bluuebunny/crossref_metadata_2025 huggingface dataset:
An Individual Patient's “Body” on Chips—How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach
Authors: Marx Uwe , Accastelli Enrico , David Rhiannon , Erfurth Hendrik , Koenig Leopold , Lauster Roland , Ramme Anja Patricia , Reinke Petra , Volk Hans-Dieter , Winter Annika , Dehne Eva-Maria
Published: September 2021

The first concepts for reproducing human systemic organismal biology in vitro were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale in vitro and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids—stem cell-derived complex three-dimensional organ models that expand and self-organize in vitro—have proven that in vitro self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells. Such premature organoids can precisely reflect a number of distinct physiological and pathophysiological features of their respective counterparts in the human body. We now develop the human-on-a-chip concepts of the past into an organismoid theory. We describe the current concept and principles to create a series of organismoids—minute, mindless and emotion-free physiological in vitro equivalents of an individual's mature human body—by an artificially short process of morphogenetic self-assembly mimicking an individual's ontogenesis from egg cell to sexually mature organism. Subsequently, we provide the concept and principles to maintain such an individual's set of organismoids at a self-sustained functional healthy homeostasis over very long time frames in vitro. Principles how to perturb a subset of healthy organismoids by means of the natural or artificial induction of diseases are enrolled to emulate an individual's disease process. Finally, we discuss using such series of healthy and perturbed organismoids in predictively selecting, scheduling and dosing an individual patient's personalized therapy or medicine precisely. The potential impact of the organismoid theory on our healthcare system generally and the rapid adoption of disruptive personalized T-cell therapies particularly is highlighted.
IL-33 in Rheumatic Diseases
Authors: Dong Yuanji , Zhong Jixin , Dong Lingli
Published: September 2021

Interleukin-33 (IL-33) is a nuclear factor mainly expressed in barrier epithelium, endothelial cells, and fibroblast reticular cells. Some inflammatory cells also express IL-33 under certain conditions. The important role of IL-33 in allergic reactions, helminth infection, cancer, tissue fibrosis, chronic inflammation, organ transplantation, and rheumatic immune diseases has been extensively studied in recent years. IL-33 primarily activates various circulating and tissue-resident immune cells, including mast cell, group 2 innate lymphoid cell (ILC2), regulatory T cell (Treg), T helper 2 cell (Th2), natural killer cell (NK cell), and macrophage. Therefore, IL-33 plays an immunomodulatory role and shows pleiotropic activity in different immune microenvironments. The IL-33/serum stimulation-2 (ST2) axis has been shown to have a detrimental effect on rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic diseases. Interestingly, IL-33 also plays a protective role in the repair of barrier epithelium and the activation of Tregs. Therefore, the role of IL-33/ST2 depends on the underlying pathological conditions in rheumatic diseases. This review focuses on the dual role of the IL-33/ST2 axis in rheumatic diseases.
Bifidobacteria Strain Typing by Fourier Transform Infrared Spectroscopy
Authors: Deidda Francesca , Bozzi Cionci Nicole , Cordovana Miriam , Campedelli Ilenia , Fracchetti Fabio , Di Gioia Diana , Ambretti Simone , Pane Marco
Published: September 2021

Fourier transform infrared (FTIR) spectroscopy, a technology traditionally used in chemistry to determine the molecular composition of a wide range of sample types, has gained growing interest in microbial typing. It is based on the different vibrational modes of the covalent bonds between atoms of a given sample, as bacterial cells, induced by the absorption of infrared radiation. This technique has been largely used for the study of pathogenic species, especially in the clinical field, and has been proposed also for the typing at different subspecies levels. The high throughput, speed, low cost, and simplicity make FTIR spectroscopy an attractive technique also for industrial applications, in particular, for probiotics. The aim of this study was to compare FTIR spectroscopy with established genotyping methods, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing (WGS), and multilocus sequence typing (MLST), in order to highlight the FTIR spectroscopy potential discriminatory power at strain level. Our study focused on bifidobacteria, an important group of intestinal commensals generally recognized as probiotics. For their properties in promoting and maintaining health, bifidobacteria are largely marketed by the pharmaceutical, food, and dairy industries. Strains belonging to Bifidobacterium longum subsp. longum and Bifidobacterium animalis subsp. lactis were taken into consideration together with some additional type strains. For B. longum subsp. longum, it was possible to discriminate the strains with all the methods used. Although two isolates were shown to be strictly phylogenetically related, constituting a unique cluster, based on PFGE, WGS, and MLST, no clustering was observed with FTIR. For B. animalis subsp. lactis group, PFGE, WGS, and MLST were non-discriminatory, and only one strain was easily distinguished. On the other hand, FTIR discriminated all the isolates one by one, and no clustering was observed. According to these results, FTIR analysis is not only equivalent to PFGE, WGS, and MLST, but also for some strains, in particular, for B. animalis subsp. lactis group, more informative, being able to differentiate strains not discernible with the other two methods based on phenotypic variations likely deriving from certain genetic changes. Fourier transform infrared spectroscopy has highlighted the possibility of using the cell surface as a kind of barcode making tracing strains possible, representing an important aspect in probiotic applications. Furthermore, this work constitutes the first investigation on bifidobacterial strain typing using FTIR spectroscopy.
Effects of Dietary Energy Levels on Rumen Fermentation, Gastrointestinal Tract Histology, and Bacterial Community Diversity in Fattening Male Hu Lambs
Authors: Wang Qiye , Zeng Yutong , Zeng Xianglin , Wang Xin , Wang Yancan , Dai Chunpeng , Li Jianzhong , Huang Pengfei , Huang Jing , Hussain Tarique , Zhu Mingzhi , Yang Huansheng
Published: September 2021

