bluuebunny/crossref_metadata_2025 huggingface dataset:
The Aquatic Invertebrate Hydra vulgaris Releases Molecular Messages Through Extracellular Vesicles
Authors: Moros Maria , Fergola Eugenio , Marchesano Valentina , Mutarelli Margherita , Tommasini Giuseppina , Miedziak Beata , Palumbo Giuliana , Ambrosone Alfredo , Tino Angela , Tortiglione Claudia
Published: December 2021

Recent body of evidence demonstrates that extracellular vesicles (EVs) represent the first language of cell-cell communication emerged during evolution. In aquatic environments, transferring signals between cells by EVs offers protection against degradation, allowing delivering of chemical information in high local concentrations to the target cells. The packaging of multiple signals, including those of hydrophobic nature, ensures target cells to receive the same EV-conveyed messages, and the coordination of a variety of physiological processes across cells of a single organisms, or at the population level, i.e., mediating the population’s response to changing environmental conditions. Here, we purified EVs from the medium of the freshwater invertebrate Hydra vulgaris, and the molecular profiling by proteomic and transcriptomic analyses revealed multiple markers of the exosome EV subtype, from structural proteins to stress induced messages promoting cell survival. Moreover, positive and negative regulators of the Wnt/β-catenin signaling pathway, the major developmental pathway acting in body axial patterning, were identified. Functional analysis on amputated polyps revealed EV ability to modulate both head and foot regeneration, suggesting bioactivity of the EV cargo and opening new perspectives on the mechanisms of developmental signalling. Our results open the path to unravel EV biogenesis and function in all cnidarian species, tracing back the origin of the cell-cell, cross-species or cross-kingdom communication in aquatic ecosystems.
Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
Authors: Liu Ying , Dong Ying , Dong Zhaojie , Song Jiawei , Zhang Zhenzhou , Liang Lirong , Liu Xiaoyan , Sun Lanlan , Li Xueting , Zhang Miwen , Chen Yihang , Miao Ran , Zhong Jiuchang
Published: December 2021

Background: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in heart and vasculature, thereby regulating their target gene and protein expression, via competitive endogenous RNA (ceRNA) mechanism. However, the exact roles and underlying mechanisms of circRNAs in hypertension and related cardiovascular diseases remain largely unknown.

Methods and Results: High-throughput RNA sequencing (RNA-seq) was used to analyze the differentially expressed (DE) circRNAs in aortic vascular tissues of spontaneously hypertensive rats (SHR). Compared with the Wistar-Kyoto (WKY) rats, there were marked increases in the levels of systolic blood pressure, diastolic blood pressure and mean blood pressure in SHR under awake conditions via the tail-cuff methodology. Totally, compared with WKY rats, 485 DE circRNAs were found in aortic vascular tissues of SHR with 279 up-regulated circRNAs and 206 down-regulated circRNAs. Furthermore, circRNA-target microRNAs (miRNAs) and the target messenger RNAs (mRNAs) of miRNAs were predicted by the miRanda and Targetscan softwares, respectively. Additionally, real-time RT-PCR analysis verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005818, rno_circRNA_0005304, rno_circRNA_0005506, and rno_circRNA_0009301 were observed in aorta of SHR when compared with that of WKY rats. Then, the potential ceRNA regulatory mechanism was constructed via integrating 5 validated circRNAs, 31 predicted miRNAs, and 266 target mRNAs. More importantly, three hub genes (NOTCH1, FOXO3, and STAT3) were recognized according to PPI network and three promising circRNA-miRNA-mRNA regulatory axes were found in hypertensive rat aorta, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0009197/ miR-509-5p/FOXO3, and rno_circRNA_0005818/miR-10b-5p/STAT3, respectively.

Conclusions: Our results demonstrated for the first time that circRNAs are expressed aberrantly in aortic vascular tissues of hypertensive rats and may serve as a sponge linking with relevant miRNAs participating in pathogenesis of hypertension and related ischemic heart diseases via the circRNA-miRNA-mRNA ceRNAnetwork mechanism.
Bridging Legends and Science: Field Evidence of a Large Tsunami that Affected the Kingdom of Tonga in the 15th Century
Authors: Lavigne Franck , Morin Julie , Wassmer Patrick , Weller Olivier , Kula Taaniela , Maea Ana V. , Kelfoun Karim , Mokadem Fatima , Paris Raphael , Malawani Mukhamad Ngainul , Faral Audrey , Benbakkar Mhammed , Saulnier-Copard Ségolène , Vidal Céline M. , Tu’I’afitu Tu’I’ahai , Kitekei’aho Fuka , Trautmann Martine , Gomez Christopher
Published: December 2021

