bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Antibiotic Resistance Genes and Antibiotic-Resistant Bacteria in Full-Scale Drinking Water Treatment System Using Metagenomics and Culturing
Authors: Gu Qihui , Sun Ming , Lin Tao , Zhang Youxiong , Wei Xianhu , Wu Shi , Zhang Shuhong , Pang Rui , Wang Juan , Ding Yu , Liu Zhenjie , Chen Ling , Chen Wei , Lin Xiuhua , Zhang Jumei , Chen Moutong , Xue Liang , Wu Qingping
Published: February 2022

The contamination of antibiotic resistance genes (ARGs) may directly threaten human health. This study used a metagenomic approach to investigate the ARG profile in a drinking water treatment system (DWTS) in south China. In total, 317 ARG subtypes were detected; specifically, genes encoding bacitracin, multidrug, and sulfonamide were widely detected in the DWTS. Putative ARG hosts included Acidovorax (6.0%), Polynucleobacter (4.3%), Pseudomonas (3.4%), Escherichia (1.7%), and Klebsiella (1.5%) as the enriched biomarkers in the DWTS, which mainly carried bacitracin, beta-lactam, and aminoglycoside ARGs. From a further analysis of ARG-carrying contigs (ACCs), Stenotrophomonas maltophilia and Pseudomonas aeruginosa were the most common pathogens among the 49 ACC pathogens in the DWTS. The metagenomic binning results demonstrated that 33 high-quality metagenome-assembled genomes (MAGs) were discovered in the DWTS; particularly, the MAG identified as S. maltophilia-like (bin.195) harbored the greatest number of ARG subtypes (n = 8), namely, multidrug (n = 6; smeD, semE, multidrug_transporter, mexE, semB, and smeC), beta-lactam (n = 1; metallo-beta-lactamase), and aminoglycoside [n = 1; aph(3’)-IIb]. The strong positive correlation between MGEs and ARG subtypes revealed a high ARG dissemination risk in the DWTS. Based on the pure-culture method, 93 isolates that belong to 30 genera were recovered from the DWTS. Specifically, multidrug-resistant pathogens and opportunistic pathogens such as P. aeruginosa, Bacillus cereus, and S. maltophilia were detected in the DWTS. These insights into the DWTS’s antibiotic resistome indicated the need for more comprehensive ARG monitoring and management in the DWTS. Furthermore, more effective disinfection methods need to be developed to remove ARGs in DWTSs, and these findings could assist governing bodies in the surveillance of antibiotic resistance in DWTSs.
Differential Effect of Dietary Fibers in Intestinal Health of Growing Pigs: Outcomes in the Gut Microbiota and Immune-Related Indexes
Authors: Luo Yuheng , Liu Yang , Li Hua , Zhao Yao , Wright André-Denis G. , Cai Jingyi , Tian Gang , Mao Xiangbing
Published: February 2022

Although dietary fibers (DFs) have been shown to improve intestinal health in pigs, it is unclear whether this improvement varies according to the type/source of DF. In the current study, we investigated the impact of dietary supplement (15%) of pea-hull fiber (PF), oat bran (OB), and their mixture (MIX, PF, and OB each accounted for 7.5%) in the growth performance as well as intestinal barrier and immunity-related indexes in growing pigs. Twenty-four cross-bred pigs (32.42 ± 1.95 kg) were divided into four groups: CON (basal diet with no additional DF), PF, OB, and MIX. After 56 days of feeding, we found that the growth performance of PF pigs was decreased (p < 0.05) compared with pigs in other groups. Results of real-time polymerase chain reaction and Western blot showed that the improvement of immune-related indexes (e.g., interleukin 10 [IL-10]) in OB and MIX pigs mainly presented in the ileum, whereas the improvement of intestinal barrier–related indexes (e.g., MUC1 and MUC2) mainly presented in the colon. Whether in the ileum or colon, such improvement of immune function may be dependent on NOD rather than TLR-associated pathways. Amplicon sequencing results showed that PF and MIX pigs shared a similar bacterial community, such as lower abundance of ileal Clostridiaceae and colonic Streptoccocus than that of CON pigs (p < 0.05). Our results indicate that OB and MIX, rather than PF, benefit the intestinal health in growing pigs, and multiple-sourced DF may reduce the adverse effect of single-soured DF on the growth performance and gut microbiota in pigs.
Proteome Analysis of Urinary Biomarkers in a Bovine IRBP-Induced Uveitis Rat Model via Data-Independent Acquisition and Parallel Reaction Monitoring Proteomics
Authors: Qin Weiwei , Qin Xuyan , Li Lujun , Gao Youhe
Published: February 2022

