bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Evaluation of Different ToS Using Heterogeneous Communication Interfaces in FANETs
Authors: Ribeiro Laura Michaella B. , Müller Ivan , Becker Leandro Buss
Published: January 2022

The use of different types-of-services (ToS), such as voice, data, and video, has become increasingly present in the execution of applications involving networks composed of multiple UAVs. These applications usually require the UAVs to share different ToS in a dynamic and ad-hoc manner, such that they can support the execution of cooperative/collaborative tasks. The use of heterogeneous communication has showed gains in maintaining the connection among highly mobile nodes, while increasing the reliable transmission of data, as is necessary in MANETS, VANETs and, more recently, FANETs. The aim of this paper is to present a performance evaluation of a heterogeneous interface manager (IM), which applies a heuristic to choose the best among several single- and multi-band wireless communication interfaces, including IEEE 802.11n, IEEE 802.11p, IEEE 802.11ac, and IEEE 802.11ax. Simulated scenarios with three, five, and eight UAV nodes are developed by integrating NS-3 and Gazebo simulation tools. The IM performance is analyzed by applying different numbers of interfaces and comparing with interfaces applied homogeneously by defining two set of results, in terms of application and MAC and PHY metrics, respectively. Finally, we also evaluate the associated performance, considering voice, data, and video streaming ToS. The results indicate that the combination of different interfaces has a very powerful effect on maintaining or increasing the communication intensity.
Role of IGF2 in the Study of Development and Evolution of Prostate Cancer
Authors: Porras-Quesada P. , González-Cabezuelo JM. , Sánchez-Conde V. , Puche-Sanz I. , Arenas-Rodríguez V. , García-López C. , Flores-Martín JF. , Molina-Hernández JM. , Álvarez-Cubero MJ. , Martínez-González LJ. , Vázquez-Alonso F.
Published: January 2022

Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of IGF2 and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.
Whole Genome Assembly of Human Papillomavirus by Nanopore Long-Read Sequencing
Authors: Yang Shuaibing , Zhao Qianqian , Tang Lihua , Chen Zejia , Wu Zhaoting , Li Kaixin , Lin Ruoru , Chen Yang , Ou Danlin , Zhou Li , Xu Jianzhen , Qin Qingsong
Published: January 2022

Human papillomavirus (HPV) is a causal agent for most cervical cancers. The physical status of the HPV genome in these cancers could be episomal, integrated, or both. HPV integration could serve as a biomarker for clinical diagnosis, treatment, and prognosis. Although whole-genome sequencing by next-generation sequencing (NGS) technologies, such as the Illumina sequencing platform, have been used for detecting integrated HPV genome in cervical cancer, it faces challenges of analyzing long repeats and translocated sequences. In contrast, Oxford nanopore sequencing technology can generate ultra-long reads, which could be a very useful tool for determining HPV genome sequence and its physical status in cervical cancer. As a proof of concept, in this study, we completed whole genome sequencing from a cervical cancer tissue and a CaSki cell line with Oxford Nanopore Technologies. From the cervical cancer tissue, a 7,894 bp-long HPV35 genomic sequence was assembled from 678 reads at 97-fold coverage of HPV genome, sharing 99.96% identity with the HPV sequence obtained by Sanger sequencing. A 7904 bp-long HPV16 genomic sequence was assembled from data generated from the CaSki cell line at 3857-fold coverage, sharing 99.99% identity with the reference genome (NCBI: U89348). Intriguingly, long reads generated by nanopore sequencing directly revealed chimeric cellular–viral sequences and concatemeric genomic sequences, leading to the discovery of 448 unique integration breakpoints in the CaSki cell line and 60 breakpoints in the cervical cancer sample. Taken together, nanopore sequencing is a unique tool to identify HPV sequences and would shed light on the physical status of HPV genome in its associated cancers.
Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine Production via Synaptic Filamentous Actin Modulation
Authors: Kim Nayoung , Yi Eunbi , Kwon Soon Jae , Park Hyo Jin , Kwon Hyung-Joon , Kim Hun Sik
Published: January 2022

