bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of favorable outcome and mortality after endovascular thrombectomy in young Chinese patients with large vascular occlusions
Authors: Li Zhiqiang , Wu Shuhui , Liang Fang , Tan Fengjiao , Li Ning , Bao Mengxin
Published: July 2023

Background

Endovascular thrombectomy (EVT) has evolved into the standard treatment for patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO). However, little information is available on the management of EVT in young patients with AIS-LVO in China. The purpose of this study was to assess the favorable outcomes and mortality rates after 90 days of EVT in young Chinese patients with AIS-LVO and their predictors.

Methods

This retrospective study included young Chinese patients aged 18–50 years with AIS-LVO. The primary efficacy endpoint was the modified Rankin scale (mRS) score at day 90, and the primary safety endpoint was mortality within 90 days. Using univariate and multivariate logistic regression analyses, the associations between clinical, imaging, and procedure variables and favorable (mRS 0–2) outcomes or mortality at 90 days were analyzed.

Results

A total of 113 patients were included in the study with a mean age of 43.1 ± 6.3 years. Symptomatic intracranial hemorrhage (sICH) occurred in 8 (7.1%) patients. Favorable functional outcomes (mRS 0–2) were recovered in 42.5% of patients at 3 months. After 90 days, the mortality rate was 32.3%. Multivariate analysis revealed that the increase in admission NIHSS score was associated with a lower probability of functional independence (aOR 1.08, 95% CI 1.02–1.15, p = 0.01 and aOR 1.01, 95% CI 1–1.01, p = 0.008, respectively) and a higher probability of death at 90 days (aOR 1.1, 95% CI 1.03–1.18, p = 0.007 and aOR 1.00, 95% CI 1–1.01, p = 0.021, respectively).

Conclusion

This study demonstrate that EVT provides higher rates of arterial recanalization, rather than better favorable outcomes and lower risk of death at 3 months in young Chinese patients with AIS-LVO. Increased NIHSS scores on admission may be associated with poor patient prognosis.
Towards personalized and optimized fitting of cochlear implants
Authors: Van Opstal A. John , Noordanus Elisabeth
Published: July 2023

A cochlear implant (CI) is a neurotechnological device that restores total sensorineural hearing loss. It contains a sophisticated speech processor that analyzes and transforms the acoustic input. It distributes its time-enveloped spectral content to the auditory nerve as electrical pulsed stimulation trains of selected frequency channels on a multi-contact electrode that is surgically inserted in the cochlear duct. This remarkable brain interface enables the deaf to regain hearing and understand speech. However, tuning of the large (>50) number of parameters of the speech processor, so-called “device fitting,” is a tedious and complex process, which is mainly carried out in the clinic through ‘one-size-fits-all’ procedures. Current fitting typically relies on limited and often subjective data that must be collected in limited time. Despite the success of the CI as a hearing-restoration device, variability in speech-recognition scores among users is still very large, and mostly unexplained. The major factors that underly this variability incorporate three levels: (i) variability in auditory-systemmalfunctionof CI-users, (ii) variability in theselectivityof electrode-to-auditory nerve (EL-AN) activation, and (iii) lack of objectiveperceptualmeasures to optimize the fitting. We argue that variability in speech recognition can only be alleviated by using objective patient-specific data for an individualized fitting procedure, which incorporates knowledge from all three levels. In this paper, we propose a series of experiments, aimed at collecting a large amount of objective (i.e., quantitative, reproducible, and reliable) data that characterize the three processing levels of the user’s auditory system. Machine-learning algorithms that process these data will eventually enable the clinician to derive reliable and personalized characteristics of the user’s auditory system, the quality of EL-AN signal transfer, and predictions of the perceptual effects of changes in the current fitting.
Investigating the influence of functional electrical stimulation on motor imagery related μ-rhythm suppression
Authors: Yakovlev Lev , Syrov Nikolay , Kaplan Alexander
Published: July 2023

Background

Motor Imagery (MI) is a well-known cognitive technique that utilizes the same neural circuits as voluntary movements. Therefore, MI practice is widely used in sport training and post-stroke rehabilitation. The suppression of the μ-rhythm in electroencephalogram (EEG) is a conventional marker of sensorimotor cortical activation during motor imagery. However, the role of somatosensory afferentation in mental imagery processes is not yet clear. In this study, we investigated the impact of functional electrical stimulation (FES) on μ-rhythm suppression during motor imagery.

Methods

Thirteen healthy experienced participants were asked to imagine their right hand grasping, while a 30-channel EEG was recorded. FES was used to influence sensorimotor activation during motor imagery of the same hand.