Uveitis, a group of intraocular inflammatory diseases, is one of the major causes of severe visual impairment among the working-age population. This study aimed to screen potential urinary biomarkers for uveitis based on proteome analysis. An experimental autoimmune uveitis (EAU) rat model induced by bovine interphotoreceptor retinoid-binding protein (IRBP) was used to mimic uveitis. In discovery phase, a total of 704 urinary proteins were identified via data-independent acquisition (DIA) proteomic technique, of which 76 were significantly changed (34, 36, and 37 on days 5, 8, and 12, respectively, after bovine IRBP immunization). Gene Ontology annotation of the differential proteins indicates that acute-phase response, innate immune response, neutrophil aggregation, and chronic inflammatory response were significantly enriched. Protein-protein interaction network indicates that these differential urinary proteins were biologically connected in EAU, as a group. In validation phase, 17 proteins having human orthologs were verified as the potential markers associated with uveitis by parallel reaction monitoring (PRM) targeted quantitative analysis. Twelve differential proteins changed even when there were no clinical manifestations or histopathological ocular damage. These 12 proteins are potential biomarkers for early diagnosis of uveitis to prevent the development of visual impairment. Five differential proteins changed at three time-points and showed progressive changes as the uveitis progressed, and another five differential proteins changed only on day 12 when EAU severity peaked. These 10 proteins may serve as potential biomarkers for prognostic evaluation of uveitis. Our findings revealed that the urinary proteome could sensitively reflect dynamic pathophysiological changes in EAU, and represent the first step towards the application of urinary protein biomarkers for uveitis.
Optogenetic Application to Investigating Cell Behavior and Neurological Disease
Authors: Zhu Danqing , Johnson Hunter J. , Chen Jun , Schaffer David V.
Published: February 2022

Cells reside in a dynamic microenvironment that presents them with regulatory signals that vary in time, space, and amplitude. The cell, in turn, interprets these signals and accordingly initiates downstream processes including cell proliferation, differentiation, migration, and self-organization. Conventional approaches to perturb and investigate signaling pathways (e.g., agonist/antagonist addition, overexpression, silencing, knockouts) are often binary perturbations that do not offer precise control over signaling levels, and/or provide limited spatial or temporal control. In contrast, optogenetics leverages light-sensitive proteins to control cellular signaling dynamics and target gene expression and, by virtue of precise hardware control over illumination, offers the capacity to interrogate how spatiotemporally varying signals modulate gene regulatory networks and cellular behaviors. Recent studies have employed various optogenetic systems in stem cell, embryonic, and somatic cell patterning studies, which have addressed fundamental questions of how cell-cell communication, subcellular protein localization, and signal integration affect cell fate. Other efforts have explored how alteration of signaling dynamics may contribute to neurological diseases and have in the process created physiologically relevant models that could inform new therapeutic strategies. In this review, we focus on emerging applications within the expanding field of optogenetics to study gene regulation, cell signaling, neurodevelopment, and neurological disorders, and we comment on current limitations and future directions for the growth of the field.
Minimally Invasive Surgery for Intracerebral and Intraventricular Hemorrhage
Authors: Zheng Zelong , Wang Qi , Sun Shujie , Luo Jinbiao
Published: February 2022

Spontaneous intracerebral hemorrhage (ICH), especially related to intraventricular hemorrhage (IVH), is the most devastating type of stroke and is associated with high mortality and morbidity. Optimal management of ICH remains one of the most controversial areas of neurosurgery and no effective treatment exists for ICH. Studies comparing conventional surgical interventions with optimal medical management failed to show significant benefit. Recent exploration of minimally invasive surgery for ICH and IVH including catheter- and mechanical-based approaches has shown great promise. Early phase clinical trials have confirmed the safety and preliminary treatment effect of minimally invasive surgery for ICH and IVH. Pending efficacy data from phase III trials dealing with diverse minimally invasive techniques are likely to shape the treatment of ICH.
Critical to Know Pcrit: A Review on Pharyngeal Critical Closing Pressure in Obstructive Sleep Apnea
Authors: Kazemeini Elahe , Van de Perck Eli , Dieltjens Marijke , Willemen Marc , Verbraecken Johan , Op de Beeck Sara , Vanderveken Olivier M.
Published: February 2022

It is crucial to understand the underlying pathophysiology of obstructive sleep apnea (OSA). Upper airway collapsibility is an important pathophysiological factor that affects the upper airway in OSA. The aim of the current study was to review the existing body of knowledge on the pharyngeal collapsibility in OSA. After a thorough search through Medline, PubMed, Scopus, and Web of science, the relevant articles were found and used in this study. Critical closing pressure (Pcrit) is the gold standard measure for the degree of collapsibility of the pharyngeal airway. Various physiological factors and treatments affect upper airway collapsibility. Recently, it has been shown that the baseline value of Pcrit is helpful in the upfront selection of therapy options. The standard techniques to measure Pcrit are labor-intensive and time-consuming. Therefore, despite the importance of Pcrit, it is not routinely measured in clinical practice. New emerging surrogates, such as finite element (FE) modeling or the use of peak inspiratory flow measurements during a routine overnight polysomnography, may enable clinicians to have an estimate of the pharyngeal collapsibility. However, validation of these techniques is needed.
The Role of VCP Mutations in the Spectrum of Amyotrophic Lateral Sclerosis—Frontotemporal Dementia
Authors: Scarian Eveljn , Fiamingo Giuseppe , Diamanti Luca , Palmieri Ilaria , Gagliardi Stella , Pansarasa Orietta
Published: February 2022

