bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression
Authors: Cao Wen-Jing , Zhang Xiao-Chang , Wan Lin-Yu , Li Qing-Yu , Mu Xiu-Ying , Guo An-Liang , Zhou Ming-Ju , Shen Li-Li , Zhang Chao , Fan Xing , Jiao Yan-Mei , Xu Ruo-Nan , Zhou Chun-Bao , Yuan Jin-Hong , Wang Sheng-Qi , Wang Fu-Sheng , Song Jin-Wen
Published: January 2022

Background

Populations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood.

Methods

In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined.

Results

The frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts.

Conclusions

The results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.
Quantifying Transboundary Plastic Pollution in Marine Protected Areas Across the Mediterranean Sea
Authors: Hatzonikolakis Yannis , Giakoumi Sylvaine , Raitsos Dionysios E. , Tsiaras Kostas , Kalaroni Sofia , Triantaphyllidis George , Triantafyllou George
Published: January 2022

Micro- and macro-plastics pollution is a growing threat for marine biodiversity, ecosystem functioning, and consequently human wellbeing. Numerical models that consider main sources of plastics and simulate their dispersal characteristics are unique tools for exploring plastic pollution in marine protected areas (MPAs). Here, we used a Lagrangian plastic drift model, taking into account various sizes/types of plastic litter, originating from major land-based sources (coastal cities and rivers), to predict plastic accumulation zones in protected areas of the Mediterranean Sea (i.e., nationally designated MPAs, Natura 2000 sites, and Cetacean Critical Habitats). The model predicted that the size of plastic litters plays a key role in their dispersion and ultimate destination (i.e., larger litter travel longer distances). Most of the studied Mediterranean countries (13 out of 15) had at least one national MPA with over 55% of macroplastics originating from sources beyond their borders. Consequently, in many cases, local efforts to reduce plastic pollution in protected areas would be insufficient, especially for macroplastics management. Transboundary collaboration among Mediterranean countries is critical for implementing successful management plans against plastic pollution in their territorial waters and specifically in MPAs.
Recent Advances of Salivary Gland Biopsy in Sjögren's Syndrome
Authors: Liao Rui , Yang Hai-Tao , Li Heng , Liu Li-Xiong , Li Kai , Li Jing-Jing , Liang Jie , Hong Xiao-Ping , Chen Yu-Lan , Liu Dong-Zhou
Published: January 2022

Sjögren's syndrome (SS) is a chronic, systemic, inflammatory autoimmune disease characterized by lymphocyte proliferation and progressive damage to exocrine glands. The diagnosis of SS is challenging due to its complicated clinical manifestations and non-specific signs. Salivary gland biopsy plays an important role in the diagnosis of SS, especially with anti-Sjögren's syndrome antigen A (SSA) and anti-SSB antibody negativity. Histopathology based on biopsy has clinical significance for disease stratification and prognosis evaluation, such as risk assessment for the development of non-Hodgkin's lymphoma. Furthermore, histopathological changes of salivary gland may be implicated in evaluating the efficacy of biological agents in SS. In this review, we summarize the histopathological features of salivary gland, the mechanism of histopathological changes and their clinical significance, as well as non-invasive imaging techniques of salivary glands as a potential alternative to salivary gland biopsy in SS.
Case Report: Uterine Adenosarcoma With Sarcomatous Overgrowth and Malignant Heterologous Elements
Authors: García-Mendoza Yunuén I. , Murguia-Perez Mario , Galván-Linares Aldo I. , Mendoza-Ramírez Saulo , García-Salinas Norma L. , Moctezuma-Ramírez Julio G. , Murillo-Ortiz Blanca O. , Bueno-Rosario Luis Jonathan , Olvera-Olvera Marco A. , Corredor-Alonso Guillermo E.
Published: January 2022

A 46- year-old woman presented a uterine adenosarcoma originating in the lower uterine segment. The diagnosis was made in an endometrial biopsy and confirmed in the pathological examination of the complete surgical specimen, both identifying heterologous malignant elements. In addition, complementary immunohistochemical studies were performed. We reviewed the literature, illustrating the clinical and morphological characteristics and the differential diagnoses to be evaluated.
Genetic Mechanisms Underlying the Evolution of Connectivity in the Human Cortex
Authors: Schmidt Ewoud R. E. , Polleux Franck
Published: January 2022

