bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Papilloma-Virus Associated Carcinomas and Warts
Authors: Schuind Anne
Published: November 2021

HPV is extremely common worldwide and mainly transmitted through sexual contact; most people are infected with HPV shortly after onset of sexual activity.

There are >200 types of HPV, of which at least 12 are cancer-causing (oncogenic or high-risk types).

HPV is a causal factor for several anogenital and a subset of oropharyngeal cancers with 2 HPV types (16 and 18) causing 72% of all HPV-associated cancers.

Cervical cancer is the fourth most common cancer among women globally with nearly 90% of the deaths occurring in low- and middle-income countries.

Comprehensive cervical cancer control includes primary prevention (vaccination against HPV), secondary prevention (screening and treatment of pre-cancerous lesions) as well as treatment of invasive cervical cancer.

The currently licensed vaccines are L1 VLP-based and prophylactic; they have been shown to be safe and highly effective in preventing HPV infections and HPV-associated lesions, precancer and cancer.

Neutralizing antibodies are the mechanism of protection for prophylactic HPV VLP-based vaccines.

Therapeutic HPV vaccines targeting the oncoproteins E6 and E7 are in clinical development.
Potential Microbiological Risk Factors Associated With Periodontitis and Periodontal Health Disparities
Authors: Wang Bing-Yan , Lu Tom , Cai Qiuyin , Ho Meng-Hsuan , Sheng Sally , Meng Hsiu-Wan , Arsto Laura , Hong Jianming , Xie Hua
Published: November 2021

Periodontitis disproportionately affects different racial and ethnic populations. In this study, we used qPCR to determine and compare oral microbial profiles in dental plaque samples from 191 periodontitis patients of different ethnic/racial backgrounds. We also obtained the periodontal parameters of these patients retrospectively using axiUm and performed statistical analysis using SAS 9.4. We found that in this patient cohort, neighborhood median incomes were significantly higher among Caucasians Americans (CAs) than among African Americans (AAs) and Hispanic Americans (HAs). Levels of total bacteria and Porphyromonas gingivalis, a keystone periodontal pathogen, were not evenly distributed among the three groups. We confirmed our previous findings that Streptococcus cristatus reduces P. gingivalis virulence potential and likely serves as a beneficial bacterium. We also showed the ratio of S. cristatus to P. gingivalis to be significantly higher in CAs than in HAs and AAs. Our results suggest that higher levels of P. gingivalis and lower ratios of S. cristatus to P. gingivalis may contribute to periodontal health disparities.
Patterns of Insulin Secretion During First-Phase Insulin Secretion in Normal Chinese Adults
Authors: Yuan Tao , Song Shuoning , Zhao Tianyi , Duo Yanbei , Wang Shihan , Gao Junxiang , Liu Shixuan , Dong Yingyue , Li Rui , Fu Yong , Zhao Weigang
Published: November 2021

Background

The increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse.

Aims

This study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM).

Methods

A total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity.

Results

Age, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend <0.05), and the differences between G1 and G2 were also statistically significant (p < 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p-value for linear trend of those indices among three groups were statistically significant (p < 0.05).

Conclusions

Two patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future.
Environmental Flow Requirements of Estuaries: Providing Resilience to Current and Future Climate and Direct Anthropogenic Changes
Authors: Chilton Daniel , Hamilton David P. , Nagelkerken Ivan , Cook Perran , Hipsey Matthew R. , Reid Robert , Sheaves Marcus , Waltham Nathan J. , Brookes Justin
Published: November 2021

Estuaries host unique biodiversity and deliver a range of ecosystem services at the interface between catchment and the ocean. They are also among the most degraded ecosystems on Earth. Freshwater flow regimes drive ecological processes contributing to their biodiversity and economic value, but have been modified extensively in many systems by upstream water use. Knowledge of freshwater flow requirements for estuaries (environmental flows or E-flows) lags behind that of rivers and their floodplains. Generalising estuarine E-flows is further complicated by responses that appear to be specific to each system. Here we critically review the E-flow requirements of estuaries to 1) identify the key ecosystem processes (hydrodynamics, salinity regulation, sediment dynamics, nutrient cycling and trophic transfer, and connectivity) modulated by freshwater flow regimes, 2) identify key drivers (rainfall, runoff, temperature, sea level rise and direct anthropogenic) that generate changes to the magnitude, quality and timing of flows, and 3) propose mitigation strategies (e.g., modification of dam operations and habitat restoration) to buffer against the risks of altered freshwater flows and build resilience to direct and indirect anthropogenic disturbances. These strategies support re-establishment of the natural characteristics of freshwater flow regimes which are foundational to healthy estuarine ecosystems.
Genetic Diversity of Polymorphic Marker Merozoite Surface Protein 1 (Msp-1) and 2 (Msp-2) Genes of Plasmodium falciparum Isolates From Malaria Endemic Region of Pakistan
Authors: Khan Shahid Niaz , Ali Rehman , Khan Sanaullah , Rooman Muhammad , Norin Sadia , Zareen Shehzad , Ali Ijaz , Ayaz Sultan
Published: November 2021

Background: Understanding the genetic diversity of Plasmodium species through polymorphic studies can assist in designing more effective control strategies of malaria like new drug formulation and development of a vaccine. Pakistan is moderate endemic for Plasmodium falciparum, but little is known about the genetic diversity of this parasite. This study aimed to investigate the molecular diversity of P. falciparum based on msp-1 and msp-2 genes in the malaria-endemic regions of Khyber Pakhtunkhwa, Pakistan.