Results

We evaluated cortical activation by estimating the μ-rhythm suppression index, which was assessed in three experimental conditions: MI, MI + FES, and FES. Our findings shows that motor imagery enhanced by FES leads to a more prominent μ-rhythm suppression. Obtained results suggest a direct effect of peripheral electrical stimulation on cortical activation, especially when combined with motor imagery.

Conclusion

This research sheds light on the potential benefits of integrating FES into motor imagery-based interventions to enhance cortical activation and holds promise for applications in neurorehabilitation.
Survey on the research direction of EEG-based signal processing
Authors: Sun Congzhong , Mou Chaozhou
Published: July 2023

Electroencephalography (EEG) is increasingly important in Brain-Computer Interface (BCI) systems due to its portability and simplicity. In this paper, we provide a comprehensive review of research on EEG signal processing techniques since 2021, with a focus on preprocessing, feature extraction, and classification methods. We analyzed 61 research articles retrieved from academic search engines, including CNKI, PubMed, Nature, IEEE Xplore, and Science Direct. For preprocessing, we focus on innovatively proposed preprocessing methods, channel selection, and data augmentation. Data augmentation is classified into conventional methods (sliding windows, segmentation and recombination, and noise injection) and deep learning methods [Generative Adversarial Networks (GAN) and Variation AutoEncoder (VAE)]. We also pay attention to the application of deep learning, and multi-method fusion approaches, including both conventional algorithm fusion and fusion between conventional algorithms and deep learning. Our analysis identifies 35 (57.4%), 18 (29.5%), and 37 (60.7%) studies in the directions of preprocessing, feature extraction, and classification, respectively. We find that preprocessing methods have become widely used in EEG classification (96.7% of reviewed papers) and comparative experiments have been conducted in some studies to validate preprocessing. We also discussed the adoption of channel selection and data augmentation and concluded several mentionable matters about data augmentation. Furthermore, deep learning methods have shown great promise in EEG classification, with Convolutional Neural Networks (CNNs) being the main structure of deep neural networks (92.3% of deep learning papers). We summarize and analyze several innovative neural networks, including CNNs and multi-structure fusion. However, we also identified several problems and limitations of current deep learning techniques in EEG classification, including inappropriate input, low cross-subject accuracy, unbalanced between parameters and time costs, and a lack of interpretability. Finally, we highlight the emerging trend of multi-method fusion approaches (49.2% of reviewed papers) and analyze the data and some examples. We also provide insights into some challenges of multi-method fusion. Our review lays a foundation for future studies to improve EEG classification performance.
Multimodal brain image fusion based on error texture elimination and salient feature detection
Authors: Li Xilai , Li Xiaosong
Published: July 2023

As an important clinically oriented information fusion technology, multimodal medical image fusion integrates useful information from different modal images into a comprehensive fused image. Nevertheless, existing methods routinely consider only energy information when fusing low-frequency or base layers, ignoring the fact that useful texture information may exist in pixels with lower energy values. Thus, erroneous textures may be introduced into the fusion results. To resolve this problem, we propose a novel multimodal brain image fusion algorithm based on error texture removal. A two-layer decomposition scheme is first implemented to generate the high- and low-frequency subbands. We propose a salient feature detection operator based on gradient difference and entropy. The proposed operator integrates the gradient difference and amount of information in the high-frequency subbands to effectively identify clearly detailed information. Subsequently, we detect the energy information of the low-frequency subband by utilizing the local phase feature of each pixel as the intensity measurement and using a random walk algorithm to detect the energy information. Finally, we propose a rolling guidance filtering iterative least-squares model to reconstruct the texture information in the low-frequency components. Through extensive experiments, we successfully demonstrate that the proposed algorithm outperforms some state-of-the-art methods. Our source code is publicly available at https://github.com/ixilai/ETEM.
Chaotic medical image encryption method using attention mechanism fusion ResNet model
Authors: Li Xiaowu , Peng Huiling
Published: July 2023

Introduction

With the rapid advancement of artificial intelligence (AI) technology, the protection of patient medical image privacy and security has become a critical concern in current research on image privacy protection. However, traditional methods for encrypting medical images have faced criticism due to their limited flexibility and inadequate security. To overcome these limitations, this study proposes a novel chaotic medical image encryption method, called AT-ResNet-CM, which incorporates the attention mechanism fused with the ResNet model.

Methods

The proposed method utilizes the ResNet model as the underlying network for constructing the encryption and decryption framework. The ResNet's residual structure and jump connections are employed to effectively extract profound information from medical images and expedite the model's convergence. To enhance security, the output of the ResNet model is encrypted using a logistic chaotic system, introducing randomness and complexity to the encryption process. Additionally, an attention mechanism is introduced to enhance the model's response to the region of interest within the medical image, thereby strengthening the security of the encrypted network.

