bluuebunny/crossref_metadata_2025 huggingface dataset:
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity
Authors: Shukla Rahul , Rajpoot Ravi Kant , Poddar Ankur , Ahuja Richa , Beesetti Hemalatha , Shanmugam Rajgokul K. , Chaturvedi Shivam , Nayyar Kaushal , Singh Deepika , Singamaneni Venugopal , Gupta Prasoon , Gupta Ajai Prakash , Gairola Sumeet , Kumar Pankaj , Bedi Y. S. , Jain Tapesh , Vashishta Bhupendra , Patil Ravindra , Madan Harish , Madan Sumit , Kalra Rinku , Sood Ruchi , Vishwakarma Ram A. , Reddy D. Srinivasa , Lal Altaf A. , Arora Upasana , Khanna Navin
Published: December 2021

Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue.
Whole-Genome Epidemiology and Characterization of Methicillin-Susceptible Staphylococcus aureus ST398 From Retail Pork and Bulk Tank Milk in Shandong, China
Authors: Zhao Xiaonan , Hu Ming , Zhao Cui , Zhang Qing , Li Lulu , Zhang Yin , Luo Yanbo , Liu Yuqing
Published: December 2021

Staphylococcus aureus (S. aureus) is now regarded as a zoonotic agent. Methicillin-susceptible S. aureus (MSSA) ST398 is a livestock-associated bacterium that is most prevalent in China, but there are currently no data available for Shandong. Therefore, the aim of this study was to investigate the epidemiology and characterization of MSSA ST398 from retail pork and bulk tank milk (BTM) in Shandong. A total of 67 S. aureus isolates were collected from retail pork between November 2017 and June 2018. Among the isolates, high antimicrobial resistance rates were observed for penicillin (97.0%), and 92.5% of the isolates were multi-drug resistant (MDR). Eight sequence types (STs) were identified in the retail pork isolates, and the predominant type was ST15 (n=26), which was followed by ST398 (n=14). Staphylococcal protein A gene (spa) typing identified spa types t034 and t1255 in MSSA ST398 from retail pork. Using whole-genome sequencing analysis, we described the phylogeny of 29 MSSA ST398 isolates that were obtained from retail pork (n=14) and BTM (n=15). The phylogenetic tree showed that the MSSA ST398 isolates from different sources had the same lineage. Among the 29 MSSA ST398 isolates, five resistance genes were detected, and all isolates carried DHA-1. Fifteen toxin genes were detected, and all isolates carried eta, hla, and hlb. In conclusion, this study found that a high risk for MSSA ST398 was present in retail pork and BTM. These findings have major implications for how investigations of MSSA ST398 outbreaks should be conducted in the One-Health context.
Heterologous Expression and Characterization of a High-Efficiency Chitosanase From Bacillus mojavensis SY1 Suitable for Production of Chitosan Oligosaccharides
Authors: Wang Jianrong , Li Xiaoming , Chen Hao , Lin Bilian , Zhao Liangzhong
Published: December 2021

Chitosanase plays an important role in enzymatic production of chitosan oligosaccharides (COSs). The present study describes the gene cloning and high-level expression of a high-efficiency chitosanase fromBacillus mojavensisSY1 (CsnBm). The gene encoding CsnBm was obtained by homologous cloning, ligated to pPICZαA, and transformed intoPichia pastorisX33. A recombinant strain designated X33-C3 with the highest activity was isolated from 120 recombinant colonies. The maximum activity and total protein concentration of recombinant strain X33-C3 were 6,052 U/ml and 3.75 g/l, respectively, which were obtained in fed-batch cultivation in a 50-l bioreactor. The optimal temperature and pH of purified CsnBm were 55°C and 5.5, respectively. Meanwhile, CsnBm was stable from pH 4.0 to 9.0 and 40 to 55°C. The purified CsnBm exhibited high activity toward colloidal chitosan with degrees of deacetylation from 85 to 95%. Furthermore, CsnBm exhibited high efficiency to hydrolyze different concentration of colloidal chitosan to produce COSs. The result of this study not only identifies a high-efficiency chitosanase for preparation of COSs, but also casts some insight into the high-level production of chitosanase in heterologous systems.
CircularLRRC7 is a Potential Tumor Suppressor Associated With miR-1281 and PDXP Expression in Glioblastoma
Authors: Kong Xue , Xu Ruiting , Wang Wei , Zeng Minghui , Li Yuan , Lin Mengyu , Zhou Wenchao , Fu Xianming , Wu Haibo
Published: December 2021