The pre-colonial history (i.e. before the 16th century) of Tonga and West Polynesia still suffers from major gaps despite significant scientific advances in recent years, particularly in the field of archaeology. By the 14th century, the powerful Tu’i Tonga kingdom united the islands of the Tongan archipelago under a centralised authority and, according to tradition, extended its influence to neighbouring island groups in the Central Pacific. However, some periods of deep crisis were identified, e.g. in the mid- 15th century, marked by an abrupt cessation of inter-archipelago migration on the deep seas in the Pacific, significant cultural changes, and a decrease in accessible natural resources. The origins of these disturbances are still debated, and they are usually assigned to internal political problems or loss of external influence vis-à-vis neighboring chiefdoms. However, the hypothesis of a major natural disaster was rarely suggested up to now, while field evidence points to the occurrence of a very large tsunami in the past, including the presence of numerous megablocks that were deposited by a “red wave” (orpeau kula, which also mean tsunami in the Tongan language) according to a local myth. Drawing on a body of new evidence from sedimentary signatures and radiocarbon dating of charcoal and marine bioclasts, geomorphology, and sedimentology, in support of previously published archaeological data, we argue that a large tsunami inundated large areas of Tongatapu island in the mid-15th century with runup heights up to 30 m, and that the Tu’i Tonga kingdom was severely impacted by this event. We also discuss the likely sources of this tsunami.
Clinical Implication of Individually Tailored Segmentation Method for Distorted Hypothalamus in Craniopharyngioma
Authors: Hong A Ram , Lee Miwoo , Lee Jung Hyun , Kim Jung Hee , Kim Yong Hwy , Choi Hyung Jin
Published: December 2021

Objective

Several attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP.

Methods

We included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements.

Results

The corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P<0.01). However, HT volume was overestimated using T1-weighted images owing to obscured MR signal of the thalamus in patients with severe HT damage. Therefore, we used T2-weighted images to evaluate its clinical implications in 72 patients with available medical data. Postoperative HT volume was negatively associated with preoperative body weight and preoperative tumor volume (r=–0.25 [95% CI -0.45 to -0.04], P=0.04 and r=–0.26 [95% CI -0.40 to -0.15], P=0.03, respectively). In the subgroup analysis of CP patients who underwent primary surgery (n=56), pre- and postoperative body weights were negatively associated with HT volume (r=–0.30 [95% CI -0.53 to -0.03], P=0.03 and r=–0.29 [95% CI -0.53 to -0.02], P=0.03, respectively).

Conclusions

Adult-onset CP patients showed negative associations between postoperative HT volume and preoperative/postoperative body weight using a new method of HT volume measurement based on T2-weighted images.
Ambulatory Endoscopic Thyroidectomy via a Chest-Breast Approach Has an Acceptable Safety Profile for Thyroid Nodule
Authors: Zhang Zeyu , Xia Fada , Li Xinying
Published: December 2021

Introduction

With the growing esthetic requirements, endoscopic thyroidectomy develops rapidly and is widely accepted by practitioners and patients to avoid the neck scar caused by open thyroidectomy. Although ambulatory open thyroidectomy is adopted by multiple medical centers, the safety and potential of ambulatory endoscopic thyroidectomy via a chest-breast approach (ETCBA) is poorly investigated.

Material and Methods

Patients with thyroid nodules who received conventional or ambulatory ETCBA at Xiangya hospital, Central South University from January 2017 to June 2020 were retrospectively included. The incidence of postoperative complications, 30-days readmission rate, financial cost, duration of hospitalization, mental health were mainly investigated.

Results

A total of 260 patients were included with 206 (79.2%) suffering from thyroid carcinoma, while 159 of 260 received ambulatory ETCBA. There was no statistically significant difference in the incidence of postoperative complications (P=0.249) or 30-days readmission rate (P=1.000). In addition, The mean economic cost of the ambulatory group had a 29.5% reduction compared with the conventional group (P<0.001). Meanwhile, the duration of hospitalization of the ambulatory group was also significantly shorter than the conventional group (P<0.001). Patients received ambulatory ETCBA showed a higher level of anxiety (P=0.041) and stress (P=0.016). Subgroup analyses showed consistent results among patients with thyroid cancer with a 12.9% higher complication incidence than the conventional ETCBA (P=0.068).