Results

Experimental simulations and analyses were conducted to evaluate the performance of the proposed approach. The results demonstrate that the proposed method outperforms alternative models in terms of encryption effectiveness, as indicated by a horizontal correlation coefficient of 0.0021 and information entropy of 0.9887. Furthermore, the incorporation of the attention mechanism significantly improves the encryption performance, reducing the horizontal correlation coefficient to 0.0010 and increasing the information entropy to 0.9965. These findings validate the efficacy of the proposed method for medical image encryption tasks, as it offers enhanced security and flexibility compared to existing approaches.

Discussion

In conclusion, the AT-ResNet-CM method presents a promising solution to address the limitations of traditional encryption techniques in protecting patient medical images. By leveraging the attention mechanism fused with the ResNet model, the method achieves improved security and flexibility. The experimental results substantiate the superiority of the proposed method in terms of encryption effectiveness, horizontal correlation coefficient, and information entropy. The proposed method not only addresses the shortcomings of traditional methods but also provides a more robust and reliable approach for safeguarding patient medical image privacy and security.
Socioeconomic status may affect association of vegetable intake with risk of ischemic cardio-cerebral vascular disease: a Mendelian randomization study
Authors: Huang Jiutian , He Ziyi , Xu Minhui , Du Jianing , Zhao Yun-tao
Published: July 2023

Background

Previous studies found that increasing vegetable intake benefits are reduced after adjustment for socioeconomic factors. Using genetic variation as an instrumental variable for vegetable intake and socioeconomic status, we investigated the relationship between vegetable intake and ischemic cardio-cerebral vascular diseases and focused on whether socioeconomic status was a possible confounder.

Methods

From three independent genome-wide association studies, we extracted instrumental variables reflecting raw and cooked vegetable intake, which were used to perform Mendelian randomization analysis. To evaluate the effects of socioeconomic factors on vegetable intake, univariate and multivariate Mendelian randomization analyses were performed using single nucleotide polymorphisms representing education attainment and household income reported in the literature. We also performed outlier assessment and a series of sensitivity analyses to confirm the results.

Results

Genetically predicted raw and cooked vegetable intake were not associated with any ischemic cardio-cerebral vascular diseases and lipid components after Bonferroni correction. Univariate Mendelian randomized analysis revealed that raw vegetable intake was positively correlated with education attainment (β = 0.04, p = 0.029) and household income (β = 0.07, p < 0.001). Multivariate Mendelian randomized model showed a positive correlation between household income and raw vegetable intake (β = 0.06, p = 0.004). Socioeconomic status was closely associated with eating habits and lifestyle related to the risk of cardiovascular diseases.

Conclusion

Genetically determined raw and cooked vegetable intake was not associated with significant benefits in terms of ischemic cardio-cerebral vascular diseases while genetically determined socioeconomic status may have an impact on vegetable intake. Socioeconomic status, which was closely associated with other eating habits and lifestyle, may affect the association between vegetable intake and ischemic cardio-cerebral vascular diseases.
New vegetable varieties of Brassica rapa and Brassica napus with modified glucosinolate content obtained by mass selection approach
Authors: Coves S. , Soengas P. , Velasco P. , Fernández J. C. , Cartea M. E.
Published: July 2023

Background

Glucosinolates (GSLs) constitute a characteristic group of secondary metabolites present in the Brassica genus. These compounds confer resistance to pests and diseases. Moreover, they show allelopathic and anticarcinogenic effects. All those effects are dependent on the chemical structure of the GSL. The modification of the content of specific GSLs would allow obtaining varieties with enhanced resistance and/or improved health benefits. Moreover, the attainment of varieties with the same genetic background but with divergent GSLs concentration will prompt the undertaking of studies on their biological effects.

Objective and Methods

The objective of this study was to evaluate the efficacy of two divergent mass selection programs to modify GSL content in the leaves of two Brassica species: nabicol (Brassica napus L.), selected by glucobrassicanapin (GBN), and nabiza (Brassica rapa L.), selected by gluconapin (GNA) through several selection cycles using cromatographic analysis.

Results

The response to selection fitted a linear regression model with no signs of variability depletion for GSL modification in either direction, but with higher efficiency in reducing the selected GSL than in the increasing. The selection was also effective in other parts of the plant, suggesting that there is a GSL translocation in the plant or a modification in their synthesis pathway that is not-organ specific. There was an indirect response of selection in other GSL; thus this information should be considered when designing breeding programs. Finally, populations obtained by selection have the same agronomic performance or even better than the original population.