Circular RNAs (circRNAs) are usually enriched in neural tissues, yet about 80% circRNAs have lower expression in gliomas relative to normal brains, highlighting the importance of circRNAs as tumor suppressors. However, the clinical impact as well as the pathways regulated by the tumor-suppressive circRNAs remain largely unknown in glioblastoma (GBM). Through bioinformatic analysis followed by experimental validation, we found that hsa_circ_0114014 (circLRRC7) was dramatically down-regulated in GBM when compared with normal brain tissues (p < 0.0001). GBM patients with a lower circLRRC7 expression had poorer progression-free survival (PFS, p < 0.05) and overall survival (OS, p < 0.05). Analyses of the predicted target miRNAs of circLRRC7 in CSCD and CRI databases, in combination with the miRNA expression data in GBMs and normal brains from GSE database, revealed miR-1281 as a potential downstream target of circLRRC7. Subsequently, the target genes of hsa-mir-1281 were predicted by TargetScan, miRDB and miRNATAR databases. Intersection analysis and correlation test indicated that PDXP was a potential target of miR-1281. In summary, circLRRC7 may be a tumor suppressor that associated with miR-1281 and PDXP expression in GBM, which may provide novel therapeutic targets for GBM treatment.
Snake Toxins Labeled by Green Fluorescent Protein or Its Synthetic Chromophore are New Probes for Nicotinic acetylcholine Receptors
Authors: Kasheverov Igor E. , Kuzmenkov Alexey I. , Kudryavtsev Denis S. , Chudetskiy Ivan S. , Shelukhina Irina V. , Barykin Evgeny P. , Ivanov Igor A. , Siniavin Andrei E. , Ziganshin Rustam H. , Baranov Mikhail S. , Tsetlin Victor I. , Vassilevski Alexander A. , Utkin Yuri N.
Published: December 2021

Fluorescence can be exploited to monitor intermolecular interactions in real time and at a resolution up to a single molecule. It is a method of choice to study ligand-receptor interactions. However, at least one of the interacting molecules should possess good fluorescence characteristics, which can be achieved by the introduction of a fluorescent label. Gene constructs with green fluorescent protein (GFP) are widely used to follow the expression of the respective fusion proteins and monitor their function. Recently, a small synthetic analogue of GFP chromophore (p-HOBDI-BF2) was successfully used for tagging DNA molecules, so we decided to test its applicability as a potential fluorescent label for proteins and peptides. This was done on α-cobratoxin (α-CbTx), a three-finger protein used as a molecular marker of muscle-type, neuronal α7 and α9/α10 nicotinic acetylcholine receptors (nAChRs), as well as on azemiopsin, a linear peptide neurotoxin selectively inhibiting muscle-type nAChRs. An activated N-hydroxysuccinimide ester of p-HOBDI-BF2 was prepared and utilized for toxin labeling. For comparison we used a recombinant α-CbTx fused with a full-length GFP prepared by expression of a chimeric gene. The structure of modified toxins was confirmed by mass spectrometry and their activity was characterized by competition with iodinated α-bungarotoxin in radioligand assay with respective receptor preparations, as well as by thermophoresis. With the tested protein and peptide neurotoxins, introduction of the synthetic GFP chromophore induced considerably lower decrease in their affinity for the receptors as compared with full-length GFP attachment. The obtained fluorescent derivatives were used for nAChR visualization in tissue slices and cell cultures.
Computational Identification of Immune- and Ferroptosis-Related LncRNA Signature for Prognosis of Hepatocellular Carcinoma
Authors: Huang Anmin , Li Ting , Xie Xueting , Xia Jinglin
Published: December 2021

Long non-coding RNAs (lncRNAs), which were implicated in many pathophysiological processes including cancer, were frequently dysregulated in hepatocellular carcinoma (HCC). Studies have demonstrated that ferroptosis and immunity can regulate the biological behaviors of tumors. Therefore, biomarkers that combined ferroptosis, immunity, and lncRNA can be a promising candidate bioindicator in clinical therapy of cancers. Many bioinformatics methods, including Pearson correlation analysis, univariate Cox proportional hazard regression analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis were applied to develop a prognostic risk signature of immune- and ferroptosis-related lncRNA (IFLSig). Finally, eight immune- and ferroptosis-related lncRNAs (IFLncRNA) were identified to develop and IFLSig of HCC patients. We found the prognosis of patients with high IFLSig will be worse, while the prognosis of patients with low IFLSig will be better. The results provide an efficient method of uniting critical clinical information with immunological characteristics, enabling estimation of the overall survival (OS). Such an integrative prognostic model with high predictive power would have a notable impact and utility in prognosis prediction and individualized treatment strategies.
Actin Bundle Nanomechanics and Organization Are Modulated by Macromolecular Crowding and Electrostatic Interactions
Authors: Castaneda Nicholas , Feuillie Cecile , Molinari Michael , Kang Ellen Hyeran
Published: December 2021