One of the most salient features defining modern humans is our remarkable cognitive capacity, which is unrivaled by any other species. Although we still lack a complete understanding of how the human brain gives rise to these unique abilities, the past several decades have witnessed significant progress in uncovering some of the genetic, cellular, and molecular mechanisms shaping the development and function of the human brain. These features include an expansion of brain size and in particular cortical expansion, distinct physiological properties of human neurons, and modified synaptic development. Together they specify the human brain as a large primate brain with a unique underlying neuronal circuit architecture. Here, we review some of the known human-specific features of neuronal connectivity, and we outline how novel insights into the human genome led to the identification of human-specific genetic modifiers that played a role in the evolution of human brain development and function. Novel experimental paradigms are starting to provide a framework for understanding how the emergence of these human-specific genomic innovations shaped the structure and function of neuronal circuits in the human brain.
Study of Brain Structure and Function in Chronic Mountain Sickness Based on fMRI
Authors: Bao Haihua , He Xin , Wang Fangfang , Kang Dongjie
Published: January 2022

Objective: Headache and memory impairment are the primary clinical symptoms of chronic mountain sickness (CMS). In this study, we used voxel-based morphometry (VBM) and the amplitude of the low-frequency fluctuation method (ALFF) based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to identify changes in the brain structure and function caused by CMS.

Materials and Methods: T1W anatomical images and a resting-state functional MRI (fMRI) of the whole brain were performed in 24 patients diagnosed with CMS and 25 normal controls matched for age, sex, years of education, and living altitude. MRI images were acquired, followed by VBM and ALFF data analyses.

Results: Compared with the control group, the CMS group had increased gray matter volume in the left cerebellum crus II area, left inferior temporal gyrus, right middle temporal gyrus, right insula, right caudate nucleus, and bilateral lentiform nucleus along with decreased gray matter volume in the left middle occipital gyrus and left middle temporal gyrus. White matter was decreased in the bilateral middle temporal gyrus and increased in the right Heschl's gyrus. Resting-state fMRI in patients with CMS showed increased spontaneous brain activity in the left supramarginal gyrus, left parahippocampal gyrus, and left middle temporal gyrus along with decreased spontaneous brain activity in the right cerebellum crus I area and right supplementary motor area.

Conclusion: Patients with CMS had differences in gray and white matter volume and abnormal spontaneous brain activity in multiple brain regions compared to the controls. This suggests that long-term chronic hypoxia may induce changes in brain structure and function, resulting in CMS.
Stroke Telerehabilitation in Calabria: A Health Technology Assessment
Authors: Contrada Marianna , Arcuri Francesco , Tonin Paolo , Pignolo Loris , Mazza Tiziana , Nudo Giuseppe , Pignataro Maria Luigina , Quintieri Maria , Iozzi Antonella , Cerasa Antonio
Published: January 2022

Introduction:Telerehabilitation (TR) is defined as a model of home service for motor and cognitive rehabilitation, ensuring continuity of care over time. TR can replace the traditional face-to-face approach as an alternative method of delivering conventional rehabilitation and applies to situations where the patient is unable to reach rehabilitation facilities or for low-income countries where outcomes are particularly poor. For this reason, in this study, we sought to demonstrate the feasibility and utility of a well-known TR intervention on post-stroke patients living in one of the poorest indebted regions of Italy, where the delivery of rehabilitation services is inconsistent and not uniform.

Materials and Methods:Nineteen patients (13 male/6 female; mean age: 61.1 ± 8.3 years) with a diagnosis of first-ever ischemic (n= 14) or hemorrhagic stroke (n= 5), who had been admitted to the intensive rehabilitation unit (IRU) of the Institute S. Anna (Crotone, Italy), were consecutively enrolled to participate in this study. After the discharge, they continued the motor treatment remotely by means of a home-rehabilitation system. The entire TR intervention was performed (online and offline) using the Virtual Reality Rehabilitation System (VRRS) (Khymeia, Italy). All patients received intensive TR five times a week for 12 consecutive weeks (60 sessions, each session lasting about 1h).

Results:We found a significant motor recovery after TR protocol as measured by the Barthel Index (BI); Fugl-Meyer motor score (FM) and Motricity Index (MI) of the hemiplegic upper limbs.

Conclusions:This was the first demonstration that a well-defined virtual reality TR tool promotes motor and functional recovery in post-stroke patients living in a low-income Italian region, such as Calabria, characterized by a paucity of specialist rehabilitation services.
Age-Specific Adult Rat Brain MRI Templates and Tissue Probability Maps
Authors: MacNicol Eilidh , Wright Paul , Kim Eugene , Brusini Irene , Esteban Oscar , Simmons Camilla , Turkheimer Federico E. , Cash Diana
Published: January 2022