Conclusion

Therefore, mass selection seems to be a good method to modify the content of specific GSL in Brassica crops.
Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis
Authors: Liang Wenli , Pan Yongmei , Liu Aixue , He Yan , Zhu Yan
Published: July 2023

Background

Statin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC.

Materials and Methods

Cohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed.

Results

Seventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I2 = 38%). Besides, for the outcome of OS and PFS, subgroup analyses showed similar results in patients with surgical and non-surgical anticancer treatments, and in patients with stage I-III and stage IV RCC (p values for subgroup difference all > 0.05).

Conclusions

Statin use may be associated with improved survival outcomes in patients with RCC. Although prospective clinical studies should be considered to validate these results, these findings suggest that statins may be potential adjuvant therapy for patients with RCC.
A pyroptosis-related gene signature that predicts immune infiltration and prognosis in colon cancer
Authors: Wu Mingjian , Hao Shuai , Wang Xiaoxiang , Su Shuguang , Du Siyuan , Zhou Sitong , Yang Ronghua , Du Hanpeng
Published: July 2023

Background

Colon cancer (CC) is a highly heterogeneous malignancy associated with high morbidity and mortality. Pyroptosis is a type of programmed cell death characterized by an inflammatory response that can affect the tumor immune microenvironment and has potential prognostic and therapeutic value. The aim of this study was to evaluate the association between pyroptosis-related gene (PRG) expression and CC.

Methods

Based on the expression profiles of PRGs, we classified CC samples from The Cancer Gene Atlas and Gene Expression Omnibus databases into different clusters by unsupervised clustering analysis. The best prognostic signature was screened and established using least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. Subsequently, a nomogram was established based on multivariate COX regression analysis. Next, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential molecular mechanisms between the high- and low-risk groups and to explore the differences in clinicopathological characteristics, gene mutation characteristics, abundance of infiltrating immune cells, and immune microenvironment between the two groups. We also evaluated the association between common immune checkpoints and drug sensitivity using risk scores. The immunohistochemistry staining was utilized to confirm the expression of the selected genes in the prognostic model in CC.

Results

The 1163 CC samples were divided into two clusters (clusters A and B) based on the expression profiles of the 33 PRGs. Genes with prognostic value were screened from the DEGs between the two clusters, and an eight PRGs prognostic model was constructed. GSEA and GSVA of the high- and low-risk groups revealed that they were mainly enriched in inflammatory response-related pathways. Compared to those in the low-risk group, patients in the high-risk group had worse overall survival, an immunosuppressive microenvironment, and worse sensitivity to immunotherapy and drug treatment.

Conclusion

Our findings provide a foundation for future research targeting pyroptosis and new insights into prognosis and immunotherapy from the perspective of pyroptosis in CC.
Prognostic value of neutrophil extracellular trap signature in clear cell renal cell carcinoma
Authors: Li Rong , Jiang Xuewen , Wang Pin , Liu Xiaoyan
Published: July 2023

Introduction

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.

Methods

Clinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.

Results

A total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.

Conclusions

The NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.
Novel compound heterozygous variants (c.971delA/c.542C > T) in SLC1A4 causes spastic tetraplegia, thin corpus callosum, and progressive microcephaly: a case report and mutational analysis
Authors: Mohamed Feda E. , Ghattas Mohammad A. , Almansoori Taleb M. , Tabouni Mohammed , Baydoun Ibrahim , Kizhakkedath Praseetha , John Anne , Alblooshi Hiba , Shaukat Qudsia , Al-Jasmi Fatma
Published: July 2023

Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) are linked to SLC1A4 genetic variants since the first reported case in 2015. SLC1A4 encodes for the neutral amino acid transporter ASCT1 which is involved in the transportation of serine between astrocytes and neurons. Although most of the reported cases are of Ashkenazi Jewish ancestry, SPATCCM has also been reported in Irish, Italian, Czech, Palestinian, and Pakistani ethnicities. Herein, we report two Pakistani male siblings from a non-consanguineous marriage presented with global developmental delay associated with spastic quadriplegia, microcephaly, and infantile spasm. Since infancy, both siblings suffered from microcephaly with brain MRI demonstrating generalized atrophy of the frontal, temporal, and parietal lobes with a prominence of the subarachnoid spaces, widening of the Sylvian fissures, and enlargement of the ventricular system not compatible with the chronological age of both patients associated with thinning of the corpus callosum. Whole-exome sequencing of both affected brothers revealed novel compound heterozygous variants in the SLC1A4 gene (NM_003038) segregating from their parents. The maternal c.971delA (p.N324Tfs*29) deletion variant disturbs the transcript reading frame leading to the generation of a premature stop codon and its subsequent degradation by nonsense-mediated mRNA decay as detected through expression analysis. The paternal c.542C > T (p.S181F) missense variant was predicted deleterious via multiple in silico prediction tools as the amino acid substitution is speculated to affect the overall ASCT1 structural confirmation due to the loss of an H-bond at the core of the protein at this position which might affect its function as concluded from the simulation analysis. The presented cases expand the genetic and clinical spectrum of ASCT1 deficiency and support the importance of including SLC1A4 gene screening in infants with unexplained global neurodevelopmental delay regardless of ethnicity.
Using PIM-Taiwan, PRISCUS, and Beers criteria to assess potentially inappropriate medication use among older adults with 90-day rehospitalization: a population-based study in Taiwan
Authors: Hsieh Kun-Pin , Huang Ru-Yu , Yang Yi-Hsin , Ho Pei-Shan , Chen Kuang-Peng , Tung Chun-Liong , Chu Ya-Lan , Tsai Jui-Hsiu
Published: July 2023

Background: Multimorbidity and polypharmacy increase the risk of hospitalization in older adults receiving potentially inappropriate medication (PIM). The current study compared the ability of PIM-Taiwan, PRISCUS, and Beers criteria to predict 90-day rehospitalization in older patients with and without PIM.

Methods: The retrospective cohort study used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about prescribed medication for adults aged ≥65 years hospitalized between 2001 and 2018. We analyzed the association of PIM with 90-day rehospitalization using logistic regression.

Results: The study cohort included 206,058 older adults (mean age: 72.5 years). In the analysis, 133,201 (64.6%), 97,790 (47.5%), and 147,450 (71.6%), were identified as having PIM exposure in PIM-Taiwan, PRICUS, and Beers criteria, respectively. PIM-Taiwan criteria found exposure to PIM affecting the cardiovascular (adjusted OR [aOR] 1.37, 95% confidence interval [CI] = 1.32–1.41), gastrointestinal (aOR 1.26, 95% CI = 1.23–1.30), central nervous (aOR 1.11, 95% CI = 1.08–1.14), and respiratory (aOR 1.16, 95% CI = 1.12–1.20) systems significantly increased the risk of 90-day rehospitalization, after adjustment for covariates. In PRISCUS criteria, exposure to PIM affecting the respiratory (aOR 1.48, 95% CI = 1.41–1.56), central nervous (aOR 1.12, 95% CI = 1.09–1.15), and cardiovascular (aOR 1.20, 95% CI = 1.16–1.24) systems significantly increased the risk. In Beers criteria, exposure to PIM affecting the cardiovascular (aOR 1.37, 95% CI = 1.32–1.41), gastrointestinal (aOR 1.38, 95% CI = 1.35–1.42), central nervous (aOR 1.18, 95% CI = 1.15–1.21), endocrine (aOR 1.10, 95% CI = 1.06–1.15), and respiratory (aOR 1.09, 95% CI = 1.04–1.13) systems significantly increased the risk. Patients with 90-day rehospitalization had higher rates of the potentially harmful drug-drug interaction (DDI) pairs of serotonin syndrome (n = 19; 48.8%), QT prolongation (n = 4; 30.8%), extrapyramidal symptoms (EPS) (n = 102; 24.5%), and hypokalemia (n = 275; 20.1%).

Conclusion: Beers criteria was more efficient in predicting 90-day rehospitalization among older adults experiencing PIM in Taiwan than either PIM-Taiwan or PRISCUS. The risk of 90-day rehospitalization was associated with the potentially harmful DDI classes of serotonin syndrome, QT prolongation, EPS, and hypokalemia.
Development and validation of pharmaceutical care barriers scale in Chinese hospitals: a cross-sectional survey
Authors: Chen Liangjiang , Yang Nan , Huang Yuankai , Xi Xiaoyu
Published: July 2023

Introduction: Chinese hospitals still face various barriers to implementing pharmaceutical care. The quantitative instrument for measuring these barriers in China is scarce. This study aims to develop and validate a scale for measuring barriers to providing pharmaceutical care in Chinese hospitals from the perspective of clinical pharmacists.

Methods: The scale was developed based on existing literature and qualitative interviews with 20 experts. The scale was included in a small-range pilot survey and then administered to a validation survey in 31 provinces in China. Exploratory factor analysis was used to identify the structure of the scale. Confirmatory factor analysis was applied to verify the structure of the scale and to validate the scale’s convergent and discriminative validity. Known-group validity was also examined. Cronbach’s alpha examined the internal consistency reliability of the scale.