Conclusion

Ambulatory ETCBA is as safe as conventional ETCBA for selective patients with thyroid nodules or thyroid cancer, however with significant economic benefits and shorter duration of hospitalization. Extra attention should be paid to manage the anxiety and stress of patients who received ambulatory ETCBA.
Refinements of the Pin-Based Pointwise Energy Slowing-Down Method for Resonance Self-Shielding Calculation—I: Theory
Authors: Choi Sooyoung , Kim Wonkyeong , Lee Deokjung
Published: December 2021

The pin-based pointwise energy slowing-down method (PSM), which is a resonance self-shielding method, has been refined to treat the nonuniformity of material compositions and temperature profile in the fuel pellet by calculating the exact collision probability in the radially subdivided fuel pellet under the isolated system. The PSM has generated the collision probability table before solving the pointwise energy slowing-down equation. It is not exact if the fuel pellet has nonuniform material compositions or temperature profile in all the subdivided regions. In the refined PSM-CPM, the pre-generated table is not required for directly calculating the collision probability in all the subdivided regions of the fuel pellet while solving the slowing-down equation. There are an advantage and a disadvantage to the method. The advantage is to exactly consider the nonuniformity of the material compositions and temperature profile in the fuel pellet. The disadvantage is the longer computing time than that of the PSM when the fuel pellet has more than five subdivided regions. However, in the practical use for UO2 pin-cells, it is still comparable for the computation time with the PSM and the conventional equivalence theory methods. In this article, using simple light water reactor 17 × 17 F A problems with a uniform material composition and temperature profile, it is demonstrated that PSMs (PSM and PSM-CPM) exhibit consistent accuracy in calculating the multiplication factor and the pin power distribution with no compromise in the computation time. More detailed accuracy assessments with various test cases, including problems representing the nonuniformity, are presented in the accompanying article.
The Effect of Urban Spatial Form on Energy Efficiency: A Cross-Sectional Study in China
Authors: Chen Zi-gui , Kong Ling-jun , Wang Min , Liu Hang-kai , Xiao Da-kai , Wu We-ping
Published: December 2021

Rational planning and optimization of urban spatial form to achieve the goal of energy efficient utilization and carbon emission reduction is one of the important ways to improve energy efficiency. We deconstruct urban spatial form into centrality, aggregation and complexity, and analyze net effect and its heterogeneity of urban spatial form on energy efficiency with OLS, quantile regression model as well as grouped regression model. The results show that the effects of urban spatial centrality and complexity on energy efficiency are nonlinear. For the vast majority of cities, strengthening urban spatial centrality will significantly improve energy efficiency, but the growth rate will gradually decrease. The impact effect of urban complexity on energy efficiency has the characteristics of U-shaped trend with an inflection point value of 0.429. And for the three-quarters of urban samples, enhancing urban spatial complexity will reduce energy efficiency. The positive effect of urban spatial aggregation on energy efficiency is only significant in cities with high quantile for energy efficiency. In terms of urban heterogeneity, the positive effects of spatial centrality and aggregation on energy efficiency are more obvious in megacities with a permanent population of more than 5 million, and the negative effect of spatial complexity on energy efficiency is more obvious in small and medium-sized cities. Whether it is promotion or inhibition, the urban samples with high energy efficiency are more affected by the change of urban spatial form. Optimizing the urban spatial form is one of the important ways to improve the energy efficiency, and the policy setting should give full consideration to the urban heterogeneity and classified policies.
Perspectives on the Ecological Role of Geophysical Sounds
Authors: Farina Almo , Mullet Tim C. , Bazarbayeva Tursynkul A. , Tazhibayeva Tamara , Bulatova Diana , Li Peng
Published: December 2021

Humans categorize unwanted sounds in the environment as noise. Consequently, noise is associated with negative human and ecological values, especially when it is derived from an anthropogenic source. Although evidence confirms that many machine-generated anthropogenic sounds have negative impacts on animal behavior and communication, natural sources of non-biological sound, such as wind, rain, running water, and sea waves (geophonies) have also been categorized as noise and are frequently dismissed or mischaracterized in acoustic studies as an outside factor of acoustic habitats rather than an integrated sonic component of ecological processes and species adaptations. While the proliferation of machine-generated sound in the Biosphere has become an intrusive phenomenon in recent history, geophony has shaped the Earth’s sonic landscapes for billions of years. Therefore, geophonies have very important sonic implications to the evolution and adaptation of soniferous species, forming essential ecological and semiotical relationships. This creates a need to distinguish geophonies from machine-generated sounds and how species respond to each accordingly, especially given their acoustic similarities in the frequency spectrum. Here, we introduce concepts and terminology that address these differences in the context of ecoacoustics. We also discuss how Acoustic Complexity Indices (ACIs) can offer new possibilities to quantifiably evaluate geophony in relation to their sonic contest.
Transcriptional Analysis of Nuclear-Encoded Mitochondrial Genes in Eight Neurodegenerative Disorders: The Analysis of Seven Diseases in Reference to Friedreich’s Ataxia
Authors: Elsadany Muhammad , Elghaish Reem A. , Khalil Aya S. , Ahmed Alaa S. , Mansour Rana H. , Badr Eman , Elserafy Menattallah
Published: December 2021