Age-specific resources in human MRI mitigate processing biases that arise from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue's relative contribution to total brain volume would change with age in the adult rat. Data from a longitudinal study of rats at 3, 5, 11, and 17 months old were used to test this hypothesis. Tissue volume was estimated from high resolution structural images using a priori information from tissue probability maps. However, existing tissue probability maps generated inaccurate gray matter probabilities in subcortical structures, particularly the thalamus. To address this issue, gray matter, white matter, and CSF tissue probability maps were generated by combining anatomical and signal intensity information. The effects of age on volumetric estimations were then assessed with mixed-effects models. Results showed that herein estimation of gray matter volumes better matched histological evidence, as compared to existing resources. All tissue volumes increased with age, and the tissue proportions relative to total brain volume varied across adulthood. Consequently, a set of rat brain templates and tissue probability maps from across the adult lifespan is released to expand the preclinical MRI community's fundamental resources.
ConGen—A Simulator-Agnostic Visual Language for Definition and Generation of Connectivity in Large and Multiscale Neural Networks
Authors: Herbers Patrick , Calvo Iago , Diaz-Pier Sandra , Robles Oscar D. , Mata Susana , Toharia Pablo , Pastor Luis , Peyser Alexander , Morrison Abigail , Klijn Wouter
Published: January 2022

An open challenge on the road to unraveling the brain's multilevel organization is establishing techniques to research connectivity and dynamics at different scales in time and space, as well as the links between them. This work focuses on the design of a framework that facilitates the generation of multiscale connectivity in large neural networks using a symbolic visual language capable of representing the model at different structural levels—ConGen. This symbolic language allows researchers to create and visually analyze the generated networks independently of the simulator to be used, since the visual model is translated into a simulator-independent language. The simplicity of the front end visual representation, together with the simulator independence provided by the back end translation, combine into a framework to enhance collaboration among scientists with expertise at different scales of abstraction and from different fields. On the basis of two use cases, we introduce the features and possibilities of our proposed visual language and associated workflow. We demonstrate that ConGen enables the creation, editing, and visualization of multiscale biological neural networks and provides a whole workflow to produce simulation scripts from the visual representation of the model.
Dynamic Functional Connectivity Alterations and Their Associated Gene Expression Pattern in Autism Spectrum Disorders
Authors: Ma Lin , Yuan Tengfei , Li Wei , Guo Lining , Zhu Dan , Wang Zirui , Liu Zhixuan , Xue Kaizhong , Wang Yaoyi , Liu Jiawei , Man Weiqi , Ye Zhaoxiang , Liu Feng , Wang Junping
Published: January 2022

Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that are highly heritable and are associated with impaired dynamic functional connectivity (DFC). However, the molecular mechanisms behind DFC alterations remain largely unknown. Eighty-eight patients with ASDs and 87 demographically matched typical controls (TCs) from the Autism Brain Imaging Data Exchange II database were included in this study. A seed-based sliding window approach was then performed to investigate the DFC changes in each of the 29 seeds in 10 classic resting-state functional networks and the whole brain. Subsequently, the relationships between DFC alterations in patients with ASDs and their symptom severity were assessed. Finally, transcription-neuroimaging association analyses were conducted to explore the molecular mechanisms of DFC disruptions in patients with ASDs. Compared with TCs, patients with ASDs showed significantly increased DFC between the right dorsolateral prefrontal cortex (DLPFC) and left fusiform/lingual gyrus, between the DLPFC and the superior temporal gyrus, between the right frontal eye field (FEF) and left middle frontal gyrus, between the FEF and the right angular gyrus, and between the left intraparietal sulcus and the right middle temporal gyrus. Moreover, significant relationships between DFC alterations and symptom severity were observed. Furthermore, the genes associated with DFC changes in ASDs were identified by performing gene-wise across-sample spatial correlation analysis between gene expression extracted from six donors’ brain of the Allen Human Brain Atlas and case-control DFC difference. In enrichment analysis, these genes were enriched for processes associated with synaptic signaling and voltage-gated ion channels and calcium pathways; also, these genes were highly expressed in autistic disorder, chronic alcoholic intoxication and several disorders related to depression. These results not only demonstrated higher DFC in patients with ASDs but also provided novel insight into the molecular mechanisms underlying these alterations.
Grain-Based Dietary Background Impairs Restoration of Blood Flow and Skeletal Muscle During Hindlimb Ischemia in Comparison With Low-Fat and High-Fat Diets
Authors: Stafeev Iurii , Boldyreva Maria , Michurina Svetlana , Mamontova Elizaveta , Ratner Elizaveta , Menshikov Mikhail , Parfyonova Yelena
Published: January 2022

Background: Among vascular pathologies associated with obesity, peripheral artery disease (PAD) occupies the important position. In clinical practice, nutritional interventions are recommended for patients with PAD. In this work, we investigated how the different dietary backgrounds affect the regeneration rate of ischemic hindlimb in mice.

Methods: Male C57BL/6J mice were housed on three types of diet: low-fat (LFD), high-fat (HFD), and grain-based diet (GBD) for 13 weeks. Metabolic parameters including FBG level, ITT, and GTT were evaluated. The blood flow was assessed by laser Doppler scanning on 7, 14, and 21 days after hindlimb ischemia. Necrotic area of m.tibialis, macrophage infiltration, and angiogenesis/arteriogenesis were evaluated by histology. Glucose uptake in recovered skeletal muscle was analyzed using [3H]-2-deoxyglucose, and GLUT1 and GLUT4 expression were assessed by Western blotting.

