the incidence risk of female breast and gynecological cancer, along with uncertain dose–response relationship. Therefore, we performed a systematic review and dose–response meta-analysis to investigate the association.

Methods

Web of Science, Embase, PubMed, The Cochrane Library, and PsycINFO were systematically searched in January 2022, with no language limits. Random-effect models were used to calculate pooled effect sizes and 95% confidence intervals between studies. Linear and non-linear dose–response analyses were performed to evaluate the dose or duration of antidepressant use affecting the incidence risk of female breast and gynecological cancer. Further subgroup analyses were systematically performed by stratifying almost all study characteristics and important potential confounders, in order to further clarify and validate the important potential hypotheses regarding the biological mechanism underlying this association.

Results

Based on a systematic literature search, 34 eligible studies (27 case–control studies and 7 cohort studies) involving 160,727 female breast and gynecological cancer patients found that antidepressant use did not increase the incidence risk of female breast and gynecological cancer (pooled OR: 1.01; 95% CI: 0.97, 1.04, I² = 71.5%, p < 0.001), and even decreased the incidence risk of ovarian cancer (pooled OR: 0.91; 95% CI: 0.83, 1, I² = 17.4%, p = 0.293). There were a non-linear dose–response relationship (p non-linearity < 0.05) between the duration of antidepressant use and incidence risk of female breast cancer, and an inverse linear dose–response relationship between antidepressant use and the incidence risk of gynecological cancer, specifically with an increase of cumulative defined daily dose or duration to a high level, like 25,550 doses (OR: 0.91, 95% CI: 0.85–0.98, p linearity < 0.05) or 4,380 days (OR: 0.82; 95% CI: 0.7, 0.96, p linearity < 0.05), compared to never antidepressant users.

Conclusion

This systematic review and dose–response meta-analysis found that antidepressant use did not increase the incidence risk of female breast and gynecological cancer and even decreased the incidence risk of ovarian cancer, along with a non-linear or linear dose–response relationship.

Systematic Review Registration

PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=313364, identifier CRD42022313364.
The missing mechanistic link: Improving behavioral treatment efficacy for pediatric chronic pain
Authors: Jotwani Maya L. , Wu Ziyan , Lunde Claire E. , Sieberg Christine B.
Published: October 2022

Pediatric chronic pain is a significant global issue, with biopsychosocial factors contributing to the complexity of the condition. Studies have explored behavioral treatments for pediatric chronic pain, but these treatments have mixed efficacy for improving functional and psychological outcomes. Furthermore, the literature lacks an understanding of the biobehavioral mechanisms contributing to pediatric chronic pain treatment response. In this mini review, we focus on how neuroimaging has been used to identify biobehavioral mechanisms of different conditions and how this modality can be used in mechanistic clinical trials to identify markers of treatment response for pediatric chronic pain. We propose that mechanistic clinical trials, utilizing neuroimaging, are warranted to investigate how to optimize the efficacy of behavioral treatments for pediatric chronic pain patients across pain types and ages.
Modified robotic-assisted laparoscopic pyeloplasty in children for ureteropelvic junction obstruction with long proximal ureteral stricture: The “double-flap” technique
Authors: Han Ce , Ma Lifei , Li Pin , Wang Jia’nan , Zhou Xiaoguang , Tao Tian , Cao Hualin , Tao Yuandong , Yang Yunjie , Zhao Yang , Zhu Weiwei , Guo Tao , Lyu Xuexue , Zhuo Ran , Zhou Huixia
Published: October 2022

Objective

The objective of this study is to introduce a novel technique of robotic-assisted laparoscopic pyeloplasty (RALP) for ureteropelvic junction obstruction (UPJO) with long proximal ureteral stricture in children.

Materials and methods

Clinical information on patients who underwent a modified RALP between July 2018 and May 2019 in our center was collected retrospectively. Our surgical modifications mainly include “double-flap” tailoring of the renal pelvis and anastomosis of spatulate ureter with the double-flap. Demographic, perioperative, postoperative, and follow-up information was recorded in detail.

Results

A total of 13 patients were included in the study. All the patients underwent a modified RALP without conversion to open surgery. They were followed up with a median time of 36 months. The anteroposterior diameter of the renal pelvis was 1.19 ± 0.21 at 6 months after the surgery, which was significantly lower than that on admission (3.93 ± 0.79). The split renal function of the children was also significantly improved from 0.37 ± 0.05) to 0.46 ± 0.02 at 6 months after surgery (p < 0.05). The diuretic renography revealed that all the patients have a T1/2 time less than 20 min postoperatively. The children were in good condition during the follow-up period.

Conclusions

Modified RALP is an effective surgical treatment for children with UPJO with long proximal ureteral stricture. The success rate of this modification has been preliminarily confirmed.
Efficacy and safety of baricitinib and tocilizumab in hospitalized patients with COVID-19: A comparison using systematic review and meta-analysis
Authors: Cherian Jerin Jose , Eerike Madhavi , Bagepally Bhavani Shankara , Das Saibal , Panda Samiran
Published: October 2022

Objective: This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC).

Methods: Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363).

Results: Treatment with baricitinib [RR, 0.69 (95% CI, 0.50–0.94), p = 0.02, i2 = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71–1.07), p = 0.19, i2 = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, −1.13 days (95% CI, −1.51 to −0.76), p < 0.001, i2 = 0.00%; tocilizumab: mean difference, −2.80 days (95% CI, −4.17 to −1.43), p < 0.001, i2 = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03–1.48), p = 0.02, i2 = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12–1.78), p < 0.001, i2 = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62–0.92), p = 0.01, i2 = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72–1.01), p = 0.07, i2 = 0.00%].