Results: 292 scales were completed and returned for a response rate of 85.6% in the pilot study. Exploratory factor analysis of the scale suggested a five-factor solution (Cognition and attitude, Knowledge and skills, Objective conditions, External cooperation, and Support from managers) accounting for 66.03% of the total variance. 443 scales were sent out in the validation study, with a response rate of 81.0%. Confirmatory factor analysis demonstrated a good fit of the structural model for pharmaceutical care barriers. It showed the scale’s good convergent and discriminative validity (The average variance extracted >0.5 and composite reliability >0.7). The scale could also identify the differences in total score among the clinical pharmacists from different hospital grades (p < 0.05). Cronbach’s alpha is between 0.658 and 0.896, indicating good internal consistency.

Conclusion: From the perspective of clinical pharmacists, this study has developed a scale to assess obstacles to pharmaceutical care. The scale comprehensively encompasses barriers to clinical pharmacists’ cognitive and ability-related aspects, hindrances encountered in collaborating with other health professionals and patients, and barriers to the working environment. The reliability and validity have been established through verification.
Reconstructing the value puzzle in health technology assessment: a pragmatic review to determine which modelling methods can account for additional value elements
Authors: Muir Jeffrey M. , Radhakrishnan Amruta , Freitag Andreas , Ozer Stillman Ipek , Sarri Grammati
Published: July 2023

Health technology assessment (HTA) has traditionally relied on cost-effectiveness analysis (CEA) as a cornerstone of evaluation of new therapies, assessing the clinical validity and utility, the efficacy, and the cost-effectiveness of new interventions. The current format of cost-effectiveness analysis, however, does not allow for inclusion of more holistic aspects of health and, therefore, value elements for new technologies such as the impact on patients and society beyond its pure clinical and economic value. This study aimed to review the recent modelling attempts to expand the traditional cost-effectiveness analysis approach by incorporating additional elements of value in health technology assessment. A pragmatic literature review was conducted for articles published between 2012 and 2022 reporting cost-effectiveness analysis including value aspects beyond the clinical and cost-effectiveness estimates; searches identified 13 articles that were eligible for inclusion. These expanded modelling approaches mainly focused on integrating the impact of societal values and health equity in cost-effectiveness analysis, both of which were championed as important aspects of health technology assessment that should be incorporated into future technology assessments. The reviewed cost-effectiveness analysis methods included modification of the current cost-effectiveness analysis methodology (distributional cost-effectiveness analysis, augmented cost-effectiveness analysis, extended cost-effectiveness analysis) or the use of multi-criteria decision analysis. Of these approaches, augmented cost-effectiveness analysis appears to have the most potential by expanding traditional aspects of value, as it uses techniques already familiar to health technology assessment agencies but also allows space for incorporation of qualitative aspects of a product’s value. This review showcases that methods to unravel additional value elements for technology assessment exist, therefore, patient access to promising technologies can be improved by moving the discussion from “if” to “how” additional value elements can inform decision-making.
Should oncologists trust cannabinoids?
Authors: Creanga-Murariu Ioana , Filipiuc Leontina Elena , Cuciureanu Magda , Tamba Bogdan-Ionel , Alexa-Stratulat Teodora
Published: July 2023

Cannabis enjoyed a “golden age” as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.
PepFect14 mediates the delivery of mRNA into human primary keratinocytes and in vivo
Authors: Periyasamy Kapilraj , Maloverjan Maria , Biswas Abhijit , Remm Anu , Pook Martin , Rebane Ana , Pooga Margus
Published: July 2023

mRNA-based vaccines and candidate therapeutics have great potential in various medical fields. For the delivery of mRNA into target cells and tissues, lipid formulations are often employed. However, this approach could cause the activation of immune responses, making it unsuitable for the treatment of inflammatory conditions. Therefore, alternative delivery systems are highly demanded. In this study, we evaluated the transport efficiency and characteristics of cell-penetrating peptide PepFect14 (PF14) and mRNA nanoparticles in the presence of different additives. Our results show that all PF14-mRNA formulations entered cultured cells, while calcium chloride enhanced the transport and production of the encoded protein in HeLa and HaCaT cell lines, and polysorbate 80 did so in primary human keratinocytes. All formulations had similar physical properties and did not remarkably affect cell viability. By selectively blocking endocytosis pathways, we show that PF14-mRNA nanoparticles primarily entered HeLa cells via macropinocytosis and HaCaT cells via both macropinocytosis and clathrin-mediated endocytosis, while none of the blockers significantly affected the delivery into primary keratinocytes. Finally, subcutaneous injection of PF14-mRNA nanoparticles before inducing mouse irritant contact dermatitis resulted in the expression of a reporter protein without provoking harmful immune responses in the skin. Together, our findings suggest that PF14-mRNA nanoparticles have the potential for developing mRNA-based therapeutics for treating inflammatory skin conditions.
Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice
Authors: Wu Fanchang , Huang Mingjun , Zuo Xue , Xie Ruiye , Liu Jinman , Ke Junyu , Li Weirong , Wang Qi , Liang Yong
Published: July 2023