Results: In our work, we developed three experimental groups with different metabolic parameters: LFD with normal glucose metabolism, GBD with mild hyperglycemia, and HFD with impaired glucose tolerance. GBD-fed mice had a tendency to increase necrosis of m. tibialis and significantly higher macrophage infiltration than LFD and HFD groups. Moreover, GBD-fed mice had a trend to decreased blood flow recovery and significantly impaired arteriogenesis. Recovered skeletal muscle of GBD-fed mice had lower glucose uptake and decreased level of GLUT4 expression.

Conclusion: Thus, we conclude that dietary background and metabolic status determine the rate of post-ischemic regeneration including angiogenesis, skeletal muscle recovery and metabolic activity. The most effective regeneration is supported by LFD, while the lowest rate of regeneration occurs on GBD.
The Interaction Between N6-Methyladenosine Modification and Non-Coding RNAs in Gastrointestinal Tract Cancers
Authors: Yao Lin , Man Chang-Feng , He Rong , He Lian , Huang Jia-Bin , Xiang Shou-Yan , Dai Zhe , Wang Xiao-Yan , Fan Yu
Published: January 2022

N6-methyladenosine (m6A) is the most common epigenetic modification of eukaryotic RNA, which can participate in the growth and development of the body and a variety of physiological and disease processes by affecting the splicing, processing, localization, transport, translation, and degradation of RNA. Increasing evidence shows that non-coding RNAs, particularly microRNA, long non-coding RNA, and circular RNA, can also regulate the RNA m6A modification process by affecting the expression of m6A-related enzymes. The interaction between m6A modification and non-coding RNAs provides a new perspective for the exploration of the potential mechanism of tumor genesis and development. In this review, we summarize the potential mechanisms and effects of m6A and non-coding RNAs in gastrointestinal tract cancers.
Opportunities and Challenges of Nanoparticles in Digestive Tumours as Anti-Angiogenic Therapies
Authors: Yang Zhengyang , Deng Wei , Zhang Xiao , An Yongbo , Liu Yishan , Yao Hongwei , Zhang Zhongtao
Published: January 2022

Digestive tumours, a common kind of malignancy worldwide, have recently led to the most tumour-related deaths. Angiogenesis, the process of forming novel blood vessels from pre-existing vessels, is involved in various physiological and pathological processes in the body. Many studies suggest that abnormal angiogenesis plays an important role in the growth, progression, and metastasis of digestive tumours. Therefore, anti-angiogenic therapy is considered a promising target for improving therapeutic efficacy. Traditional strategies such as bevacizumab and regorafenib can target and block the activity of proangiogenic factors to treat digestive tumours. However, due to resistance and some limitations, such as poor pharmacokinetics, their efficacy is not always satisfactory. In recent years, nanotechnology-based anti-angiogenic therapies have emerged as a new way to treat digestive tumours. Compared with commonly used drugs, nanoparticles show great potential in tumour targeted delivery, controlled drug release, prolonged cycle time, and increased drug bioavailability. Therefore, anti-angiogenic nanoparticles may be an effective complementary therapy to treat digestive tumours. In this review, we outline the different mechanisms of angiogenesis, the effects of nanoparticles on angiogenesis, and their biomedical applications in various kinds of digestive tumours. In addition, the opportunities and challenges are briefly discussed.
Precision Cardio-Oncology: Use of Mechanistic Pharmacokinetic and Pharmacodynamic Modeling to Predict Cardiotoxicities of Anti-Cancer Drugs
Authors: Wen Hai-ni , Wang Chen-yu , Li Jin-meng , Jiao Zheng
Published: January 2022

The cardiotoxicity of anti-cancer drugs presents as a challenge to both clinicians and patients. Significant advances in cancer treatments have improved patient survival rates, but have also led to the chronic effects of anti-cancer therapies becoming more prominent. Additionally, it is difficult to clinically predict the occurrence of cardiovascular toxicities given that they can be transient or irreversible, with large between-subject variabilities. Further, cardiotoxicities present a range of different symptoms and pathophysiological mechanisms. These notwithstanding, mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) modeling offers an important approach to predict cardiotoxicities and offering precise cardio-oncological care. Efforts have been made to integrate the structures of physiological and pharmacological networks into PK-PD modeling to the end of predicting cardiotoxicities based on clinical evaluation as well as individual variabilities, such as protein expression, and physiological changes under different disease states. Thus, this review aims to report recent progress in the use of PK-PD modeling to predict cardiovascular toxicities, as well as its application in anti-cancer therapies.
Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation
Authors: Xiang Zhenxian , He Qiuming , Huang Li , Xiong Bin , Xiang Qingming
Published: January 2022

Background

Tumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.

Methods

Tissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.

Results

High-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).