The structural and mechanical properties of actin bundles are essential to eukaryotic cells, aiding in cell motility and mechanical support of the plasma membrane. Bundle formation occurs in crowded intracellular environments composed of various ions and macromolecules. Although the roles of cations and macromolecular crowding in the mechanics and organization of actin bundles have been independently established, how changing both intracellular environmental conditions influence bundle mechanics at the nanoscale has yet to be established. Here we investigate how electrostatics and depletion interactions modulate the relative Young’s modulus and height of actin bundles using atomic force microscopy. Our results demonstrate that cation- and depletion-induced bundles display an overall reduction of relative Young’s modulus depending on either cation or crowding concentrations. Furthermore, we directly measure changes to cation- and depletion-induced bundle height, indicating that bundles experience alterations to filament packing supporting the reduction to relative Young’s modulus. Taken together, our work suggests that electrostatic and depletion interactions may act counteractively, impacting actin bundle nanomechanics and organization.
Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
Authors: Feng Jikun , Li Jianxia , Huang Xinjian , Yi Jiarong , Wu Haoming , Zou Xuxiazi , Zhong Wenjing , Wang Xi
Published: December 2021

Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs.

Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction.

Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982–0.992), p < 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845–0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010–1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717–0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617–0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041).

Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.
Identification of Potential circRNA-microRNA-mRNA Regulatory Network in Skeletal Muscle
Authors: Das Arundhati , Shyamal Sharmishtha , Sinha Tanvi , Mishra Smruti Sambhav , Panda Amaresh C.
Published: December 2021

Circular RNAs (circRNAs) are a newly discovered family of regulatory RNAs generated through backsplicing. Genome-wide profiling of circRNAs found that circRNAs are ubiquitously expressed and regulate gene expression by acting as a sponge for RNA-binding proteins (RBPs) and microRNAs (miRNAs). To identify circRNAs expressed in mouse skeletal muscle, we performed high-throughput RNA-sequencing of circRNA-enriched gastrocnemius muscle RNA samples, which identified more than 1,200 circRNAs. In addition, we have identified more than 14,000 and 15,000 circRNAs in aging human skeletal muscle tissue and satellite cells, respectively. A subset of abundant circRNAs was analyzed by RT-PCR, Sanger sequencing, and RNase R digestion assays to validate their expression in mouse skeletal muscle tissues. Analysis of the circRNA-miRNA-mRNA regulatory network revealed that conserved circNfix might associate with miR-204-5p, a suppressor of myocyte enhancer factor 2c (Mef2c) expression. To support the hypothesis that circNfix might regulate myogenesis by controlling Mef2c expression, silencing circNfix moderately reduced Mef2c mRNA expression and inhibited C2C12 differentiation. We propose that circNfix promotes MEF2C expression during muscle cell differentiation in part by acting as a sponge for miR-204-5p.
The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans
Authors: Liu Yang , Zhu Xinting , Wang Kejia , Zhang Bo , Qiu Shuyi
Published: December 2021

G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases play key roles in G4 metabolism and function, and these processes are closely related to physiological and pathological processes. In recent years, more and more functional and mechanistic details of G4 helicases have been discovered; therefore, it is necessary to carefully sort out the current research efforts. Here, we provide a systematic summary of G4 unwinding helicases from the perspective of functions and molecular mechanisms. First, we provide a general introduction about helicases and G4s. Next, we comprehensively summarize G4 unfolding helicases in humans and their proposed cellular functions. Then, we review their study methods and molecular mechanisms. Finally, we share our perspective on further prospects. We believe this review will provide opportunities for researchers to reach the frontiers in the functions and molecular mechanisms of human G4 unwinding helicases.
Diagnostic Utility of Integrated11C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study
Authors: Chang Yan , Liu Jiajin , Wang Liang , Li Xin , Wang Zhenjun , Lin Mu , Jin Wei , Zhu Mingwei , Xu Baixuan
Published: December 2021

Objective: We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer’s disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated 11C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value.

Methods: Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an 11C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated.

Results: Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 ± 0.10 vs. 1.42 ± 0.16 and 1.17 ± 0.08; p < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 ± 0.06 vs. 1.21 ± 0.06; p < 0.0001) and significantly lower than in AD patients (1.66 ± 0.06 vs. 1.86 ± 0.17; p < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 ± 0.02) relative to AD patients (1.05 ± 0.02 vs. 0.99 ± 0.04; p < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR.

