bluuebunny/crossref_metadata_2025 huggingface dataset:
Children with Cerebral Palsy can imagine actions like their normally developed peers
Authors: Galli Jessica , Garofalo Gioacchino , Brunetti Sara , Loi Erika , Portesi Michela , Pelizzari Giovanni , Rossi Andrea , Fazzi Elisa , Buccino Giovanni
Published: September 2022

The present study aimed at assessing whether children with Cerebral Palsy (CP) can imagine object directed actions similarly to their normally developed peers. We asked children with CP (n = 12) and paired healthy controls (n = 12) to imagine in first person perspective eight daily actions, after observing them through videoclips presented on a computer screen. During motor imagery (MI) children were interrupted at a specific timepoint (e.g., at 2.5 s) from the start. Two frames extracted from the videoclips were then presented on the screen. One of the two depicted the correct timepoint at which the imagined action was interrupted, while the other represented an earlier or later timepoint. Children had to respond by pressing the key associated to the correct frame. Children also underwent VMIQ-2 questionnaire. Both groups performed similarly in the questionnaire and in the requested task, where they showed the same error rate. Errors mainly concerned the later frame, suggesting a similar strategy to solve the task in the two groups. The results support the view that children with CP can imagine actions similarly to their normally developed peers. This encourages the use of MI as a rehabilitative tool in children with motor impairment.
A functional magnetic resonance imaging examination of audiovisual observation of a point-light string quartet using intersubject correlation and physical feature analysis
Authors: Lillywhite Amanda , Nijhof Dewy , Glowinski Donald , Giordano Bruno L. , Camurri Antonio , Cross Ian , Pollick Frank E.
Published: September 2022

We use functional Magnetic Resonance Imaging (fMRI) to explore synchronized neural responses between observers of audiovisual presentation of a string quartet performance during free viewing. Audio presentation was accompanied by visual presentation of the string quartet as stick figures observed from a static viewpoint. Brain data from 18 musical novices were obtained during audiovisual presentation of a 116 s performance of the allegro of String Quartet, No. 14 in D minor by Schubert played by the ‘Quartetto di Cremona.’ These data were analyzed using intersubject correlation (ISC). Results showed extensive ISC in auditory and visual areas as well as parietal cortex, frontal cortex and subcortical areas including the medial geniculate and basal ganglia (putamen). These results from a single fixed viewpoint of multiple musicians are greater than previous reports of ISC from unstructured group activity but are broadly consistent with related research that used ISC to explore listening to music or watching solo dance. A feature analysis examining the relationship between brain activity and physical features of the auditory and visual signals yielded findings of a large proportion of activity related to auditory and visual processing, particularly in the superior temporal gyrus (STG) as well as midbrain areas. Motor areas were also involved, potentially as a result of watching motion from the stick figure display of musicians in the string quartet. These results reveal involvement of areas such as the putamen in processing complex musical performance and highlight the potential of using brief naturalistic stimuli to localize distinct brain areas and elucidate potential mechanisms underlying multisensory integration.
Source localization using virtual magnetoencephalography helmets: A simulation study toward a prior-based tailored scheme
Authors: Arviv Oshrit , Harpaz Yuval , Tsizin Evgeny , Benoliel Tal , Ekstein Dana , Medvedovsky Mordekhay
Published: September 2022

Magnetoencephalography (MEG) source estimation of brain electromagnetic fields is an ill-posed problem. A virtual MEG helmet (VMH), can be constructed by recording in different head positions and then transforming the multiple head-MEG coordinates into one head frame (i.e., as though the MEG helmet was moving while the head remained static). The constructed VMH has sensors placed in various distances and angles, thus improving the spatial sampling of neuromagnetic fields. VMH has been previously shown to increase total information in comparison to a standard MEG helmet. The aim of this study was to examine whether VMH can improve source estimation accuracy. To this end, controlled simulations were carried out, in which the source characteristics are predefined. A series of VMHs were constructed by applying two or three translations and rotations to a standard 248 channel MEG array. In each simulation, the magnetic field generated by 1 to 5 dipoles was forward projected, alongside noise components. The results of this study showed that at low noise levels (e.g., averaged data of similar signals), VMHs can significantly improve the accuracy of source estimations, compared to the standard MEG array. Moreover, when utilizing a priori information, tailoring the constructed VMHs to specific sets of postulated neuronal sources can further improve the accuracy. This is shown to be a robust and stable method, even for proximate locations. Overall, VMH may add significant precision to MEG source estimation, for research and clinical benefits, such as in challenging epilepsy cases, aiding in surgical design.
Beef intake and risk of rheumatoid arthritis: Insights from a cross-sectional study and two-sample Mendelian randomization
Authors: Chen Weiwei , Liu Ke , Huang Lin , Mao Yingying , Wen Chengping , Ye Ding , He Zhixing
Published: September 2022

Background

Beef is common in daily diet, but its association with the risk of rheumatoid arthritis (RA) remains uncertain. The objective of this study is to explore the relationship between beef intake and the risk of RA.

