bluuebunny/crossref_metadata_2025 huggingface dataset:
CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders
Authors: Baier Andrea , Szyszka Ryszard
Published: October 2022

Casein kinases are involved in a variety of signaling pathways, and also in inflammation, cancer, and neurological diseases. Therefore, they are regarded as potential therapeutic targets for drug design. Recent studies have highlighted the importance of the casein kinase 1 superfamily as well as protein kinase CK2 in the development of several neurodegenerative pathologies, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. CK1 kinases and their closely related tau tubulin kinases as well as CK2 are found to be overexpressed in the mammalian brain. Numerous substrates have been detected which play crucial roles in neuronal and synaptic network functions and activities. The development of new substances for the treatment of these pathologies is in high demand. The impact of these kinases in the progress of neurodegenerative disorders, their bona fide substrates, and numerous natural and synthetic compounds which are able to inhibit CK1, TTBK, and CK2 are discussed in this review.
Believing and social interactions: effects on bodily expressions and personal narratives
Authors: Seitz Rüdiger J. , Angel Hans-Ferdinand , Paloutzian Raymond F. , Taves Ann
Published: October 2022

The processes of believing integrate external perceptual information from the environment with internal emotional states and prior experience to generate probabilistic neural representations of events, i.e., beliefs. As these neural representations manifest mostly below the level of a person’s conscious awareness, they may inadvertently affect the spontaneous person’s bodily expressions and prospective behavior. By yet to be understood mechanisms people can become aware of these representations and reflect upon them. Typically, people can communicate the content of their beliefs as personal statements and can summarize the narratives of others to themselves or to other people. Here, we describe that social interactions may benefit from the consistency between a person’s bodily expressions and verbal statements because the person appears authentic and ultimately trustworthy. The transmission of narratives can thus lay the groundwork for social cooperation within and between groups and, ultimately, between communities and nations. Conversely, a discrepancy between bodily expressions and narratives may cause distrust in the addressee(s) and eventually may destroy social bonds.
Isolation of ferret astrocytes reveals their morphological, transcriptional, and functional differences from mouse astrocytes
Authors: Roboon Jureepon , Hattori Tsuyoshi , Nguyen Dinh Thi , Ishii Hiroshi , Takarada-Iemata Mika , Kannon Takayuki , Hosomichi Kazuyoshi , Maejima Takashi , Saito Kengo , Shinmyo Yohei , Mieda Michihiro , Tajima Atsushi , Kawasaki Hiroshi , Hori Osamu
Published: October 2022

Astrocytes play key roles in supporting the central nervous system structure, regulating synaptic functions, and maintaining brain homeostasis. The number of astrocytes in the cerebrum has markedly increased through evolution. However, the manner by which astrocytes change their features during evolution remains unknown. Compared with the rodent brain, the brain of the ferret, a carnivorous animal, has a folded cerebral cortex and higher white to gray matter ratio, which are common features of the human brain. To further clarify the features of ferret astrocytes, we isolated astrocytes from ferret neonatal brains, cultured these cells, and compared their morphology, gene expression, calcium response, and proliferating ability with those of mouse astrocytes. The morphology of cultured ferret astrocytes differed from that of mouse astrocytes. Ferret astrocytes had longer and more branched processes, smaller cell bodies, and different calcium responses to glutamate, as well as had a greater ability to proliferate, compared to mouse astrocytes. RNA sequencing analysis revealed novel ferret astrocyte-specific genes, including several genes that were the same as those in humans. Astrocytes in the ferret brains had larger cell size, longer primary processes in larger numbers, and a higher proliferation rate compared to mouse astrocytes. Our study shows that cultured ferret astrocytes have different features from rodent astrocytes and similar features to human astrocytes, suggesting that they are useful in studying the roles of astrocytes in brain evolution and cognitive functions in higher animals.
Where do you live and what do you do? Two questions that might impact your kidney health
Authors: Aoun Mabel , Chelala Dania
Published: October 2022

In many cases the social determinants of health need to be assessed through their interaction with environmental factors. This review looks at the impact of physical location and occupation of individuals on their kidney health. It examines the effect of living at high altitude on kidney function and the relationship between extreme cold or hot temperatures and the incidence of kidney injury. It reviews as well the many occupations that have been linked to kidney disease in high-income and low-and-middle-income countries. As a conclusion, this overview proposes preventive recommendations that could be individualized based on weather, altitude, socio-economic level of the country and occupation of the individual.
The prevalence and associated factors of dysphagia in Parkinson's disease: A systematic review and meta-analysis
Authors: Gong Siyuan , Gao Yan , Liu Jihong , Li Jia , Tang Xueqin , Ran Qian , Tang Rongzhu , Liao Chunlian
Published: October 2022

Background

The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic review and meta-analysis was to evaluate the prevalence of dysphagia in PD and to clarify its associated factors.

Methods

Two researchers systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, SinoMed and VIP databases and manually searched references in the retrieved articles to identify potential research subjects. The last search was conducted on June 28, 2022. Finally, a total of 58 studies including 60 observations with 20,530 PD patients were included in our meta-analysis.