Natural killer (NK) cells are innate cytotoxic lymphocytes that efficiently eliminate malignant and virus-infected cells without prior activation via the directed and focused release of lytic granule contents for target cell lysis. This cytolytic process is tightly regulated at discrete checkpoint stages to ensure the selective killing of diseased target cells and is highly dependent on the coordinated regulation of cytoskeletal components. The actin-binding protein filamin crosslinks cortical actin filaments into orthogonal networks and links actin filament webs to cellular membranes to modulate cell migration, adhesion, and signaling. However, its role in the regulation of NK cell functions remains poorly understood. Here, we show that filamin A (FLNa), a filamin isoform with preferential expression in leukocytes, is recruited to the NK cell lytic synapse and is required for NK cell cytotoxicity through the modulation of conjugate formation with target cells, synaptic filamentous actin (F-actin) accumulation, and cytotoxic degranulation, but not granule polarization. Interestingly, we also find that the loss of FLNa augments the target cell-induced expression of IFN-γ and TNF-α by NK cells, correlating with enhanced activation signals such as Ca2+ mobilization, ERK, and NF-κB, and a delayed down-modulation of the NKG2D receptor. Thus, our results identify FLNa as a new regulator of NK cell effector functions during their decision to kill target cells through a balanced regulation of NK cell cytotoxicity vs cytokine production. Moreover, this study implicates the cross-linking/bundling of F-actin mediated by FLNa as a necessary process coordinating optimal NK effector functions.
Growth Parameters and Spawning Season Estimation of Four Important Flyingfishes in the Kuroshio Current Off Taiwan and Implications From Comparisons With Global Studies
Authors: Chang Shui-Kai , Yuan Tzu-Lun , Hoyle Simon D. , Farley Jessica H. , Shiao Jen-Chieh
Published: January 2022

Growth shapes the life history of fishes. Establishing appropriate aging procedures and selecting representative growth models are important steps in developing stock assessments. Flyingfishes (Exocoetidae) have ecological, economic, and cultural importance to many coastal countries including Taiwan. There are 29 species of flyingfishes found in the Kuroshio Current off Taiwan and adjacent waters, comprising 56% of the flyingfishes taxa recorded worldwide. Among the six dominant species in Taiwan, four are of special importance. This study reviews aging data of these four species, documents major points of the aging methods to address three aging issues identified in the literature, and applies multi-model inference to estimate sex-combined and sex-specific growth parameters for each species. The candidate growth models examined included von Bertalanffy, Gompertz, Logistic, and Richards models, and the resulting optimal model tended to be the von Bertalanffy model for sex-combined data and Gompertz and von Bertalanffy models for sex-specific cases. The study also estimates hatch dates from size data collected from 2008 to 2017; the results suggest that the four flyingfishes have two spawning seasons per year. Length-weight relationships are also estimated for each species. Finally, the study combines the optimal growth estimates from this study with estimates for all flyingfishes published globally, and statistically classifies the estimates into clusters by hierarchical clustering analysis of logged growth parameters. The results demonstrate that aging materials substantially affect growth parameter estimates. This is the first study to estimate growth parameters of flyingfishes with multiple model consideration. This study provides advice for aging flyingfishes based on the three aging issues and the classification analysis, including a recommendation of using the asterisci for aging flyingfishes to avoid complex otolith processing procedures, which could help researchers from coastal countries to obtain accurate growth parameters for many flyingfishes.
High-Resolution Vertical Observations of Phytoplankton Groups Derived From an in-situ Fluorometer in the East China Sea and Tsushima Strait
Authors: Xu Qian , Wang Shengqiang , Sukigara Chiho , Goes Joaquim I. , Gomes Helga do Rosario , Matsuno Takeshi , Zhu Yuanli , Xu Yongjiu , Luang-on Jutarak , Watanabe Yuji , Yoo Sinjae , Ishizaka Joji
Published: January 2022

Vertical distribution of phytoplankton composition in the East China Sea (ECS) and Tsushima Strait (TS) was highly variable in the region where the Changjiang River diluted water (CDW), Kuroshio water (KW), and Tsushima water (TW) intersected. An in-situ multiple excitation fluorometer was used to obtain the high-resolution phytoplankton groups data from every meter of the water column. Sharp differences were noted in the distribution of phytoplankton groups in the CDW, KW, and TW. In the CDW, brown algae were generally present ~60% of all depths with exception of subsurface chlorophyll-a maximum (SCM), whereas cyanobacteria (>40%) and green algae plus cryptophytes (>40%) were found above and below the SCM, respectively. In TW, where chlorophyll a (CHL) was lower than in the CDW, brown algae predominated the water column (>60%) and SCM (>80%), except the surface layer where cyanobacteria dominated. In KW, a high fraction of cyanobacteria (>40%) extended up to 40 m, while brown and green algae dominated (>60%) the deeper waters below 40 m at western and eastern stations, respectively. These results can be further related to water property and nutrient concentration of the water masses in each region. This new data show that the in-situ multiple excitation fluorometer can be a powerful tool to estimate high-resolution vertical profiles of phytoplankton groups on a large scale in marine environments.
Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury
Authors: Mao Xin-li , Cai Yue , Chen Ya-hong , Wang Yi , Jiang Xiu-xiu , Ye Li-ping , Li Shao-wei
Published: January 2022

Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects.
Successful Use of Extracorporeal Life Support and Continuous Renal Replacement Therapy in the Treatment of Cardiogenic Shock Induced by Tumor Lysis Syndrome in a Pediatric Patient With Lymphoma: A Case Report
Authors: Wang Zhulin , Zhang Fang , Xiang Long , Yang Yinyu , Wang Wei , Li Biru , Ren Hong
Published: January 2022

The use of extracorporeal membrane oxygenation (ECMO) in the treatment of cardiopulmonary failure in children with malignant tumors is controversial. There are few reports on the use of ECMO in the treatment of children with tumor lysis syndrome. This article reports a case of a 9-year-old girl who presented with hyperkalemia and cardiogenic shock. The discovery of an abdominal mass with critical ultrasound provided key evidence for the initial diagnosis of tumor lysis syndrome. Cardiopulmonary resuscitation was performed for 1 h. Veno-arterial ECMO was installed at the bedside to provide cardiopulmonary support for the patient and was combined with continuous renal replacement therapy (CRRT) to improve her internal environment. The patient was ultimately diagnosed with mature B-cell lymphoma with tumor lysis syndrome. A severe electrolyte disorder led to cardiogenic shock. After the electrolyte imbalance was corrected, the patient's heart function gradually improved, ECMO was successfully weaned, and chemotherapy was continued with the support of CRRT. One month after ECMO weaning, the organ function of the patient had recovered and there were no serious complications. In this case report, we paid attention to the rapid diagnosis of the etiology behind a patient's shock with critical ultrasound as well as the initiation and management of extracorporeal cardiopulmonary resuscitation (ECPR), which provided us with valuable experience using VA-ECMO on critically ill children with tumors. It is also important evidence for the use of ECMO in the treatment of children with cardiopulmonary arrest secondary to malignancy.
Convergency and Stability Responses of Bacterial Communities to Salinization in Arid and Semiarid Areas: Implications for Global Climate Change in Lake Ecosystems
Authors: Hu Yang , Jiang Xingyu , Shao Keqiang , Tang Xiangming , Qin Boqiang , Gao Guang
Published: January 2022

Climate change has given rise to salinization and nutrient enrichment in lake ecosystems of arid and semiarid areas, which have posed the bacterial communities not only into an ecotone in lake ecosystems but also into an assemblage of its own unique biomes. However, responses of bacterial communities to climate-related salinization and nutrient enrichment remain unclear. In September 2019, this study scrutinized the turnover of bacterial communities along gradients of increasing salinity and nutrient by a space-for-time substitution in Xinjiang Uyghur Autonomous Region, China. We find that salinization rather than nutrient enrichment primarily alters bacterial communities. The homogenous selection of salinization leads to convergent response of bacterial communities, which is revealed by the combination of a decreasing β-nearest taxon index (βNTI) and a pronounced negative correlation between niche breadth and salinity. Furthermore, interspecific interactions within bacterial communities significantly differed among distinct salinity levels. Specifically, mutualistic interactions showed an increase along the salinization. In contrast, topological parameters show hump-shaped curves (average degree and density) and sunken curves (modularity, density, and average path distance), the extremums of which all appear in the high-brackish environment, hinting that bacterial communities are comparatively stable at freshwater and brine environments but are unstable in moderately high-brackish lake.
Bacterial Diversity, Organic Acid, and Flavor Analysis of Dacha and Ercha Fermented Grains of Fen Flavor Baijiu
Authors: Xue Yu’ang , Tang Fengxian , Cai Wenchao , Zhao Xinxin , Song Wen , Zhong Ji’an , Liu Zhongjun , Guo Zhuang , Shan Chunhui
Published: January 2022