Neurodegenerative diseases (NDDs) are challenging to understand, diagnose, and treat. Revealing the genomic and transcriptomic changes in NDDs contributes greatly to the understanding of the diseases, their causes, and development. Moreover, it enables more precise genetic diagnosis and novel drug target identification that could potentially treat the diseases or at least ease the symptoms. In this study, we analyzed the transcriptional changes of nuclear-encoded mitochondrial (NEM) genes in eight NDDs to specifically address the association of these genes with the diseases. Previous studies show strong links between defects in NEM genes and neurodegeneration, yet connecting specific genes with NDDs is not well studied. Friedreich’s ataxia (FRDA) is an NDD that cannot be treated effectively; therefore, we focused first on FRDA and compared the outcome with seven other NDDs, including Alzheimer’s disease, amyotrophic lateral sclerosis, Creutzfeldt–Jakob disease, frontotemporal dementia, Huntington’s disease, multiple sclerosis, and Parkinson’s disease. First, weighted correlation network analysis was performed on an FRDA RNA-Seq data set, focusing only on NEM genes. We then carried out differential gene expression analysis and pathway enrichment analysis to pinpoint differentially expressed genes that are potentially associated with one or more of the analyzed NDDs. Our findings propose a strong link between NEM genes and NDDs and suggest that our identified candidate genes can be potentially used as diagnostic markers and therapeutic targets.
Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss
Authors: Dai Xiao-Peng , Wu Feng-Ying , Cui Cheng , Liao Xue-Jiao , Jiao Yan-Mei , Zhang Chao , Song Jin-Wen , Fan Xing , Zhang Ji-Yuan , He Qing , Wang Fu-Sheng
Published: December 2021

Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4+ T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4+ T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4+ T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4+ T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4+ T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4+ T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4+ T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4+ T cell aggregates imply the potential role in CD4+ T cell loss during HIV-1 infection. Furthermore, platelet-CD4+ T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4+ T cell counterparts. The platelet-CD4+ T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4+ T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.
Lens Biometry in Congenital Lens Deformities: A Swept-Source Anterior Segment OCT Analysis
Authors: Chen Ze-xu , Jia Wan-Nan , Jiang Yong-Xiang
Published: December 2021

Aims: To investigate the lens biometric parameters in congenital lens deformities, using a novel technique of swept-source anterior segment optical coherence tomography (SS-ASOCT).

Methods: This prospective study included patients with microspherophakia (MSP), coloboma lentis (CL), and posterior lenticonus (PL). For this cohort, 360-degree high-resolution lens images were obtained using the latest SS-ASOCT (CASIA2, Tomey Corp, Nagoya, Japan). The lens biometric parameters were calculated by the CASIA2 built-in software for anterior lens radius (ALR), posterior lens radius (PLR), anteroposterior distance (APD), anterior chamber depth (ACD), equatorial diameter (Eq Dia), rear projection length (RPL), and maximum diameter of the lesion (MDL).

Results: This study included two eyes each with MSP and CL and one eye with PL. The lens of MSP was spherical and posteriorly dislocated, with decreased ALR and PLR, Eq Dia, but increased APD. In patients with CL, the coloboma was isolated, bilateral, inferior, and located toward the maldeveloped ciliary body. High astigmatism was mainly lenticular, and this was calculated by the ALR and PLR. Regarding the site of coloboma, a significant decrease in ALR was observed, while the PLR and APD were not affected. The PL eyes had a cone-shaped protrusion of the posterior lens surface with a subtle cataractous region around the apex. An extremely high posterior surface curvature was observed with a mean PLR of 1.67 mm. The RPL and MDL were about 1.80 and 0.4 mm, respectively, which were homogenous at different sections.

Conclusions: The CASIA2 is a valuable option for in vivo crystalline lens measurement for congenital lens deformities, enabling the accurate diagnosis and providing illuminating insights into the pathogenesis of MSP, CL, and PL
In vitro Assessment of Solar Filters for Erythropoietic Protoporphyria in the Action Spectrum of Protoporphyrin IX
Authors: Sernicola Alvise , Cama Elena , Pelizzo Maria Guglielmina , Tessarolo Enrico , Nicolli Annamaria , Viero Giulia , Alaibac Mauro
Published: December 2021

Introduction: Subjects with erythropoietic protoporphyria rely on broad-spectrum sunscreens with high sun protection factor, which is not informative on efficacy in the absorption spectrum of protoporphyrin IX, spanning visible radiation and peaking around 408 nm. Photoactivation of protoporphyrin IX is responsible for painful skin photosensitivity in erythropoietic protoporphyria.