Results

The meta-analysis estimated that the pooled prevalence rate of dysphagia in PD was 36.9% (95% CI: 30.7–43.6%) and instrumental examination showed a higher prevalence (57.3%, 95% CI: 44.3–69.1%). Oceania showed the highest prevalence of dysphagia in PD (56.3%) compared to Africa (39.5%), Asia (38.6%), Europe (36.1%) and America (28.9%). Dysphagia in PD was associated with older age, lower body mass index, longer disease duration, higher Hoehn and Yahr stage and levodopa equivalent daily dose, PIGD subtype, severe motor symptoms, drooling and higher levels of depression, and lower quality of life.

Conclusions

In conclusion, our meta-analysis showed that dysphagia occurs in more than one-third of PD patients and was associated with several demographic characteristics and PD-related characteristics, motor symptoms, non-motor symptoms, as well as decreased quality of life. It deserves early screening, diagnosis, and treatment in clinical practice to prevent serious complications from dysphagia.
Retreatment with a flow diverter for recurrent blood blister-like aneurysms after embolization: A single-center case series
Authors: Yan Yazhou , Zhu Shijie , Yao Hao , Wu Yina , Lu Zhiwen , Fang Yibin , Zhao Kaijun , Huang Qinghai
Published: October 2022

Background and purpose

Treatment of blood blister-like aneurysms (BBAs) has been a significant challenge mainly due to their high recurrence rate even after stent-assisted coiling (SAC) embolization. This study aims to evaluate the safety and efficacy of treating recurrent BBAs after SAC with a flow diverter (FD).

Methods

A retrospective series of patients with recurrent BBAs who underwent the retreatment with the FD from June 2018 to December 2021 was included to analyze perioperative safety and immediate postoperative and follow-up outcomes.

Results

The study enrolled 13 patients with recurrent BBAs previously treated with SAC. Within previous stents, an FD was deployed for retreatment, including eight Tubridge FDs and five PEDs. The time interval between initial treatment and FD implantation was 14–90 days. A total of 11 cases were treated with a single FD alone; two cases were treated with further endovascular coiling embolization, followed by FD implantation. The angiographic follow-up (6–12 months) was available in 12 patients, and all 12 recurrent BBAs were completely occluded. No perioperative complication was detected, and no rebleeding was found during the clinical follow-up (6–36 months).

Conclusion

The use of the FD to manage recurrent BBAs after SAC is technically feasible, safe, and effective. The key to the success of the procedure is to ensure that the FD stent is fully open and has good apposition with the previously implanted stent.
Neutrophil-to-lymphocyte ratio predicts parenchymal hematoma after mechanical thrombectomy in basilar artery occlusion
Authors: Hao Yonggang , Hu Zhizhou , Zhu Xiurong , Chen Zhao , Jiang He , Lei Yang , Liao Jiasheng , Lv Kefeng , Wang Kuiyun , Wang Hongjun , Liao Jiachuan , Zi Wenjie , Jiang Shunfu , Zheng Chong
Published: October 2022

Background

parenchymal hematoma (PH) is a severe complication of endovascular treatment (EVT) for acute basilar artery occlusion (ABAO). This study aimed to evaluate the incidence and predictors of PH after EVT for ABAO.

Methods

Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study, we enrolled patients treated with mechanical thrombectomy from the BASILAR registry. PH was assessed in accordance with the Heidelberg Bleeding Classification. Logistic regression was used to identify predictors of PH.

Results

A total of 639 patients were included. Forty-eight patients (7.5%) were diagnosed with PH within 48 h of EVT. Ninety-day mortality was higher in patients with PH compared with those without (81.3 vs. 42.8%, P < 0.001). Favorable neurological outcomes (modified Rankin scale score, 0–3) rates was lower in patients with PH compared with those without (6.3 vs. 34.5%, P < 0.001). With a multivariate analysis, hypertension [odds ratio (OR) = 2.30, 95% confidence interval (CI) 1.04–5.08], pre-treatment National Institutes of Health Stroke Score (NIHSS, >25; OR = 3.04, 95% CI 1.43–6.45), and Neutrophil-to-lymphocyte ratio (NLR, >10; OR = 1.88, 95% CI 1.02–3.48) were associated with PH after EVT.

Conclusions

PH occurred at a rate of 7.5% after EVT in patients with ABAO. Hypertension, higher baseline NIHSS, and higher NLR value increase the risk of PH after EVT for ABAO.
Cognitive theories of autism based on the interactions between brain functional networks
Authors: Alamdari Sarah Barzegari , Sadeghi Damavandi Masoumeh , Zarei Mojtaba , Khosrowabadi Reza
Published: October 2022