Fen flavor Baijiu needs two rounds of fermentation, which will obtain Dacha after initial fermentation and Ercha after secondary fermentation. The quality of Baijiu is closely related to the microbes within fermented grains. However, the bacterial diversity in Dacha and Ercha fermented grains of Fen flavor Baijiu has not been reported. In the present study, the structure and diversity of bacteria communities within fermented grains of Fen flavor Baijiu were analyzed and evaluated using MiSeq platform’s HTS with a sequencing target of the V3-V4 region of the 16S rRNA gene. Through the analysis of physical and chemical indexes and electronic senses, the relationship between bacterial flora, organic acid, taste, and aroma in fermented grains was clarified. The results indicated that Lactobacillus was the main bacteria in Dacha, and the mean relative content was 97.53%. The bacteria within Ercha samples were Pseudomonas and Bacillus, mean relative content was 37.16 and 28.02%, respectively. The diversity of bacterial communities in Ercha samples was significantly greater than that in Dacha samples. The correlation between Lactobacillus and organic acids, especially lactic acid, led to the difference between Dacha and Ercha organic acids, which also made the pH value of Dacha lower and the sour taste significantly higher than Ercha. Lactobacillus was significantly positively correlated with a variety of aromas, which made Dacha the response value of aromas higher. In addition, Bacillus had a significant positive correlation with bitterness and aromatic compounds, which led to a higher response value of bitterness in Ercha and made it present an aromatic aroma. This study provides an in-depth analysis of the difference between different stages of Fen flavor Baijiu, and theoretical support for the standard production and improvement in quality of Fen flavor Baijiu in the future.
Nuclear Exportin 1 (XPO1) Binds to the Nuclear Localization/Export Signal of the Turnip Mosaic Virus NIb to Promote Viral Infection
Authors: Zhang Mingzhen , Gong Pan , Ge Linhao , Li Yinzi , Chang Zhaoyang , Qiao Rui , Zhou Xueping , Wang Aiming , Li Fangfang
Published: January 2022

The nuclear localization signal (NLS) and nuclear export signal (NES) are key signatures of proteins for controlling nuclear import and export. The NIb protein of turnip mosaic virus (TuMV) is an RNA-dependent RNA polymerase (RdRP) that is absolutely required for viral genome replication. Previous studies have shown that NIb is a nucleocytoplasmic shuttling protein and contains four putative NES and four putative NLS motifs. Here, we analyzed the function of these NESs and NLSs, and identified two functional NESs and one functional NLS. Mutation of the identified functional NESs or NLS inhibited viral RNA accumulation and systemic infection. Exportin 1 (XPO1) is a nuclear export receptor that binds directly to cargo proteins harboring a leucine-rich NES and translocates them to the cytoplasm. We found that XPO1 contains two NIb-binding domains, which recognize the NLS and NES of NIb, respectively, to mediate the nucleocytoplasmic transport of NIb and promote viral infection. Taken together, these data suggest that the nucleocytoplasmic transport of NIb is modulated by XPO1 through its interactions with the functional NLS and NES of NIb to promote viral infection.
UL11 Protein Is a Key Participant of the Duck Plague Virus in Its Life Cycle
Authors: Yang Linjiang , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Huang Juan , Tian Bin , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Zhao Xinxin , Zhang Shaqiu , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Yu Yanlin , Zhang Ling
Published: January 2022

Tegument protein UL11 plays a critical role in the life cycle of herpesviruses. The UL11 protein of herpesviruses is important for viral particle entry, release, assembly, and secondary envelopment. Lipid raft is cholesterol-rich functional microdomains in cell membranes, which plays an important role in signal transduction and substance transport. Flotillin and prohibition, which are considered to be specific markers of lipid raft. However, little is known about the function of duck plague virus (DPV) UL11 in the life cycle of the viruses and the relationship between the lipid raft and UL11. In this study, an interference plasmid shRNA126 for UL11 was used. Results showed that UL11 is involved in the replication, cell to cell spread, viral particle assembly, and release processes. Furthermore, UL11 was verified that it could interact with the lipid raft through sucrose density gradient centrifugation and that function correlates with the second glycine of the UL11. When the lipid raft was depleted using the methyl-β-cyclodextrin, the release of the DPV was decreased. Moreover, UL11 can decrease several relative viral genes mRNA levels by qRT-PCR and Western blot test. Altogether, these results highlight an important role for UL11 protein in the viral replication cycle.
Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis
Authors: Hou Yan-Pei , Diao Tian-Tian , Xu Zhi-Hui , Mao Xin-Yue , Wang Chang , Li Bing
Published: January 2022

Background: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome leading to end-stage renal disease, and this study aimed to explore the hub genes and pathways associated with FSGS to identify potential diagnostic and therapeutic targets.

Methods: We downloaded the microarray datasets GSE121233 and GSE129973 from the Gene Expression Omnibus (GEO) database. The datasets comprise 25 FSGS samples and 25 normal samples. The differential expression genes (DEGs) were identified using the R package “limma”. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID) to identify the pathways and functional annotation of the DEGs. The protein–protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. The hub genes of the DEGs were then evaluated using the cytoHubba plugin of Cytoscape. The expression of the hub genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the FSGS rat model, and receiver operating characteristic (ROC) curve analysis was performed to validate the accuracy of these hub genes.