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurological diseases which, respectively, and primarily affect motor neurons and frontotemporal lobes. Although they can lead to different signs and symptoms, it is now evident that these two pathologies form a continuum and that hallmarks of both diseases can be present within the same person in the so-called ALS-FTD spectrum. Many studies have focused on the genetic overlap of these pathologies and it is now clear that different genes, such as C9orf72, TARDBP, SQSTM1, FUS, and p97/VCP can be mutated in both the diseases. VCP was one of the first genes associated with both FTD and ALS representing an early example of gene overlapping. VCP belongs to the type II AAA (ATPases Associated with diverse cellular activities) family and is involved in ubiquitinated proteins degradation, autophagy, lysosomal clearance and mitochondrial quality control. Since its numerous roles, mutations in this gene lead to different pathological features, first and foremost TDP-43 mislocalization. This review aims to outline recent findings on VCP roles and on how its mutations are linked to the neuropathology of ALS and FTD.
Identifying and Predicting Autism Spectrum Disorder Based on Multi-Site Structural MRI With Machine Learning
Authors: Duan YuMei , Zhao WeiDong , Luo Cheng , Liu XiaoJu , Jiang Hong , Tang YiQian , Liu Chang , Yao DeZhong
Published: February 2022

Although emerging evidence has implicated structural/functional abnormalities of patients with Autism Spectrum Disorder(ASD), definitive neuroimaging markers remain obscured due to inconsistent or incompatible findings, especially for structural imaging. Furthermore, brain differences defined by statistical analysis are difficult to implement individual prediction. The present study has employed the machine learning techniques under the unified framework in neuroimaging to identify the neuroimaging markers of patients with ASD and distinguish them from typically developing controls(TDC). To enhance the interpretability of the machine learning model, the study has processed three levels of assessments including model-level assessment, feature-level assessment, and biology-level assessment. According to these three levels assessment, the study has identified neuroimaging markers of ASD including the opercular part of bilateral inferior frontal gyrus, the orbital part of right inferior frontal gyrus, right rolandic operculum, right olfactory cortex, right gyrus rectus, right insula, left inferior parietal gyrus, bilateral supramarginal gyrus, bilateral angular gyrus, bilateral superior temporal gyrus, bilateral middle temporal gyrus, and left inferior temporal gyrus. In addition, negative correlations between the communication skill score in the Autism Diagnostic Observation Schedule (ADOS_G) and regional gray matter (GM) volume in the gyrus rectus, left middle temporal gyrus, and inferior temporal gyrus have been detected. A significant negative correlation has been found between the communication skill score in ADOS_G and the orbital part of the left inferior frontal gyrus. A negative correlation between verbal skill score and right angular gyrus and a significant negative correlation between non-verbal communication skill and right angular gyrus have been found. These findings in the study have suggested the GM alteration of ASD and correlated with the clinical severity of ASD disease symptoms. The interpretable machine learning framework gives sight to the pathophysiological mechanism of ASD but can also be extended to other diseases.
A Multielectrode Array-Based Recording System for Analyzing Ultrasound-Driven Neural Responses in Brain Slices in vitro
Authors: Furukawa Ryo , Kaneta Hiroki , Tateno Takashi
Published: February 2022

Ultrasound stimulation is expected to be useful for transcranial local and deep stimulation of the brain, which is difficult to achieve using conventional electromagnetic stimulation methods. Previous ultrasound stimulation experiments have used various types of acute in vitro preparations, including hippocampus slices from rodents and Caenorhabditis elegans tissue. For in vivo preparations, researchers have used the cortices of rodents as targets for transcranial ultrasound stimulation. However, no previous studies have used in vitro ultrasound stimulation in rodent cortical slices to examine the mechanisms of ultrasound-driven central neural circuits. Here we demonstrate the optimal experimental conditions for an in vitro ultrasound stimulation system for measuring activity in brain slices using a multielectrode array substrate. We found that the peak amplitudes of the ultrasound-evoked cortical responses in the brain slices depend on the intensities and durations of the ultrasound stimulation parameters. Thus, our findings provide a new in vitro experimental setup that enables activation of a brain slice via ultrasound stimulation. Accordingly, our results indicate that choosing the appropriate ultrasound waveguide structure and stimulation parameters is important for producing the desired intensity distribution in a localized area within a brain slice. We expect that this experimental setup will facilitate future exploration of the mechanisms of ultrasound-driven neural activity.
Enhancing the Cognitive Effects of Flavonoids With Physical Activity: Is There a Case for the Gut Microbiome?
Authors: Cheatham Carol L. , Nieman David C. , Neilson Andrew P. , Lila Mary Ann
Published: February 2022