Cognitive functions are directly related to interactions between the brain's functional networks. This functional organization changes in the autism spectrum disorder (ASD). However, the heterogeneous nature of autism brings inconsistency in the findings, and specific pattern of changes based on the cognitive theories of ASD still requires to be well-understood. In this study, we hypothesized that the theory of mind (ToM), and the weak central coherence theory must follow an alteration pattern in the network level of functional interactions. The main aim is to understand this pattern by evaluating interactions between all the brain functional networks. Moreover, the association between the significantly altered interactions and cognitive dysfunctions in autism is also investigated. We used resting-state fMRI data of 106 subjects (5–14 years, 46 ASD: five female, 60 HC: 18 female) to define the brain functional networks. Functional networks were calculated by applying four parcellation masks and their interactions were estimated using Pearson's correlation between pairs of them. Subsequently, for each mask, a graph was formed based on the connectome of interactions. Then, the local and global parameters of the graph were calculated. Finally, statistical analysis was performed using a two-sample t-test to highlight the significant differences between autistic and healthy control groups. Our corrected results show significant changes in the interaction of default mode, sensorimotor, visuospatial, visual, and language networks with other functional networks that can support the main cognitive theories of autism. We hope this finding sheds light on a better understanding of the neural underpinning of autism.
Modeling intracranial electrodes. A simulation platform for the evaluation of localization algorithms
Authors: Blenkmann Alejandro O. , Solbakk Anne-Kristin , Ivanovic Jugoslav , Larsson Pål Gunnar , Knight Robert T. , Endestad Tor
Published: October 2022

Introduction

Intracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows the investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid inferences about the anatomical localization of brain function. Multiple methods have been developed to localize the electrodes, mainly relying on pre-implantation MRI and post-implantation computer tomography (CT) images. However, they are hard to validate because there is no ground truth data to test them and there is no standard approach to systematically quantify their performance. In other words, their validation lacks standardization. Our work aimed to model intracranial electrode arrays and simulate realistic implantation scenarios, thereby providing localization algorithms with new ways to evaluate and optimize their performance.

Results

We implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these. We successfully modeled realistic implantation scenarios, including different sizes, inter-electrode distances, and brain areas. In total, ∼3,300 grids and strips were fitted over the brain surface, and ∼850 depth electrode arrays penetrating the cortical tissue were modeled. Realistic CT artifacts were simulated at the electrode locations under 12 different noise levels. Altogether, ∼50,000 thresholded CT artifact arrays were simulated in these scenarios, and validated with real data from 17 patients regarding the coordinates’ spatial deformation, and the CT artifacts’ shape, intensity distribution, and noise level. Finally, we provide an example of how the simulation platform is used to characterize the performance of two cluster-based localization methods.

Conclusion

We successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate thresholded CT artifacts and their noise. These methods provide a basis for developing more complex models, while simulations allow systematic evaluation of the performance of electrode localization techniques. The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.
Cognitive psychology-based artificial intelligence review
Authors: Zhao Jian , Wu Mengqing , Zhou Liyun , Wang Xuezhu , Jia Jian
Published: October 2022

Most of the current development of artificial intelligence is based on brain cognition, however, this replication of biology cannot simulate the subjective emotional and mental state changes of human beings. Due to the imperfections of existing artificial intelligence, this manuscript summarizes and clarifies that artificial intelligence system combined with cognitive psychology is the research direction of artificial intelligence. It aims to promote the development of artificial intelligence and give computers human advanced cognitive abilities, so that computers can recognize emotions, understand human feelings, and eventually achieve dialog and empathy with humans and other artificial intelligence. This paper emphasizes the development potential and importance of artificial intelligence to understand, possess and discriminate human mental states, and argues its application value with three typical application examples of human–computer interaction: face attraction, affective computing, and music emotion, which is conducive to the further and higher level of artificial intelligence research.
Multicolor high-resolution whole-brain imaging for acquiring and comparing the brain-wide distributions of type-specific and projection-specific neurons with anatomical annotation in the same brain
Authors: Ding Zhangheng , Zhao Jiangjiang , Luo Tianpeng , Lu Bolin , Zhang Xiaoyu , Chen Siqi , Li Anan , Jia Xueyan , Zhang Jianmin , Chen Wu , Chen Jianwei , Sun Qingtao , Li Xiangning , Gong Hui , Yuan Jing
Published: October 2022

Visualizing the relationships and interactions among different biological components in the whole brain is crucial to our understanding of brain structures and functions. However, an automatic multicolor whole-brain imaging technique is still lacking. Here, we developed a multicolor wide-field large-volume tomography (multicolor WVT) to simultaneously acquire fluorescent signals in blue, green, and red channels in the whole brain. To facilitate the segmentation of brain regions and anatomical annotation, we used 4′, 6-diamidino-2-phenylindole (DAPI) to provide cytoarchitecture through real-time counterstaining. We optimized the imaging planes and modes of three channels to overcome the axial chromatic aberration of the illumination path and avoid the crosstalk from DAPI to the green channel without the modification of system configuration. We also developed an automatic contour recognition algorithm based on DAPI-staining cytoarchitecture to shorten data acquisition time and reduce data redundancy. To demonstrate the potential of our system in deciphering the relationship of the multiple components of neural circuits, we acquired and quantified the brain-wide distributions of cholinergic neurons and input of ventral Caudoputamen (CP) with the anatomical annotation in the same brain. We further identified the cholinergic type of upstream neurons projecting to CP through the triple-color collocated analysis and quantified its proportions in the two brain-wide distributions. Both accounted for 0.22%, implying CP might be modulated by non-cholinergic neurons. Our method provides a new research tool for studying the different biological components in the same organ and potentially facilitates the understanding of the processing mechanism of neural circuits and other biological activities.
An automated heart rate-based algorithm for sleep stage classification: Validation using conventional polysomnography and an innovative wearable electrocardiogram device
Authors: Pini Nicolò , Ong Ju Lynn , Yilmaz Gizem , Chee Nicholas I. Y. N. , Siting Zhao , Awasthi Animesh , Biju Siddharth , Kishan Kishan , Patanaik Amiya , Fifer William P. , Lucchini Maristella
Published: October 2022

