bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidance for the Interpretation of Continual Cuffless Blood Pressure Data for the Diagnosis and Management of Hypertension
Authors: Sola Josep , Cortes Meritxell , Perruchoud David , De Marco Bastien , Lobo Melvin D. , Pellaton Cyril , Wuerzner Gregoire , Fisher Naomi D. L. , Shah Jay
Published: May 2022

Hypertension remains the leading risk factor for death worldwide. Despite its prevalence, success of blood pressure (BP) management efforts remains elusive, and part of the difficulty lies in the tool still used to diagnose, measure, and treat hypertension: the sphygmomanometer introduced by Samuel Siegfried Karl von Basch in 1867. In recent years, there has been an explosion of devices attempting to provide estimates of BP without a cuff, overcoming many limitations of cuff-based BP monitors. Unfortunately, the differences in underlying technologies between traditional BP cuffs and newer cuffless devices, as well as hesitancy of changing a well-implemented standard, still generate understandable skepticism about and reluctance to adopt cuffless BP monitors in clinical practice. This guidance document aims to navigate the scientific and medical communities through the types of cuffless devices and present examples of robust BP data collection which are better representations of a person's true BP. It highlights the differences between data collected by cuffless and traditional cuff-based devices and provides an initial framework of interpretation of the new cuffless datasets using, as an example, a CE-marked continual cuffless BP device (Aktiia BP Monitor, Aktiia, Switzerland). Demonstration of novel BP metrics, which have the potential to change the paradigm of hypertension diagnosis and treatment, are now possible for the first time with cuffless BP monitors that provide continual readings over long periods. Widespread adoption of continual cuffless BP monitors in healthcare will require a collaborative and thoughtful process, acknowledging that the transition from a legacy to a novel medical technology will be slow. Finally, this guidance concludes with a call to action to international scientific and expert associations to include cuffless BP monitors in original scientific research and in future versions of guidelines and standards.
Interacting Bioenergetic and Stoichiometric Controls on Microbial Growth
Authors: Chakrawal Arjun , Calabrese Salvatore , Herrmann Anke M. , Manzoni Stefano
Published: May 2022

Microorganisms function as open systems that exchange matter and energy with their surrounding environment. Even though mass (carbon and nutrients) and energy exchanges are tightly linked, there is a lack of integrated approaches that combine these fluxes and explore how they jointly impact microbial growth. Such links are essential to predicting how the growth rate of microorganisms varies, especially when the stoichiometry of carbon- (C) and nitrogen (N)-uptake is not balanced. Here, we present a theoretical framework to quantify the microbial growth rate for conditions of C-, N-, and energy-(co-) limitations. We use this framework to show how the C:N ratio and the degree of reduction of the organic matter (OM), which is also the electron donor, availability of electron acceptors (EAs), and the different sources of N together control the microbial growth rate under C, nutrient, and energy-limited conditions. We show that the growth rate peaks at intermediate values of the degree of reduction of OM under oxic and C-limited conditions, but not under N-limited conditions. Under oxic conditions and with N-poor OM, the growth rate is higher when the inorganic N (NInorg)-source is ammonium compared to nitrate due to the additional energetic cost involved in nitrate reduction. Under anoxic conditions, when nitrate is both EA and NInorg-source, the growth rates of denitrifiers and microbes performing the dissimilatory nitrate reduction to ammonia (DNRA) are determined by both OM degree of reduction and nitrate-availability. Consistent with the data, DNRA is predicted to foster growth under extreme nitrate-limitation and with a reduced OM, whereas denitrifiers are favored as nitrate becomes more available and in the presence of oxidized OM. Furthermore, the growth rate is reduced when catabolism is coupled to low energy yielding EAs (e.g., sulfate) because of the low carbon use efficiency (CUE). However, the low CUE also decreases the nutrient demand for growth, thereby reducing N-limitation. We conclude that bioenergetics provides a useful conceptual framework for explaining growth rates under different metabolisms and multiple resource-limitations.
PVBase: A MALDI-TOF MS Database for Fast Identification and Characterization of Potentially Pathogenic Vibrio Species From Multiple Regions of China
Authors: Liu Tingting , Kang Lin , Xu Jinglin , Wang Jing , Gao Shan , Li Yanwei , Li Jiaxin , Yuan Yuan , Yuan Bing , Wang Jinglin , Zhao Baohua , Xin Wenwen
Published: May 2022