Materials and methods

We investigated the association between beef intake and risk of RA by multivariate logistic regression, based on the National Health and Nutrition Examination Survey (NHANES) 1999–2016 involving 9,618 participants. The dose–response relationship between beef intake and RA was explored as well. Furthermore, we performed Mendelian randomization (MR) analysis to examine the causal effect of beef intake on RA. Genetic instruments for beef intake were selected from a genome-wide association study (GWAS) including 335,576 individuals from the UK Biobank study, and summary statistics relating to RA were obtained from a GWAS meta-analysis of 14,361 RA patients and 43,923 controls. The inverse-variance weighted (IVW) approach was used to estimate the causal association, and MR-Egger regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were applied to evaluate the pleiotropy and outliers.

Results

Compared with the lowest quintile (0 to ≤33.50 g/d), beef intake was found to be significantly associated with the risk of RA [odds ratio (OR): 1.94; 95% confidence interval (CI): 1.20–3.12] in the third quintile (50.26 to ≤76.50 g/d). Moreover, a reversed “U” dose–response relationship between beef and RA (Pnon–linearity = 0.023) was found. In the MR analysis, beef intake was associated with an increased risk of RA (OR: 3.05; 95% CI: 1.11–8.35; P = 0.030) by the IVW method. The results from MR-Egger regression and MR-PRESSO test showed that there were no pleiotropic variations and outliers.

Conclusion

This study indicated that there is suggestive evidence to support the causal effect of beef intake on the risk of RA, while further studies are warranted to elucidate the exact association.
Nutrient patterns and non-alcoholic fatty liver disease in Iranian Adul: A case-control study
Authors: Salehi-sahlabadi Ammar , Teymoori Farshad , Ahmadirad Hamid , Mokhtari Ebrahim , Azadi Mina , Seraj Shaikh Sanjid , Hekmatdoost Azita
Published: September 2022

Backgrounds

The current literature boasts the importance of diet in preventing or managing liver complications. However, there is limited evidence on the association of nutrient patterns (NP) with these complications. In this case-control study, we aimed to examine the possible relationship between nutrient patterns and the risk of non-alcoholic fatty liver disease (NAFLD) amongst the adult Iranian population.

Methods

This case-control study is being conducted at the Metabolic Liver Disease Research Center at Isfahan University of Medical Sciences in 2019. The study included 225 newly diagnosed cases of NAFLD and 450 controls. A validated semi-quantitative food frequency questionnaire (FFQ) assessed dietary intake. Principal component analysis using Varimax rotation obtained nutrient patterns. Logistic regression was performed to estimate NAFLD risk.

Results

We identified four major nutrient patterns. The first nutrient pattern was high in consumption of lactose, animal protein, vitamin D, riboflavin, pantothenic acid, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin A, thiamine, niacin, copper, and selenium, while the third featured plant protein, zinc, copper, magnesium, manganese, chromium, and selenium. The fourth was characterized by fructose, vitamin A, pyridoxine, vitamin C, and potassium. After adjusting for confounders, individuals in the highest tertile of NP4 had lower odds of NAFLD (OR: 0.56, 95% CI: 0.32–0.98, P_trend = 0.042); compared to those who were in the lowest tertile.

Conclusion

High compliance to a nutrient pattern characterized by fructose, vitamin C, vitamin A, pyridoxine, and potassium mainly supplied from fruits, vegetables, and nuts is inversely proportional to the odds of NAFLD. Also our findings indicate a very high fiber intake, a relatively optimal dietary fat profile, and a pretty low sugar intake for cases and controls, unseen in western countries. However, these initial findings need to be approved with further studies to confirm the relationship between nutrient patterns and NAFLD.
Evaluation of the protective roles of alpha-lipoic acid supplementation on nanomaterial-induced toxicity: A meta-analysis of in vitro and in vivo studies
Authors: Luo Xiaogang , Xie Dongli , Wu Tong , Xu Wei , Meng Qingyang , Cao Kangli , Hu Jianchen
Published: September 2022

Extensive exposure to nanomaterials causes oxidative stress and inflammation in various organs and leads to an increased risk of adverse health outcomes; therefore, how to prevent the toxic effects are of great concern to human. Alpha-lipoic acid (ALA) has anti-oxidant and anti-inflammatory activities, suggesting it may be effective to prevent nanomaterial-induced toxicity. However, the results obtained in individual studies remained controversial. We aimed to comprehensively evaluate the effects of ALA supplementation on nanomaterial-induced toxicity by performing a meta-analysis. Databases of PubMed, EMBASE, and Cochrane Library were searched up to May 2022. STATA 15.0 software was used for statistical analysis. Twelve studies were included. Meta-analysis of eightin vivostudies showed ALA supplementation could exert significant effects on nanomaterial-induced oxidative stress (by reducing MDA, ROS and increasing GSH, CAT, GPx, and SOD), inflammation (by downregulating NO, IgG, TNF-α, IL-6, and CRP), apoptosis (by activation of pro-apoptotic caspase-3), DNA damage (by a reduction in the tail length) and organ damage (by a decrease in the liver biomarker ALT and increases in brain neuron biomarker AChE and heart biomarker CPK). Pooled analysis of fourin vitrostudies indicated ALA intervention increased cell viability, decreased ROS levels, inhibited cell apoptosis and chelated metal ions. Subgroup analyses revealed changing the levels of GSH, IL-6, and metal ions were the main protective mechanisms of ALA supplementation because they were not changed by any subgroup factors. In conclusion, ALA supplementation may represent a potential strategy for the prevention of the toxicity induced by nanomaterials.
Comprehensive analysis of the prognostic value and immune infiltration of FGFR family members in gastric cancer
Authors: Yang Chengcheng , Song Dingli , Zhao Fengyu , Wu Jie , Zhang Boxiang , Ren Hong , Sun Qi , Qin Sida
Published: September 2022