Background

The rapid advancement in wearable solutions to monitor and score sleep staging has enabled monitoring outside of the conventional clinical settings. However, most of the devices and algorithms lack extensive and independent validation, a fundamental step to ensure robustness, stability, and replicability of the results beyond the training and testing phases. These systems are thought not to be feasible and reliable alternatives to the gold standard, polysomnography (PSG).

Materials and methods

This validation study highlights the accuracy and precision of the proposed heart rate (HR)-based deep-learning algorithm for sleep staging. The illustrated solution can perform classification at 2-levels (Wake; Sleep), 3-levels (Wake; NREM; REM) or 4- levels (Wake; Light; Deep; REM) in 30-s epochs. The algorithm was validated using an open-source dataset of PSG recordings (Physionet CinC dataset, n = 994 participants, 994 recordings) and a proprietary dataset of ECG recordings (Z3Pulse, n = 52 participants, 112 recordings) collected with a chest-worn, wireless sensor and simultaneous PSG collection using SOMNOtouch.

Results

We evaluated the performance of the models in both datasets in terms of Accuracy (A), Cohen’s kappa (K), Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predicted Value (NPV). In the CinC dataset, the highest value of accuracy was achieved by the 2-levels model (0.8797), while the 3-levels model obtained the best value of K (0.6025). The 4-levels model obtained the lowest SE (0.3812) and the highest SP (0.9744) for the classification of Deep sleep segments. AHI and biological sex did not affect scoring, while a significant decrease of performance by age was reported across the models. In the Z3Pulse dataset, the highest value of accuracy was achieved by the 2-levels model (0.8812), whereas the 3-levels model obtained the best value of K (0.611). For classification of the sleep states, the lowest SE (0.6163) and the highest SP (0.9606) were obtained for the classification of Deep sleep segment.

Conclusion

The results of the validation procedure demonstrated the feasibility of accurate HR-based sleep staging. The combination of the proposed sleep staging algorithm with an inexpensive HR device, provides a cost-effective and non-invasive solution deployable in the home environment and robust across age, sex, and AHI scores.
Low-temperature vacuum permeation of sodium tripolyphosphate and trehalose suppresses the denaturation of myofibrillar proteins in peeled shrimp (Litopenaeus vannamei) during frozen storage
Authors: Du Qi , Fang Chuangdong , Qi He , Benjakul Soottawat , Aubourg Santiago P. , Zhang Bin
Published: October 2022

Phosphates and trehalose are widely accepted additives in animal muscle products. In this study, the effects of pre-soaking with sodium tripolyphosphate (STPP) and trehalose under vacuum permeation (VP) conditions on the physicochemical properties of shrimp muscle were evaluated over 120 d of frozen storage. The results indicate the STPP/trehalose-VP treatments significantly reduced the thawing loss and prevented changes in the texture, myofibrillar protein (MP) content, and Ca2+-ATPase activity of shrimp muscle during frozen storage compared with results of control and individual STPP or trehalose soaking treatments. The histological structure analysis revealed the permeated STPP/trehalose distinctly inhibited the dissociation of muscle fibers and reduced physical damage to connective tissues during storage. Furthermore, analysis of the thermal properties indicated STPP/trehalose treatment increased the Tg’ values of shrimp muscle tissues, likely by restricting the mobility of water molecules in muscle tissues and embedding proteins in the glassy matrix. Thus, the physical destruction caused by ice crystal growth was greatly reduced, due to the absence of water molecules around muscle proteins during frozen storage. Accordingly, the combined STPP/trehalose-VP treatment significantly enhanced the stability of frozen shrimp, and the results support the application of traditional cryoprotective additives. The treated shrimp can be stored at comparatively higher temperatures with limited physicochemical reactions during frozen storage.
Effect of fruit intake on functional constipation: A systematic review and meta-analysis of randomized and crossover studies
Authors: Huo Jinghong , Wu Lingyu , Lv Jinming , Cao Hongdou , Gao Qinghan
Published: October 2022