Results: A total of 45 DEGs including 18 upregulated and 27 downregulated DEGs, were identified in the two GSE datasets (GSE121233 and GSE129973). Among them, five hub genes with a high degree of connectivity were selected. From the PPI network, of the top five hub genes, FN1 was upregulated, while ALB, EGF, TTR, and KNG1 were downregulated. The qRT-PCR analysis of FSGS rats confirmed that the expression of FN1 was upregulated and that of EGF and TTR was downregulated. The ROC analysis indicated that FN1, EGF, and TTR showed considerable diagnostic efficiency for FSGS.

Conclusion: Three novel FSGS-specific genes were identified through bioinformatic analysis combined with experimental validation, which may promote our understanding of the molecular underpinning of FSGS and provide potential therapeutic targets for the clinical management.
Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment
Authors: Bao Qianqian , Huang Qianqian , Chen Yunna , Wang Qiang , Sang Ran , Wang Lei , Xie Ying , Chen Weidong
Published: January 2022

Extracellular vesicles (EVs) are nanosized particles released by numerous kinds of cells, which are now increasingly considered as essential vehicles of cell-to-cell communication and biomarkers in disease diagnosis and treatment. They contain a variety of biomolecular components, including lipids, proteins and nucleic acids. These functional molecules can be transmitted between tumor cells and other stromal cells such as endothelial cells, fibroblasts and immune cells utilizing EVs. As a result, tumor-derived EVs can deliver molecules to remodel the tumor microenvironment, thereby influencing cancer progression. On the one hand, tumor-derived EVs reprogram functions of endothelial cells, promote cancer-associated fibroblasts transformation, induce resistance to therapy and inhibit the immune response to form a pro-tumorigenic environment. On the other hand, tumor-derived EVs stimulate the immune response to create an anti-tumoral environment. This article focuses on presenting a comprehensive and critical overview of the potential role of tumor-derived EVs-mediated communication in the tumor microenvironment.
High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats
Authors: Leal Pedro Ernesto de Pinho Tavares , da Silva Alexandre Alves , Rocha-Gomes Arthur , Riul Tania Regina , Cunha Rennan Augusto , Reichetzeder Christoph , Villela Daniel Campos
Published: January 2022

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.
Language Learning Under Varied Conditions: Neural Indices of Speech Perception in Bilingual Turkish-German Children and in Monolingual Children With Developmental Language Disorder (DLD)
Authors: Rinker Tanja , Yu Yan H. , Wagner Monica , Shafer Valerie L.
Published: January 2022

Lateral temporal measures of the auditory evoked potential (AEP) including the T-complex (positive Ta and negative Tb), as well as an earlier negative peak (Na) index maturation of auditory/speech processing. Previous studies have shown that these measures distinguish neural processing in children with typical language development (TD) from those with disorders and monolingual from bilingual children. In this study, bilingual children with Turkish as L1 and German as L2 were compared with monolingual German-speaking children with developmental language disorder (DLD) and monolingual German-speaking children with TD in order to disentangle effects of limited language input vs. reduced perceptual abilities in the processing of speech and non-speech stimuli. Sensory processing reflected by the T-complex (or from lateral temporal electrode sites) was compared in response to a German vowel and a sine-wave tone in the three groups of children, ages 5 through 6 years. Stimuli were presented while children watched a muted video. Auditory evoked potentials (AEPs) were time-locked to the vowels and tones. AEPs to the frequent (standard) stimuli within an oddball paradigm were analyzed at the left (T7) and right (T8) temporal electrode sites.The results revealed language status (monolingual, bilingual, and DLD), stimulus (vowel and tone), and language test measures (receptive and expressive) all influenced the T-complex amplitudes. Particularly, the peak amplitude of Ta was modulated by language status and stimulus type. Bilingual children had significantly more negative Ta responses than the monolingual children with TD for both vowels and tones while DLD children differed from TD children only for the vowel stimulus. The amplitude of the T-complex was overall more negative at the left than at the right site. The Na peak latency was longer for the bilingual group than that observed for the two monolingual groups. The Tb latency was shorter for DLD and bilingual groups than that for TD children in the vowel condition, but no such latency difference between DLD and bilingual children was found. We suggest that the attenuated T-complex for bilingual children indicates continued plasticity of the auditory cortex to allow for learning of novel, second-language speech sounds.
Development of Inclusion Complexes With Relative Humidity Responsive Capacity as Novel Antifungal Agents for Active Food Packaging
Authors: Muñoz-Shugulí Cristina , Rodríguez-Mercado Francisco , Mascayano Carolina , Herrera Andrea , Bruna Julio E. , Guarda Abel , Galotto María J.
Published: January 2022

Background:Allyl isothiocyanate is an excellent antimicrobial compound that has been applied in the development of active food packaging materials in the last years. However, the high volatility of this compound could prevent a lasting effect over time. In order to avoid this problem, cyclodextrin inclusion complexes have been proposed as an alternative, being beta-cyclodextrin (β-CD) as the main candidate. In addition, β-CD could act as a relative humidity-responsive nanoparticle. In this regard, the aim of this study was to develop inclusion complexes based on β-CD and AITC as relative humidity-responsive agents, which can be used in the design of active food packaging materials.