Conclusion

The combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.
Maternal Sweeteners Intake Modulates Gut Microbiota and Exacerbates Learning and Memory Processes in Adult Male Offspring
Authors: de la Garza Ana Laura , Romero-Delgado Bianca , Martínez-Tamez Alejandra Mayela , Cárdenas-Tueme Marcela , Camacho-Zamora Bianka Dianey , Matta-Yee-Chig Daniel , Sánchez-Tapia Mónica , Torres Nimbe , Camacho-Morales Alberto
Published: January 2022

Background: There is increasing evidence that gut microbiota in offspring is derived in part from maternal environment such as diet. Thus, sweeteners intake including caloric or non-caloric during perinatal period can induce gut dysbiosis and program the offspring to develop cognitive problems later in life.

Objective: To determine the effect of maternal high-sweeteners intake during gestation and lactation on gut microbiota shifts in adult male offspring rats and the impact on cognitive dysfunction.

Methods: Thirty-four male pups from dams fed standard diet (Control-C, n = 10), high-sucrose diet (HS-C, n = 11), high-honey diet (Ho-C, n = 8), and high-stevia diet (HSt-C, n = 5) were fed standard diet after weaning, and body weight and food intake were recorded once a week for 26 weeks. Learning and memory tests were performed at week 23 of life using the Barnes maze. Fecal samples from the breastfeeding and adulthood periods were collected and analyzed by sequencing the 16S rRNA V3-V4 region of gut microbiota.

Results: Maternal high-sucrose and stevia diets programmed the male offspring, and changes in microbial diversity by Shannon index were observed after weaning (p < 0.01). Furthermore, maternal high-stevia diet programming lasted into adulthood. The increase of Firmicutes abundance and the decrease in phylum Bacteroidetes were significant in HS-C and HSt-C groups. This led to an increase in the Firmicutes/Bacteroidetes index, although only in HS-C group was statistically significant (p < 0.05). Of note, the downstream gram-negative Bacteroidales and the upregulation of the gram-positive Clostridiales abundance contribute to cognitive dysfunction.

Conclusion: These results suggest that dams fed a high-sucrose and stevia diets during gestation and lactation favor a deficient memory performance in adult male offspring rats through shifts gut microbiota diversity and relative abundance at several taxa.
Impact of Sampling Time Variability on Tacrolimus Dosage Regimen in Pediatric Primary Nephrotic Syndrome: Single-Center, Prospective, Observational Study
Authors: Huang Lingfei , Wang Junyan , Yang Jufei , Zhang Huifen , Hu Yan , Miao Jing , Mao Jianhua , Fang Luo
Published: January 2022

Background: Tacrolimus (TAC) is an important immunosuppressant for children with primary nephrotic syndrome (PNS). The relationship between sampling time variability in TAC therapeutic drug monitoring and dosage regimen in such children is unknown.

Methods: In this single-center, prospective, observational study, we evaluated the sampling time variability, concentration error (CE), relative CE (RCE), and the impact of the sampling time on TAC dosage regimens in 112 PNS children with 188 blood samples. Nominal concentration (Cnom) at 12-h after last TAC dose was simulated based on observed concentration (Cobs) via previously published pharmacokinetic models, then CE and RCE were calculated. Inappropriate dosing adjustments resulting from deviated sampling time were evaluated based on a target Cnom of 5–10 ng/ml.

Results: We found that 32 and 68% of samples were respectively collected early (2–180 min) and delayed (4–315 min). Furthermore, 24, 22, 22, and 32% of blood samples were drawn within deviations of ≤0.5, 0.5–1, 1–2, and >2 h, respectively, and 0.3 ng/ml of CE and 6% RCE per hour of deviation occurred. Within a deviation of >2 h, 25% of Cobs might result in inappropriate dosing adjustments. Early and delayed sampling might result in inappropriate dose holding or unnecessary dose increments, respectively, in patients with Cobs ∼ 5 ng/ml.

Conclusions: Variable sampling time might lead to inappropriate dosing adjustment in a minority of children with PNS, particularly those with TAC Cobs ∼ 5 ng/ml collected with a deviation of >2 h.
Sidastrum paniculatum (L.) Fryxell (Malvaceae): A Promising Source of Bioactive Sulfated Flavonoids Against Aedes aegypti L
Authors: Marques Sany D. G. , Fernandes Diégina A. , Teles Yanna C. F. , Menezes Renata. P. B. , Maia Mayara S. , Scotti Marcus T. , Agra Maria F. , Silva Tania M. S. , de Souza Maria de Fátima Vanderlei
Published: January 2022