Age-related cognitive changes can be the first indication of the progression to dementias, such as Alzheimer’s disease. These changes may be driven by a complex interaction of factors including diet, activity levels, genetics, and environment. Here we review the evidence supporting relationships between flavonoids, physical activity, and brain function. Recent in vivo experiments and human clinical trials have shown that flavonoid-rich foods can inhibit neuroinflammation and enhance cognitive performance. Improved cognition has also been correlated with a physically active lifestyle, and with the functionality and diversity of the gut microbiome. The great majority (+ 90%) of dietary flavonoids are biotransformed into phytoactive phenolic metabolites at the gut microbiome level prior to absorption, and these prebiotic flavonoids modulate microbiota profiles and diversity. Health-relevant outcomes from flavonoid ingestion may only be realized in the presence of a robust microbiome. Moderate-to-vigorous physical activity (MVPA) accelerates the catabolism and uptake of these gut-derived anti-inflammatory and immunomodulatory metabolites into circulation. The gut microbiome exerts a profound influence on cognitive function; moderate exercise and flavonoid intake influence cognitive benefits; and exercise and flavonoid intake influence the microbiome. We conclude that there is a potential for combined impacts of flavonoid intake and physical exertion on cognitive function, as modulated by the gut microbiome, and that the combination of a flavonoid-rich diet and routine aerobic exercise may potentiate cognitive benefits and reduce cognitive decline in an aging population, via mechanisms mediated by the gut microbiome. Mechanistic animal studies and human clinical interventions are needed to further explore this hypothesis.
Understanding the Dynamics of the Developing Adolescent Brain Through Team Science
Authors: Zanolie Kiki , Ma Ili , Bos Marieke G. N. , Schreuders Elisabeth , Vandenbroucke Annelinde R. E. , van Hoorn Jorien , van Duijvenvoorde Anna C. K. , Wierenga Lara , Crone Eveline A. , Güroğlu Berna
Published: February 2022

One of the major goals for research on adolescent development is to identify the optimal conditions for adolescents to grow up in a complex social world and to understand individual differences in these trajectories. Based on influential theoretical and empirical work in this field, achieving this goal requires a detailed understanding of the social context in which neural and behavioral development takes place, along with longitudinal measurements at multiple levels (e.g., genetic, hormonal, neural, behavioral). In this perspectives article, we highlight the promising role of team science in achieving this goal. To illustrate our point, we describe meso (peer relations) and micro (social learning) approaches to understand social development in adolescence as crucial aspects of adolescent mental health. Finally, we provide an overview of how our team has extended our collaborations beyond scientific partners to multiple societal partners for the purpose of informing and including policymakers, education and health professionals, as well as adolescents themselves when conducting and communicating research.
18F-FDG PET/CT and MRI in the Management of Multiple Myeloma: A Comparative Review
Authors: Mesguich Charles , Hulin Cyrille , Latrabe Valérie , Lascaux Axelle , Bordenave Laurence , Hindié Elif
Published: February 2022

During the last two decades, the imaging landscape of multiple myeloma (MM) has evolved with whole-body imaging techniques such as fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) and MRI replacing X-ray skeletal survey. Both imaging modalities have high diagnostic performance at the initial diagnosis of MM and are key players in the identification of patients needing treatment. Diffusion-weighted MRI has a high sensitivity for bone involvement, while 18F-FDG PET/CT baseline parameters carry a strong prognostic value. The advent of more efficient therapeutics, such as immunomodulatory drugs and proteasome inhibitors, has called for the use of sensitive imaging techniques for monitoring response to treatment. Diffusion-weighted MRI could improve the specificity of MRI for tumor response evaluation, but questions remain regarding its role as a prognostic factor. Performed at key time points of treatment in newly diagnosed MM patients, 18F-FDG PET/CT showed a strong association with relapse risk and survival. The deployment of minimal residual disease detection at the cellular or the molecular level may raise questions on the role of these imaging techniques, which will be addressed. This review summarizes and outlines the specificities and respective roles of MRI and 18F-FDG PET/CT in the management of MM.
The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue Versus Circulating Tumor DNA in Chinese Patients With Non-Small Cell Lung Cancer
Authors: Cai Jun , Jiang Huihui , Li Shuqing , Yan Xiaoxia , Wang Meng , Li Na , Zhu Cuimin , Dong Hui , Wang Dongjuan , Xu Yue , Xie Hui , Wu Shouxin , Lou Jingwei , Zhao Jiangman , Li Qingshan
Published: February 2022

Background

Circulating tumor DNA (ctDNA) sequence analysis shows great potential in the management of non-small cell lung cancer (NSCLC) and the prediction of drug sensitivity or resistance in many cancers. Here, we drew and compared the somatic mutational profile using ctDNA and tumor tissue sequence analysis in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), and assess its potential clinical value.