This study investigated rumen fermentation and histological and microbial diversity in male Hu lamb fed diets with different metabolizable energy (ME) levels (MEA, 9.17 MJ/kg, MEB, 10.00 MJ/kg, and MEC, 10.82 MJ/kg). Thirty-six male Hu lambs were randomly allotted to three treatments, and the feeding trial lasted for 67 days. Rumen fermentation results suggest that the iso-valerate had a significant effect on dietary energy level. The papillary height (PH) of rumen was the highest in the MEB group, the crypt depth (CD) was significantly increased in the duodenum and jejunum, and the villus height (VH)-to-CD ratio (VH/CD) was significantly decreased in the duodenum by increasing dietary energy levels; the VH, villus width (VW), and VH/CD also had significant differences in the ileum. 16S rRNA sequencing results showed that the operational taxonomic units (OTUs) number, the ACE, and Chao1 indices were linearly decreased by increasing dietary energy level; 24 phyla including 124 genera were identified, and the relative abundance of Papillibacter and Quinella linearly decreased by increasing the dietary energy level. Compared to MEA and MEB groups, the relative abundance of unidentified_Veillonellaceae and Anaerovibrio was significantly increased in the MEC group at the genus level. The relative abundance of the carbohydrate metabolism pathway predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was linearly increased by increasing the dietary energy levels. Three metabolic pathways identified in Kyoto Encyclopedia of Genes and Genomes (KEGG) level 3 were significantly influenced as the dietary energy level increased. In summary, these results demonstrated that the dietary energy levels affected the rumen fermentation parameters, morphological structures of the gastrointestinal tract (GIT), and the composition and function of rumen microflora in male Hu sheep.
Analysis of Phenol Biodegradation in Antibiotic and Heavy Metal Resistant Acinetobacter lwoffii NL1
Authors: Xu Nan , Qiu Chong , Yang Qiyuan , Zhang Yunzeng , Wang Mingqi , Ye Chao , Guo Minliang
Published: September 2021

Phenol is a common environmental contaminant. The purpose of this study was to isolate phenol-degrading microorganisms from wastewater in the sections of the Chinese Medicine Manufactory. The phenol-degrading Acinetobacter lwoffii NL1 was identified based on a combination of biochemical characteristics and 16S rRNA genes. To analyze the molecular mechanism, the whole genome of A. lwoffii NL1 was sequenced, yielding 3499 genes on one circular chromosome and three plasmids. Enzyme activity analysis showed that A. lwoffii NL1 degraded phenol via the ortho-cleavage rather than the meta-cleavage pathway. Key genes encoding phenol hydroxylase and catechol 1,2-dioxygenase were located on a megaplasmid (pNL1) and were found to be separated by mobile genetic elements; their function was validated by heterologous expression in Escherichia coli and quantitative real-time PCR. A. lwoffii NL1 could degrade 0.5 g/L phenol within 12 h and tolerate a maximum of 1.1 g/L phenol, and showed resistance against multiple antibiotics and heavy metal ions. Overall, this study shows that A. lwoffii NL1 can be potentially used for efficient phenol degradation in heavy metal wastewater treatment.
Rhizosphere Microbial Communities Are Significantly Affected by Optimized Phosphorus Management in a Slope Farming System
Authors: Deng Qianxin , Zhang Tong , Xie Deti , Yang Yuheng
Published: September 2021

Soil rhizosphere microorganisms play crucial roles in promoting plant nutrient absorption and maintaining soil health. However, the effects of different phosphorus (P) managements on soil microbial communities in a slope farming system are poorly understood. Here, rhizosphere microbial communities under two P fertilization levels—conventional (125 kg P2O5 ha–1, P125) and optimal (90 kg P2O5 ha–1, P90)—were compared at four growth stages of maize in a typical sloped farming system. The richness and diversity of rhizosphere bacterial communities showed significant dynamic changes throughout the growth period of maize, while different results were observed in fungal communities. However, both the P fertilization levels and the growth stages influenced the structure and composition of the maize rhizosphere microbiota. Notably, compared to P125, Pseudomonas, Conexibacter, Mycobacterium, Acidothermus, Glomeromycota, and Talaromyces were significantly enriched in the different growth stages of maize under P90, while the relative abundance of Fusarium was significantly decreased during maize harvest. Soil total nitrogen (TN) and pH are the first environmental drivers of change in bacterial and fungal community structures, respectively. The abundance of Gemmatimonadota, Proteobacteria, and Cyanobacteria showed significant correlations with soil TN, while that of Basidiomycota and Mortierellomycota was significantly related to pH. Additionally, P90 strengthened the connection between bacteria, but reduced the links between fungi at the genus level. Our work helps in understanding the role of P fertilization levels in shaping the rhizosphere microbiota and may manipulate beneficial microorganisms for better P use efficiency.
4.1N-Mediated Interactions and Functions in Nerve System and Cancer
Authors: Yang Qin , Liu Jing , Wang Zi
Published: September 2021