Functional constipation (FC) is commonly treated with fruits whose efficacy remains unclear. We conducted a meta-analysis of fruit intervention for FC and provided evidence-based recommendations. We searched seven databases from inception to July 2022. All randomized and crossover studies on the effectiveness of fruits on FC were included. We conducted sensitivity and subgroup analysis. A total of 11 studies were included in this review. Four trials showed that kiwifruits have significantly increased stool frequency (MD = 0.26, 95% CI (0.22, 0.30), P < 0.0001, I2 = 0%) than palm date or orange juice in the fixed-effect meta-analysis. Three high-quality studies suggested that kiwifruits have a better effect than ficus carica paste on the symptom of the FC assessed by the Bristol stool scale in the fixed-effect meta-analysis [MD = 0.39, 95% CI (0.11, 0.66), P < 0.05, I2 = 27%]. Besides, five trials showed that fruits can increase the amount of Lactobacillus acidophilus [MD = 0.82, 95% CI (0.25, 1.39), P < 0.05, I2 = 52%], analyzed with the random-effect model. Subgroup meta-analysis based on the types of fruits suggested that fruits including pome fruit, citrus fruit, and berries have increased the effect of Bifidobacterium t more than the stone fruits in the random effect meta-analysis [MD = 0.51, 95% CI (0.23, 0.79), P < 0.05, I2 = 84%]. Totally, fruit intake may have potential symptom alleviation on the FC as evidence shows that they can affect stool consistency, stool frequency, and gut microbiota. Further large-scale studies are needed to gain more confident conclusions concerning the association between fruit intake and FC in the future.
Higher niacin intakes improve the lean meat rate of Ningxiang pigs by regulating lipid metabolism and gut microbiota
Authors: Wang Zhaobin , Zeng Xianglin , Zhang Cheng , Wang Qianqian , Zhang Weidong , Xie Junyan , Chen Jiashun , Hu Qin , Wang Qiye , Yang Huansheng , Yin Yulong
Published: October 2022

As one of the local pig breeds in China with a high fat rate, improving the lean meat rate of Ningxiang pigs through nutritional intervention is an urgent issue to be solved. As an important feed additive, niacin plays an important role in lipid metabolism. The purpose of this study was to investigate the regulation and mechanism of niacin on fat deposition in Ningxiang pigs. Thirty-four Ningxiang pigs (53.34 ± 2.78 kg) were randomly divided into two groups with five replicates each, with three to four Ningxiang pigs per replicate. The control group was fed a basal diet (contained 22 mg/kg niacin), and the experimental group was fed the same diet supplemented with an additional 100 mg/kg of niacin. The experimental period lasted 60 days. One Ningxiang pig was selected for slaughter sampling for each replicate. This study found that lean meat percentage of Ningxiang pigs in the experimental group was significantly increased (P < 0.05), accompanied by a significant decrease in fat percentage (P < 0.05). 16S rRNA sequencing analysis found an abundance of Streptococcus in the experimental group (P < 0.05), along with significantly decreased levels of Lactobacillus (P < 0.05). The changes in some OTUs belonging to Firmicutes, Bacteroidota, and Actinobacteriota were closely related to the changes in the fat rate and lean meat rate of Ningxiang pigs (P < 0.05). LC–MS metabolomics analysis found that about 43.75% of the differential metabolites were related to lipids and lipid-like molecules in the liver (P < 0.05). Spearman's correlation analysis showed correlations between the carcass traits, microbiota, and liver metabolites. In conclusion, niacin improves lean meat percentage and reduces fat deposition by regulating lipid metabolism and gut microbiota composition in Ningxiang pigs.
Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model
Authors: Rehman Ata Ur , Siddiqui Nimra Zafar , Farooqui Nabeel Ahmed , Alam Gulzar , Gul Aneesa , Ahmad Bashir , Asim Muhammad , Khan Asif Iqbal , Xin Yi , Zexu Wang , Song Ju Hyo , Xin Wang , Lei Sun , Wang Liang
Published: October 2022

Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. It has previously been reported that natural polysaccharides have been studied with regard to regulating the gut microbiota, which plays an important role in T2DM. Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. The administration of MEP effectively regulated hyperglycemia and hyperlipidemia and improved insulin sensitivity. We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM.
Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease
Authors: Yang Lei , Yang Zelin , Zuo Chunjian , Lv Xiaolong , Liu Tianyu , Jia Chenhao , Chen Huanwen
Published: October 2022

Background

Genetic studies have previously reported that single-nucleotide polymorphisms (SNPs) in CHRNA genes (such as CHRNA3, CHRNA4, CHRNA5, or CHRNA3-CHRNA5-CHRNB4 clusters) are linked to the risk of neoplastic and non-neoplastic diseases. However, these conclusions were controversial and no systematic research synopsis has been available. We aimed to synthesize current knowledge of variants in the CHRNA genes on the risk of diseases.

Methods

We systematically searched for publications using PubMed, Medline, and Web of Science on or before 25 August 2021. A total of 1,818 publications were identified, of which 29 were deemed eligible for inclusion that could be used to perform meta-analysis based on at least three data sources to assess whether the morbidity associated with neoplastic and non-neoplastic diseases can be attributed to SNPs in CHRNA genes. To further evaluate the authenticity of cumulative evidence proving significant associations, the present study covered the Venice criteria and false-positive report probability tests. Through the Encyclopedia of DNA Elements (ENCODE) project, we created functional annotations for strong associations.