Methods

In this study, 221 tumor tissues and 174 plasma samples from NSCLC patients were analyzed by hybridization capture-based next-generation sequencing (NGS) panel including 95 cancer-associated genes. Tumor response assessments were applied to 137 patients with advanced-stage (III and IV) NSCLC who first received targeted agents.

Results

Twenty significantly mutated genes were identified such as TP53, EGFR, RB1, KRAS, PIK3CA, CD3EAP, CTNNB1, ERBB2, APC, BRAF, TERT, FBXW7, and HRAS. Among them, TP53 was the most frequently mutated gene and had a higher mutation probability in male (p = 0.00124) and smoking (p < 0.0001) patients. A total of 48.35% (191/395) of NSCLC patients possessed at least one actionable alteration according to the OncoKB database. Although the sensitivity of genomic profiling from ctDNA was lower than that from tumor tissue DNA, the mutational landscape of target genes from ctDNA is similar to that from tumor tissue DNA, which led to 61.22% (30/49) of mutational concordance in NSCLC. Additionally, the mutational concordance between tissue DNA and ctDNA in LUAD differs from that in LUSC, which is 63.83% versus 46.67%, indicating that NSCLC subtypes influence the specificity of mutation detection in plasma-derived ctDNA. Lastly, patients with EGFR and TP53 co-alterations showed similar responses to Gefitinib and Icotinib, and the co-occurring TP53 mutation was most likely to be a poor prognostic factor for patients receiving Gefitinib, indicating that the distributions and types of TP53 mutations may contribute to the efficacy and prognosis of molecular targeted therapy.

Conclusions

As a promising alternative for tumor genomic profiling, ctDNA analysis is more credible in LUAD than in LUSC. Genomic subtyping has strong potential in prognostication and therapeutic decision-making for NSCLC patients, which indicated the necessity for the utility of target NGS in guiding clinical management.
The Diagnostic and Grading Accuracy of 68Ga-DOTATATE and 18F-FDG PET/MR for Pancreatic Neuroendocrine Neoplasms
Authors: Zhou Jinxin , Zhao Runze , Pan Yu , Ju Huijun , Huang Xinyun , Jiang Yu , Jin Jiabin , Zhang Yifan
Published: February 2022

Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68Ga-DOTATATE (G-SUVmax) and 18F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades.
ECM Depletion Is Required to Improve the Intratumoral Uptake of Iron Oxide Nanoparticles in Poorly Perfused Hepatocellular Carcinoma
Authors: Yeow Yen Ling , Wu Jiansha , Wang Xiao , Winteringham Louise , Feindel Kirk W. , Tirnitz-Parker Janina E. E. , Leedman Peter J. , Ganss Ruth , Hamzah Juliana
Published: February 2022

Improving tumor access for drug delivery is challenging, particularly in poorly perfused tumors. The availability of functional tumor blood vessels for systemic access is vital to allow drugs or imaging agents to accumulate in the tumor parenchyma. We subjected mice engineered to develop hepatocellular carcinoma (HCC), to treatment with tumor necrosis factor alpha (TNFα) conjugated to a CSG peptide (CSGRRSSKC). CSG binds to the laminin-nidogen-1 complex of the extracellular matrix (ECM) in HCC. When produced as a recombinant fusion protein, the TNFα-CSG functions as an ECM depletion agent via an immune-mediated mechanism to improve tumor perfusion. Tumor perfusion in HCC was dramatically improved after daily intravenous (i.v.) injection of 5 µg TNFα-CSG for five consecutive days. Following treatment, we assessed the tumor accessibility to accumulate an imaging agent, superparamagnetic iron-oxide nanoparticles (IO-NP). Here, we compared the passive delivery of an i.v. dose of IO-NP in HCC following ECM depletion after TNFα-CSG treatment, to the intratumoral accumulation of a comparable dose of CSG-targeted IO-NP in HCC with intact ECM. Magnetic resonance imaging (MRI) T2-weighted scans and T2 relaxation times indicate that when the tumor ECM is intact, HCC was resistant to the intratumoral uptake of IO-NP, even when the particles were tagged with CSG peptide. In contrast, pre-treatment with TNFα-CSG resulted in the highest IO-NP accumulation in tumors. These findings suggest poorly perfused HCC may be resistant to molecular-targeted imaging agents including CSG-IO-NP. We demonstrate that specific ECM depletion using TNFα-CSG improves nanoparticle delivery into poorly perfused tumors such as HCC.
Circulating Tumor DNA Mutations in Progressive Gastrointestinal Stromal Tumors Identify Biomarkers of Treatment Resistance and Uncover Potential Therapeutic Strategies
Authors: Ko Tun Kiat , Lee Elizabeth , Ng Cedric Chuan-Young , Yang Valerie Shiwen , Farid Mohamad , Teh Bin Tean , Chan Jason Yongsheng , Somasundaram Nagavalli
Published: February 2022