Scaffolding protein 4.1N is a neuron-enriched 4.1 homologue. 4.1N contains three conserved domains, including the N-terminal 4.1-ezrin-radixin-moesin (FERM) domain, internal spectrin–actin–binding (SAB) domain, and C-terminal domain (CTD). Interspersed between the three domains are nonconserved domains, including U1, U2, and U3. The role of 4.1N was first reported in the nerve system. Then, extensive studies reported the role of 4.1N in cancers and other diseases. 4.1N performs numerous vital functions in signaling transduction by interacting, locating, supporting, and coordinating different partners and is involved in the molecular pathogenesis of various diseases. In this review, recent studies on the interactions between 4.1N and its contactors (including the α7AChr, IP3R1, GluR1/4, GluK1/2/3, mGluR8, KCC2, D2/3Rs, CASK, NuMA, PIKE, IP6K2, CAM 1/3, βII spectrin, flotillin-1, pp1, and 14-3-3) and the 4.1N-related biological functions in the nerve system and cancers are specifically and comprehensively discussed. This review provides critical detailed mechanistic insights into the role of 4.1N in disease relationships.
Age at Disease Onset Associates With Oxidative Stress, Neuroinflammation, and Impaired Synaptic Plasticity in Relapsing-Remitting Multiple Sclerosis
Authors: Stampanoni Bassi Mario , Gilio Luana , Iezzi Ennio , Moscatelli Alessandro , Pekmezovic Tatjana , Drulovic Jelena , Furlan Roberto , Finardi Annamaria , Mandolesi Georgia , Musella Alessandra , Galifi Giovanni , Fantozzi Roberta , Bellantonio Paolo , Storto Marianna , Centonze Diego , Buttari Fabio
Published: September 2021

Age at onset is the main risk factor for disease progression in patients with relapsing-remitting multiple sclerosis (RR-MS). In this cross-sectional study, we explored whether older age is associated with specific disease features involved in the progression independent of relapse activity (PIRA). In 266 patients with RR-MS, the associations between age at onset, clinical characteristics, cerebrospinal fluid (CSF) levels of lactate, and that of several inflammatory molecules were analyzed. The long-term potentiation (LTP)-like plasticity was studied using transcranial magnetic stimulation (TMS). Older age was associated with a reduced prevalence of both clinical and radiological focal inflammatory disease activity. Older patients showed also increased CSF levels of lactate and that of the pro-inflammatory molecules monocyte chemoattractant protein 1 (MCP-1)/CCL2, macrophage inflammatory protein 1-alpha (MIP-1α)/CCL3, and interleukin (IL)-8. Finally, TMS evidenced a negative correlation between age and LTP-like plasticity. In newly diagnosed RR-MS, older age at onset is associated with reduced acute disease activity, increased oxidative stress, enhanced central inflammation, and altered synaptic plasticity. Independently of their age, patients with multiple sclerosis (MS) showing similar clinical, immunological, and neurophysiological characteristics may represent ideal candidates for early treatments effective against PIRA.
A Dual-Task Paradigm Using the Oral Trail Making Test While Walking to Study Cognitive-Motor Interactions in Older Adults
Authors: Langeard Antoine , Torre Marta Maria , Temprado Jean-Jacques
Published: September 2021

Objective: With aging, gait becomes more dependent on executive functions, especially on switching abilities. Therefore, cognitive-motor dual-task (DT) paradigms should study the interferences between gait and switching tasks. This study aimed to test a DT paradigm based on a validated cognitive switching task to determine whether it could distinguish older-old adults (OO) from younger-old adults (YO).

Methods: Sixty-five healthy older participants divided into 29 younger-old (<70 years) and 36 older-old (≥70 years) age groups were evaluated in three single-task (ST) conditions as follows: a cognitive task including a processing speed component [Oral Trail Making Test part A (OTMT-A)], a cognitive task including a switching component [Oral Trail Making Test part B (OTMT-B)], and a gait evaluation at normal speed. They were also evaluated under two DT conditions, i.e., one associating gait with OTMT-A and the other associating gait with OTMT-B. Cognitive and gait performances were measured. The comparison of cognitive and gait performances between condition, logistic regression, and receiver operating characteristic (ROC) analyses were performed.

Results: The cognitive and gait performances were differently affected by the different conditions (i.e., ST, DT, OTMT-A, and OTMT-B). The OTMT-B produced higher interference on gait and cognitive performances. Moreover, a higher number of errors on the OTMT-B performed while walking was associated with the older-old age group.