Alzheimer’s disease (AD) poses a significant threat to the global elderly population. Traditional Chinese medicine (TCM) has been widely utilized in the treatment of AD. Osthole, a bioactive ingredient classified as an “emperor” in many TCM formulas, has been demonstrated to effectively alleviate AD symptoms. However, its low bioavailability in the brain has limited its clinical application. This study aimed to increase the intracerebral bioavailability of osthole by using borneol as a “courier,” based on the classical “Emperor–Minister–Assistant–Courier” model, and to investigate the enhanced pharmacological performance of osthole on AD. Results indicated that a suitable in situ thermosensitive gel matrix for intranasal administration mixed with osthole and borneol consists of P407 at 20%, P188 at 7%, and PEG300 at 6%. The concentration of osthole in the cerebrospinal fluid increased almost tenfold after intranasal administration of osthole/borneol compared to oral administration. Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression, thereby expediting the nose-to-brain route and guiding osthole as “emperor” to its target in the brain. Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio, improving T-SOD and catalase expression, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice compared to osthole alone. Overall, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol and provided a wider application of TCM for AD treatment with higher intracerebral bioavailability.
HDL functionality is dependent on hepatocyte stress defense factors Nrf1 and Nrf2
Authors: Trites Michael J. , Stebbings Brynne M. , Aoki Hiroyuki , Phanse Sadhna , Akl May G. , Li Lei , Babu Mohan , Widenmaier Scott B.
Published: July 2023

High density lipoproteins (HDL) promote homeostasis and counteract stressful tissue damage that underlie cardiovascular and other diseases by mediating reverse cholesterol transport, reducing inflammation, and abrogating oxidative damage. However, metabolically stressful conditions associated with atherosclerosis can impair these effects. Hepatocytes play a major role in the genesis and maturation of circulating HDL, and liver stress elicits marked regulatory changes to circulating HDL abundance and composition, which affect its functionality. The mechanisms linking liver stress to HDL function are incompletely understood. In this study, we sought to determine whether stress defending transcription factors nuclear factor erythroid 2 related factor-1 (Nrf1) and −2 (Nrf2) promote hepatocyte production of functional HDL. Using genetically engineered mice briefly fed a mild metabolically stressful diet, we investigated the effect of hepatocyte-specific deletion of Nrf1, Nrf2, or both on circulating HDL cholesterol, protein composition, and function. Combined deletion, but not single gene deletion, reduced HDL cholesterol and apolipoprotein A1 levels as well as the capacity of HDL to accept cholesterol undergoing efflux from cultured macrophages and to counteract tumor necrosis factor α-induced inflammatory effect on cultured endothelial cells. This coincided with substantial alteration to the HDL proteome, which correlated with liver gene expression profiles of corresponding proteins. Thus, our findings show complementary actions by hepatocyte Nrf1 and Nrf2 play a role in shaping HDL abundance and composition to promote production of functionally viable HDL. Consequently, our study illuminates the possibility that enhancing stress defense programming in the liver may improve atheroprotective and perhaps other health promoting actions of HDL.
The combined effects of napping and self-selected motivation music during warming up on cognitive and physical performance of karate athletes
Authors: Bentouati Emna , Romdhani Mohamed , Abid Rihab , Khemila Syrine , Garbarino Sergio , Souissi Nizar
Published: July 2023

Introduction: It has been established that napping or listening to motivational music during warm-up is an effective strategy to enhance cognitive and physical performances. However, which could provide better enhancement warrants further investigation. This study aimed to examine the effect of a 30-min nap opportunity (N30), a warm-up with self-selected motivational music (WUMM), and the combination of N30 with WUMM (WUMM + N30) on cognitive and physical performances in karate athletes.

Method: In a randomized order, 14 national-level male karate athletes performed four experimental sessions: control, N30, WUMM, and WUMM + N30. Simple (SRT) and choice (CRT) reaction times, selective attention, subjective sleepiness (ESS), mood state (POMS), countermovement jump (CMJ), and karate agility test (KAT) were evaluated before and after an all-out exhaustive task [i.e., the Karate Specific Test (KST)]. Ratings of perceived exertion (RPE) were measured immediately after the KST.