The authors assessed the protective efficacy of six sunscreens in vitro in the absorption spectrum of protoporphyrin IX.

Method: Transmittance measurements were performed in the 300–850 nm wavelengths on samples of six photoprotective products applied to polymethyl methacrylate plates. Porphyrin protection factor was calculated in the 300–700 nm region to provide a measurement for the efficacy of each product based on the action spectrum of protoporphyrin IX.

Results: Product A showed the highest porphyrin protection factor among tested products with a median value of 4.22. Product A is a sunscreen containing organic filters, titanium dioxide and synthetic iron oxides, pigmentary grade active ingredients that absorb visible radiation. Other products showed inefficient protection in the visible, with transmittance between 75 and 95% at 500 nm. The low porphyrin protection factor of inorganic filter product B was attributed to particle micronization, as declared by the manufacturer.

Conclusion: Adding porphyrin protection factor to sunscreen labeling could help patients with erythropoietic protoporphyria and other photosensitivity disorders identify products tailored on their specific needs. The development of sunscreens providing protection from visible radiation and excellent cosmetical tolerability could improve the lifestyle of patients with erythropoietic protoporphyria.
Effect ofBacillus velezensis JC-K3 on Endophytic Bacterial and Fungal Diversity in Wheat Under Salt Stress
Authors: Ji Chao , Wang Xiaohui , Song Xin , Zhou Qisheng , Li Chaohui , Chen Zhizhang , Gao Qixiong , Li Huying , Li Jintai , Zhang Pengcheng , Cao Hui
Published: December 2021

Plant growth-promoting bacteria (PGPB) can effectively reduce salt damage in plants. Currently, there are many studies on the effects of PGPB on the microbial community structure of rhizosphere soil under salt stress, but fewer studies on the community structure of endophytic bacteria and fungi. We propose that inoculation of endophytic bacteria into the rhizosphere of plants can significantly affect the microbial community structure of the plant’s above-ground and underground parts, which may be the cause of the plant’s “Induced Systemic Tolerance.” The isolated endophytes were re-inoculated into the rhizosphere under salinity stress. We found that, compared with the control group, inoculation with endophytic Bacillus velezensis JC-K3 not only increased the accumulation of wheat biomass, but also increased the content of soluble sugar and chlorophyll in wheat, and reduced the absorption of Na in wheat shoots and leaves. The abundance of bacterial communities in shoots and leaves increased and the abundance of fungal communities decreased after inoculation with JC-K3. The fungal community richness of wheat rhizosphere soil was significantly increased. The diversity of bacterial communities in shoots and leaves increased, and the richness of fungal communities decreased. JC-K3 strain improved wheat’s biomass accumulation ability, osmotic adjustment ability, and ion selective absorption ability. In addition, JC-K3 significantly altered the diversity and abundance of endophytic and rhizosphere microorganisms in wheat. PGPB can effectively reduce plant salt damage. At present, there are many studies on the effect of PGPB on the microbial community structure in rhizosphere soil under salt stress, but there are few studies on the community structure changes of endophytic bacteria and fungi in plants.
Identification and Validation of a Prognostic Prediction Model of m6A Regulator-Related LncRNAs in Hepatocellular Carcinoma
Authors: Jin Chen , Li Rui , Deng Tuo , Li Jialiang , Yang Yan , Li Haoqi , Chen Kaiyu , Xiong Huihua , Chen Gang , Wang Yi
Published: December 2021