The potentially pathogenic species of the genus Vibrio pose a threat to both humans and animals, creating medical burdens and economic losses to the mariculture industry. Improvements in surveillance and diagnosis are needed to successfully manage vibriosis outbreaks. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can provide rapid diagnosis and has been widely used in the identification of Vibrio spp. The main weakness of this technology is the limited number of strains and species of Vibrio in the existing commercial database. Here, we develop a new in-house database named PVBase containing 790 main spectra projections (MSP) of ten Vibrio species that come from various regions of China and include abundant clinical and environmental strains. PVBase was validated through a blind test of 65 Vibrio strains. The identification accuracy and scoring of Vibrio strains was greatly improved through the addition of PVBase. Identification accuracy increased from 73.4 to 100%. The number of strains with identification scores above 2.2 increased from 53.1% to 96.9% and 53.1% of strains had an identification score above 2.59. Moreover, perfect discrimination was obtained when using all of the MSPs created for the Vibrio species, even for very closely related species such as V. cholerae, V. albensis, and V. mimicus or V. alginolyticus, V. parahaemolyticus, and V. harveyi. In addition, we used phyloproteomic analysis to study whether there are differences in protein fingerprints of different regions or pathogenic strains. We found that MSP characteristics of Vibrio species were not related to their region or source. With the construction of PVBase, the identification efficiency of potentially pathogenic Vibrio species has been greatly improved, which is an important advance for epidemic prevention and control, and aquaculture disease detection.
AlphaFold 2 and NMR Spectroscopy: Partners to Understand Protein Structure, Dynamics and Function
Authors: Laurents Douglas V.
Published: May 2022

The artificial intelligence program AlphaFold 2 is revolutionizing the field of protein structure determination as it accurately predicts the 3D structure of two thirds of the human proteome. Its predictions can be used directly as structural models or indirectly as aids for experimental structure determination using X-ray crystallography, CryoEM or NMR spectroscopy. Nevertheless, AlphaFold 2 can neither afford insight into how proteins fold, nor can it determine protein stability or dynamics. Rare folds or minor alternative conformations are also not predicted by AlphaFold 2 and the program does not forecast the impact of post translational modifications, mutations or ligand binding. The remaining third of human proteome which is poorly predicted largely corresponds to intrinsically disordered regions of proteins. Key to regulation and signaling networks, these disordered regions often form biomolecular condensates or amyloids. Fortunately, the limitations of AlphaFold 2 are largely complemented by NMR spectroscopy. This experimental approach provides information on protein folding and dynamics as well as biomolecular condensates and amyloids and their modulation by experimental conditions, small molecules, post translational modifications, mutations, flanking sequence, interactions with other proteins, RNA and virus. Together, NMR spectroscopy and AlphaFold 2 can collaborate to advance our comprehension of proteins.
The Construction and Analysis of Immune Infiltration and Competing Endogenous RNA Network in Acute Ischemic Stroke
Authors: Ma ZhaoLei , Liu Chun-Feng , Zhang Li , Xiang Ning , Zhang Yifan , Chu Lan
Published: May 2022

Acute ischemic stroke (AIS) is a common neurological disease that seriously endangers both the physical and mental health of human. After AIS, activated immune cells are recruited to the stroke site, where inflammatory mediators are released locally, and severe immune inflammatory reactions occur within a short time, which affects the progress and prognosis of IS. Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a closed-loop structure and high stability. Studies have found that circRNA can affect the course of IS. However, there is no report on ceRNA’s pathogenesis in AIS that is mediated by circRNA. In this study, the CIBERSORT algorithm was used to analyze the distribution of immune cells in patients with AIS. mRNA dataset was downloaded from the GEO database, and the weighted gene co-expression network analysis (WGCNA) method was used to construct weighted gene co-expression to determine 668 target genes, using GO, KEGG enrichment analysis, construction of protein-protein interaction (PPI) network analysis, and molecular complex detection (MCODE) plug-in analysis. The results showed that the biological function of the target gene was in line with the activation and immune regulation of neutrophils; signal pathways were mostly enriched in immune inflammation-related pathways. A Venn diagram was used to obtain 52 intersection genes between target genes and disease genes. By analyzing the correlation between the intersection genes and immune cells, we found that the top 5 hub genes were TOM1, STAT3, RAB3D, MDM2, and FOS, which were all significantly positively correlated with neutrophils and significantly negatively correlated with eosinophils. A total of 52 intersection genes and the related circRNA and miRNA were used as input for Cytoscape software to construct a circRNA-mediated ceRNA competition endogenous network, where a total of 18 circRNAs were found. Further analysis of the correlation between circRNA and immune cells found that 4 circRNAs are positively correlated with neutrophils. Therefore, we speculate that there may be a regulatory relationship between circRNA-mediated ceRNA and the immune mechanism in AIS. This study has important guiding significance for the progress, outcome of AIS, and the development of new medicine.
Trauma Disrupts Reinforcement Learning in Rats—A Novel Animal Model of Chronic Stress Exposure
Authors: Bielawski Tomasz , Drapała Jarosław , Krowicki Paweł , Stańczykiewicz Bartłomiej , Frydecka Dorota
Published: May 2022