Conclusion: Using validated cognitive flexibility tasks, this DT paradigm confirms the high interference between switching tasks and gait in older age. It is easily implemented, and its sensitivity to age may highlight its possible usefulness to detect cognitive or motor declines.
EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer’s Disease
Authors: Yeung Jason H. Y. , Palpagama Thulani H. , Wood Oliver W. G. , Turner Clinton , Waldvogel Henry J. , Faull Richard L. M. , Kwakowsky Andrea
Published: September 2021

Alzheimer’s disease (AD) is a neuropathological disorder characterized by the presence and accumulation of amyloid-beta plaques and neurofibrillary tangles. Glutamate dysregulation and the concept of glutamatergic excitotoxicity have been frequently described in the pathogenesis of a variety of neurodegenerative disorders and are postulated to play a major role in the progression of AD. In particular, alterations in homeostatic mechanisms, such as glutamate uptake, have been implicated in AD. An association with excitatory amino acid transporter 2 (EAAT2), the main glutamate uptake transporter, dysfunction has also been described. Several animal and few human studies examined EAAT2 expression in multiple brain regions in AD but studies of the hippocampus, the most severely affected brain region, are scarce. Therefore, this study aims to assess alterations in the expression of EAAT2 qualitatively and quantitatively through DAB immunohistochemistry (IHC) and immunofluorescence within the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus (STG) regions, between human AD and control cases. Although no significant EAAT2 density changes were observed between control and AD cases, there appeared to be increased transporter expression most likely localized to fine astrocytic branches in the neuropil as seen on both DAB IHC and immunofluorescence. Therefore, individual astrocytes are not outlined by EAAT2 staining and are not easily recognizable in the CA1–3 and dentate gyrus regions of AD cases, but the altered expression patterns observed between AD and control hippocampal cases could indicate alterations in glutamate recycling and potentially disturbed glutamatergic homeostasis. In conclusion, no significant EAAT2 density changes were found between control and AD cases, but the observed spatial differences in transporter expression and their functional significance will have to be further explored.
Left Atrial Dilatation and Reduced Left Ventricular Ejection Fraction Are Associated With Cardioembolic Stroke
Authors: Hosseini Farahabadi Maryam , Milani-Nejad Shadi , Liu Shimeng , Yu Wengui , Shafie Mohammad
Published: September 2021

Objective: Left atrial (LA) dilatation and heart failure are independent risk factors for ischemic stroke. The goal of this study is to evaluate the association between LA dilatation and reduced left ventricular ejection fraction (EF) with cardioembolic stroke.

Methods: Four hundred fifty-three patients with ischemic stroke admitted to the University of California, Irvine between 2016 and 2017 were included based on the following criteria: age >18 and availability of echocardiogram. Stroke was categorized into cardioembolic and non-cardioembolic. EF was categorized into normal: 52–72% (male), 54–74% (female), mildly abnormal: 41–51% (male), 41–53% (female), moderately abnormal: 30–40%, and severely abnormal: <30%. LA volume was categorized into normal (≤34 ml/m2) vs. enlarged (≥35 ml/m2). Other variables included gender, hypertension [systolic blood pressure (SBP) ≥ 140 or diastolic blood pressure (DBP) ≥ 90], and known history of atrial fibrillation (Afib).

Results: Two hundred eighteen patients had cardioembolic, and 235 had non-cardioembolic stroke. Among patients with cardioembolic stroke, 49 (22.4%) and 142 (65%) had reduced EF and enlarged LA, respectively, as compared with 19 (8.1%) and 65 (27.7%) patients with non-cardioembolic stroke (p < 0.0001). The odds of cardioembolic stroke were 2.0 (95% CI: 0.1–6.0) and 8.8 times (95% CI: 1.9–42.3) higher in patients with moderately and severely reduced EF, respectively, than in patients with normal EF. The odds of cardioembolic stroke was 2.4 times (95% CI: 1.5–3.9) higher in patients with enlarged LA than in patients with normal LA size. Compared with patients with normal LA and EF, patients with combined enlarged LA and reduced EF had significantly higher rates of Afib (43.4 vs. 9.0%, p < 0.0001) and cardioembolic stroke (78.3 vs. 43.4%, p < 0.0001).

Conclusions: LA dilatation along with reduced EF is a reliable predictor of Afib and cardioembolic stroke. Further studies are warranted to determine the benefit of anticoagulation for secondary stroke prevention in such patient population.
Near-Infrared Spectroscopy-Derived Dynamic Cerebral Autoregulation in Experimental Human Endotoxemia—An Exploratory Study
Authors: Eleveld Nick , Hoedemaekers Cornelia W. E. , van Kaam C. Ruud , Leijte Guus P. , van den Brule Judith M. D. , Pickkers Peter , Aries Marcel J. H. , Maurits Natasha M. , Elting Jan Willem J.
Published: September 2021

Cerebral perfusion may be altered in sepsis patients. However, there are conflicting findings on cerebral autoregulation (CA) in healthy participants undergoing the experimental endotoxemia protocol, a proxy for systemic inflammation in sepsis. In the current study, a newly developed near-infrared spectroscopy (NIRS)-based CA index is investigated in an endotoxemia study population, together with an index of focal cerebral oxygenation.