Aedes aegypti L. is known as the most relevant vector mosquito for viruses such as yellow fever, chikungunya, dengue, and Zika, especially in places with unplanned urbanization, and erratic water supply. Plants used in folk medicine have become a useful source of active compounds with the potential to control the dissemination of Ae. aegypti. Compounds isolated from Malvaceae sensu lato have been previously reported as larvicides, repellents, and insecticides. Recent studies have demonstrated the anti Ae. aegypti activity of sulfated flavonoids, an uncommon type of flavonoid derivatives. This research reports the phytochemical investigation of Sidastrum paniculatum (L.) Fryxell, a Malvaceae species with the potential against Ae. aegypti. Chromatographic procedures resulted in the isolation of the compounds: stearic acid (1), N-trans-feruloyltyramine (2), acacetin (3), apigenin (4), tiliroside (5), along with the sulfated flavonoids: wissadulin (6), 7,4′-di-O-methyl-8-O-sulfate flavone (7), yannin (8), beltraonin (9a), 7-O-sulfate isoscutellarein (paniculatumin) (9b), and condadin (10). This is the first report of compound 7-O-sulfate isoscutellarein (9b). The structures were elucidated by spectroscopic analysis (NMR, LC-HRMS and FT-IR). The sulfated flavonoids identified were submitted to a ligand-based and structure-based virtual screening against two targets: 1YIY (from adult Ae. aegypti) and 1PZ4 (from Ae. aegypti larvae). The results indicated that when the O-sulfate group is bearing the position 7, the structures are potentially active in 1PZ4 protein. On the other hand, flavonoids with the O-sulfate group bearing position 8 were showed to be more likely to bind to the 1YIY protein. Our findings indicated that S. paniculatum is a promising source of sulfated flavonoids with potential against Ae. aegypti.
Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging
Authors: De Silva Leanne , Fu Ju-Yen , Htar Thet Thet , Wan Kamal Wan Hamirul Bahrin , Kasbollah Azahari , Muniyandy Saravanan , Chuah Lay-Hong
Published: January 2022

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.
Microbiopsy Sampling for Examining Age-Related Differences in Skeletal Muscle Fiber Morphology and Composition
Authors: Hester Garrett M. , VanDusseldorp Trisha A. , Ha Phuong L. , Kiani Kaveh , Olmos Alex A. , Jabbari Melody , Kalladanthyil Shania , An SooBin , Bailly Alyssa R. , Dalton Benjamin E. , Bryantsev Anton L.
Published: January 2022

Introduction: The increasingly popular microbiopsy is an appealing alternative to the more invasive Bergström biopsy given the challenges associated with harvesting skeletal muscle in older populations. Parameters of muscle fiber morphology and composition derived from the microbiopsy have not been compared between young and older adults.

Purpose: The purpose of this study was to examine muscle fiber morphology and composition in young (YM) and older (OM) males using the microbiopsy sampling technique. A secondary aim was to determine if specific strength is associated with serum levels of C-terminal agrin fragment [CAF; an indicator of neuromuscular junction (NMJ) degradation].

Methods: Thirty healthy, YM (n = 15, age = 20.7 ± 2.2 years) and OM (n = 15, age = 71.6 ± 3.9 years) underwent ultrasound imaging to determine whole-muscle cross-sectional area (CSA) of the vastus lateralis and rectus femoris as well as isometric and isokinetic (60°⋅s–1 and 180°⋅s–1) peak torque testing of the knee extensors. Microbiopsy samples of the vastus lateralis were collected from 13 YM and 11 OM, and immunofluorescence was used to calculate CSA and proportion of type I and type II fibers.

Results: Peak torque was lower in OM at all velocities (p ≤ 0.001; d = 1.39–1.86) but only lower at 180°⋅s–1 (p = 0.003; d = 1.23) when normalized to whole-muscle CSA. Whole-muscle CSA was smaller in OM (p = 0.001; d = 1.34), but atrophy was not present at the single fiber level (p > 0.05). Per individual, ∼900 fibers were analyzed, and type I fiber CSA was larger (p = 0.05; d = 0.94) in OM which resulted in a smaller type II/I fiber CSA ratio (p = 0.015; d = 0.95). CAF levels were not sensitive to age (p = 0.159; d = 0.53) nor associated with specific strength or whole-muscle CSA in OM.

Conclusion: The microbiopsy appears to be a viable alternative to the Bergström biopsy for histological analyses of skeletal muscle in older adults. NMJ integrity was not influential for age-related differences in specific strength in our healthy, non-sarcopenic older sample.
Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice
Authors: Zhu Lin , An Julia , Chinnarasu Sivaprakasam , Luu Thao , Pettway Yasminye D. , Fahey Kelly , Litts Bridget , Kim Hye-Young H. , Flynn Charles R. , Linton MacRae F. , Stafford John M.
Published: January 2022