Trauma, as well as chronic stress that characterizes a modern fast-paced lifestyle, contributes to numerous psychopathologies and psychological problems. Psychiatric patients with traumas, as well as healthy individuals who experienced traumas in the past, are often characterized by diminished cognitive abilities. In our protocol, we used an animal model to explore the influence of chronic trauma on cognitive abilities and behavior in the group of 20 rats (Rattus norvegicus). The experimental group was introduced to chronic (12 consecutive days) exposure to predator odor (bobcat urine). We measured the reinforcement learning of each individual before and after the exposition via the Probabilistic Selection Task (PST) and we used Social Interaction Test (SIT) to assess the behavioral changes of each individual before and after the trauma. In the experimental group, there was a significant decrease in reinforcement learning after exposure to a single trauma (Wilcoxon Test, p = 0.034) as well as after 11 days of chronic trauma (Wilcoxon-test, p = 0.01) in comparison to pre-trauma performance. The control group, which was not exposed to predator odor but underwent the same testing protocol, did not present significant deterioration in reinforcement learning. In cross-group comparisons, there was no difference between the experimental and control group in PST before odor protocol (U Mann-Whitney two-sided, p = 0.909). After exposure to chronic trauma, the experimental group deteriorated in PST performance compared to control (U Mann-Whitney Two-sided, p = 0.0005). In SIT, the experimental group spent less time in an Interaction Zone with an unfamiliar rat after trauma protocol (Wilcoxon two-sided test, p = 0.019). Major strengths of our models are: (1) protocol allows investigating reinforcement learning before and after exposition to chronic trauma, with the same group of rats, (2) translational scope, as the PST is displayed on touchscreen, similarly to human studies, (3) protocol delivers chronic trauma that impairs reward learning, but behaviorally does not induce full-blown anhedonia, thus rats performed voluntarily throughout all the procedures.
Exosomes in the Field of Neuroscience: A Scientometric Study and Visualization Analysis
Authors: Long Junzi , Zhang Yasu , Liu Xiaomin , Pan Mengyang , Gao Qian
Published: May 2022

Exosomes have received great attention for their diagnostic, therapeutic, and prognostic roles in the field of neuroscience over the past decade. This scientometric study aimed to quantitatively and qualitatively evaluate knowledge structure, hot topics, and research trends of studies about exosomes in the field of neuroscience using visualization tools. Web of Science Core collection databases were searched for relevant publications between 2005 and 2021. The Carrot2 online system, BICOMB, gCLUTO, and Ucinet software were utilized for key word analysis, and co-citations analyses were conducted in Citespace and VOSviewer. Altogether, 21 high-frequency key words were collected from 856 included articles, and 5 clusters were identified through biclustering analyses. The strategic diagram and social network analysis further determined research hotspots and trends. Co-citation analysis results revealed a few crucial works that contributed to the development of research on exosomes in the field of neuroscience. Moreover, the important sources that had contributed to the development of this field were identified. Our findings suggested that Alzheimer's disease-related research remained a hot topic in this field till now, and recent researchers had extended their scopes to more cognitive impairments. Importantly, researches related to exosomes in multiple sclerosis and Parkinson's disease were promising. While exosomes in acute central nervous system injury had not been sufficiently investigated, with continuous improvement in exosome-based delivery technology, this subject might make a breakthrough in terms of therapeutic innovations in the immediate future.
Efficient Simulation of 3D Reaction-Diffusion in Models of Neurons and Networks
Authors: McDougal Robert A. , Conte Cameron , Eggleston Lia , Newton Adam J. H. , Galijasevic Hana
Published: May 2022

Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well-represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma. We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON's 1D mechanisms for ion channels, synapses, pumps, and so forth. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.
Expression of Protein Acetylation Regulators During Peripheral Nerve Development, Injury, and Regeneration
Authors: Sun Junjie , Ji Yuhua , Liang Qingyun , Ming Mengru , Chen Yuhan , Zhang Qi , Zhou Songlin , Shen Mi , Ding Fei
Published: May 2022