Methods: Continuous-wave NIRS data were obtained from 11 healthy participants receiving a continuous infusion of bacterial endotoxin for 3 h (ClinicalTrials.gov NCT02922673) under extensive physiological monitoring. Oxygenated–deoxygenated hemoglobin phase differences in the (very)low frequency (VLF/LF) bands and the Tissue Saturation Index (TSI) were calculated at baseline, during systemic inflammation, and at the end of the experiment 7 h after the initiation of endotoxin administration.

Results: The median (inter-quartile range) LF phase difference was 16.2° (3.0–52.6°) at baseline and decreased to 3.9° (2.0–8.8°) at systemic inflammation (p = 0.03). The LF phase difference increased from systemic inflammation to 27.6° (12.7–67.5°) at the end of the experiment (p = 0.005). No significant changes in VLF phase difference were observed. The TSI (mean ± SD) increased from 63.7 ± 3.4% at baseline to 66.5 ± 2.8% during systemic inflammation (p = 0.03) and remained higher at the end of the experiment (67.1 ± 4.2%, p = 0.04). Further analysis did not reveal a major influence of changes in several covariates such as blood pressure, heart rate, PaCO2, and temperature, although some degree of interaction could not be excluded.

Discussion: A reversible decrease in NIRS-derived cerebral autoregulation phase difference was seen after endotoxin infusion, with a small, sustained increase in TSI. These findings suggest that endotoxin administration in healthy participants reversibly impairs CA, accompanied by sustained microvascular vasodilation.
The Time-Robustness Analysis of Individual Identification Based on Resting-State EEG
Authors: Di Yang , An Xingwei , Zhong Wenxiao , Liu Shuang , Ming Dong
Published: September 2021

An ongoing interest towards identification based on biosignals, such as electroencephalogram (EEG), magnetic resonance imaging (MRI), is growing in the past decades. Previous studies indicated that the inherent information about brain activity may be used to identify individual during resting-state of eyes open (REO) and eyes closed (REC). Electroencephalographic (EEG) records the data from the scalp, and it is believed that the noisy EEG signals can influence the accuracies of one experiment causing unreliable results. Therefore, the stability and time-robustness of inter-individual features can be investigated for the purpose of individual identification. In this work, we conducted three experiments with the time interval of at least 2 weeks, and used different types of measures (Power Spectral Density, Cross Spectrum, Channel Coherence and Phase Lags) to extract the individual features. The Pearson Correlation Coefficient (PCC) is calculated to measure the level of linear correlation for intra-individual, and Support Vector Machine (SVM) is used to obtain the related classification accuracy. Results show that the classification accuracies of four features were 85–100% for intra-experiment dataset, and were 80–100% for fusion experiments dataset. For inter-experiments classification of REO features, the optimized frequency range is 13–40 Hz for three features, Power Spectral Density, Channel Coherence and Cross Spectrum. For inter-experiments classification of REC, the optimized frequency range is 8–40 Hz for three features, Power Spectral Density, Channel Coherence and Cross Spectrum. The classification results of Phase Lags are much lower than the other three features. These results show the time-robustness of EEG, which can further use for individual identification system.
Signal Generation, Acquisition, and Processing in Brain Machine Interfaces: A Unified Review
Authors: Salahuddin Usman , Gao Pu-Xian
Published: September 2021

Brain machine interfaces (BMIs), or brain computer interfaces (BCIs), are devices that act as a medium for communications between the brain and the computer. It is an emerging field with numerous applications in domains of prosthetic devices, robotics, communication technology, gaming, education, and security. It is noted in such a multidisciplinary field, many reviews have surveyed on various focused subfields of interest, such as neural signaling, microelectrode fabrication, and signal classification algorithms. A unified review is lacking to cover and link all the relevant areas in this field. Herein, this review intends to connect on the relevant areas that circumscribe BMIs to present a unified script that may help enhance our understanding of BMIs. Specifically, this article discusses signal generation within the cortex, signal acquisition using invasive, non-invasive, or hybrid techniques, and the signal processing domain. The latest development is surveyed in this field, particularly in the last decade, with discussions regarding the challenges and possible solutions to allow swift disruption of BMI products in the commercial market.
Bone Scintigraphy of Vertebral Fractures With a Whole-Body CZT Camera in a PET-Like Utilization
Authors: Bahloul Achraf , Verger Antoine , Blum Alain , Chawki Mohammad Bilal , Perrin Mathieu , Melki Saifeddine , Karcher Gilles , Marie Pierre-Yves , Imbert Laetitia
Published: September 2021

Objective: An image display with a standardized uptake value (SUV) scale is recommended for analyzing PET exams, thus requiring the reconstruction of accurate images for both SUV measurement and visual analysis. This study aimed to determine whether such images may also be obtained with a high-speed CZT-SPECT/CT system, with a further application for the longitudinal monitoring of vertebral fractures.