Hepatocellular carcinoma (HCC) is a highly invasive malignancy prone to recurrence, and patients with HCC have a low 5-year survival rate. Long non-coding RNAs (lncRNAs) play a vital role in the occurrence and development of HCC. N6-methyladenosine methylation (m6A) is the most common modification influencing cancer development. Here, we used the transcriptome of m6A regulators and lncRNAs, along with the complete corresponding clinical HCC patient information obtained from The Cancer Genome Atlas (TCGA), to explore the role of m6A regulator-related lncRNA (m6ARlnc) as a prognostic biomarker in patients with HCC. The prognostic m6ARlnc was selected using Pearson correlation and univariate Cox regression analyses. Moreover, three clusters were obtained via consensus clustering analysis and further investigated for differences in immune infiltration, immune microenvironment, and prognosis. Subsequently, nine m6ARlncs were identified with Lasso-Cox regression analysis to construct the prognostic signature m6A-9LPS for patients with HCC in the training cohort (n = 226). Based on m6A-9LPS, the risk score for each case was calculated. Patients were then divided into high- and low-risk subgroups based on the cutoff value set by the X-tile software. m6A-9LPS showed a strong prognosis prediction ability in the validation cohort (n = 116), the whole cohort (n = 342), and even clinicopathological stratified survival analysis. Combining the risk score and clinical characteristics, we established a nomogram for predicting the overall survival (OS) of patients. To further understand the mechanism underlying the m6A-9LPS-based classification of prognosis differences, KEGG and GO enrichment analyses, competitive endogenous RNA (ceRNA) network, chemotherapeutic agent sensibility, and immune checkpoint expression level were assessed. Taken together, m6A-9LPS could be used as a precise prediction model for the prognosis of patients with HCC, which will help in individualized treatment of HCC.
A Muscle Biosignature Differentiating Between Limb-Girdle Muscular Dystrophy and Idiopathic Inflammatory Myopathy on Magnetic Resonance Imaging
Authors: Hsu Wen-Chi , Lin Yu-Ching , Chuang Hai-Hua , Yeh Kun-Yun , Chan Wing P. , Ro Long-Sun
Published: December 2021

Background: The overlapping clinical presentations of limb-girdle muscular dystrophy (LGMD) and idiopathic inflammatory myopathy (IIM) make clinical diagnosis challenging. This study provides a comprehensive evaluation of the distributions and characteristics of muscle fat substitution and edema and aims to differentiate those two diseases.

Methods: This retrospective study reviewed magnetic resonance imaging (MRI) of seventeen patients with pathologically proved diagnosis, comprising 11 with LGMD and 6 with IIM. The fat-only and water-only images from a Dixon sequence were used to evaluate muscle fat substitution and edema, respectively. The degrees of muscle fat substitution and edema were graded and compared using the appropriate statistical methods.

Results: In LGMD, more than 50% of patients had high-grade fat substitution in the majority of muscle groups in the thigh and calf. However, <50% of IIM patients had high-grade fat substitution in all muscle groups. Moreover, LGMD patients had significantly higher grade fat substitution than IIM patients in all large muscle groups (p < 0.05). However, there was no significant difference in edema in the majority of muscle groups, except the adductor magnus (p = 0.012) and soleus (p = 0.009) with higher grade edema in IIM. Additionally, all the adductor magnus muscles in LGMD (100%) showed high-grade fat substitution, but none of them showed high-grade edema.

Conclusions: MRI could be a valuable tool to differentiate LGMD from IIM based on the discrepancy in muscle fat substitution, and the adductor magnus muscle could provide a biosignature to categorizing LGMD.
Visual Discomfort and Variations in Chromaticity in Art and Nature
Authors: Penacchio Olivier , Haigh Sarah M. , Ross Xortia , Ferguson Rebecca , Wilkins Arnold J.
Published: December 2021

Visual discomfort is related to the statistical regularity of visual images. The contribution of luminance contrast to visual discomfort is well understood and can be framed in terms of a theory of efficient coding of natural stimuli, and linked to metabolic demand. While color is important in our interaction with nature, the effect of color on visual discomfort has received less attention. In this study, we build on the established association between visual discomfort and differences in chromaticity across space. We average the local differences in chromaticity in an image and show that this average is a good predictor of visual discomfort from the image. It accounts for part of the variance left unexplained by variations in luminance. We show that the local chromaticity difference in uncomfortable stimuli is high compared to that typical in natural scenes, except in particular infrequent conditions such as the arrangement of colorful fruits against foliage. Overall, our study discloses a new link between visual ecology and discomfort whereby discomfort arises when adaptive perceptual mechanisms are overstimulated by specific classes of stimuli rarely found in nature.
Detecting Noise-Induced Cochlear Synaptopathy by Auditory Brainstem Response in Tinnitus Patients With Normal Hearing Thresholds: A Meta-Analysis
Authors: Chen Feifan , Zhao Fei , Mahafza Nadeem , Lu Wei
Published: December 2021

Noise-induced cochlear synaptopathy (CS) is defined as a permanent loss of synapses in the auditory nerve pathway following noise exposure. Several studies using auditory brainstem response (ABR) have indicated the presence of CS and increased central gain in tinnitus patients with normal hearing thresholds (TNHT), but the results were inconsistent. This meta-analysis aimed to review the evidence of CS and its pathological changes in the central auditory system in TNHT. Published studies using ABR to study TNHT were reviewed. PubMed, EMBASE, and Scopus databases were selected to search for relevant literature. Studies (489) were retrieved, and 11 were included for meta-analysis. The results supported significantly reduced wave I amplitude in TNHT, whereas the alternations in wave V amplitude were inconsistent among the studies. Consistently increased V/I ratio indicated noise-induced central gain enhancement. The results indicated the evidence of noise-induced cochlear synaptopathy in tinnitus patients with normal hearing. However, inconsistent changes in wave V amplitude may be explained by that the failure of central gain that triggers the pathological neural changes in the central auditory system and/or that increased central gain may be necessary to generate tinnitus but not to maintain tinnitus.
The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study
Authors: Cao Fei , Yang Yi , Si Tongguo , Luo Jun , Zeng Hui , Zhang Zhewei , Feng Duiping , Chen Yi , Zheng Jiaping
Published: December 2021