Results: Compared to the control, all interventions improved cognitive outcomes, mood, and sleepiness. No effects on physical performances (CMJ and KAT) were found after N30. Compared to N30, WUMM + N30 improved SRT pre- and post-exercise (pre: p < 0.05, d = 0.72; post: p < 0.001, d = 0.14), CRT (pre: p < 0.001, d = 0.07; post: p < 0.001, d = 0.10), attention (pre: p < 0.05, d = 0.06; post: p < 0.01, d = 0.06), mood (pre: p < 0.001, d = 2.53; post: p < 0.001, d = 0.23), and decreased ESS scores (pre: p < 0.01, d = 1.41; post: p < 0.05, d = 1.18). However, there was no significant difference between WUMM and N30. KST performance was not affected by the experimental conditions. However, the KST-induced performance deficit in CMJ and KAT was smaller following WUMM + N30 compared to WUMM and N30. RPE scores were lower following WUMM + N30 and WUMM.

Conclusion: These findings suggest that a combination of listening to self-selected motivational music during warm-up with a 30-min nap could be an effective strategy to enhance cognitive and physical performance decline caused by fatigue induced by exercise.
Interplant carbon and nitrogen transfers mediated by common arbuscular mycorrhizal networks: beneficial pathways for system functionality
Authors: Luo Xie , Liu Yining , Li Siyue , He Xinhua
Published: July 2023

Arbuscular mycorrhizal fungi (AMF) are ubiquitous in soil and form nutritional symbioses with ~80% of vascular plant species, which significantly impact global carbon (C) and nitrogen (N) biogeochemical cycles. Roots of plant individuals are interconnected by AMF hyphae to form common AM networks (CAMNs), which provide pathways for the transfer of C and N from one plant to another, promoting plant coexistence and biodiversity. Despite that stable isotope methodologies (13C, 14C and 15N tracer techniques) have demonstrated CAMNs are an important pathway for the translocation of both C and N, the functioning of CAMNs in ecosystem C and N dynamics remains equivocal. This review systematically synthesizes both laboratory and field evidence in interplant C and N transfer through CAMNs generated through stable isotope methodologies and highlights perspectives on the system functionality of CAMNs with implications for plant coexistence, species diversity and community stability. One-way transfers from donor to recipient plants of 0.02-41% C and 0.04-80% N of recipient C and N have been observed, with the reverse fluxes generally less than 15% of donor C and N. Interplant C and N transfers have practical implications for plant performance, coexistence and biodiversity in both resource-limited and resource-unlimited habitats. Resource competition among coexisting individuals of the same or different species is undoubtedly modified by such C and N transfers. Studying interplant variability in these transfers with 13C and 15N tracer application and natural abundance measurements could address the eco physiological significance of such CAMNs in sustainable agricultural and natural ecosystems.
A group III patatin-like phospholipase gene pPLAIIIδ regulates lignin biosynthesis and influences the rate of seed germination in Arabidopsis thaliana
Authors: Simiyu David Charles , Jang Jin Hoon , Lee Ok Ran
Published: July 2023

The lignification of plant secondary walls is an important process that provides plants with mechanical support. However, the presence of lignin in the secondary walls affects the readily availability of cellulose required in various industries, including the biofuel, paper, and textile industries. Thus, plants with less lignin are ideal for usage in such industries. Molecular studies have identified genes that regulate plant lignification, including group III plant-specific patatin-related phospholipase genes. Recent studies have reported decreased lignin content when pPLAIIIα, pPLAIIIγ (from Arabidopsis thaliana), and pPLAIIIβ (from Panax ginseng) were overexpressed in Arabidopsis. However, the role played by a closely related gene pPLAIIIδ in lignin biosynthesis has not yet been reported. In this study, we found that overexpression of the pPLAIIIδ significantly reduced the lignin content in secondary cell walls, whereas the silencing of the gene increased secondary walls lignification. Transcript level analysis showed that the key structural and regulatory genes involved in the lignin biosynthesis pathway decreased in overexpression, and increased in plants with silenced pPLAIIIδ. Further analysis revealed that pPLAIIIδ played an influential role in several physiological processes including seed germination, and chlorophyll accumulation. Moreover, the gene also influenced the size of plants and plant organs, including leaves, seeds, and root hairs. Generally, our study provides important insights toward the use of genetic engineering for lignin reduction in plants and provides information about the agronomical and physiological suitability of pPLAIIIδ transgenic plants for utilization in biomass processing industries.