Results

Meta-analyses were done for nine genetic variants with two diseases {chronic obstructive pulmonary disease (COPD) and lung cancer (LC)}that had at least three data sources. Interestingly, eight polymorphisms were significantly related to changes in the susceptibility COPD and LC (p < 0.05). Of these, strong evidence was assigned to six variants (28 significant associations): CHRNA3 rs1051730, CHRNA3 rs6495309, and CHRNA5 rs16969968 with COPD risk, and CHRNA3 rs1051730, CHRNA3 rs578776, CHRNA3 rs6495309, CHRNA3 rs938682, CHRNA5 rs16969968, and CHRNA5 rs588765 with LC risk; moderate evidence was assigned to five SNPs (12 total associations) with LC or COPD risk. Data from ENCODE and other public databases showed that SNPs with strong evidence may be located in presumptive functional regions.

Conclusions

Our study summarized comprehensive evidence showing that common mutations in CHRNA genes are strongly related to LC and COPD risk. The study also elucidated the vital function of CHRNA genes in genetic predispositions to human diseases.
Vascular normalization and immunotherapy: Spawning a virtuous cycle
Authors: Swamy Kumara
Published: October 2022

Anti-angiogenics, radiotherapy (especially stereotactic body radiotherapy, SBRT)/chemotherapy, and immunotherapy form a critical trimodal approach in modern cancer therapy. The normalization window, however short, is the beachhead for the strategic initiation of a decipherable disruption of cancer cells. This opening can be the opportunity for designing controlled stepwise cancer cell death (CCD) and immunological augmentation. The next step is to induce immunogenic cell death (ICD) through chemotherapy/radiotherapy concurrently with the facilitation of professional phagocytosis. Immunotherapy at this stage, when interstitial pressure decreases considerably, leads to the improved perfusion of oxygen with solutes and improved immune-friendly pH and is additionally expected to open up the tumor microenvironment (TME) for a “flood” of tumor-infiltrating lymphocytes. Furthermore, there would be enhanced interaction in “hot” nodules and the incorporation of immune reaction in “cold” nodules. Simultaneously, the added adjuvant-assisted neoantigen–immune cell interaction will likely set in a virtuous cycle of CCD induction followed by tumor cell-specific antigenic reaction boosting CCD, in turn promoting the normalization of the vasculature, completing the loop. There should be a conscious concern to protect the extracellular matrix (ECM), which will nurture the long-term immunological cross-talk to discourage dormancy, which is as essential as obtaining a complete response in imaging. The caveat is that the available therapies should be appropriately ranked during the start of the treatment since the initial administration is the most opportune period. A fast-paced development in the nanomedicine field is likely to assist in all the steps enumerated.
FGF1 protects FGFR1-overexpressing cancer cells against drugs targeting tubulin polymerization by activating AKT via two independent mechanisms
Authors: Szymczyk Jakub , Sochacka Martyna , Chudy Patryk , Opalinski Lukasz , Otlewski Jacek , Zakrzewska Malgorzata
Published: October 2022

Cancer drug resistance is a common, unpredictable phenomenon that develops in many types of tumors, resulting in the poor efficacy of current anticancer therapies. One of the most common, and yet the most complex causes of drug resistance is a mechanism related to dysregulation of tumor cell signaling. Abnormal signal transduction in a cancer cell is often stimulated by growth factors and their receptors, including fibroblast growth factors (FGFs) and FGF receptors (FGFRs). Here, we investigated the effect of FGF1 and FGFR1 activity on the action of drugs that disrupt tubulin polymerization (taltobulin, paclitaxel, vincristine) in FGFR1-positive cell lines, U2OS stably transfected with FGFR1 (U2OSR1) and DMS114 cells. We observed that U2OSR1 cells exhibited reduced sensitivity to the tubulin-targeting drugs, compared to U2OS cells expressing a negligible level of FGFRs. This effect was dependent on receptor activation, as inhibition of FGFR1 by a specific small-molecule inhibitor (PD173074) increased the cells’ sensitivity to these drugs. Expression of functional FGFR1 in U2OS cells resulted in increased AKT phosphorylation, with no change in total AKT level. U2OSR1 cells also exhibited an elevated MDR1 and blocking MDR1 activity with cyclosporin A increased the toxicity of paclitaxel and vincristine, but not taltobulin. Analysis of tubulin polymerization pattern using fluorescence microscopy revealed that FGF1 in U2OSR1 cells partially reverses the drug-altered phenotype in paclitaxel- and vincristine-treated cells, but not in taltobulin-treated cells. Furthermore, we showed that FGF1, through activation of FGFR1, reduces caspase 3/7 activity and PARP cleavage, preventing apoptosis induced by tubulin-targeting drugs. Next, using specific kinase inhibitors, we investigated which signaling pathways are responsible for the FGF1-mediated reduction of taltobulin cytotoxicity. We found that AKT kinase is a key factor in FGF1-induced cell protection against taltobulin in U2OSR1 and DMS114 cells. Interestingly, only direct inhibition of AKT or dual-inhibition of PI3K and mTOR abolished this effect for cells treated with taltobulin. This suggests that both canonical (PI3K-dependent) and alternative (PI3K-independent) AKT-activating pathways may regulate FGF1/FGFR1-driven cancer cell survival. Our findings may contribute to the development of more effective therapies and may facilitate the prevention of drug resistance in FGFR1-positive cancer cells.
Intravoxel incoherent motion to differentiate spinal metastasis: A pilot study
Authors: Zhang Enlong , Li Yuan , Xing Xiaoying , Qin Siyuan , Yuan Huishu , Lang Ning
Published: October 2022

Background

To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) to discriminate spinal metastasis from tuberculous spondylitis.