Mounting evidence has shown that CETP has important physiological roles in adapting to chronic nutrient excess, specifically, to protect against diet-induced insulin resistance. However, the underlying mechanisms for the protective roles of CETP in metabolism are not yet clear. Mice naturally lack CETP expression. We used transgenic mice with a human CETP minigene (huCETP) controlled by its natural flanking region to further understand CETP-related physiology in response to obesity. Female huCETP mice and their wild-type littermates were fed a high-fat diet for 6 months. Blood lipid profile and liver lipid metabolism were studied. Insulin sensitivity was analyzed with euglycemic-hyperinsulinemic clamp studies combined with 3H-glucose tracer techniques. While high-fat diet feeding induced obesity for huCETP mice and their wild-type littermates lacking CETP expression, insulin sensitivity was higher for female huCETP mice than for their wild-type littermates. There was no difference in insulin sensitivity for male huCETP mice vs. littermates. The increased insulin sensitivity in females was largely caused by the better insulin-mediated suppression of hepatic glucose production. In huCETP females, CETP in the circulation decreased HDL-cholesterol content and increased liver cholesterol uptake and liver cholesterol and oxysterol contents, which was associated with the upregulation of LXR target genes in long-chain polyunsaturated fatty acid biosynthesis and PPARα target genes in fatty acid β-oxidation in the liver. The upregulated fatty acid β-oxidation may account for the improved fatty liver and liver insulin action in female huCETP mice. This study provides further evidence that CETP has beneficial physiological roles in the metabolic adaptation to nutrient excess by promoting liver fatty acid oxidation and hepatic insulin sensitivity, particularly for females.
Maize Growth Responses to a Humic Product in Iowa Production Fields: An Extensive Approach
Authors: Olk Daniel C. , Dinnes Dana L. , Callaway Chad R.
Published: January 2022

Field evaluations of commercial humic products have seldom involved replication across location or year. To evaluate the consistency of humic product efficacy in field conditions, we determined the effects of a humic product on maize (Zea mays L.) growth in high-yielding Midwestern (US) fields through the following two extensive approaches: (i) replicated strip plots in five site—year combinations from 2010 to 2013; and (ii) demonstration strips in 30–35 production fields annually from 2009 to 2011 that covered major areas of Iowa. Mechanized combine measurements of grain yield showed increases of 0.2–0.4 Mg ha–1 (1–4%) with humic product application for all five site—year combinations of the replicated strip plots. Six of 10 humic treatments within the fields responded positively (P < 0.07), and the positive responses of two more treatments approached significance at the benchmark of P = 0.10. In the demonstration strips, maize grain weight in hand-collected samples increased significantly (P < 0.004) with humic product application in each of the three growing seasons, and across all the three seasons by 6.5% (P < 0.001). Grain weight increased numerically for 76 of the 98 demonstration strips. Yield component analysis for both the replicated strip plots and the demonstration strips attributed the yield boosts largely to increased ear length, especially of the shorter ears. Humic product application caused significantly (P < 0.10) greater total leaf area in all eight field treatments at three site—year combinations. Humic product application did not consistently affect nutrient concentrations of the grain or stover or any measured soil property. These results represent among the widest geographic evaluations published on field efficacy of a humic product. They demonstrate the capability of a humic product to improve maize growth in high-yielding conditions.
An Efficient Root Transformation System for Recalcitrant Vicia sativa
Authors: Nguyen Vy , Searle Iain R.
Published: January 2022

Common vetch (Vicia sativa) is a multi-purpose legume widely used in pasture and crop rotation systems. Vetch seeds have desirable nutritional characteristics and are often used to feed ruminant animals. Although transcriptomes are available for vetch, problems with genetic transformation and plant regeneration hinder functional gene studies in this legume species. Therefore, the aim of this study was to develop a simple, efficient and rapid hairy root transformation system for common vetch to facilitate functional gene analysis. At first, we infected the hypocotyls of 5-day-old in vitro or in vivo, soil-grown seedlings with Rhizobium rhizogenes K599 using a stabbing method and produced transgenic hairy roots after 24 days at 19 and 50% efficiency, respectively. We later improved the hairy root transformation in vitro by infecting different explants (seedling, hypocotyl-epicotyl, and shoot) with R. rhizogenes. We observed hairy root formation at the highest efficiency in shoot and hypocotyl-epicotyl explants with 100 and 93% efficiency, respectively. In both cases, an average of four hairy roots per explant were obtained, and about 73 and 91% of hairy roots from shoot and hypocotyl-epicotyl, respectively, showed stable expression of a co-transformed marker β-glucuronidase (GUS). In summary, we developed a rapid, highly efficient, hairy root transformation method by using R. rhizogenes on vetch explants, which could facilitate functional gene analysis in common vetch.
Kaolin Film Increases Gas Exchange Parameters of Coffee Seedlings During Transference From Nursery to Full Sunlight
Authors: de Abreu Deivisson Pelegrino , Roda Newton de Matos , de Abreu Gideao Pelegrino , Bernado Wallace de Paula , Rodrigues Weverton Pereira , Campostrini Eliemar , Rakocevic Miroslava
Published: January 2022