Conclusion: Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.
Dynamic Diversity of Glial Response Among Species in Spinal Cord Injury
Authors: Perez Jean-Christophe , Gerber Yannick N. , Perrin Florence E.
Published: December 2021

The glial scar that forms after traumatic spinal cord injury (SCI) is mostly composed of microglia, NG2 glia, and astrocytes and plays dual roles in pathophysiological processes induced by the injury. On one hand, the glial scar acts as a chemical and physical obstacle to spontaneous axonal regeneration, thus preventing functional recovery, and, on the other hand, it partly limits lesion extension. The complex activation pattern of glial cells is associated with cellular and molecular crosstalk and interactions with immune cells. Interestingly, response to SCI is diverse among species: from amphibians and fishes that display rather limited (if any) glial scarring to mammals that exhibit a well-identifiable scar. Additionally, kinetics of glial activation varies among species. In rodents, microglia become activated before astrocytes, and both glial cell populations undergo activation processes reflected amongst others by proliferation and migration toward the injury site. In primates, glial cell activation is delayed as compared to rodents. Here, we compare the spatial and temporal diversity of the glial response, following SCI amongst species. A better understanding of mechanisms underlying glial activation and scar formation is a prerequisite to develop timely glial cell-specific therapeutic strategies that aim to increase functional recovery.
Multivariate FMRI Signatures of Learning in a Hebb Repetition Paradigm With Tone Sequences
Authors: Loo Corey , Lee Andy C. H. , Buchsbaum Bradley R.
Published: December 2021

Important information from the environment often arrives to the brain in temporally extended sequences. Language, music, actions, and complex events generally unfold over time. When such informational sequences exceed the limited capacity of working memory, the human brain relies on its ability to accumulate information in long-term memory over several encounters with a complex stimulus. A longstanding question in psychology and neuroscience is whether the neural structures associated with working memory storage—often viewed as capacity limited and temporary—have any builtin ability to store information across longer temporal delays. According to the classic Hebbian dual memory theory, temporally local “activity traces” underlie immediate perception and working memory, whereas “structural traces” undergird long-term learning. Here we examine whether brain structures known to be involved in working maintenance of auditory sequences, such as area Spt, also show evidence of memory persistence across trials. We used representational similarity analysis (RSA) and the Hebb repetition paradigm with supracapacity tonal sequences to test whether repeated sequences have distinguishable multivoxel activity patterns in the auditory-motor networks of the brain. We found that, indeed, area Spt and other nodes of the auditory dorsal stream show multivoxel patterns for tone sequences that become gradually more distinct with repetition during working memory for supracapacity tone-sequences. The findings suggest that the structures are important for working memory are not “blank slates,” wiped clean from moment to moment, but rather encode information in a way can lead to cross-trial persistence.
Abnormalities of Cerebral White Matter Microstructure in Children With New-Onset, Untreated Idiopathic-Generalized Epilepsy
Authors: Long Ran , Wang Yuting , Chen Lizhou , Deng Dingmei , Mei Lan , Mou Jingping , Tang Guangcai , Han Fugang , Kemp Graham John , Gong Qiyong , Qiu Lihua
Published: December 2021

Despite evidence for microstructural brain alterations in epilepsy patients, little is known about how these develop with age and the progress of the disease. The aim of this study was to investigate microstructural abnormalities of the white matter (WM) in children with new-onset, untreated idiopathic-generalized epilepsy (IGE) using the MRI technique of diffusion tensor imaging (DTI). The study was approved by the institutional review board, and all individuals or their parents gave signed informed consent. In total, 45 patients with IGE (age 5–18 years, male: female 26:19) and 32 healthy controls (HCs; age 5–18 years, male: female 21:11) were included. Voxel-based analysis (VBA) was used to compare patients and controls, and Pearson correlation analysis was used to investigate relationships between altered DTI metrics and clinical parameters. Compared with controls, patients with IGE showed increased mean diffusivity (MD) in the left splenium of the corpus callosum, increased fractional anisotropy (FA) in the right WM of the superior and middle frontal gyri, increased axial diffusivity (AD) in the WM of right corona radiata and left occipital lobe, and decreased AD in the WM of the left thalamus and the right middle cerebellar peduncle. There was no correlation between the altered diffusion parameters and clinical measures. Our study demonstrated several distinct microstructural impairments in children with new-onset, untreated IGE, of which altered AD might be the most sensitive marker of dysmyelination. The increased FA in the IGE group might suggest an initiating or compensatory mechanism that is activated prior to cognitive decline in these children.
Recovery of Body Awareness After Stroke: An Observational Study
Authors: Serrada Ines , Hordacre Brenton , Hillier Susan
Published: December 2021

Background: Body awareness (BA) is a process that involves sensory awareness originating from the body's physiological states, processes and actions, and is shaped by one's attitudes, perceptions, beliefs and experience of social and cultural context. Impairments in body awareness after stroke are believed to be common and may be an important influence on recovery outcomes. However, recovery of body awareness is poorly understood and receives little consideration in rehabilitation.