Liquid biopsy circulating tumor DNA (ctDNA)-based approaches may represent a non-invasive means for molecular interrogation of gastrointestinal stromal tumors (GISTs). We deployed a customized 29-gene Archer® LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor KIT mutations (n = 41, 89.1%), while 3 were PDGFRA exon 18 D842V mutants and the rest (n = 2) were wild type for KIT and PDGFRA. In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest (n = 32) were metastatic. Among ten patients, including 7 on tyrosine kinase inhibitors, with evidence of disease progression at study inclusion, mutations in ctDNA were detected in 7 cases (70%). Known somatic mutations in KIT (n = 5) or PDGFRA (n = 1) in ctDNA were identified only among 6 of the 10 patients. These KIT mutants included duplication, indels, and single-nucleotide variants. The median mutant AF in ctDNA was 11.0% (range, 0.38%–45.0%). In patients with metastatic progressive KIT-mutant GIST, tumor burden was higher with detectable KIT ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, p = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases (n = 14) or metastatic cases without evidence of disease progression (n = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable PIK3CA exon 9 c.1633G>A mutation, were detected. ctDNA mutations were not detectable when patients responded to a switch in TKI therapy. In conclusion, detection of GIST-related mutations in ctDNA using a customized targeted NGS panel represents an attractive non-invasive means to obtain clinically tractable information at the time of disease progression.
Single Center Experience With Pediatric Patients With GATA2 Deficiency
Authors: Ovsyannikova Galina , Pavlova Anna , Deordieva Ekaterina , Raykina Elena , Pshonkin Alexey , Maschan Alexey , Maschan Michael
Published: February 2022

GATA2 deficiency is one of the most common predisposing conditions for MDS in young individuals. It is characterized by autosomal dominant inheritance and a high rate of de novo mutations. Here we describe the clinical phenotype and hematological presentation of 10 pediatric patients with GATA2 deficiency presented to the Dmitry Rogachev Center between 2013 and 2020. All patients had been referred for neutropenia or suspected aplastic anemia. While some patients presented with an immunological phenotype, others displayed monosomy 7 and MDS. The clinical presentation with MDS in infancy and the constitutional phenotypes in our patients underline the great variability in clinical manifestation. Careful description of cohorts with GATA2 deficiency from different countries and genetic backgrounds will help to unravel the enormous heterogeneity of this recently discovered genetic disorder.
Effects of Irbesartan and Amlodipine Besylate Tablets on the Intestinal Microflora of Rats With Hypertensive Renal Damage
Authors: Yu Jing , Ma Yan , He Xin , Long Xiao Na , Xu Jun , Wang Lei , Feng Zhi-Peng , Peng Hong-Ying
Published: February 2022

Objective: The present study aimed to investigate the effects of irbesartan and amlodipine besylate tablets on the intestinal microflora of rats with hypertensive renal damage.

Methods: Eighteen 12-week-old male spontaneous hypertensive rats were randomly divided into three groups. The Ai-HDG group was given irbesartan at 15 mg/kg per day by gavage, the Ci-HDG group was given amlodipine besylate tablets at 1 mg/kg per day by gavage, and the Wi-HDG group, i.e., the control, was given the same dose of distilled water per day by gavage. The treatment lasted for 6 weeks. Six 12-week-old male Wistar–Kyoto rats were used as the reference group. Bacterial DNA was extracted from the feces of all the rats for high-throughput sequencing before and after the experiment. Operational taxonomic units were used to analyze the species of the intestinal flora, and the alpha diversity index was used to analyze the diversity. The relative abundance of the intestinal microflora in each group of rats was therefore analyzed at the phylum and genus levels.

Results: Compared with the Wi-HDG group, the alpha diversity of the Ai-HDG group increased (p < 0.05), while in the Ci-HDG group, only the Shannon index increased significantly. At the phylum level, compared with the control group, in the Ai-HDG and Ci-HDG groups, Firmicutes (F) decreased, Bacteroides (B) increased, and the F/B ratio decreased (p < 0.05). At the genus level, compared with the Wi-HDG group, the Ai-HDG and Ci-HDG groups did not show a significantly delayed decline in lactic acid bacteria. However, in the Ai-HDG group, the relative abundance of Bifidobacteria increased.