Background

Fibroblast growth factor receptors (FGFRs) modulate numerous cellular processes in tumor cells and tumor microenvironment. However, the effect of FGFRs on tumor prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains controversial.

Methods

The expression of four different types of FGFRs was analyzed via GEPIA, TCGA-STAD, and GTEX databases and our 27 pairs of GC tumor samples and the adjacent normal tissue. Furthermore, the Kaplan–Meier plot and the TCGA database were utilized to assess the association of FGFRs with clinical prognosis. The R software was used to evaluate FGFRs co-expression genes with GO/KEGG Pathway Enrichment Analysis. In vitro and in vivo functional analyses and immunoblotting were performed to verify FGFR4 overexpression consequence. Moreover, the correlation between FGFRs and cancer immune infiltrates was analyzed by TIMER and TCGA databases. And the efficacy of anti-PD-1 mAb treatment was examined in NOG mouse models with overexpressed FGFR1 or FGFR4.

Results

The expression of FGFRs was considerably elevated in STAD than in the normal gastric tissues and was significantly correlated with poor OS and PFS. ROC curve showed the accuracy of the FGFRs in tumor diagnosis, among which FGFR4 had the highest ROC value. Besides, univariate and multivariate analysis revealed that FGFR4 was an independent prognostic factor for GC patients. According to a GO/KEGG analysis, the FGFRs were implicated in the ERK/MAPK, PI3K-AKT and extracellular matrix (ECM) receptor signaling pathways. In vivo and in vitro studies revealed that overexpression of FGFR4 stimulated GC cell proliferation, invasion, and migration. In addition, FGFR1 expression was positively correlated with infiltrating levels of CD8+ T-cells, CD4+ T-cells, macrophages, and dendritic cells in STAD. In contrast, FGFR4 expression was negatively correlated with tumor-infiltrating lymphocytes. Interestingly, overexpression of FGFR1 in the NOG mouse model improved the immunotherapeutic impact of GC, while overexpression of FGFR4 impaired the effect. When combined with an FGFR4 inhibitor, the anti-tumor effect of anti-PD-1 treatment increased significantly in a GC xenograft mouse model with overexpressed FGFR4.

Conclusions

FGFRs has critical function in GC and associated with immune cell infiltration, which might be a potential prognosis biomarker and predictor of response to immunotherapy in GC.
Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study
Authors: Peters Niek A. , Constantinides Alexander , Ubink Inge , van Kuik Joyce , Bloemendal Haiko J. , van Dodewaard Joyce M. , Brink Menno A. , Schwartz Thijs P. , Lolkema Martijn P.J.K. , Lacle Miangela M. , Moons Leon M. , Geesing Joost , van Grevenstein Wilhelmina M.U. , Roodhart Jeanine M. L. , Koopman Miriam , Elias Sjoerd G. , Borel Rinkes Inne H.M. , Kranenburg Onno
Published: September 2022

Background

Mesenchymal Consensus Molecular Subtype 4 (CMS4) colon cancer is associated with poor prognosis and therapy resistance. In this proof-of-concept study, we assessed whether a rationally chosen drug could mitigate the distinguishing molecular features of primary CMS4 colon cancer.

Methods

In the ImPACCT trial, informed consent was obtained for molecular subtyping at initial diagnosis of colon cancer using a validated RT-qPCR CMS4-test on three biopsies per tumor (Phase-1, n=69 patients), and for neoadjuvant CMS4-targeting therapy with imatinib (Phase-2, n=5). Pre- and post-treatment tumor biopsies were analyzed by RNA-sequencing and immunohistochemistry. Imatinib-induced gene expression changes were associated with molecular subtypes and survival in an independent cohort of 3232 primary colon cancer.

Results

The CMS4-test classified 52/172 biopsies as CMS4 (30%). Five patients consented to imatinib treatment prior to surgery, yielding 15 pre- and 15 post-treatment samples for molecular analysis. Imatinib treatment caused significant suppression of mesenchymal genes and upregulation of genes encoding epithelial junctions. The gene expression changes induced by imatinib were associated with improved survival and a shift from CMS4 to CMS2.