Protein acetylation, regulated by acetyltransferases and deacetylases, is an important post-translational modification that is involved in numerous physiological and pathological changes in peripheral nerves. There is still no systematical analysis on the expression changes of protein acetylation regulators during sciatic nerve development, injury, and regeneration. Here, we sequenced and analyzed the transcriptome of mouse sciatic nerves during development and after injury. We found that the changes in the expression of most regulators followed the rule that “development is consistent with regeneration and opposite to injury.” Immunoblotting with pan-acetylated antibodies also revealed that development and regeneration are a process of increased acetylation, while injury is a process of decreased acetylation. Moreover, we used bioinformatics methods to analyze the possible downstream molecules of two key regulators, histone deacetylase 1 (Hdac1) and lysine acetyltransferase 2b (Kat2b), and found that they were associated with many genes that regulate the cell cycle. Our findings provide an insight into the association of sciatic nerve development, injury, and regeneration from the perspective of protein acetylation.
Causal Analysis of Activity in Social Brain Areas During Human-Agent Conversation
Authors: De Castro Martins Caio , Chaminade Thierry , Cavazza Marc
Published: May 2022

This article investigates the differences in cognitive and neural mechanisms between human-human and human-virtual agent interaction using a dataset recorded in an ecologically realistic environment. We use Convergent Cross Mapping (CCM) to investigate functional connectivity between pairs of regions involved in the framework of social cognitive neuroscience, namely the fusiform gyrus, superior temporal sulcus (STS), temporoparietal junction (TPJ), and the dorsolateral prefrontal cortex (DLPFC)—taken as prefrontal asymmetry. Our approach is a compromise between investigating local activation in specific regions and investigating connectivity networks that may form part of larger networks. In addition to concording with previous studies, our results suggest that the right TPJ is one of the most reliable areas for assessing processes occurring during human-virtual agent interactions, both in a static and dynamic sense.
De-Oiled Citrus Peels as Feedstock for the Production of Pectin Oligosaccharides and Its Effect on Lactobacillus fermentum, Probiotic Source
Authors: Sarkar Rohan , Nain Lata , Kundu Aditi , Dutta Anirban , Das Debarup , Sethi Shruti , Saha Supradip
Published: May 2022

Following the extraction of essential oil, citrus (Mousambi, Kinnow, and Orange) peel wastes were used to produce pectin. The yield of essential oil and pectin was maximum in orange. Pectin was characterized by Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectroscopy. The degree of esterification (DE) and methoxyl content (MC) was maximum in orange whereas, the equivalent weight was maximum in Mousambi. A significant increase (61.8%) in the Lactobacillus fermentum population was observed with pectin as compared with sugar. Three sources followed the Orange > Kinnow > Mousambi trend as a prebiotic source. It was attributed to higher DE as well as higher MC. Enhancement in the bacterial population was in the range of 79.16–87.50%. The present work confirms the potential of pectin as a probiotic source for the enhancement of the bacterial population. Thus, it has a large scope for use in the food industry targeting a circular economy.
Associations of the Geriatric Nutritional Risk Index With Femur Bone Mineral Density and Osteoporosis in American Postmenopausal Women: Data From the National Health and Nutrition Examination Survey
Authors: Wang Jie , Xing Fei , Sheng Ning , Xiang Zhou
Published: May 2022

Background

The geriatric nutritional risk index (GNRI) has been used as a significant tool to access the nutritional status of the elderly. However, the relationship between the GNRI and femur bone mineral density (BMD) and the risk of osteoporosis remains unclear in American postmenopausal women.

Objectives

We aimed to explore associations between the GNRI with femur BMD and the risk of osteoporosis in American postmenopausal women.

Methods

We merged the continuous National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018 to ensure a large and representative sample, including 3,152 participants. The linear relationship between the GNRI and femur BMD was assessed via a weighted multivariate linear regression model. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between the GNRI and the risk of osteoporosis were assessed by a weighted logistic regression model. Moreover, the nonlinear relationship was also characterized by smooth curve fitting (SCF) and a weighted generalized additive model (GAM).

Results

After adjusting for all covariates, the weighted multivariable linear regression models demonstrated that the GNRI was positively correlated with femur BMD. The weighted logistic regression models demonstrated that each unit of increased GNRI value was associated with a decreased risk of osteoporosis of 4.13%. When categorizing GNRI based on quartiles, ORs between the risk of osteoporosis and the GNRI across quintiles 2, 3, and 4 compared with quintile 1 were 0.5565 (95% CI: 0.4791, 0.6463; P < 0.000001), 0.5580 (95% CI: 0.4600, 0.6769; P < 0.000001), and 0.3475 (95% CI: 0.2681, 0.4505; P < 0.000001). The trends similar to the above were also observed in SCF and GAM.