Materials and Methods: SPECT image reconstruction was optimized with an IEC phantom according to both image quality parameters and accuracy of measured activity. The optimized reconstruction process was applied to ≤15 min 99mTc-HDP SPECT spine recordings previously acquired from 25 patients (74 ± 12 years old) at both early (1.3 ± 1.1 months) and late (5.2 ± 2.3 months) stages after an acute vertebral fracture.

Results: A SPECT reconstruction with 32 equivalent iterations was selected based on the association of high detectability for spheres down to 0.6 ml in volume, with accurate measured activity, although the latter was affected by partial volume effect for spheres ≤5.6 ml. Coherent measurements were obtained on these high-quality SPECT images for the SUVmax from the intact vertebrae of patients, which were stable between basal SPECT/CT and follow-up SPECT/CT (for T1 vertebrae: 5.7 ± 1.1 vs. 5.8 ± 1.1, p = 0.76), and from initially fractured vertebrae, which were dramatically higher on the basal compared with the follow-up SPECT (21.0 ± 8.5 vs. 11.2 ± 4.2, p < 0.001), whereas inverse changes in SUVmax were observed for newly compacted fractures identified on follow-up SPECT (74.4 ± 2.0 vs. 21.8 ± 10.3, p = 0.002). Finally, an image display with an SUV scale was shown to be advantageous for highlighting areas with >7.5 SUV, a level reached by 98% of vertebral fractures of <7 months and 4% of reference intact vertebrae.

Conclusion: Bone scintigraphy of vertebral fractures may be obtained with this CZT-SPECT/CT system with fast 3D acquisitions and high-quality images displayed with a reliable SUV scale, approaching what is achieved and recommended for PET imaging.
Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation
Authors: de Castro Josimar Macedo , Stein Dirson João , Medeiros Helouise Richardt , de Oliveira Carla , Torres Iraci L. S.
Published: September 2021

Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation. Therefore, we aimed to investigate the effects of CR on SMT and on hypothalamic inflammatory biomarkers in obese adult male Wistar rats, and whether NR supplementation alone or in combination with CR affects these parameters. Obesity was induced in rats through a cafeteria diet for 6 weeks. After that, a group of obese rats was exposed to CR, associated or not associated with NR supplementation (400 mg/kg), for another 4 weeks. As a result, obese rats, with or without CR, presented lower relative weight of SMT when compared with eutrophic rats. Rats under CR presented lower absolute SMT weight compared with obese and eutrophic rats, in addition to presenting elevated hypothalamic levels of TNF-α. NR supplementation, in all groups, enhanced weight loss and increased relative weight of the SMT. Furthermore, in animals under CR, NR reversed increases TNF-α levels in the hypothalamus. In this study, these data, although succinct, are the first to evidence the effects of NR on SMT and neuroinflammation when associated with CR, especially in obesity conditions. Therefore, this provides preliminary support for future studies in this investigative field. Furthermore, NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.
Analysis and Potential Value of Compounds Extracted From Star Ruby, Rio Red, and Ruby Red Grapefruit, and Grapefruit Juice Processing Residues via Steam Explosion
Authors: Dorado Christina , Cameron Randall G. , Manthey John A. , Bai Jinhe , Ferguson Kyle L.
Published: September 2021

Culled whole grapefruit (WG) and grapefruit juice processing residues (GP) are currently incorporated into low-cost animal feed. If individual chemical components found within these side streams could be recovered as high-value coproducts, this would improve the overall value of the grapefruit crop. In this study, pectic hydrocolloids, sugars, volatiles, phenolics, and flavonoids were extracted from Star Ruby, Rio Red, and Ruby Red GP and WG using a continuous pilot scale steam explosion system. Up to 97% of grapefruit juice oils and peel oils could be volatilized and contained 87–94% d-limonene. The recovery of pectin, as determined by galacturonic acid content, was between 2.06 and 2.72 g 100 g−1. Of the phenolics and flavonoids analyzed in this study, narirutin and naringin were extracted in the amounts of up to 10,000 and 67,000 μg g−1, respectively.
Relationship Between Nutrition Knowledge and Dietary Intake: An Assessment Among a Sample of Italian Adults
Authors: Scalvedi Maria Luisa , Gennaro Laura , Saba Anna , Rossi Laura
Published: September 2021

Background:Assessing nutrition knowledge provides useful information especially if coupled with the self-perception of nutrition knowledge that could lead to bias and personal conviction. The objective of this study was to assess nutrition knowledge (NK) and its relationship with eating habits in a group of adults.

Methods:A cross-sectional study with the administration of self-reported questionnaires was conducted on a sample of 591 parents (43 ± 5.82 years old) of primary school pupils recruited from the municipality of Rome (urban) and province (rural). The fieldwork was carried out in May 2017. An indicator to evaluate adherence to Italian dietary guidelines was developed. ANOVA (Welch's ANOVA in case of unequal variances) test and chi-squared test were used fixing the significance level at 5% (p< 0.05).