Conclusion

Imatinib may have value as a CMS-switching drug in primary colon cancer and induces a gene expression program that is associated with improved survival.
INPP4B inhibits glioma cell proliferation and immune escape via inhibition of the PI3K/AKT signaling pathway
Authors: Sun Xiaoming , Chen Yani , Tao Xiaoyang , Zhang Wenzi , Wang Xinyu , Wang Xianhui , Ruan Zhihua , Chen Zhuo
Published: September 2022

INPP4B (Inositol polyphosphate 4-phosphatase type II) has been regarded as a suppressor of several human tumors, but its biological function, expression, and clinical significance in glioma tissues and cell lines are unclear. Notably, whether INPP4B participates in immune escape of glioma deserves urgent attention. Here, we confirmed that INPP4B expression is often downregulated in low- and high-grade human glioma tissues, in tissues from an orthotopic mouse model of brain glioma and in glioma cells. We found that INPP4B overexpression restrained the proliferation, migration, apoptosis resistance, PD-L1 expression, and T cell suppression by glioma cells, whereas INPP4B silencing had the opposite effects. Moreover, we showed that INPP4B inhibited glioma cell proliferation, migration, and PD-L1 expression by downregulating PI3K/AKT signaling. Collectively, these data support that INPP4B may inhibit glioma progression, and particularly, glioma’s immune escape. Thus, INPP4B may constitute a valuable target for glioma treatment.
Low back pain and its determinants among wait staff in Gondar town, North West Ethiopia: A cross-sectional study
Authors: Yalew Ermias Solomon , Adem Kedir Sany , Kibret Alemu Kassaw , Gashaw Moges
Published: September 2022

Background

Low back pain is a common public health issue in the working population and one of the leading causes of disability. It is the leading cause of work-related conditions and the most common reason for filing a workers' compensation claim in low- and middle-income countries. Ethiopia is a developing country; there is a shortage of working materials, skilled labor, and a lack of awareness of ergonomics posture, which lead to lifting heavy objects, long periods of standing, repetitive twisting, and same sustained posture for long periods of time without a shift. As a result, the purpose of this study was to assess the prevalence and associated factors of work-related low back pain among restaurant wait staff in Gondar, Ethiopia, in the year 2019.

Methods

Institution-based cross-sectional study, including 420 restaurant wait personnel, was undertaken from 1 March to 30 April 2019. A simple random sampling procedure was used to choose the restaurants and wait staff. A standardized Nordic questionnaire was used to collect data. Data were entered into Epi Info 7 and analyzed in SPSS version 20. The univariate and multivariate logistic regression analyses were calculated. The significance of associations was reported by a P-value of < 0.05 and an adjusted odds ratio (AOR). The model fitness checked by the Hosmer–Lemeshow goodness of fit test was used.

Result

In this study, a total of 420 participants (99.53% response rate) ranging in age from 17 to 53 years old participated, with 184 (43.8%) participants reporting low back pain at some point in the past 12 months. Female participants had a higher prevalence of 130 (70.6%). Sex (AOR = 2.98; 95% CI: 1.07–8.30), frequent exercise (AOR 0.47; 95% CI: 0.24, 0.93), extended standing (AOR 8.82; 95% CI: 3.30, 20.32], and repetitive tasks (AOR 7.49; 95% CI: 4.29, 13.19) were all found to be significant predictors in low back pain.

Conclusion

More than two-fifth of waitresses and waiters reported low back discomfort at some point in the past 12 months. Predisposing factors for low back discomfort among restaurant wait staff included being female, standing for long periods of time while serving, and performing repetitive tasks. Regular exercise was found to be a protective factor against low back pain in wait staff. Delivering ongoing safety training is among the most potent essential measures required in preventing low back pain.
Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network
Authors: Moussaoui Dehlia , Surbone Anna , Adam Cécile , Diesch-Furlanetto Tamara , Girardin Céline , Bénard Julie , Vidal Isabelle , Bernard Fanette , Busiah Kanete , Bouthors Thérèse , Primi Marie-Pierre , Ansari Marc , Vulliemoz Nicolas , Gumy-Pause Fabienne
Published: September 2022

Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland. Testicular tissue cryopreservation was accepted by 90% of families, with a total of 35 patients included. The average patient age was 8.5 years (range 7 months to 18.5 years). Malignancies were the most common diagnosis (31 patients, 88.6%) with 16 (45.7%) solid tumors and 15 (42.9%) hematological malignancies. Four (11.4%) patients had a benign condition. The main indication for testicular tissue cryopreservation was conditioning for hematologic stem cell transplantation (25 patients, 71.4%). Testicular tissue was cryopreserved according to the freezing protocol of Louvain Catholic University (Belgium), which includes either only immature testicular tissue freezing, or mature and immature testicular tissue freezing depending on the age of the patient and the presence or absence of haploid cells. The median number of spermatogonia per tubule cross-section was 2 (range 0–6) and spermatozoa were found in only one patient. Tumoral cells were found in one testicular biopsy of a leukemic patient. There were two minor adverse events and none of them required medical treatment or surgical revision. Five patients died during follow-up. Our data demonstrate the feasibility and safety of a program of testicular tissue cryopreservation coordinated by a multidisciplinary team of fertility preservation. Despite the experimental aspect of the procedure, the acceptation rate was high, which highlights the willingness of families and patients to participate in testicular tissue cryopreservation.
Chinese herbal medicine anticancer cocktail soup activates immune cells to kill colon cancer cells by regulating the gut microbiota-Th17 axis
Authors: Nie Xiaoli , Geng Zixiang , Liu Jianjun , Qi Li , Wang Zetian , Liu Te , Tang Jianguo
Published: September 2022