Conclusion

This study indicated that nutritional status, represented by the GNRI, was positively associated with femur BMD and negatively associated with the risk of osteoporosis in American postmenopausal women. The GNRI may be a good tool to identify American postmenopausal women who need further bone health nutritional support.
The Efficacy and Safety of Transarterial Chemoembolization Plus Iodine 125 Seed Implantation in the Treatment of Hepatocellular Carcinoma With Oligometastases: A Case Series Reports
Authors: Zhang Weihua , Wu Linxia , Chen Lei , Ren Yanqiao , Sun Tao , Sun Bo , Zhu Licheng , Liu Yiming , Zheng Chuansheng
Published: May 2022

Background

Patients with different primary tumor oligometastases can obtain survival benefits from external radiotherapy. The study was conducted to explore the efficacy and safety of transarterial chemoembolization (TACE) plus iodine 125 seed (TACE-I) implantation for hepatocellular carcinoma (HCC) oligometastases.

Methods

187 patients who received TACE-I in our institution were retrospectively reviewed from January 2014 to December 2018. Thirty-two patients were included in the analysis. The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints of the study were tumor response and PFS of the metastatic sites.

Results

The median OS (mOS) of patients was 18 months, and the median PFS (mPFS) was 7 months. The objective response rate (ORR) and disease control rate (DCR) of patients three months after receiving TACE-I were 34.4% and 71.9%, respectively. The ORR and DCR of patients for metastatic sites were 50% and 81.3%, respectively. The mPFS of patients for metastatic sites was 14 months. The univariable and multivariable regression analyses indicated that the ECOG score was an independent predictor for mOS and mPFS. The number of iodine seeds and ECOG scores were independent predictors for mPFS for metastatic sites. After patients received TACE-I, the most common adverse events were abdominal pain, fever, and appetite. The adverse events of patients were relieved after receiving symptomatic treatments.

Conclusion

Iodine 125 seed implantation may be an effective and safe treatment for patients with hepatocellular carcinoma with oligometastasis, thereby providing a new selective option for these patients.
Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer—Prevalence and Current Clinical Practice
Authors: Patel Priyanka H. , Tunariu Nina , Levine Daniel S. , de Bono Johann S. , Eeles Rosalind A. , Khoo Vincent , Murray Julia , Parker Christopher C. , Pathmanathan Angela , Reid Alison , van As Nicholas , Tree Alison C.
Published: May 2022

Aims

Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT).

Methods

Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan–Meier method and log-rank test were used to calculate progression-free and overall survival.

Results

A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone.

Conclusions

In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators.
Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age
Authors: Secchi Teresa , Baselli Lucia Augusta , Russo Maria Chiara , Borzani Irene Maria , Carta Federica , Lopopolo Maria Amalia , Foà Michaela , La Vecchia Adriano , Agostoni Carlo , Agosti Massimo , Dellepiane Rosa Maria
Published: May 2022

Background

In primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years.

Objective

This study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF).

Methods

Pediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5–15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis.

Results

Lung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1–52) at baseline, OR 3.9 (CI 0.2–191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2–2) at baseline, OR 1.6 (CI 0.1–13.6) at follow-up].

Conclusion

Within the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.
Late-Pregnancy Dysglycemia After Negative Testing for Gestational Diabetes and Risk of the Large-for-Gestational-Age Newborns: A Nest Case-Control Study Based on the Xi'an Longitudinal Mother-Child Cohort Study
Authors: He Zhangya , Mi Yang , Yang Hexiang , Ji Jing , Gao Jiayi , Zhang Wanyu , Wu Pei , Xu Zhangrui , Wang Shanshan , Luo Xiaoqin
Published: May 2022

Background

The implications of gestational diabetes mellitus (GDM) on the short- and long-term health outcomes of both mother and child have been extensively studied. However, studies related to negative Oral Glucose Tolerance Test (OGTT) results in the second trimester but dysglycemia in late pregnancy on maternal and infant pregnancy outcomes are rare.