Methods:Two different β-CD:AITC inclusion complexes (2:1 and 1:1 molar ratios) were obtained by the co-precipitation method. Entrapment efficiency was determined by gas chromatography, while inclusion complexes were characterized through thermal, structural, and physicochemical techniques. Antifungal capacity of inclusion complexes was determined in a headspace system. Furthermore, the AITC release from inclusion complexes to headspace at different percentages of relative humidity was evaluated by gas chromatography, and this behavior was related with molecular dynamic studies.

Key Findings and Conclusions:The entrapment efficiency of inclusion complexes was over to 60%. Two coexisting structures were proposed for inclusion complexes through spectroscopic analyses and molecular dynamic simulation. The water sorption capacity of inclusion complexes depended on relative humidity, and they exhibited a strong fungicide activity againstBotrytis cinerea. Furthermore, the AITC release to headspace occurred in three stages, which were related with changes in β-CD conformational structure by water sorption and the presence of the different coexisting structures. In addition, a strong influence of relative humidity on AITC release was evidenced. These findings demonstrate that β-CD:AITC inclusion complexes could be used as potential antifungal agents for the design of food packaging materials, whose activity would be able to respond to relative humidity changes.
Surgical Navigation, Augmented Reality, and 3D Printing for Hard Palate Adenoid Cystic Carcinoma En-Bloc Resection: Case Report and Literature Review
Authors: García-Sevilla Mónica , Moreta-Martinez Rafael , García-Mato David , Arenas de Frutos Gema , Ochandiano Santiago , Navarro-Cuéllar Carlos , Sanjuán de Moreta Guillermo , Pascau Javier
Published: January 2022

Adenoid Cystic Carcinoma is a rare and aggressive tumor representing less than 1% of head and neck cancers. This malignancy often arises from the minor salivary glands, being the palate its most common location. Surgical en-bloc resection with clear margins is the primary treatment. However, this location presents a limited line of sight and a high risk of injuries, making the surgical procedure challenging. In this context, technologies such as intraoperative navigation can become an effective tool, reducing morbidity and improving the safety and accuracy of the procedure. Although their use is extended in fields such as neurosurgery, their application in maxillofacial surgery has not been widely evidenced. One reason is the need to rigidly fixate a navigation reference to the patient, which often entails an invasive setup. In this work, we studied three alternative and less invasive setups using optical tracking, 3D printing and augmented reality. We evaluated their precision in a patient-specific phantom, obtaining errors below 1 mm. The optimum setup was finally applied in a clinical case, where the navigation software was used to guide the tumor resection. Points were collected along the surgical margins after resection and compared with the real ones identified in the postoperative CT. Distances of less than 2 mm were obtained in 90% of the samples. Moreover, the navigation provided confidence to the surgeons, who could then undertake a less invasive and more conservative approach. The postoperative CT scans showed adequate resection margins and confirmed that the patient is free of disease after two years of follow-up.
Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China
Authors: Guo Lan-Wei , Lyu Zhang-Yan , Meng Qing-Cheng , Zheng Li-Yang , Chen Qiong , Liu Yin , Xu Hui-Fang , Kang Rui-Hua , Zhang Lu-Yao , Cao Xiao-Qin , Liu Shu-Zheng , Sun Xi-Bin , Zhang Jian-Gong , Zhang Shao-Kai
Published: January 2022

Background

About 15% of lung cancers in men and 53% in women are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in non-smokers in China.

Methods

A large-sample size, population-based study was conducted under the framework of the Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set.

Results

A total of 214,764 eligible subjects were included, with a mean age of 55.19 years. Subjects were randomly divided into the training (107,382) and validation (107,382) sets. Elder age, being male, a low education level, family history of lung cancer, history of tuberculosis, and without a history of hyperlipidemia were the independent risk factors for lung cancer. Using these six variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.753, 0.752, and 0.755 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a moderate predictive discrimination, with the AUC was 0.668, 0.678, and 0.685 for the 1-, 3- and 5-year lung cancer risk.