Aims: To investigate if body awareness changes over time following stroke; and identify if body awareness after stroke is associated with sensation, motor impairment, self-efficacy and quality of life.

Methods: An exploratory longitudinal observational study was performed. Participants with a stroke diagnosis and associated motor impairment were recruited from an acute stroke unit. An assessment battery consisting of sensory and motor impairment and function, body awareness, self-efficacy and quality of life measures were used at baseline, 1, 3 and 6 months.

Results: A total of 105 people with stroke were recruited. Most recovery in sensation and body awareness occurred within the first month after stroke (all p < 0.01). Sensation and body awareness were correlated with other clinical outcomes (motor impairment, self-efficacy and quality of life), demographics, and stroke specific clinical characteristics (all p < 0.01).

Conclusions: This is the first study to track recovery of body awareness after stroke and investigate the relationship it may have in recovery of sensation, motor impairment and function, self-efficacy and quality of life. Further research is now warranted to continue investigation of body awareness and to develop effective stroke-specific assessment and intervention strategies.
Clinical and Economic Outcomes of Intravenous Brivaracetam Compared With Levetiracetam for the Treatment of Seizures in United States Hospitals
Authors: Beaty Silky , Rosenthal Ning A. , Gayle Julie , Dongre Prashant , Ricchetti-Masterson Kristen
Published: December 2021

Background: Seizures are common among hospitalized patients. Levetiracetam (LEV), a synaptic vesicle protein 2A (SV2A) ligand, is a common intravenous (IV) anti-seizure medication option in hospitals. Brivaracetam (BRV), a selective SV2A ligand for treatment of focal seizures in patients ≥16 years, has greater binding affinity, higher lipophilicity, and faster brain entry than IV LEV. Differences in clinical outcomes and associated costs between IV BRV and IV LEV in treating hospitalized patients with seizure remain unknown.

Objectives: To compare the clinical outcomes, costs, and healthcare resource utilization between patients with seizure treated with IV BRV and those with IV LEV within hospital setting.

Design/Methods: A retrospective cohort analysis was performed using chargemaster data from 210 United States hospitals in Premier Healthcare Database. Adult patients (age ≥18 years) treated intravenously with LEV or BRV (with or without BZD) and a seizure discharge diagnosis between July 1, 2016 and December 31, 2019 were included. The cohorts were propensity score-matched 4:1 on baseline characteristics. Outcomes included intubation rates, intensive care unit (ICU) admission, length of stay (LOS), all-cause and seizure-related readmission, total hospitalization cost, and in-hospital mortality. A multivariable regression analysis was performed to determine the association between treatment and main outcomes adjusting for unbalanced confounders.

Results: A total of 450 patients were analyzed (IV LEV, n = 360 vs. IV BRV, n = 90). Patients treated with IV BRV had lower crude prevalence of ICU admission (14.4 vs. 24.2%, P < 0.05), 30-day all-cause readmission (1.1 vs. 6.4%, P = 0.06), seizure-related 30-day readmission (0 vs. 4.2%, P < 0.05), similar mean total hospitalization costs ($13,715 vs. $13,419, P = 0.91), intubation (0 vs. 1.1%, P = 0.59), and in-hospital mortality (4.4 vs. 3.9%, P = 0.77). The adjusted odds for ICU admission (adjusted odds ratio [aOR] = 0.6; 95% confidence interval [CI]:0.31, 1.16; P = 0.13), 30-day all-cause readmission (aOR = 0.17; 95% CI:0.02, 1.24; P = 0.08), and in-hospital mortality (aOR = 1.15; 95% CI:0.37, 3.58, P = 0.81) were statistically similar between comparison groups.

Conclusion: The use of IV BRV may provide an alternative to IV LEV for management of seizures in hospital setting due to lower or comparable prevalence of ICU admission, intubation, and 30-day seizure-related readmission. Additional studies with greater statistical power are needed to confirm these findings.
Monocyte/High-Density Lipoprotein Ratio Predicts the Prognosis of Large Artery Atherosclerosis Ischemic Stroke
Authors: Li Youyu , Chen Daqing , Sun Laifang , Chen Zhibo , Quan Weiwei
Published: December 2021

Objective: Monocyte to high-density lipoprotein ratio is considered as a new inflammatory marker and has been used to predict the severity of coronary heart disease and the incidence of adverse cardiovascular events (ACEs). However, there is a lack of data relative to large artery atherosclerosis (LAA) ischemic stroke. We investigated whether the monocyte to high-density lipoprotein (HDL) ratio (MHR) is related to the 3-month functional prognosis of LAA ischemic stroke.