Chinese herbal medicines are effective for treating colon cancer (CC). CC development is reportedly associated with gut microbiota dysbiosis and immune function dysregulation. Herein we explored the therapeutic effects of a Chinese herbal medicine anticancer cocktail soup (CHMACS) on mice with CC and also explored its regulatory effects on gut microbiota. In vivo experiments indicated that CHMACS significantly inhibited the proliferation and tumorigenicity of CC cells. Further, CHMACS treatment decreased the proportion of CD8+ T, natural killer, and Th17 cells. HPLC/MS analysis showed that CHMACS comprised 227 active components. 16S rRNA sequencing revealed, for example, an increase in the relative abundance of uncultured_bacterium_g_Turicibacter and a decrease in that of uncultured_bacterium_g_Coriobacteriaceae_UCG-002 in gut microbiota of CHMACS-treated mice. Microbial diversity cluster analysis revealed that Verrucomicrobia, Spirochaetes, Fusobacteria, Patescibacteria, and Firmicutes contributed the most to fecal microbial diversity. Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis and clusters of orthologous groups of protein annotation indicated that CHMACS treatment induced amino acid metabolism and suppressed carbohydrate metabolism. Moreover, we found a strong association between changes in metabolites and immune cell maturation and activation. To summarize, our findings suggest that CHMACS kills CC cells by regulating gut microbiota and activating immune cells.
Analysis of pharmacovigilance databases for spontaneous reports of adverse drug reactions related to substandard and falsified medical products: A descriptive study
Authors: Pozsgai Kevin , Szűcs Gergő , Kőnig-Péter Anikó , Balázs Orsolya , Vajda Péter , Botz Lajos , Vida Róbert György
Published: September 2022

Introduction: The public health threat of substandard and falsified medicines has been well known in the last two decades, and several studies focusing on the identification of products affected and preventing consumption have been published. However, the number of these products reaching patients and causing health consequences and adverse drug reactions is not a well-researched area.

Objectives: Our aim was to identify and describe the characteristics of cases that are related to adverse drug reactions potentially originating from counterfeit medication using publicly available pharmacovigilance data.

Methods: A descriptive study was performed based on pharmacovigilance data retrieved from Individual Case Safety Reports (ICSRs) identified in the European Medicines Agency’s EudraVigilance and FDA Adverse Event Reporting System (FAERS) databases in April 2022 using selected MedDRA preferred terms: counterfeit product administered, product counterfeit, product label counterfeit, product packaging counterfeit, suspected counterfeit product, adulterated product, product tampering, and suspected product tampering. ICSRs were analyzed by age and gender, by year of reporting, region of origin, reporter’s profession, and severity of the outcome. The disproportionality method was used to calculate pharmacovigilance signal measures.

Results: A total of 5,253 cases in the FAERS and 1,049 cases in the EudraVigilance database were identified, generally affecting middle-aged men with a mean age of 51.055 (±19.62) in the FAERS and 64.18% of the cases between 18 and 65 years, while the male to female ratios were 1.18 and 1.5. In the FAERS database, we identified 138 signals with 95% confidence interval including sildenafil (n = 314; PRR, 12.99; ROR, 13.04; RRR, 11.97), tadalafil (n = 200; PRR, 11.51; ROR, 11.55; RRR, 10.94), and oxycodone (n = 190; PRR, 2.47; ROR, 2.14; RRR, 2.47). While in the EV data 31, led by vardenafil (n = 16, PRR = 167.19; 101.71–274.84; 95% CI, RRR = 164.66; 100.17–270.66; 95% CI, ROR = 169.47; 103.09–278.60; 95% CI, p < 0.001), entecavir (n = 46, PRR = 161.26, RRR = 154.24, ROR = 163.32, p < 0.001), and tenofovir (n = 20, PRR = 142.10, RRR = 139.42, ROR = 143.74, p < 0.001).

Conclusion: The application of pharmacovigilance datasets to identify potential counterfeit medicine ADRs can be a valuable tool in recognition of potential risk groups of consumers and the affected active pharmaceutical ingredients and products. However, the further development and standardization of ADR reporting, pharmacovigilance database analysis, and prospective and real-time collection of potential patients with health consequences are warranted in the future.
Multi-omics approaches for deciphering the complexity of traditional Chinese medicine syndromes in stroke: A systematic review
Authors: Liu Tingting , Qin Mingzhen , Xiong Xuejiao , Lai Xinxing , Gao Ying
Published: September 2022

Background: Deciphering the biological basis of traditional Chinese medicine (TCM) syndromes in complex diseases is challenging. Rapid advances in multi-omics approaches provide new opportunities to unveil the biological basis of TCM syndromes. We intend to summarize the latest significant progress and highlight the crucial value of applying multi-omics approaches to reveal TCM syndromes of stroke in a new horizon.