Conclusions

We developed and validated a simple and non-invasive lung cancer risk model in non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in non-smokers.
SDHA Germline Variants in Adult Patients With SDHA-Mutant Gastrointestinal Stromal Tumor
Authors: Pantaleo Maria A. , Urbini Milena , Schipani Angela , Nannini Margherita , Indio Valentina , De Leo Antonio , Vincenzi Bruno , Brunello Antonella , Grignani Giovanni , Casagrande Mariaelena , Fumagalli Elena , Conca Elena , Saponara Maristella , Gruppioni Elisa , Altimari Annalisa , De Biase Dario , Tallini Giovanni , Ravegnini Gloria , Turchetti Daniela , Seri Marco , Ardizzoni Andrea , Secchiero Paola , Astolfi Annalisa
Published: January 2022

Background

SDH-deficient gastrointestinal stromal tumors (GIST) account for 20–40% of all KIT/PDGFRA-negative GIST and are due to mutations in one of the four SDH-complex subunits, with SDHA mutations as the most frequent. Here we sought to evaluate the presence and prevalence of SDHA variants in the germline lineage in a population of SDHA-deficient GIST.

Methods

Germline SDHA status was assessed by Sanger sequencing on a series of 14 patients with gastric SDHA-deficient GIST.

Results

All patients carried a germline SDHA pathogenic variant, ranging from truncating, missense, or splicing variants. The second hit was the loss of the wild-type allele or an additional somatic mutation. One-third of the patients were over 50 years old. GIST was the only disease presentation in all cases except one, with no personal or familial cancer history. Seven metastatic cases received a multimodal treatment integrating surgery, loco-regional and medical therapy. The mean follow-up time was of 10 years, confirming the indolent clinical course of the disease.

Conclusion

SDHA germline variants are highly frequent in SDHA-deficient GIST, and the disease may occur also in older adulthood. Genetic testing and surveillance of SDHA-mutation carriers and relatives should be performed.
Small Fiber Polyneuropathy May Be a Nexus Between Autonomic Nervous System Dysregulation and Pain in Interstitial Cystitis/Bladder Pain Syndrome
Authors: Wolff Dylan T. , Walker Stephen J.
Published: January 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a highly heterogeneous chronic and debilitating condition which effects millions of women and men in the United States. While primarily defined by urinary symptoms and pain perceived to be emanating from the bladder, IC/BPS patients frequently have co-occurring conditions and symptoms, many of which affect diverse body systems related to autonomic nervous system function. The impact on the autonomic system appears to stem from increased sympathetic innervation of the urinary tract, along with increased systemic sympathetic tone and decreased parasympathetic tone. Concurrent with these findings is evidence for destruction of peripheral sympathetic innervation to the sweat glands which may relate to small fiber polyneuropathy. It is unknown to what degree the wider alterations in autonomic function are also related to destruction/alterations in the small fibers carrying autonomic innervation. This potential nexus is an important point of investigation to better understand the unclarified pathophysiology of interstitial cystitis/bladder pain syndrome, the numerous co-occurring symptoms and syndromes, and for the identification of novel targeted therapeutic strategies.
A Novel Homozygous PKP2 Variant in Severe Neonatal Non-compaction and Concomitant Ventricular Septal Defect: A Case Report
Authors: Katanyuwong Poomiporn , Khongkraparn Arthaporn , Wattanasirichaigoon Duangrurdee
Published: January 2022