Materials and Methods: A retrospective analysis was conducted on 316 LAA ischemic stroke patients. The 3-month functional outcome was divided into good and poor according to the modified Rankin Scale (mRS) score. Multivariate logistic regression analysis was performed to evaluate the correlation between MHR and prognosis of ischemic stroke.

Results: The MHR level of poor functional outcome group was higher than that of the good functional outcome group [0.44 (0.3, 0.55) vs. 0.38 (0.27, 0.5), P = 0.025]. Logistic stepwise multiple regression revealed that MHR [odds ratio (OR) 9.464, 95%CI 2.257–39.678, P = 0.002] was an independent risk factor for the 3-month poor outcome of LAA ischemic stroke. Compared to the lower MHR tertile, the upper MHR tertile had a 3.03-fold increase (95% CI 1.475–6.225, P = 0.003) in the odds of poor functional outcome after adjustment for potential confounders. Moreover, a multivariable-adjusted restricted cubic spline (RCS) showed a positive close to a linear pattern of this association.

Conclusion: Elevated MHR was independently associated with an increased risk of poor 3-month functional outcome of patients with LAA ischemic stroke.
Risk Factors for Progression in Vestibular Schwannomas After Incomplete Resection: A Single Center Retrospective Study
Authors: Li Jiuhong , Deng Xueyun , Ke Daibo , Cheng Jian , Zhang Si , Hui Xuhui
Published: December 2021

Background and Purpose: The risk factors for progression in vestibular schwannomas (VSs) after incomplete resection (IR) remain to be elucidated. The purpose of this study was to investigate the risk factors for progression in remnant VSs after surgery.

Methods: From January 2009 to January 2018, 140 consecutive patients who underwent IR of VSs via suboccipital retrosigmoid approach in our institution were retrospectively analyzed. During follow-up, if progression was detected, the patient was classified into Progressive Group (PG); if the residual tumor was stable or shrank, the patient was classified into Stable Group (SG). Univariate analysis and multivariate analysis were used to evaluate the risk factors for progression after IR of VSs.

Results: After a mean follow-up of 80.4 months (range, 24–134 months), 35 (25.0%) patients (PG) had a progression, and no progression was detected in 105 (75.0%) patients (SG). The average tumor size was 36.5 ± 8.9 mm in PG and 31.0 ± 9.8 mm in SG, respectively. The residual tumor volume was 304.6 ± 443.3 mm3 in PG and 75.9 ± 60.0 mm3 in SG, respectively. Univariate analysis showed that preoperative tumor size, residual tumor volume, and irregular internal auditory canal (IAC) expansion were significantly different between the two groups, whereas gender, age, cystic component, or Ki-67 labeling index (LI) did not differ significantly between the two groups. Multivariate analysis showed residual tumor volume was the independent risk factor for progression.

Conclusions: VSs that underwent IR with larger preoperative size, greater residual tumor volume, or irregular IAC expansion may have a higher progression rate. Strict follow-up with shorter interval in these patients to detect early progression is necessary.
A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study
Authors: Kan Juntao , Cheng Junrui , Hu Chun , Chen Liang , Liu Siyu , Venzon Dawna , Murray Mary , Li Shuguang , Du Jun
Published: December 2021

Dietary therapy may be beneficial in alleviating symptoms of chronic fatigue syndrome (CFS), a disorder that is characterized by extreme fatigue and other symptoms, but the cause of which remains unclear. The aim of this study was to evaluate the protective effect of a botanical product containing cistanche (Cistanche tubulosa [Schenk] Wight) and ginkgo (Ginkgo biloba L.) extracts on adults with CFS in a randomized, double-blind, placebo-controlled clinical trial. A total of 190 subjects (35–60 years old, non-obese) with CFS were randomized to receive one tablet of a low dose (120-mg ginkgo and 300-mg cistanche), a high dose (180-mg ginkgo and 450-mg cistanche) or a placebo once daily for 60 days. Blood samples and responses on the Chalder fatigue scale (CFQ 11), the World Health Organization's quality of life questionnaire (WHOQOL), and the sexual life quality questionnaire (SLQQ) were collected at baseline and post-intervention. CFS symptoms of impaired memory or concentration, physical fatigue, unrefreshing sleep, and post-exertional malaise were significantly improved (p < 0.001) in both of the treatment groups. The botanical intervention significantly decreased physical and mental fatigue scores of CFQ 11 and improved WHOQOL and SLQQ scores of the subjects (p < 0.01). Levels of blood ammonia and lactic acid in the treatment groups were significantly lower than those of the placebo group (low-dose: p < 0.05; high-dose: p < 0.01). In addition, the change in lactic acid concentration was negatively associated with the severity of CFS symptoms (p = 0.0108) and was correlated with the change in total physical fatigue score of the CFQ (p = 0.0302). Considering the trivial effect size, the results may lack clinical significance. In conclusion, this botanical product showed promising effects in ameliorating the symptoms of CFS. Clinical trials with improved assessment tools, an expanded sample size, and an extended follow-up period are warranted to further validate the findings.

Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT02807649.
Nutrient Adequacy of Global Food Production
Authors: Chen Canxi , Chaudhary Abhishek , Mathys Alexander
Published: December 2021

A major challenge for countries around the world is to provide a nutritionally adequate diet to their population with limited available resources. A comprehensive analysis that reflects the adequacy of domestic food production for meeting national nutritional needs in different countries is lacking. Here we combined national crop, livestock, aquaculture, and fishery production statistics for 191 countries obtained from UN FAO with food composition databases from USDA and accounted for food loss and waste occurring at various stages to calculate the amounts of calories and 24 essential nutrients destined for human consumption. We then compared the domestic production quantities of all nutrients with their population-level requirements estimated from age- and sex-specific intake recommendations of WHO to assess the nutrient adequacy of the national food production. Our results show inadequate production of seven out of 24 nutrients (choline, calcium, polyunsaturated fatty acids, vitamin A, vitamin E, folate, and iron) in most countries, despite the overall adequacy of the total global production. High-income countries produce adequate amounts of dietary nutrients in general, while the foods produced in low-income countries mainly comprising roots and cereal products often lack in important micronutrients such as choline, calcium, and vitamin B12. South Asian food production barely fulfills half of the required vitamin A. Our study identifies target nutrients for each country whose domestic production should be encouraged for improving nutritional adequacy through interventions such as increasing the production of foods or fortified foods that are rich in these inadequate nutrients while not undermining the local environment. This assessment can serve as an evidence base for nutrition-sensitive policies facilitating the achievement of the Sustainable Development Goals of zero hunger and good health and well-being.
Sex-Specific Effects of Synbiotic Exposure in Mice on Addictive-Like Behavioral Alterations Induced by Chronic Alcohol Intake Are Associated With Changes in Specific Gut Bacterial Taxa and Brain Tryptophan Metabolism
Authors: Pizarro Nieves , Kossatz Elk , González Pedro , Gamero Alba , Veza Emma , Fernández Cristina , Gabaldón Toni , de la Torre Rafael , Robledo Patricia
Published: December 2021

Chronic alcohol intake has been shown to disrupt gut microbiota homeostasis, but whether microbiota modulation could prevent behavioral alterations associated with chronic alcohol intake remains unknown. We investigated the effects of synbiotic dietary supplementation on the development of alcohol-related addictive behavior in female and male mice and evaluated whether these effects were associated with changes in bacterial species abundance, short-chain fatty acids, tryptophan metabolism, and neurotransmitter levels in the prefrontal cortex and hippocampus. Chronic intermittent exposure to alcohol during 20 days induced escalation of intake in both female and male mice. Following alcohol deprivation, relapse-like behavior was observed in both sexes, but anxiogenic and cognitive deficits were present only in females. Synbiotic treatment reduced escalation and relapse to alcohol intake in females and males. In addition, the anxiogenic-like state and cognitive deficits observed in females following alcohol deprivation were abolished in mice exposed to synbiotic. Alcohol-induced differential alterations in microbial diversity and abundance in both sexes. In females, synbiotic exposure abrogated the alterations provoked by alcohol in Prevotellaceae UCG-001 and Ruminococcaceae UCG-014 abundance. In males, synbiotic exposure restored the changes induced by alcohol in Akkermansia and Muribaculum uncultured bacterium abundance. Following alcohol withdrawal, tryptophan metabolites, noradrenaline, dopamine, and γ-aminobutyric acid concentrations in the prefrontal cortex and the hippocampus were correlated with bacterial abundance and behavioral alterations in a sex-dependent manner. These results suggested that a dietary intervention with a synbiotic to reduce gut dysbiosis during chronic alcohol intake may impact differently the gut-brain-axis in females and males.
Determination of 35 Free Amino Acids in Tea Using Ultra-Performance Liquid Chromatography Coupled With Quadrupole Time-of-Flight Mass Spectrometry
Authors: Li Jian , Ma Junmei , Li Qiang , Fan Sufang , Fan Lixin , Ma Hongyu , Zhang Yan , Zheng Lei
Published: December 2021