Conclusion: After the administration of irbesartan and amlodipine besylate, the disorder of intestinal flora in the rats with hypertensive renal damage improved. However, irbesartan was better than amlodipine besylate at improving the diversity of the intestinal flora in these rats.
Carotid Intraplaque Neovascularization and Future Vascular Events in Patients With Asymptomatic Carotid Stenosis
Authors: Cui Liuping , Xing Yingqi , Wang Lijuan , Liu Kangding , Chen Hongxiu , Li Cong , Chen Ying
Published: February 2022

Objective: Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis.

Methods: We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events.

Results: The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p < .05). Grade 2 intraplaque neovascularization (hazard ratio: 4.530, 95% confidence interval, 1.337–15.343, p < .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis.

Conclusion: Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.
Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review
Authors: Rajabian Arezoo , Rajabian Fatemeh , Babaei Fatemeh , Mirzababaei Mohammadreza , Nassiri-Asl Marjan , Hosseinzadeh Hossein
Published: February 2022

Potassium ion (K+) channels are pore-forming transmembrane proteins that control the transport of K+ ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K+ channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K+ channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 in vivo studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (KATP), and small (SKCa) and large (BKCa) conductance calcium-activated K+ channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K+ channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K+ channels can facilitate drug development for the treatment of various K+ channel-related disorders.
Study on Influencing Factors of Semen Quality in Fertile Men
Authors: Wang Ning , Gu Haike , Gao Yiyuan , Li Xiaoyan , Yu Ge , Lv Fang , Shi Cuige , Wang Shangming , Song Meifang , Zhang Shucheng
Published: February 2022

Objective

To establish a system for evaluation of semen quality in fertile men by factor analysis (FA).

Methods

The FA method was used to analyze five sperm test indicators for fertile men (sperm pH, sperm motility, sperm progressive motility, semen density, and total sperm number) to determine the evaluation standard of semen quality. Pearson analysis was adopted for correlation testing.

Results

The comprehensive score formula for semen quality of normal fertile men was as follows: comprehensive score of semen quality = (0.38272 F1 + 0.36359 F2 + 0.20018 F3)/94.699. Across the whole fertile population, semen quality was found to be correlated with abstinence period, age of first spermatorrhea, and frequency of intercourse. Smoking, drinking, and place of residence were correlated with semen quality in the high semen quality population. In the population with medium semen quality, only the abstinence period was associated with semen quality.

Conclusion

It is feasible to evaluate the semen quality of fertile men using the FA method. The comprehensive indicators of semen volume, sperm motility, and semen pH can be used as evaluative measures. Across the whole fertile population, the abstinence period and age of first spermatorrhea were correlated with semen quality. In the high semen quality population, smoking and drinking were negatively correlated with semen quality, and participants living in rural areas had better semen quality.
CINCINNATA-Like TCP Transcription Factors in Cell Growth – An Expanding Portfolio
Authors: Rath Monalisha , Challa Krishna Reddy , Sarvepalli Kavitha , Nath Utpal
Published: February 2022

Post-mitotic cell growth is a key process in plant growth and development. Cell expansion drives major growth during morphogenesis and is influenced by both endogenous factors and environmental stimuli. Though both isotropic and anisotropic cell growth can contribute to organ size and shape at different degrees, anisotropic cell growth is more likely to contribute to shape change. While much is known about the mechanisms that increase cellular turgor and cell-wall biomass during expansion, the genetic factors that regulate these processes are less studied. In the past quarter of a century, the role of the CINCINNATA-like TCP (CIN-TCP) transcription factors has been well documented in regulating diverse aspects of plant growth and development including flower asymmetry, plant architecture, leaf morphogenesis, and plant maturation. The molecular activity of the CIN-TCP proteins common to these biological processes has been identified as their ability to suppress cell proliferation. However, reports on their role regulating post-mitotic cell growth have been scanty, partly because of functional redundancy among them. In addition, it is difficult to tease out the effect of gene activity on cell division and expansion since these two processes are linked by compensation, a phenomenon where perturbation in proliferation is compensated by an opposite effect on cell growth to keep the final organ size relatively unaltered. Despite these technical limitations, recent genetic and growth kinematic studies have shown a distinct role of CIN-TCPs in promoting cellular growth in cotyledons and hypocotyls, the embryonic organs that grow solely by cell expansion. In this review, we highlight these recent advances in our understanding of how CIN-TCPs promote cell growth.
Deciphering Novel Transcriptional Regulators of Soybean Hypocotyl Elongation Based on Gene Co-expression Network Analysis
Authors: Shen Zhikang , Chen Min
Published: February 2022