Methods

This study included 50 patients with spinal metastasis (32 lung cancer, 7 breast cancer, 11 renal cancer), and 20 with tuberculous spondylitis. The IVIM parameters, including the single-index model (apparent diffusion coefficient (ADC)-stand), double exponential model (ADCslow, ADCfast, and f), and the stretched-exponential model parameters (distributed diffusion coefficient (DDC) and α), were acquired. Receiver operating characteristic (ROC) and the area under the ROC curve (AUC) analysis was used to evaluate the diagnostic performance. Each parameter was substituted into a logistic regression model to determine the meaningful parameters, and the combined diagnostic performance was evaluated.

Results

The ADCfast and f showed significant differences between spinal metastasis and tuberculous spondylitis (all p < 0.05). The logistic regression model results showed that ADCfast and f were independent factors affecting the outcome (P < 0.05). The AUC values of ADCfast and f were 0.823 (95% confidence interval (CI): 0.719 to 0.927) and 0.876 (95%CI: 0.782 to 0.969), respectively. ADCfast combined with f showed the highest AUC value of 0.925 (95% CI: 0.858 to 0.992).

Conclusions

IVIM MR imaging might be helpful to differentiate spinal metastasis from tuberculous spondylitis, and provide guidance for clinical treatment.
Symptoms and experiences of frailty in lung cancer patients with chemotherapy: A mixed-method approach
Authors: Duan Liran , Cui Huixia , Zhang Wenlu , Wu Shan
Published: October 2022

Objective

The aim of this study was to explore the symptoms and experiences of frailty in lung cancer patients treated with chemotherapy.

Methods

Quantitative and qualitative research methods were implemented. A total of 302 patients aged > 18 years were recruited by convenience sampling method. Quantitative data were collected through the General Demographic Characteristics questionnaire, the Frailty Phenotype scale, the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Fourteen patients with a score of Frailty Phenotype scale ≥ 3 were drawn and their interviews were thematically analyzed.

Results

The mean Frailty Phenotype score was (1.63±1.35), suggesting that most of the patients were in pre-frailty conditions. A total of 64 (21.2%) patients were non-frail, 168 (55.6%) patients were pre-frail, 70 (23.2%) patients were frail. The mean CFS, HADS scores, and PSQI scores were (26.86±8.93), (15.42±9.73), and (6.18±4.39), respectively. The Number of chemotherapy times was positively associated with frailty. Anxiety fatigue, depression and poor sleep quality positively correlated with frailty. The qualitative research showed four themes. Theme 1: the most reported symptoms of frailty were physical symptoms and psychological symptoms. Physical symptoms included fatigue, low physical activity, weight loss and poor sleep quality. Psychological symptoms included anxiety, depression and low social activities. Theme 2: frailty was mainly related to lung cancer and chemotherapeutic drugs, which can cause decreased appetite, constipation and altered taste. Theme 3: patients used bad coping strategies to manage the symptoms of frailty. Theme 4: the social support of patients was weak, especially regarding emotional support.

Conclusion

The most frequent symptoms reported by lung cancer patients treated with chemotherapy were anxiety, fatigue, depression, low physical activity and poor sleep quality. Patients also complained of bad coping strategies and weak support. Medical staff should strengthen the management of frailty, aiming at improving the quality of life in lung cancer patients treated with chemotherapy.
Transfusion of stored autologous blood in patients with low-grade pseudomyxoma peritonei: A retrospective analysis of its safety and outcome
Authors: Gao Xiaoyun , Kou Liduo , Guan Hang , Tian Hua , Jia Junhui , Bai Yu , Bai Wei , Di Yanhui , Ma Ruiqing , Wang Xinhua
Published: October 2022

Background

Pseudomyxoma peritonei is a rare disease that presents as a malignant tumor on the peritoneal surface. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for this disease and frequently requires a red blood cell transfusion. However, due to the limited collection and supply of allogeneic blood, surgical treatment may be delayed due to inadequate preparation of allogeneic blood in the course of clinical treatment. This study aimed to evaluate the safety and efficacy of transfusion of stored autologous blood in patients with low-grade pseudomyxoma peritonei.