Methods: We systematically searched PubMed, EMBASE, Web of Science Core Collection (WOSCC), Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang database and China Biology Medicine Database (SinoMed) for relevant studies from their inception to 31 March 2022, and conducted a comprehensive systematic review (PROSPERO registration number: CRD42021285922).

Results: A total of 43 relevant studies were included in the final systematic review, genomics, transcriptomics, proteomics, and metabolomics were all involved. Some gene polymorphisms, differential lncRNAs, mRNAs, miRNAs, proteins, and metabolites may be associated with TCM syndromes of stroke. In addition, some studies conducted a preliminary exploration on the different diseases with the same TCM syndrome. The results showed that thioredoxin-dependent peroxidase reductase may be the specific marker protein of Liver-yang transforming into wind syndrome, and the network formed by mir-146b-5p, -199a-5p, and 23 targeted mRNAs may be the biomarker of Blood-stasis syndrome.

Conclusion: Multi-omics technologies have served as powerful tools to investigate the complexity of TCM syndromes and may hold the promise of promoting the modernization of TCM as well as personalized medicine of TCM in stroke.
A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization
Authors: Yang Zhihua , Lin Shanshan , Feng Wanying , Liu Yangxi , Song Zhihui , Pan Guiyun , Zhang Yuhang , Dai Xiangdong , Ding Xinya , Chen Lu , Wang Yi
Published: September 2022

Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the “guide” to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.
Multitargeting nature of muscarinic orthosteric agonists and antagonists
Authors: Myslivecek Jaromir
Published: September 2022

Muscarinic receptors (mAChRs) are typical members of the G protein-coupled receptor (GPCR) family and exist in five subtypes from M1 to M5. Muscarinic receptor subtypes do not sufficiently differ in affinity to orthosteric antagonists or agonists; therefore, the analysis of receptor subtypes is complicated, and misinterpretations can occur. Usually, when researchers mainly specialized in CNS and peripheral functions aim to study mAChR involvement in behavior, learning, spinal locomotor networks, biological rhythms, cardiovascular physiology, bronchoconstriction, gastrointestinal tract functions, schizophrenia, and Parkinson’s disease, they use orthosteric ligands and they do not use allosteric ligands. Moreover, they usually rely on manufacturers’ claims that could be misleading. This review aimed to call the attention of researchers not deeply focused on mAChR pharmacology to this fact. Importantly, limited selective binding is not only a property of mAChRs but is a general attribute of most neurotransmitter receptors. In this review, we want to give an overview of the most common off-targets for established mAChR ligands. In this context, an important point is a mention the tremendous knowledge gap on off-targets for novel compounds compared to very well-established ligands. Therefore, we will summarize reported affinities and give an outline of strategies to investigate the subtype’s function, thereby avoiding ambiguous results. Despite that, the multitargeting nature of drugs acting also on mAChR could be an advantage when treating such diseases as schizophrenia. Antipsychotics are a perfect example of a multitargeting advantage in treatment. A promising strategy is the use of allosteric ligands, although some of these ligands have also been shown to exhibit limited selectivity. Another new direction in the development of muscarinic selective ligands is functionally selective and biased agonists. The possible selective ligands, usually allosteric, will also be listed. To overcome the limited selectivity of orthosteric ligands, the recommended process is to carefully examine the presence of respective subtypes in specific tissues via knockout studies, carefully apply “specific” agonists/antagonists at appropriate concentrations and then calculate the probability of a specific subtype involvement in specific functions. This could help interested researchers aiming to study the central nervous system functions mediated by the muscarinic receptor.
Melatonin-induced physiology and transcriptome changes in banana seedlings under salt stress conditions
Authors: Wei Junya , Liang Jinhao , Liu Debing , Liu Yuewei , Liu Guoyin , Wei Shouxing
Published: September 2022