Hypocotyl elongation is the key step of soybean seed germination, as well an important symbol of seedling vitality, but the regulatory mechanisms remain largely elusive. To address the problem, bioinformatics approaches along with the weighted gene co-expression network analysis (WGCNA) were carried out to elucidate the regulatory networks and identify key regulators underlying soybean hypocotyl elongation at transcriptional level. Combining results from WGCNA, yeast one hybridization, and phenotypic analysis of transgenic plants, a cyan module significantly associated with hypocotyl elongation was discerned, from which two novel regulatory submodules were identified as key candidates underpinning soybean hypocotyl elongation by modulating auxin and light responsive signaling pathways. Taken together, our results constructed the regulatory network and identified novel transcriptional regulators of soybean hypocotyl elongation based on WGCNA, which provide new insights into the global regulatory basis of soybean hypocotyl elongation and offer potential targets for soybean improvement to acquire cultivars with well-tuned hypocotyl elongation and seed germination vigor.
Nurses’ Perceptions of the Quality of Perinatal Care Provided to Lesbian Women
Authors: Tzur-Peled Sharona , Kushnir Talma , Sarid Orly
Published: February 2022

Aim

Based on the Theory of Reasoned Action (TRA), we examined whether attitudes of nurses from different ethnic groups, subjective norms, behavioral intentions, assessments of relationships and communication were associated with their perceptions of the quality of perinatal care provided to lesbian women.

Background

Nurses administer healthcare, provide pertinent information and consultation to lesbians from pregnancy planning through birth.

Introduction

During the past few decades, worldwide, there has been a rise in lesbian-parenting. Despite the changes in Israeli society’s public and legal reality, intolerance and discrimination to the homosexual population is still prevalent in Israel’s healthcare system.

Methods

A cross-sectional study conducted between 12/2015-4/2016. Of the 270 nurses approached, 184 completed a self-report anonymous questionnaire (a response rate of 74%).

Findings

This is an important and timely study reflecting nurses’ perceptions of the quality of perinatal care provided to lesbians. The study findings reflect that attitudes, subjective norms, behavioral intentions, assessments of relationships and communication of nurses from different ethnic groups are associated with their perceptions of the quality of perinatal care provided to the lesbians. The hierarchical regression analysis demonstrated that attitudes, subjective norms, behavioral intentions, assessments of relationships and communication of nurses contributed 56% to the variance of nurses’ perception of their own quality of perinatal care.

Discussion

TRA conceptualization predicted the quality of care of nurses from different ethnic groups treating lesbians in a perinatal setting.

Conclusion

TRA provides a useful framework for understanding and predicting the motivational effect of health care personnel with the lesbian population, being at risk for stigmatization and receiving less quality perinatal care.

Implications for nursing and heath policy

Our findings revealed the importance of formulating a recognized policy in the field of LGBT medicine at the national level. Further training of nurses as to the lesbians’ unique health needs, might improve the nurses’ relationships and communication as well as the quality of perinatal nursing care.
Evaluation of the InterRAI Early Years for Degree of Preterm Birth and Gross Motor Delay
Authors: Iantosca Jo Ann M. , Stewart Shannon L.
Published: February 2022

Background

The interRAI 0–3 Early Years was recently developed to support intervention efforts based on the needs of young children and their families. One aspect of child development assessed by the Early Years instrument are motor skills, which are integral for the maturity of cognition, language, social-emotional and other developmental outcomes. Gross motor development, however, is negatively impacted by pre-term birth and low birth weight. For the purpose of known-groups validation, an at-risk sample of preterm children using the interRAI 0–3 Early Years was included to examine correlates of preterm risk and the degree of gross motor delay.

Methods

Participant data included children and families (n = 591) from 17 health agencies in Ontario, Canada. Data were collected as part of a pilot study using the full interRAI 0–3 Early Years assessment. Correlational analyses were used to determine relationships between prenatal risk and preterm birth and bivariate analyses examined successful and failed performance of at-risk children on gross motor items. A Kruskal-Wallis test was used to determine the mean difference in gross motor scores for children born at various weeks gestation.

Results

Correlational analysis indicated that prenatal and perinatal factors such as maternal nicotine use during pregnancy did not have significant influence over gross motor achievement for the full sample, however, gross motor scores were lower for children born pre-term or low birth weight based on bivariate analysis. Gross motor scores decreased from 40 weeks’ gestation (mean rank = 310.77), to moderate to late preterm (mean rank = 258.96), and to very preterm (mean rank = 234.54), however extremely preterm (mean rank = 236.28) performed comparably to very preterm.

Interpretation

The interRAI 0–3 was evaluated to determine its efficacy and report findings which confirm the literature regarding delay in gross motor performance for preterm children. Findings confirm that pre-term and low birth weight children are at greater risk for motor delay via the interRAI 0–3 Early Years gross motor domain.