Increases in water use efficiency (WUE) and the reduction of negative impacts of high temperatures associated with high solar radiation are being achieved with the application of fine particle film of calcined and purified kaolin (KF) on the leaves and fruits of various plant species. KF was applied on young Coffea arabica and Coffea canephora plants before their transition from nursery to full sunlight during autumn and summer. The effects of KF were evaluated through the responses of leaf temperature (Tleaf), net CO2 assimilation rate (A), stomatal conductance (gs), transpiration (E), WUE, crop water stress index (CWSI), index of relative stomatal conductance (Ig), initial fluorescence (F0), and photosynthetic index (PI) in the first 2–3 weeks after the plant transitions to the full sun. All measurements were performed at midday. In Coffea plants, KF decreased the Tleaf up to 6.7°C/5.6°C and reduced the CWSI. The plants that were not protected with KF showed lower A, gs, E, and Ig than those protected with KF. C. canephora plants protected with KF achieved higher WUE compared with those not protected by 11.23% in autumn and 95.58% in summer. In both Coffea sp., KF application reduced F0, indicating reduced physical dissociation of the PSII reaction centers from the light-harvesting system, which was supported with increased PI. The use of KF can be recommended as a management strategy in the transition of Coffea seedlings from the nursery shade to the full sunlight, to protect leaves against the excessive solar radiation and high temperatures, especially in C. canephora during the summer.
Higher Education Students’ Reflective Journal Writing and Lifelong Learning Skills: Insights From an Exploratory Sequential Study
Authors: Alt Dorit , Raichel Nirit , Naamati-Schneider Lior
Published: January 2022

Reflective journal (RJ) writing has been recognized as an effective pedagogical tool for nurturing students’ lifelong learning skills. With the paucity of empirical work on the dimensionality of reflective writing, this research sought to qualitatively analyze students’ RJ writing and design a generic reflection scheme for identifying dimensions of reflective thinking. Drawing on the theoretical scheme, another aim was to design and validate a questionnaire to measure students’ perceptions of their reflective writing experiences. The last aim was to quantitatively measure the link between perceived reflective writing and students’ tendency to use RJs in their future careers and personal lives. This exploratory sequential research included the following steps: First, experts’ review and analysis of 1312 RJ entries were attained. This step led to the design of a theoretical scheme of reflective writing and a 31-item questionnaire, used to gather data from 171 students (second-year pre-service teachers and third-year health managers). Partial Least Squares analysis corroborated the structure suggested by the theoretical scheme: two timelines–reflections regarding the current course assignments and those related to the student’s future development. Students’ tendency to use reflective skills in their future professional lives was highly connected to their long-term reflections, including learning experiences linked to academic, professional, personal, and multicultural development. The current study’s suggested validated generic scheme can be adapted and integrated into different curricula, thereby possibly increasing the potential of infusing RJ instructional strategies into higher education curricula, improving the quality of reflection in student journals, and promoting lifelong learning skills.
Design Innovation and Entrepreneurship Organization Based on Psychological Cognitiveness of the Space Narrative
Authors: Hu Jieming , Zhang Xin
Published: January 2022

The high-quality workspace can be used as a physical carrier for design innovation and entrepreneurial organizational culture to continuously change the psychological cognition and behavior of employees in community of practice. The spatial narrative of the culture of design innovation and entrepreneurial organizations means to integrate entrepreneurship and organizational culture into the space through visual presentation. Whether the spatial narrative is successful or not needs to be judged by whether the change of people’s psychological cognition achieves the expected effect. The traditional qualitative research methods such as interviews and questionnaires cannot fully and accurately present the psychological cognitive mechanism of design Innovation and entrepreneurship organization members. We use virtual reality technology combined with electrophysiological technology to conduct experiments. We use these technologies to conduct quantitative experiments on psychological cognition in community of practice. This study will select a design innovation and entrepreneurial organization, randomly select 20 participants, and divide them into 2 groups for experimentation. The VR scene is based on their real office space as a prototype. Put the visual elements of corporate culture in one of the VR scenes. The other VR scene as a reference does not incorporate visual elements of organizational culture. Participants participated in the experiment in these two VR scenarios. There are many advanced devices that can accurately test individual psychological changes, but the ErgoLab man-machine environment test platform, can collect and compare these data [physiological data, electroencephalogram (EEG) data, and behavior data] in real-time and comprehensively, which is its advantage. According to the experimental results, judge the changes in the psychological cognitive data of the participants before and after the placement of the spatial narrative in design innovation and entrepreneurial organizations. The experiment combined interviews and questionnaires to ensure the authenticity of the quantitative data. The conclusion of the experiment will produce an accurate quantitative study on the psychological cognition of the spatial narrative of design innovation and entrepreneurial organizational culture. A sense of organizational belonging, collective sense, pride, mission, and work fun can be generated in the workspace.