Methods

We conducted a nest case-control study within the Xi'an Longitudinal Mother-Child Cohort study (XAMC) to investigate the risk of adverse pregnancy outcomes in mothers and children with maternal negative mid-pregnancy OGTT results but high glycated hemoglobin (HbA1c) levels (≥5.7%) in late pregnancy. All target women who delivered from January 1st, 2017 to December 31st, 2018 in Northwest Women's and Children's Hospital in Xi'an were enrolled as the case group (HbA1c ≥ 5.7%). Others with HbA1c < 5.7% but without GDM were selected as the control group (HbA1c < 5.7%) by matching with the same delivery period. The logistic regression models were used to find out the risk factors of adverse pregnancy outcomes in the target population.

Results

A total of 2,116 and 1,907 women were finally enrolled in the case and control groups, respectively. Compared to the control group, more newborns with macrosomia (9.2% vs 4.1%, P < 0.001) and large for gestational age (LGA) (23.7% vs. 13.5%, P < 0.001), but less small for gestational age (SGA) (4.4% vs. 6.1%, P = 0.017) were found in the case group. The differences in other outcomes were not statistically significant. The multiple logistic regression analysis showed that gestational age, fetal length, prenatal HbA1c, and total cholesterol (TG) were independent risk factors for newborns with large-for-gestational-age (LGA). The case group had a 2.516-fold (95% CI, 1.692–3.739) risk of delivering LGA newborns compared to the control group.

Conclusion

The glycemic management during the late pregnancy of non-GDM women should be given special consideration to reduce the risk of overweight offspring at birth.
Evaluation of Risk and Preventive Factors for Necrotizing Enterocolitis in Premature Newborns. A Systematic Review of the Literature
Authors: Campos-Martinez Ana M. , Expósito-Herrera J. , Gonzalez-Bolívar M. , Fernández-Marin E. , Uberos Jose
Published: May 2022

Necrotizing enterocolitis (NEC) is a serious condition related to prematurity and the initiation of enteral feeding. In this article, we review the evidence published in recent years on necrotizing enterocolitis risk factors (prematurity, feeding with low-weight formula, existence of intestinal dysbiosis) and protective factors (human milk or donated milk supply, supplementation of human milk with oligosaccharides, probiotics administration, and the determination of disease predictive biomarkers). A systematic review was conducted of preventive, risk and predictive factors for necrotizing enterocolitis in neonates prior to 37 weeks' gestational age, based on a literature search for clinical trials, meta-analyses, randomized controlled trials and systematic reviews published between January 2018 and October 2021. For this purpose, the PubMed, MEDLINE, and Cochrane Library databases were consulted. The literature search obtained 113 articles, of which 19 were selected for further analysis after applying the inclusion and exclusion criteria. The conclusions drawn from this analysis were that adequate knowledge of risk factors that can be prevented or modified (such as alteration of the intestinal microbiota, oxidative stress, metabolic dysfunction at birth, or alteration of the immunity modulation) can reduce the incidence of NEC in premature infants. These factors include the supplementation of enteral nutrition with human milk oligosaccharides (with prebiotic and immunomodulatory effects), the combined administration of probiotics (especially the Lactobacillus spp and Bifidobacterium spp combination, which inhibits bacterial adhesion effects, improves the intestinal mucosa barrier function, strengthens the innate and adaptive immune system and increases the secretion of bioactive metabolites), the supplementation of human milk with lactoferrin and the use of donated milk fortified in accordance with the characteristics of the premature newborn. The determination of factors that can predict the existence of NEC, such as fecal calprotectin, increased TLR4 activity, and IL6 receptor, can lead to an early diagnosis of NEC. Although further studies should be conducted to determine the values of predictive biomarkers of NEC, and/or the recommended doses and strains of probiotics, lactoferrin or oligosaccharides, the knowledge acquired in recent years is encouraging.
Nutritional Support for Pediatric Severe Traumatic Brain Injury
Authors: Elliott Elizabeth , Shoykhet Michael , Bell Michael J. , Wai Kitman
Published: May 2022

In critically ill children with severe traumatic brain injury (sTBI), nutrition may help facilitate optimal recovery. There is ongoing research regarding nutritional practices in the pediatric intensive care unit (PICU). These are focused on identifying a patient's most appropriate energy goal, the mode and timing of nutrient delivery that results in improved outcomes, as well as balancing these goals against inherent risks associated with nutrition therapy. Within the PICU population, children with sTBI experience complex physiologic derangements in the acute post-injury period that may alter metabolic demand, leading to nutritional needs that may differ from those in other critically ill patients. Currently, there are relatively few studies examining nutrition practices in PICU patients, and even fewer studies that focus on pediatric sTBI patients. Available data suggest that contemporary neurocritical care practices may largely blunt the expected hypermetabolic state after sTBI, and that early enteral nutrition may be associated with lower morbidity and mortality. In concordance with these data, the most recent guidelines for the management of pediatric sTBI released by the Brain Trauma Foundation recommend initiation of enteral nutrition within 72 h to improve outcome (Level 3 evidence). In this review, we will summarize available literature on nutrition therapy for children with sTBI and identify gaps for future research.
Vancomycin, Daptomycin, Antistaphylococcal β-Lactam, and Trimethoprim-Sulfamethoxazole Monotherapy and Combination Therapy in the Management of Methicillin-Resistant Staphylococcus aureus: A Network Meta-Analysis
Authors: Xu Xiaonan , Lu Ni , Song Pan , Zhou Mingzhen , Li Yuanxiao , Wang Zirui , Gao Xin
Published: May 2022