Left ventricular non-compaction (LVNC) is a rare and genetically heterogeneous cardiomyopathy. The disorder vastly affects infants and young children. Severe neonatal LVNC is relatively rare. The prevalence of genetic defects underlying pediatric and adult-onset LVNC is about 17–40%. Mutations of MYH7 and MYBPC3 sarcomeric genes are found in the vast majority of the positive pediatric cases. PKP2 encodes plakophilin-2, a non-sarcomeric desmosomal protein, which has multiple roles in cardiac myocytes including cell–cell adhesion, tightening gap junction, and transcriptional factor. Most of the reported PKP2 mutations are heterozygous missense and truncating variants, and they are associated with an adult-onset autosomal dominant disorder, namely arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Homozygous PKP2 mutations have been rarely described. Herein, we present a rare case of an infant with neonatal onset of congestive heart failure owing to severe LVNC and multiple muscular VSD. Medical treatments failed to control the heart failure and the patient died at 11 months of age. Whole-exome sequencing identified a novel homozygous PKP2 variant, c.1511-1G>C, in the patient. An mRNA analysis revealed aberrant transcript lacking exon 7, which was predicted to cause a frameshift and truncated peptide (p.Gly460GlufsTer2). The heterozygous parents had normal cardiac structures and functions as demonstrated by electrocardiogram and echocardiography. Pathogenic variants of sarcomeric genes analyzed were not found in the patient. We conducted a literature review and identified eight families with biallelic PKP2 mutations. We observed that three families (our included) with null variants were linked to lethal phenotypes, while homozygous missense mutations resulted in less severe manifestations: adolescent-onset ARVD/C and childhood-onset DCM. Our data support a previous notion that severe neonatal LVNC might represent a unique entity and had distinct genetic spectrum. In conclusion, the present study has extended the phenotypes and genotypes of PKP2-related disorders and lethal LVNC.
Use of Physiologically-Based Kinetics Modelling to Reliably Predict Internal Concentrations of the UV Filter, Homosalate, After Repeated Oral and Topical Application
Authors: Najjar Abdulkarim , Schepky Andreas , Krueger Christopher-Tilman , Dent Matthew , Cable Sophie , Li Hequn , Grégoire Sebastien , Roussel Laurene , Noel-Voisin Audrey , Hewitt Nicola J. , Cardamone Estefania
Published: January 2022

Ethical and legal considerations have led to increased use of non-animal methods to evaluate the safety of chemicals for human use. We describe the development and qualification of a physiologically-based kinetics (PBK) model for the cosmetic UV filter ingredient, homosalate, to support its safety without the need of generating further animal data. The intravenous (IV) rat PBK model, using PK-Sim®, was developed and validated using legacy in vivo data generated prior to the 2013 EU animal-testing ban. Input data included literature or predicted physicochemical and pharmacokinetic properties. The refined IV rat PBK model was subject to sensitivity analysis to identify homosalate-specific sensitive parameters impacting the prediction of Cmax (more sensitive than AUC(0-∞)). These were then considered, together with population modeling, to calculate the confidence interval (CI) 95% Cmax and AUC(0-∞). Final model parameters were established by visual inspection of the simulations and biological plausibility. The IV rat model was extrapolated to oral administration, and used to estimate internal exposures to doses tested in an oral repeated dose toxicity study. Next, a human PBK dermal model was developed using measured human in vitro ADME data and a module to represent the dermal route. Model performance was confirmed by comparing predicted and measured values from a US-FDA clinical trial (Identifier: NCT03582215, https://clinicaltrials.gov/). Final exposure estimations were obtained in a virtual population and considering the in vitro and input parameter uncertainty. This model was then used to estimate the Cmax and AUC(0–24 h) of homosalate according to consumer use in a sunscreen. The developed rat and human PBK models had a good biological basis and reproduced in vivo legacy rat and human clinical kinetics data. They also complied with the most recent WHO and OECD recommendations for assessing the confidence level. In conclusion, we have developed a PBK model which predicted reasonably well the internal exposure of homosalate according to different exposure scenarios with a medium to high level of confidence. In the absence of in vivo data, such human PBK models will be the heart of future completely non-animal risk assessments; therefore, valid approaches will be key in gaining their regulatory acceptance.

Clinical Trial Registration: https://clinicaltrials.gov/, identifier, NCT03582215
The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study
Authors: Van Meijel Rens L. J. , Wang Ping , Bouwman Freek , Blaak Ellen E. , Mariman Edwin C. M. , Goossens Gijs H.
Published: January 2022

Adipose tissue (AT) oxygen tension (pO2) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, and cross-over study to investigate the effects of seven consecutive days of MIH (FiO2 15%, 3x2h/d) compared to normoxia (FiO2 21%) exposure on the AT proteome in overweight/obese men. In vivo AT insulin sensitivity was determined by the gold standard hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous AT biopsies were collected under normoxic fasting conditions following both exposure regimens (day 8). AT proteins were isolated and quantified using liquid chromatography-mass spectrometry. After correction for blood contamination, 1,022 AT protein IDs were identified, of which 123 were differentially expressed following MIH (p < 0.05). We demonstrate for the first time that MIH exposure, which markedly reduces in vivo AT oxygen tension, impacts the human AT proteome. Although we cannot exclude that a single differentially expressed protein might be a false positive finding, several functional pathways were altered by MIH exposure, also after adjustment for multiple testing. Specifically, differentially expressed proteins were involved in redox systems, cell-adhesion, actin cytoskeleton organization, extracellular matrix composition, and energy metabolism. The MIH-induced change in AT TMOD3 expression was strongly related to altered in vivo AT insulin sensitivity, thus linking MIH-induced effects on the AT proteome to metabolic changes in overweight/obese humans.