Soil salinization poses a serious threat to the ecological environment and agricultural production and is one of the most common abiotic stresses in global agricultural production. As a salt-sensitive plant, the growth, development, and production of bananas (Musa acuminata L.) are restricted by salt stress. Melatonin is known to improve the resistance of plants to stress. The study analyzed the effects of 100 μM melatonin on physiological and transcriptome changes in banana varieties (AAA group cv. Cavendish) under 60 mmol/l of NaCl salt stress situation. The phenotypic results showed that the application of exogenous melatonin could maintain banana plants’ health growth and alleviate the damage caused by salt stress. The physiological data show that the application of exogenous melatonin can enhance salt tolerance of banana seedlings by increasing the content of proline content and soluble protein, slowing down the degradation of chlorophyll, reducing membrane permeability and recovery of relative water content, increasing the accumulation of MDA, and enhancing antioxidant defense activity. Transcriptome sequencing showed that melatonin-induced salt tolerance of banana seedlings involved biological processes, molecular functions, and cellular components. We also found that differentially expressed genes (DEGs) are involved in a variety of metabolic pathways, including amino sugar and nucleotide sugar metabolism, phenylalanine metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, and linoleic acid metabolism. These major metabolism and biosynthesis may be involved in the potential mechanism of melatonin under salt stress. Furthermore, some members of the transcription factor family, such as MYB, NAC, bHLH, and WRKY, might contribute to melatonin alleviating salt stress tolerance of the banana plant. The result laid a basis for further clarifying the salt stress resistance mechanism of bananas mediated by exogenous melatonin and provides theoretical bases to utilize melatonin to improve banana salt tolerance in the future.
Do overqualified employees hide knowledge? The mediating role of psychological contract breach
Authors: Zhang Huiqin , Li Linzhen , Shan Xuanming , Chen Anhang
Published: September 2022

Although the negative effects of a sense of overqualification on organizations and individuals have been examined, it is debatable whether overqualified employees hide knowledge. Relying on the social comparison theory and psychological contract theory, this paper tried to investigate the non-linear relationship between perceived overqualification and knowledge hiding via psychological contract breach by surveying employees with bachelor’s degrees or above and eventually recruited 475 participants. The results indicated that psychological contract breach acts a partial mediating role in the inverted U-shaped relationship between perceived overqualification and knowledge hiding, while leader-member exchange acts as a moderator. The finding manifests that overqualification encourages employees to hide knowledge, but their possibly vigorous aspects will be displayed when a certain limit is exceeded. This study benefits organizations by advising them to dialectically treat and properly place overqualified employees and contributes to the research on overqualified employees’ knowledge management by offering a new explanation and complete understanding of perceived overqualification and knowledge hiding, with specific focus given to the psychological states of employees.
School structure, bullying by teachers, moral disengagement, and students’ aggression: A mediation model
Authors: Ivaniushina Valeria , Alexandrov Daniel
Published: September 2022

Aim

Understanding interrelations between the factors predicting students’ aggressive behavior is a priority for bullying-prevention programs. Our study explores two possible mechanisms linking school disciplinary structure and students’ aggression. We test students’ moral disengagement and bullying by teachers as mediational pathways from school authoritative discipline to students’ aggressive behavior.

Methods

We used a regionally representative sample of 213 schools that participated in a school climate survey in Kaluga Oblast (a federal subject of Russia) in 2019. The analytical sample contained the anonymous responses of 16,809 students from grades 6–9 (12–15 years old); 51% of the respondents were girls. The analytical procedure consisted of structural equation modeling (SEM), which was implemented in Mplus 8.7.

Results

The mediation model fit the data well, suggesting that the clarity and fairness of school rules negatively predicted peer aggression, while student moral disengagement and bullying by teachers independently and partially mediated this association.

Conclusion

We confirm that authoritative school climate, characterized by a clear and fair disciplinary structure, is associated with a decrease in bullying. Novel result is the evidence for mediating mechanisms and the influence of teachers’ aggression on students’ behavior. Prevention programs designed to increase the fairness and consistency of school rules, eliminate bullying and humiliation from teachers, and decrease students’ moral disengagement may reduce violence and victimization at school.
Principals' leadership styles and its impact on teachers' performance at college level
Authors: Sarwar Uzma , Tariq Rameez , Yong Qi Zhan
Published: September 2022

In this study, we examined the impact of principals' leadership style on the performance of teachers at the college level. For this purpose, we collect data from 300 college teachers via a random sampling approach. A self-administrated questionnaire (five-point Likert Scale) was used to collect data. For detecting relationships and differences among the opinions of the study's participants, correlation and the t-test were used. This study has revealed that the majority of college principals practice a democratic style of leadership at a higher level, Laissez-faire at a moderate level, and autocratic at a low level in their colleges. Moreover, it has been also revealed that when principals increase the use of a democratic leadership style, teacher performance may progress as well. The findings revealed that principals' leadership style had a positive impact on the performance of teachers. The study exposed a strong statistically positive relationship between college principals' leadership style and teacher performance. Thus, the results of this study suggest that college principals' should adopt the leadership style according to the level of teachers. The leadership style should be changed with specific situations in the colleges.
Childhood behavioral inhibition and attachment: Links to generalized anxiety disorder in young adulthood
Authors: Zdebik Magdalena A. , Pascuzzo Katherine , Bureau Jean-François , Moss Ellen
Published: September 2022