Methods

Pseudomyxoma peritonei patients who received cytoreductive surgery combined with heat-infused peritoneal chemotherapy were divided into two groups: transfusion of allogeneic blood and transfusion of stored autologous blood. A comparison of the differences in multiple factors between the two groups was performed, including tumor recurrence, survival time, hemoglobin and hematocrit levels, coagulation function (prothrombin time, activated partial thromboplastin time, and fibrinogen), total hospital stay duration, and incidence of serious adverse events after surgery.

Results

Propensity scores matching analysis yielded 34 patients with allogeneic blood transfusion and 34 patients with stored autologous blood transfusion. Comparison analysis did not show statistical differences in several factors, including age, tumor grade, tumor recurrence rate after surgery, etc., between the two groups. The cytoreductive degree was considered an independent risk factor for tumor recurrence. The pseudomyxoma peritonei patients in the autologous transfusion group had a higher 5-year survival rate and a longer survival time. Moreover, transfusion of stored autologous blood did not increase the rate of tumor recurrence, or the total hospital stay duration after surgery, the hemoglobin level and coagulation function were well stabilized within 24 h after surgery, and there was a low incidence of serious adverse events.

Conclusion

The clinical application of transfusion of stored autologous blood in pseudomyxoma peritonei patients is safe and effective.
Quantitative parameters of enhanced dual-energy computed tomography for differentiating lung cancers from benign lesions in solid pulmonary nodules
Authors: He Changjiu , Liu Jieke , Li Yong , Lin Libo , Qing Haomiao , Guo Ling , Hu Shibei , Zhou Peng
Published: October 2022

Objectives

This study aimed to investigate the ability of quantitative parameters of dual-energy computed tomography (DECT) and nodule size for differentiation between lung cancers and benign lesions in solid pulmonary nodules.

Materials and Methods

A total of 151 pathologically confirmed solid pulmonary nodules including 78 lung cancers and 73 benign lesions from 147 patients were consecutively and retrospectively enrolled who underwent dual-phase contrast-enhanced DECT. The following features were analyzed: diameter, volume, Lung CT Screening Reporting and Data System (Lung-RADS) categorization, and DECT-derived quantitative parameters including effective atomic number (Zeff), iodine concentration (IC), and normalized iodine concentration (NIC) in arterial and venous phases. Multivariable logistic regression analysis was used to build a combined model. The diagnostic performance was assessed by area under curve (AUC) of receiver operating characteristic curve, sensitivity, and specificity.

Results

The independent factors for differentiating lung cancers from benign solid pulmonary nodules included diameter, Lung-RADS categorization of diameter, volume, Zeff in arterial phase (Zeff_A), IC in arterial phase (IC_A), NIC in arterial phase (NIC_A), Zeff in venous phase (Zeff_V), IC in venous phase (IC_V), and NIC in venous phase (NIC_V) (all P < 0.05). The IC_V, NIC_V, and combined model consisting of diameter and NIC_V showed good diagnostic performance with AUCs of 0.891, 0.888, and 0.893, which were superior to the diameter, Lung-RADS categorization of diameter, volume, Zeff_A, and Zeff_V (all P < 0.001). The sensitivities of IC_V, NIC_V, and combined model were higher than those of IC_A and NIC_A (all P < 0.001). The combined model did not increase the AUCs compared with IC_V (P = 0.869) or NIC_V (P = 0.633).

Conclusion

The DECT-derived IC_V and NIC_V may be useful in differentiating lung cancers from benign lesions in solid pulmonary nodules.
The value of chest computed tomography in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients: A preliminary study
Authors: Long Kui , Zhou Hui , Li Yajuan , Liu Liang , Cai Jiahui
Published: October 2022

Introduction

Lung cancer can be masked by coexisting stable tuberculosis lesions, which may result in delayed lung cancer diagnosis and treatment. Information about pulmonary tuberculosis patients who are at high-risk of developing lung cancer is scarce. We aimed to examine the value of chest computed tomography (CT) in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients.

Methods

In this single-centered, retrospective, observational study, we enrolled 41 middle-aged and elderly patients with pulmonary tuberculosis who developed lung cancer in the same lobe from January 30, 2011 to December 30, 2020. Comparisons of the clinical and chest CT data were made with age-matched and sex-matched control groups of patients with stable pulmonary tuberculosis but no lung cancer diagnosis (n = 38).

Results

Seventeen patients in the lung cancer group (41%) were initially misdiagnosed. Compared to lesions in the control group, lesions in the lung cancer group were significantly more likely to demonstrate the following CT features: large size, vessel convergence, lobulation, spiculation, spinous protuberance, bronchial obstruction or stenosis, vacuolation, ground-glass opacification, heterogeneous or homogeneous enhancement, and gradual increase in size. Nodular enlargement showed the best diagnostic performance in the diagnosis of lung cancer in a lobe affected by tuberculosis (area under the receiver operating characteristic curve = 0.974; P <0.001; accuracy = 98.2%; sensitivity =94.7%; specificity = 100%).

Conclusion

Chest CT might play an important role in early diagnosis of lung cancer in a lobe affected by tuberculosis. Regular CT re-examination is necessary in continuous controls monitoring of patients with stable pulmonary tuberculosis. The study indicates necessity of prospective study in this field.