Results:The percentage of correct answers to nutrition knowledge was 46%, with the expert recommendation section having the highest percentage (59%). The majority of the respondents (66%) were confident that they had a high level of nutrition knowledge. In 37% of the sample, nutrition knowledge and self-perception nutrition knowledge levels were found to be associated. A total of 40% of the sample showed eating habits congruent with nutrition knowledge level. In the investigated sample, living in rural areas, being young, and having low school education level were factors associated with low nutrition literacy or/and unhealthy eating habits.

Conclusions:This study provided a demonstration that an assessment based on a multidimensional and multilevel approach is helpful to identify knowledge gaps and to profile critical segments to put in place targeted policy interventions.
A Maternal High Fat Diet Leads to Sex-Specific Programming of Mechanical Properties in Supraspinatus Tendons of Adult Rat Offspring
Authors: Bolam Scott M. , Satokar Vidit V. , Konar Subhajit , Coleman Brendan , Monk Andrew Paul , Cornish Jillian , Munro Jacob T. , Vickers Mark H. , Albert Benjamin B. , Musson David S.
Published: September 2021

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.

Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.

Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.

Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.
Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy
Authors: Li Bolei , Gong Tao , Hao Yu , Zhou Xuedong , Cheng Lei
Published: September 2021

The past two decades witnessed a revolution in our understanding of host–microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.
Overexpression of Pyruvate Dehydrogenase Kinase-3 Predicts Poor Prognosis in Urothelial Carcinoma
Authors: Kuo Yu-Hsuan , Chan Ti-Chun , Lai Hong-Yue , Chen Tzu-Ju , Wu Li-Ching , Hsing Chung-Hsi , Li Chien-Feng
Published: September 2021

Background

The mitochondrial pyruvate dehydrogenase complex (PDC) link glycolysis to the tricarboxylic acid cycle by decarboxylating pyruvate to acetyl coenzyme A irreversibly. Cancer cells are characterized by a shift in cellular metabolism from mitochondrial respiration to glycolysis. PDC activity inhibition mediated by phosphorylation via pyruvate dehydrogenase kinase (PDK) has been linked to cancer. However, the clinical significance of PDKs in urothelial cancer prognosis is not clear. We investigated the role and prognostic value of PDK3 expression in patients with upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC).

Patients and Methods

We retrospectively analyzed clinical data and pathological features. Formalin-fixed urothelial carcinoma (UC) tissues were collected and embedded in paraffin. The correlation of PDK3 expression with clinical characteristics, pathological findings and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS) were analyzed by Pearson’s chi-square test, Kaplan–Meier analysis, and the multivariate Cox proportional hazards model.

Results

Data from 295 patients with UBUC and 340 patients with UTUC were evaluated. High PDK3 expression significantly correlated with several pathologic variables such as high T stage, lymph node metastases, high tumor grade, vascular invasion, and high mitotic rate (all P < 0.001). High PDK3 expression was associated with poor disease-specific survival (DSS) (P < 0.0001) and metastatic free survival (MFS) (P < 0.0001) in a Kaplan–Meier analysis. Additionally, multivariate analysis demonstrated increased PDK3 expression is a significant predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.79, P = 0.009; in UTUC, 2.561, P = 0.03] and MFS (HR in UBUC, 1.907, P = 0.024; in UTUC, 1.793, P = 0.044). The gene co-expression analysis showed abundant PDK3 co-upregulated genes were involved in the processes of DNA replication and repair through the Gene Ontology classification system.

Conclusion

High PDK3 expression has been linked to negative pathologic characteristics and poor oncological outcomes, suggesting that it could be used as a predictive biomarker for UC. PDK3 mRNA levels and its co-upregulated genes were strongly associated with DNA replication and repair. These results suggest that PDK3 may play a key role in tumor proliferation and development.
Social Factors Predictive of Intensive Care Utilization in Technology-Dependent Children, a Retrospective Multicenter Cohort Study
Authors: Slain Katherine N. , Barda Amie , Pronovost Peter J. , Thornton J. Daryl
Published: September 2021

Objective: Technology-dependent children with medical complexity (CMC) are frequently admitted to the pediatric intensive care unit (PICU). The social risk factors for high PICU utilization in these children are not well described. The objective of this study was to describe the relationship between race, ethnicity, insurance status, estimated household income, and PICU admission following the placement of a tracheostomy and/or gastrostomy (GT) in CMC.

Study Design: This was a retrospective multicenter study of children <19 years requiring tracheostomy and/or GT placement discharged from a hospital contributing to the Pediatric Health Information System (PHIS) database between January 2016 and March 2019. Primary predictors included estimated household income, insurance status, and race/ethnicity. Additional predictor variables collected included patient age, sex, number of chronic complex conditions (CCC), history of prematurity, and discharge disposition following index hospitalization. The primary outcome was need for PICU readmission within 30 days of hospital discharge. Secondary outcomes included repeated PICU admissions and total hospital costs within 1 year of tracheostomy and/or GT placement.