Objective: The aim was to evaluate the efficacy and safety of vancomycin or daptomycin (VAN/DAP), antistaphylococcal β-lactam (ASBL), trimethoprim-sulfamethoxazole (TMP-SMX), and combination therapy of VAN/DAP + ASBL in the management of methicillin-resistant Staphylococcus aureus (MRSA).

Methods: Databases including PubMed, Cochrane Library, Embase database, and google scholar were searched on 1 September 2021. The randomized control trials (RCTs) and comparable clinical studies of VAN/DAP, VAN/DAP + ASBL, ASBL, and TMP-SMX in the management of MRSA were identified. A network meta-analysis was conducted with STATA 14.0.

Results: Seven RCTs and two matched cohorts with 1,048 patients were included in the analysis. The pooled results showed that VAN/DAP + ASBL had a significantly lower rate of persistent bacteremia >3 days than VAN/DAP alone [OR:0.46, 95%CI (0.26, 0.81), p < 0.001]. No obvious differences were observed in the outcomes of all-cause mortality, relapsed bacteremia, microbiological treatment failure, embolic or metastatic infection, and total adverse events. However, the ranking results showed that VAN/DAP + ASBL had slightly better efficacy (all-cause mortality, persistent bacteremia >3 days, duration of bacteremia, microbiological treatment failure, and relapsed bacteremia) but slightly higher adverse events than VAN/DAP alone. No obvious differences in the comparisons of VAN/DAP vs. ASBL, and VAN/DAP vs TMP-SMX in the analyzed outcomes. The ranking results revealed that ASBL and TMP-SMX did not have better efficacy or lower adverse events compared with the treatment of VAN/DAP.

Conclusion: The efficacy of VAN/DAP + ASBL was slightly but not significantly better than VAN/DAP alone in the management of MRSA.
Emerging Roles of Non-Coding RNAs in Childhood Asthma
Authors: Liang Juan , Liu Xiao-Hua , Chen Xue-Mei , Song Xiu-Ling , Li Wen , Huang Yuge
Published: May 2022

Asthma is a chronic airway inflammatory disease in children characterized by airway inflammation, airway hyperresponsiveness and airway remodeling. Childhood asthma is usually associated with allergy and atopy, unlike adult asthma, which is commonly associated with obesity, smoking, etc. The pathogenesis and diagnosis of childhood asthma also remains more challenging than adult asthma, such as many diseases showing similar symptoms may coexist and be confused with asthma. In terms of the treatment, although most childhood asthma can potentially be self-managed and controlled with drugs, approximately 5–10% of children suffer from severe uncontrolled asthma, which carries significant health and socioeconomic burdens. Therefore, it is necessary to explore the pathogenesis of childhood asthma from a new perspective. Studies have revealed that non-coding RNAs (ncRNAs) are involved in the regulation of respiratory diseases. In addition, altered expression of ncRNAs in blood, and in condensate of sputum or exhalation affects the progression of asthma via regulating immune response. In this review, we outline the regulation and pathogenesis of asthma and summarize the role of ncRNAs in childhood asthma. We also hold promise that ncRNAs may be used for the development of biomarkers and support a new therapeutic strategy for childhood asthma.
Hepatic Organoid-Based High-Content Imaging Boosts Evaluation of Stereoisomerism-Dependent Hepatotoxicity of Stilbenes in Herbal Medicines
Authors: Liu Juan , Li Tingting , Li Ruihong , Wang Jie , Li Pengyan , Niu Ming , Zhang Le , Li Chunyu , Wang Tao , Xiao Xiaohe , Wang Jia-bo , Wang Yunfang
Published: May 2022