The purpose of this research was to develop a simple, sensitive, and accurate method for simultaneous determination of 35 free amino acids using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Tea samples were extracted with boiling water bath, and then separated by XBridge BEH Amide column by gradient elution. The exact mass and MS/MS spectra of the target compound was detected under the TOF–MS and Information dependent acquisition (IDA)–MS/MS mode. The results demonstrated good linearity (R2 > 0.9980) in the range of 0.5–1,000 ng/mL. The limits of detection (LODs) were 0.13–25.00 mg/kg and the limits of quantitation (LOQs) were 0.25–50.00 mg/kg. The recovery rate ranged from 70.1 to 105.1% with relative standard deviations (RSDs) <11% (n = 6). This research provides a targeted strategy for developing an analysis method for amino acids in tea.
Claims on Ready-to-Eat Cereals: Are Those With Claims Healthier?
Authors: Parra-Murillo María , Lowery Caitlin M. , Gómez Luis F. , Mora-Plazas Mercedes , Taillie Lindsey Smith , Dillman Carpentier Francesca R.
Published: December 2021

Background:The use of advertising content strategies that suggest consuming a product will confer nutrient- and health-related benefits influences household food purchasing decisions, which increases consumption of energy-dense, nutrient-poor products. We examined the presence of marketing claims regarding nutrient content, health and nature in ready-to-eat (RTE) cereal packages in relation to the products' nutritional quality.

Methods:A cross-sectional content analysis was conducted on 178 RTE cereal packages available in the six largest supermarket chains in four Colombian cities from August to November 2018. The nutritional quality of products was assessed through the nutrient profile model established by the Chilean Law of Food Labeling and Advertising law.

Results:All products sampled exceeded the regulation threshold for at least one nutrient of concern (e.g., high-in calories and/or sugar). The majority (66.3%) of packages had claims related to nature, 57.3% had nutrient-content claims, and 15.7% had health benefit or risk avoidance claims. Most products with nature, nutrient-content, and health claims were high in energy (99.2, 98.0, and 92.9%, respectively) and sugar (88.1, 87.3, and 92.9%, respectively).

Conclusion:RTE cereal products offered in major Colombian supermarket chains are heavily marketed using nutrition- and nature-related claims. Nearly all products with claims are high in energy and sugar, despite the messages conveyed by the claims to consumers. Results support the implementation of mandatory regulations restricting claims on food and beverage products high in nutrients of concern.
Nutrition Status of Children, Teenagers, and Adults From National Health and Nutrition Surveys in Mexico From 2006 to 2020
Authors: Shamah-Levy Teresa , Cuevas-Nasu Lucia , Romero-Martínez Martín , Gómez-Humaran Ignacio Méndez , Ávila-Arcos Marco Antonio , Rivera Juan A.
Published: December 2021

Background: Population-level health and nutrition surveys provide critical anthropometric data used to monitor trends of the prevalence of under nutrition and overweight in children under 5 years old, and overweight and obesity in the population over 5 years of age.

Objective: Analyze the children malnutrition and overweight and obesity in children, teenagers and adults through the National Health and Nutrition Surveys information available from public databases.

Materials and Methods: Comparable anthropometric data was gathered by five Mexican National Health and Nutrition Surveys (in Spanish, ENSANUT). In pre-school-age children, under nutrition status was identified through underweight (Z-score below −2 in weight-for-age), stunting (chronic malnutrition) (Z-score below −2 for length/height-for-age), or wasting (Z-score below −2, for weight-for-length/height); overweight status was defined as a body mass index (BMI, kg/m2) for age over +2. For school-age children and adolescents, a Z-score BMI between +1 and +2 deviations was defined as overweight, and between +2 and +5.5 as obesity. In adults (≥20 years of age), overweight status was classified as a BMI between 25.0 and 29.9, and obesity as ≥30.

Results: The anthropometric data presented derives from the databases of five survey years of the Mexican National Health and Nutrition Survey: 2006, 2012, 2016, 2018, and 2020. They include a total of 210,915 subjects with complete anthropometric data (weight, length/height) distributed on five survey moments; subjects were categorized by age group: pre-school-age children (n = 25,968), school-age children (n = 42,255), adolescents (n = 39,275), and adults (n = 103,417). Prevalence of malnutrition by indicator was calculated: in pre-school-age children: low height- and weight-for-age, low weight-for-height, and overweight; and in school-age children, adolescents, and adults, the indicators calculated were overweight and obesity.

Conclusions: Results demonstrate the importance of maintaining systematic, reliable, and timely national anthropometric data in the population, in order to detect and track trends and to form the basis of nutrition-related public policy.