Objective

To assess the efficacy and safety of transarterial Chemoembolization (TACE) combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma (HCC).

Patients and Methods

The data of patients with unresectable HCC administered a combination therapy with TACE and lenvatinib plus sintilimab were retrospectively assessed. Patients received lenvatinib orally once daily 2 weeks before TACE, followed by sintilimab administration at 200 mg intravenously on day 1 of a 21-day therapeutic cycle after TACE. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by the modified RECIST criteria.

Results

Median duration of follow-up was 12.5 months (95%CI 9.1 to 14.8 months). ORR was 46.7% (28/60). Median DOR in confirmed responders was 10.0 months (95%CI 9.0-11.0 months). Median progression-free survival (PFS) was 13.3 months (95%CI 11.9-14.7 months). Median overall survival (OS) was 23.6 months (95%CI 22.2-25.0 months).

Conclusions

TACE combined with lenvatinib plus sintilimab is a promising therapeutic regimen in unresectable hepatocellular carcinoma.
Tumor Associated Macrophages: Origin, Recruitment, Phenotypic Diversity, and Targeting
Authors: Hourani Tetiana , Holden James A. , Li Wenyi , Lenzo Jason C. , Hadjigol Sara , O’Brien-Simpson Neil M.
Published: December 2021

The tumor microenvironment (TME) is known to have a strong influence on tumorigenesis, with various components being involved in tumor suppression and tumor growth. A protumorigenic TME is characterized by an increased infiltration of tumor associated macrophages (TAMs), where their presence is strongly associated with tumor progression, therapy resistance, and poor survival rates. This association between the increased TAMs and poor therapeutic outcomes are stemming an increasing interest in investigating TAMs as a potential therapeutic target in cancer treatment. Prominent mechanisms in targeting TAMs include: blocking recruitment, stimulating repolarization, and depletion methods. For enhancing targeting specificity multiple nanomaterials are currently being explored for the precise delivery of chemotherapeutic cargo, including the conjugation with TAM-targeting peptides. In this paper, we provide a focused literature review of macrophage biology in relation to their role in tumorigenesis. First, we discuss the origin, recruitment mechanisms, and phenotypic diversity of TAMs based on recent investigations in the literature. Then the paper provides a detailed review on the current methods of targeting TAMs, including the use of nanomaterials as novel cancer therapeutics.
Interest and Limits of [18F]ML-10 PET Imaging for Early Detection of Response to Conventional Chemotherapy
Authors: Jouberton Elodie , Schmitt Sébastien , Maisonial-Besset Aurélie , Chautard Emmanuel , Penault-Llorca Frédérique , Cachin Florent
Published: December 2021

One of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies evaluating PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The [18F]FDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter in vivo, several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of [18F]ML-10 (2-(5-[18F]fluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with [18F]ML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis). [18F]ML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response.
Suspected Adverse Drug Reactions in Pediatric Cancer Patients in China: An Analysis of Henan Province Spontaneous Reporting System Database
Authors: Jiao Zhiming , Feng Zhanchun , Yan Ziqi , Zhang Jinwen , Li Gang , Wang Ganyi , Wang Qianyu , Feng Da
Published: December 2021

Introduction

Adverse drug reactions (ADRs) in pediatric cancer patients have not yet received due attention in the world. Antineoplastic drugs are frequently related to ADRs. Few studies focus on the ADR and the intervention measures in pediatric cancer patients.

Methods

ADR reports submitted to Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to gender, age, disease types, past history of ADR, occurrence time of ADR, polypharmacy, route of administration, off-label drug use, name of suspected drugs per ADR report, and severity of ADR reports.

Results

A total of 431 ADR reports related to antineoplastic drugs in pediatric patients were collected, 31.55% were serious ADRs (SADRs). The median age of patients was six years (inter quartile range, IQR: 3-11), the age groups with higher reporting rates were concentrated in 1-3-year-olds (130). Past history of ADR, occurrence time of ADR and polypharmacy were statistically associated with SADR. Myelosuppression was the most frequent ADR (15.55%), cytarabine was the most frequent drug (26.22%). The signal mining method produced 14 signals, three signals were off-label ADRs.