The complexity of chemical components of herbal medicines often causes great barriers to toxicity research. In our previous study, we have found the critical divergent hepatotoxic potential of a pair of stilbene isomers in a famous traditional Chinese herb, Polygonum multiflorum (Heshouwu in Chinese). However, the high-throughput in vitro evaluation for such stereoisomerism-dependent hepatotoxicity is a critical challenge. In this study, we used a hepatic organoids–based in vitro hepatotoxic evaluation system in conjunction with using high content imaging to differentiate in vivo organ hepatotoxicity of the 2,3,5,4′-tetrahydroxy-trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer (cis-SG). By using such an organoid platform, we successfully differentiated the two stereoisomers’ hepatotoxic potentials, which were in accordance with their differences in rodents and humans. The lesion mechanism of the toxic isomer (cis-SG) was further found as the mitochondrial injury by high-content imaging, and its hepatotoxicity could be dose-dependently inhibited by the mitochondrial protective agent. These results demonstrated the utility of the organoids-based high-content imaging approach in evaluating and predicting organ toxicity of natural products in a low-cost and high-throughput way. It also suggested the rationale to use long-term cultured organoids as an alternative toxicology platform to identify early and cautiously the hepatotoxic new drug candidates in the preclinical phase.
Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line
Authors: Scisciola Lucia , Fontanella Rosaria Anna , Surina  , Garofalo Giovanna , Rizzo Maria Rosaria , Paolisso Giuseppe , Barbieri Michelangela
Published: May 2022

The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis via the activation of Sirtuin 1 and Sirtuin 6 pathways.
Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis
Authors: Chen Li , Kong Desong , Xia Siwei , Wang Feixia , Li Zhanghao , Zhang Feng , Zheng Shizhong
Published: May 2022

Liver fibrosis is a repair process of chronic liver injuries induced by toxic substances, pathogens, and inflammation, which exhibits a feature such as deposition of the extracellular matrix. The initiation and progression of liver fibrosis heavily relies on excessive activation of hepatic stellate cells (HSCs). The activated HSCs express different kinds of chemokine receptors to further promote matrix remodulation. The long-term progression of liver fibrosis will contribute to dysfunction of the liver and ultimately cause hepatocellular carcinoma. The liver also has abundant innate immune cells, including DCs, NK cells, NKT cells, neutrophils, and Kupffer cells, which conduct complicated functions to activation and expansion of HSCs and liver fibrosis. Autophagy is one specific type of cell death, by which the aberrantly expressed protein and damaged organelles are transferred to lysosomes for further degradation, playing a crucial role in cellular homeostasis. Autophagy is also important to innate immune cells in various aspects. The previous studies have shown that dysfunction of autophagy in hepatic immune cells can result in the initiation and progression of inflammation in the liver, directly or indirectly causing activation of HSCs, which ultimately accelerate liver fibrosis. Given the crosstalk between innate immune cells, autophagy, and fibrosis progression is complicated, and the therapeutic options for liver fibrosis are quite limited, the exploration is essential. Herein, we review the previous studies about the influence of autophagy and innate immunity on liver fibrosis and the molecular mechanism to provide novel insight into the prevention and treatment of liver fibrosis.
A New Triple-Band Four-Way Filtering Power Divider With Highly Improved Performance
Authors: Li Yibing , Zhou Xin , Sun Xiaohang , Gu Xiaojun , Xu Bin , Zhang Xinde , Ping Kang
Published: May 2022

This letter presents a new triple-band four-way filtering power divider (FPD) with greatly improved frequency selectivity and in-band isolation. By elaborately developing a multi-port multi-mode topology between four identical multi-mode resonators and feedlines, a triple-band four-way FPD is attained. In order to validate the feasibility of the proposal, one prototype is designed, fabricated, and measured. Both the simulated and measured results of the designed FPD are provided with a good agreement. Results indicate that this triple-band four-way FPD exhibits not only sharp selective filtering performance, but also satisfactory port-to-port isolations.
Network Analysis of SIFIs Based on Tail Systemic Linkage
Authors: Tan Keqi , Chen Yu , Liao Yujie
Published: May 2022

This article applies several distinct methods including the systemic linkage method and network analysis to address intranational systemic risk interdependencies. Specifically, we initially quantify dynamic systemic linkages among US and Chinese systemically important financial institutions through time-varying adjacency matrices related to an extreme value theory (EVT) approach and then visualize them using network analysis. Numerical and graphical results show that intranational systemic linkages are obviously enhancive under extreme scenarios such as large negative shocks in the financial system. In addition, we apply a tail event-driven network quantile regression (TENQR) model to address the interdependence and dynamics of the entire network. The estimation results show that the network factors respond more strongly when the market suffers extreme stress.