Conclusion: As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.
Pharmacogenomic-guided clozapine administration based on HLA-DQB1, HLA-B and SLCO1B3-SLCO1B7 variants: an effectiveness and cost-effectiveness analysis
Authors: Ninomiya Kohei , Saito Takeo , Ikeda Masashi , Iwata Nakao , Girardin François R.
Published: October 2022

The identification of pharmacogenetic factors that increase the susceptibility to clozapine-induced agranulocytosis or granulocytopenia (CIAG) has received increasing interest. The SLCO1B3-SCLO1B7 variant (rs149104283) and single amino acid changes in human leukocyte antigen (HLA) HLA-DQB1 (126Q) and HLA-B (158T) were associated with an increased risk of CIAG. In this study, we evaluated the effectiveness and cost-effectiveness of adding the SLCO1B3-SCLO1B7 to HLA variants as a new pharmacogenomic (PGx) approach and explored the evolution of a cohort of schizophrenic patients taking long-term clozapine as a third-line antipsychotic medication. The decision model included probabilistic and deterministic sensitivity analyses to assess the expected costs and quality-adjusted life-years (QALYs). The current monitoring scheme was compared with the PGx-guided strategy, where all patients underwent pre-emptively a genetic test before taking clozapine, over 10 years. By adding the SLCO1B3-SCLO1B7 variant into HLA variants, CIAG sensitivity increased from 36.0% to 43.0%, the specificity decreased from 89.0% to 86.9%, and the probability of cost-effectiveness improved from 74.1% to 87.8%. The incremental cost-effectiveness ratio was £16,215 per QALY and remained below the conventional decision threshold (£30,000 or US$50,000 per QALY). Therefore, the SLCO1B3-SCLO1B7 variant, as an additional risk allele to HLA variants, increases preemptive test sensitivity and improves the effectiveness and cost-effectiveness of PGx-guided clozapine administration.
Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
Authors: Latuske Patrick , von Heimendahl Moritz , Deiana Serena , Wotjak Carsten T. , du Hoffmann Johann
Published: October 2022

Cognitive flexibility, the ability to adapt to unexpected changes, is critical for healthy environmental and social interactions, and thus to everyday functioning. In neuropsychiatric diseases, cognitive flexibility is often impaired and treatment options are lacking. Probabilistic reversal learning (PRL) is commonly used to measure cognitive flexibility in rodents and humans. In PRL tasks, subjects must sample choice options and, from probabilistic feedback, find the current best choice which then changes without warning. However, in rodents, pharmacological models of human cognitive impairment tend to disrupt only the first (or few) of several contingency reversals, making quantitative assessment of behavioral effects difficult. To address this limitation, we developed a novel rat PRL where reversals occur at relatively long intervals in time that demonstrates increased sensitivity to the non-competitive NMDA receptor antagonist MK-801. Here, we quantitively compare behavior in time-based PRL with a widely used task where reversals occur based on choice behavior. In time-based PRL, MK-801 induced sustained reversal learning deficits both in time and across reversal blocks but, at the same dose, only transient weak effects in performance-based PRL. Moreover, time-based PRL yielded better estimates of behavior and reinforcement learning model parameters, which opens meaningful pharmacological windows to efficiently test and develop novel drugs preclinically with the goal of improving cognitive impairment in human patients.
Efficacy evaluation of Buyang Huanwu Decoction in the treatment of ischemic stroke in the recovery period: A systematic review of randomized controlled trials
Authors: Wang Raoqiong , Ren Junhao , Li Shuangyang , Bai Xue , Guo Wubin , Yang Sijin , Wu Qibiao , Zhang Wei
Published: October 2022

Background and purpose: Buyang Huanwu decoction (BYHWD) is widely used in the treatment of ischemic stroke in the recovery period, and many clinical trials have been reported, but its clinical efficacy and safety have not been fully evaluated. In this study, we conducted a systematic review and meta-analysis to evaluate the clinical efficacy and safety of BYHWD in the recovery period.

Materials and methods: Eight databases, including CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Cochrane Library, EMBASE, and Web of Science, were searched from the establishment of the database to 13 April 2022. We selected all eligible randomized controlled trials of BYHWD in the treatment of ischemic stroke during the recovery period. Systematic review and meta-analysis were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The National Institutes of Health Stroke Score (NIHSS) was the primary outcome, and the Chinese Stroke Scale (CSS), activities of daily living (ADL), and adverse drug reaction (ADR) were the secondary outcomes.

Results: A total of 39 randomized controlled trials were included, and 3,683 patients in the recovery period of ischemic stroke were recruited. Compared with conventional treatment alone, BYHWD combined with conventional treatment significantly decreased the NIHSS score (MD = -1.44, 95% CI: 1.75, -1.12, p < 0.00001), the CSS score (MD = -1.18, 95% CI: 2.02, -0.34, p = 0.006), improved the ADL (MD = 4.33, 95% CI: 3.06, 5.61, p < 0.00001), and did not increase the adverse reactions of patients (OR = 0.88, 95% CI: 0.48, 1.61, p = 0.67).

Conclusion: BYHWD is an effective and safe therapy for the recovery of ischemic stroke. To further determine the efficacy and safety of BYHWD in the treatment of ischemic stroke in the recovery period, more high-quality, multicenter, and prospective RCTs are needed.