Conclusions

This study described the characteristics of ADRs in pediatric cancer patients. By conducting signal mining method, three off-label ADRs need further study. We should pay more attention to these ADRs and develop relative management strategies. More researches are needed to achieve a better understanding of the characteristics of ADRs in pediatric cancer patients of China.
Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension
Authors: Šuláková Terezie , Strnadel Jiří , Pavlíček Jan , Poláková Radka , Seeman Tomáš , Feber Janusz
Published: December 2021

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP).

Objectives: To analyze TOD and EVA in normotensive (BP <95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C).

Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years.

Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD.

Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04.

Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.
Relationship Between Conventional Medicine Chapters in ICD-10 and Kampo Pattern Diagnosis: A Cross-Sectional Study
Authors: Wu Xuefeng , Le Thomas K. , Maeda-Minami Ayako , Yoshino Tetsuhiro , Horiba Yuko , Mimura Masaru , Watanabe Kenji
Published: December 2021

Objectives: The newest revision to the International Classification of Diseases, the 11th edition (ICD-11) includes disease classifications from East Asian medicine, including traditional Japanese medicine (Kampo medicine). These disease classifications allow for comparisons between disease classifications from conventional medicine and Kampo medicine.

Design/Location/Subjects/Interventions: This is an exploratory, cross-sectional study exploring the relationship between conventional medicine diagnoses and Kampo medicine diagnoses at a large Kampo clinic in Japan. Patients were seen from October 1st, 2014 to June 30th, 2019 and were 20 years of age or older.

Outcome measures: Patients presented with one or more conventional medicine ICD-10 codes into the clinic and were given one descriptor from the ICD-11 within the heat-cold module, excess-deficiency module, and an optional body constituents module. The distribution of these Kampo medicine codes was examined in relation to conventional medicine chapters.

Results: 1,209 patients were included in our final analysis. Patient number, ages, sex ratio, and BMI varied within conventional medicine ICD-10 chapters and Kampo medicine descriptor codes. Certain conventional medicine chapters are related to specific Kampo medicine descriptor codes, such as chapter IV (endocrine, nutritional, and metabolic diseases) with excess, heat, and kidney qi deficiency.

Conclusion: The advent of the ICD-11 allows for systematic, standardized comparisons between Kampo medicine, and contemporary medicine. In this exploratory study, our findings support the independence of Kampo medicine pattern descriptors with ICD-10 conventional medicine chapters. Code overrepresentations in relation to conventional medicine diseases and by age and sex should be an area of future investigation to best understand how to synergize and improve patient care.
Understanding the Role of Purinergic P2X7 Receptors in the Gastrointestinal System: A Systematic Review
Authors: Cheng Nathalie , Zhang Li , Liu Lu
Published: December 2021

Background: The role of purinergic P2X7 receptor (P2X7R) is of interest due to its involvement in inflammation and mediating immune cell responses. P2X7R is particularly implicated in the development of inflammatory bowel disease (IBD). However, the extent of the actions of P2X7R in the gastrointestinal (GI) system under physiological and pathophysiological conditions remains to be elucidated. This systematic review aimed to identify, summarize and evaluate the evidence for a critical role of P2X7R in the GI system.

Methods: We searched PubMed, Embase and Scopus with search terms pertained to P2X7R in the GI system in disease or physiological state, including “P2X7 or P2X7 receptor or purinergic signaling” in combination with any of the terms “intestine or colon or gut or gastrointestinal,” “pathology or inflammation or disease or disorder,” and “physiology or expression.” Titles and abstracts were screened for potentially eligible full texts, and animal and human studies published in English were included in this study. Data were extracted from papers meeting inclusion criteria. Meta-analysis was not feasible given the study diversity.

Results: There were 48 papers included in this review. We identified 14 experimental colitis models, three sepsis models and one ischemia-reperfusion injury model. Among them, 11 studies examined P2X7R in GI infections, six studies on immune cell regulation, four studies on GI inflammation, two studies on GI malignancies, three studies involving intestinal injury due to various causes, two studies on ATP-activated P2X7R in the GI system and two studies on metabolic regulation.

Conclusion: Evidence supports P2X7R mediating inflammation and immune cell responses in GI inflammation, infections and injury due to IBD and other challenges to the intestinal wall. P2X7R inhibition by gene knockout or by application of P2X7R antagonists can reduce tissue damage by suppressing inflammation. P2X7R is also implicated in GI malignancies and glucose and lipid homeostasis. P2X7R blockade, however, did not always lead to beneficial outcomes in the various pathological models of study.