Generalized anxiety disorder (GAD) is under-treated yet prevalent among young adults. Identifying early risk factors for GAD would contribute to its etiological model and identify potential targets for intervention. Insecure attachment patterns, specifically ambivalent and disorganized, have long been proposed as childhood risk factors for GAD. Similarly, childhood behavioral inhibition has been consistently associated with anxiety disorders in adulthood, including GAD. Intolerance of uncertainty (IU), the tendency to react negatively to uncertain situations, has also been shown to be a crucial component of GAD. Furthermore, maternal anxiety is an important feature of developmental models of anxiety including GAD. Yet, to date, no study has examined, within a comprehensive model, how attachment and behavioral inhibition in childhood, maternal anxiety in adolescence, and IU in emerging adulthood contribute to GAD in adulthood. The present study thus examines these links using a longitudinal design with 62 Canadian participants and their mothers. At age 6, participants' attachment and behavioral inhibition were assessed observationally. Maternal anxiety was measured when participants were 14 years of age. IU and GAD were assessed when participants were 21 and 23 years of age, respectively. Structural equation modeling showed that IU mediates the relationships between behavioral inhibition and GAD, while controlling for maternal anxiety. Ambivalent and disorganized-controlling attachment patterns are also indirectly associated with increased GAD symptoms via greater IU scores. Furthermore, a direct and positive effect of behaviorally disorganized attachment was found on GAD symptoms. This longitudinal study supports integrating attachment, behavioral inhibition, and IU in a model of GAD.
Profiles and correlates of language and social communication differences among young autistic children
Authors: Reetzke Rachel , Singh Vini , Hong Ji Su , Holingue Calliope B. , Kalb Luther G. , Ludwig Natasha N. , Menon Deepa , Pfeiffer Danika L. , Landa Rebecca J.
Published: September 2022

Delays in early language development are characteristic of young autistic children, and one of the most recognizable first concerns that motivate parents to seek a diagnostic evaluation for their child. Although early language abilities are one of the strongest predictors of long-term outcomes, there is still much to be understood about the role of language impairment in the heterogeneous phenotypic presentation of autism. Using a person-centered, Latent Profile Analysis, we first aimed to identify distinct patterns of language and social communication ability in a clinic-based sample of 498 autistic children, ranging in age from 18 to 60 months (M = 33 mo, SD = 12 mo). Next, a multinomial logistic regression analysis was implemented to examine sociodemographic and child-based developmental differences among the identified language and social communication profiles. Three clinically meaningful profiles were identified from parent-rated and clinician-administered measures: Profile 1 (48% of the sample) “Relatively Low Language and Social Communication Abilities,” Profile 2 (34% of the sample) “Relatively Elevated Language and Social Communication Abilities,” and Profile 3 (18% of the sample) “Informant Discrepant Language and Relatively Elevated Social Communication Abilities.” Overall, young autistic children from the lowest-resource households exhibited the lowest language and social communication abilities, and the lowest non-verbal problem-solving and fine-motor skills, along with more features of attention-deficit/hyperactivity disorder and atypical auditory processing. These findings highlight the need for effective community-based implementation strategies for young autistic children from low-resource households and underrepresented communities to improve access to individualized quality care.
Learned uncertainty: The free energy principle in anxiety
Authors: McGovern H. T. , De Foe Alexander , Biddell Hannah , Leptourgos Pantelis , Corlett Philip , Bandara Kavindu , Hutchinson Brendan T.
Published: September 2022

Generalized anxiety disorder is among the world’s most prevalent psychiatric disorders and often manifests as persistent and difficult to control apprehension. Despite its prevalence, there is no integrative, formal model of how anxiety and anxiety disorders arise. Here, we offer a perspective derived from the free energy principle; one that shares similarities with established constructs such as learned helplessness. Our account is simple: anxiety can be formalized as learned uncertainty. A biological system, having had persistent uncertainty in its past, will expect uncertainty in its future, irrespective of whether uncertainty truly persists. Despite our account’s intuitive simplicity—which can be illustrated with the mere flip of a coin—it is grounded within the free energy principle and hence situates the formation of anxiety within a broader explanatory framework of biological self-organization and self-evidencing. We conclude that, through conceptualizing anxiety within a framework of working generative models, our perspective might afford novel approaches in the clinical treatment of anxiety and its key symptoms.
Fear of being infected with COVID-19 virus among the medical social workers and its relationship to their future orientation
Authors: Snoubar Yaser , Zengin Oǧuzhan
Published: September 2022

COVID-19 has been studied extensively for its direct effects on healthcare workers. Despite this, very little is known about the effect of COVID-19 fear on future orientation. Studying medical social workers’ fear of being infected with COVID-19 and their future orientation was the primary method used to examine this relationship. 204 Turkish medical social workers on the pandemic’s front lines were included in the total sample. Social workers were found to be extremely concerned about contracting COVID-19. Although only gender is a significant predictor of the fear of contracting COVID-19 infection, the study also found that female social workers have a higher fear of infection than males. Also, no correlation exists between social workers’ vaccination status and their fear of contracting COVID-19. There was a weak negative correlation between social workers’ fear of contracting COVID-19 and their future orientation, but in general, social workers had a positive future orientation. Medical social workers and front-line health care providers can use these findings to develop effective and culturally appropriate intervention programs to reduce COVID-19 concerns and foster a forward-looking outlook.