Results: Patients requiring a PICU readmission within 30 days of index hospitalization for tracheostomy or GT placement accounted for 6% of the 20,085 included subjects. In multivariate analyses, public insurance [OR 1.28 (95% C.I. 1.12–1.47), p < 0.001] was associated with PICU readmission within 30 days of hospital discharge while living below the federal poverty threshold (FPT) was associated with a lower odds of 30-day PICU readmission [OR 0.7 (95% C.I. 0.51–0.95), p = 0.0267]. Over 20% (n = 4,197) of children required multiple (>1) PICU admissions within one year from index hospitalization. In multivariate analysis, Black children [OR 1.20 (95% C.I. 1.10–1.32), p < 0.001] and those with public insurance [OR 1.34 (95% C.I. 1.24–1.46), p < 0.001] had higher odds of multiple PICU admissions. Social risk factors were not associated with total hospital costs accrued within 1 year of tracheostomy and/or GT placement.

Conclusions: In a multicenter cohort study, Black children and those with public insurance had higher PICU utilization following tracheostomy and/or GT placement. Future research should target improving healthcare outcomes in these high-risk populations.
COVID-19 Pandemic Impact on Respiratory Infectious Diseases in Primary Care Practice in Children
Authors: Kaur Ravinder , Schulz Steven , Fuji Naoko , Pichichero Michael
Published: September 2021

Background: The coronavirus disease 2019 (COVID-19) pandemic led to day care and school closures and children staying home for several months. When they gradually returned, aggressive regulations were implemented in New York State to reduce viral transmission.

Method: An ongoing prospective study occurring in the Rochester, NY region, focused on early childhood respiratory infectious diseases, afforded an opportunity to assess the impact of the pandemic on the incidence of these illnesses in a primary care outpatient setting. Physician-diagnosed, medically attended infection visits were assessed in two child cohorts, age 6–36 months old: from March 15 to December 31, 2020 (the pandemic period) compared to the same months in 2019 (prepandemic). Nasopharyngeal colonization by potential otopathogens during healthy/well-child and acute otitis media (AOM) visits was evaluated.

Results: One hundred and forty-four children were included in the pandemic cohort and 215 in the prepandemic cohort. The pandemic cohort of children experienced 1.8-fold less frequent infectious disease visits during the pandemic (p < 0.0001). Specifically, visits for AOM were 3.7-fold lower (p < 0.0001), viral upper respiratory infections (URI) 3.8-fold lower (p < 0.0001), croup 27.5-fold lower (p < 0.0001), and bronchiolitis 7.4-fold lower (p = 0.04) than the prepandemic cohort. Streptococcus pneumoniae (p = 0.03), Haemophilus influenzae (p < 0.0001), and Moraxella catarrhalis (p < 0.0001) nasopharyngeal colonization occurred less frequently among children during the pandemic.

Conclusion: In primary care pediatric practice, during the first 9 months of the COVID-19 pandemic, significant decreases in the frequency of multiple respiratory infections and nasopharyngeal colonization by potential bacterial respiratory pathogens occurred in children age 6–36 months old.
Case Report: Pediatric Renal Sarcoidosis and Prognostic Factors in Reviewed Cases
Authors: Klaus Richard , Jansson Annette Friederike , Griese Matthias , Seeman Tomas , Amann Kerstin , Lange-Sperandio Bärbel
Published: September 2021

Background: Pediatric sarcoidosis is a complex inflammatory disorder with multisystemic manifestations. Kidney involvement in children is rare, and prognostic factors are unknown.

Case Report and Methods: We report the case of a 16-year-old girl with multiorgan sarcoidosis and renal involvement. The patient presented with tubulointerstitial nephritis, acute kidney injury (AKI), chest CT disseminated noduli, granulomatous iridocyclitis, giant-cell sialadenitis, and arthralgia. The kidney biopsy revealed non-granulomatous interstitial nephritis. Treatment consisted of initial high-dose methylprednisolone pulse followed by oral prednisolone and methotrexate. Full remission was achieved. In addition, we performed a literature review using PubMed and analyzed data on pediatric renal sarcoidosis cases.

Results: We identified 36 cases of pediatric sarcoidosis with renal involvement on presentation and data on the end-of-follow-up glomerular filtration rate (GFR). The data from the literature review showed that renal involvement was slightly more prevalent in males (60%). AKI was present in most of the described patients (84%). Oral prednisolone was used in 35 of 36 cases; in more severe cases, other immunosuppressants were used. We newly identified renal concentration impairment and granulomatous interstitial nephritis as factors with a clear trend toward GFR loss at the end of follow-up, emphasizing the importance of kidney biopsy in symptomatic patients. In contrast, higher GFR at presentation and hypercalcemia were rather favorable factors. According to the identified predictive factors, our patient has a good prognosis and is in remission.

Conclusion: The factors indicating a trend toward an unfavorable renal outcome in pediatric sarcoidosis are renal concentration impairment and granulomatous interstitial nephritis at presentation, while a higher GFR is beneficial.