Methods: A total of 199/723 blood samples, tested positive by microscopy for falciparum malaria, were collected from four districts (Dera Ismail Khan, Karak, Mardan, and Peshawar) of Khyber Pakhtunkhwa. Nested PCR amplification technique was employed to target block 2 of msp-1 and the central domain of msp-2 genes, including their respective allelic families K1, MAD20, RO33, FC27, and 3D7/IC, and to detect the extent of genetic diversity of P. falciparum clinical isolates.

Results: Among the 199 microscopy-positive P. falciparum samples, a total of 192 were confirmed using PCR. Ninety-seven amplicons were observed for msp-1 and 95 for msp-2. A total of 33 genotypes, 17 for msp-1 (eight K1, six MAD20, and three RO33) and 16 for msp-2 (nine FC27 and seven 3D7/IC), were identified. The specific allelic frequency of the K1 family was higher (44.3%) than that of MAD20 (33.0%) and RO33 (23.0%) for msp-1, while the FC27 allelic family was dominant (60.0%) compared with 3D7/IC (40.0%) for msp-2. No polyclonal infection was observed in msp-1 and msp-2. The expected heterozygosity was 0.98 and 0.97 for msp-1 and msp-2, respectively.

Conclusion: It was concluded that the P. falciparum populations are highly polymorphic, and diverse allelic variants of msp-1 and msp-2 are present in Khyber Pakhtunkhwa, Pakistan.
Case Report: Novel Compound Heterozygous Variants in TRIOBP Associated With Congenital Deafness in a Chinese Family
Authors: Zhou Cong , Xiao Yuanyuan , Xie Hanbing , Wang Jing , Liu Shanling
Published: November 2021

Autosomal recessive non-syndromic deafness-28 (DFNB28) is characterized by prelingual, profound sensorineural hearing loss (HL). The disease is related to variants of the TRIOBP gene. TRIO and F-actin binding protein (TRIOBP) plays crucial roles in modulating the assembly of the actin cytoskeleton and are responsible for the proper structure and function of stereocilia in the inner ear. This study aimed to identify pathogenic variants in a patient with HL. Genomic DNA obtained from a 33-year-old woman with HL was evaluated using a disease-targeted gene panel. Using next generation sequencing and bioinformatics analysis, we identified two novel TRIOBP c.1170delC (p.S391Pfs*488) and c.3764C > G (p.S1255*) variants. Both parents of the patient were heterozygous carriers of the gene. The two variants have not been reported in general population databases or published literature. The findings of this study will broaden the spectrum of pathogenic variants in the TRIOBP gene.
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype
Authors: Wen Xinmei , Zhu Wenjia , Xia Nan L. , Li Qianwen , Di Li , Zhang Shu , Chen Hai , Lu Yan , Wang Min , Xu Min , Wang Suobin , Shen Xin-Ming , Lu Jie , Da Yuwei
Published: November 2021

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in SOD1 (p.R116C and p.R116G) causing familial ALS. In this study, we report a novel heterozygous missense mutation in the SOD1 gene (p.R116S) in a family with inherited ALS manifested as fast-deteriorating pure lower motor neuron symptoms. The patient displayed similar clinical picture and prognostic value to previous reported cases with different R116 substitution mutations. Modeling of all R116 substitutions in the resolved SOD1 protein structure revealed a shared mechanism with destroyed hydrogen bonds between R116 and other two residues, which might lead to protein unfolding and oligomer formation, ultimately conferring neurotoxicity.
Immunological Microenvironment Alterations in Follicles of Patients With Autoimmune Thyroiditis
Authors: Huang Ning , Liu Dandan , Lian Ying , Chi Hongbin , Qiao Jie
Published: November 2021

Autoimmune thyroiditis (AIT) is the most prevalent autoimmune endocrine disease, with a higher incidence in women than in men. Immunological abnormalities may lead to the impairment of ovarian folliculogenesis; however, whether the presence of AIT affects immunological microenvironment in follicles remains controversial. We performed a cross-sectional study including 122 patients, aged 20–40 years, who underwent IVF/ICSI treatment owing to isolated male or tube factor infertility. Patients were divided into AIT and control groups according to clinical presentation, thyroid function, and thyroid autoantibody measurements. Follicular fluid was collected and the distribution of cytokines/chemokines in follicular fluid was measured by flow cytometry using multiplex bead assays between the two groups. Based on differences in levels of intrafollicular chemokines and cytokines between the AIT and control groups, the relevant inflammatory cascade was further demonstrated. Among the 12 chemokines analyzed, three (CXCL9, CXCL10, and CXCL11) showed significantly elevated levels in the follicular fluid of patients with AIT. Among the 11 cytokines detected, compared with those in the control group, significantly higher levels of IFNγ were observed in patients with AIT. IFNγ dose-dependently stimulated the expression and secretion of CXCL9/10/11 in cultured primary granulosa cells. The percentage of CXCR3+ T lymphocytes was significantly elevated in the follicular microenvironment of patients with AIT. We concluded that the IFNγ-CXCL9/10/11-CXCR3+ T lymphocyte inflammatory cascade is activated in the follicular microenvironment of patients with AIT. These findings indicate that a considerable immune imbalance occurred in the follicular microenvironment of patients with AIT.
Digenic Inheritance: Evidence and Gaps in Hemophagocytic Lymphohistiocytosis
Authors: Steen Erica A. , Hermiston Michelle L. , Nichols Kim E. , Meyer Lauren K.
Published: November 2021

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder characterized by the inability to properly terminate an immune response. Familial HLH (FHLH) and related immune dysregulation syndromes are associated with mutations in the genes PRF1, UNC13D, STX11, STXBP2, LYST, AP3B1, and RAB27A, all of which are required for the assembly, exocytosis, and function of cytotoxic granules within CD8+ T cells and natural killer (NK) cells. Loss-of-function mutations in these genes render the cytotoxicity pathway ineffective, thereby failing to eradicate immune stimuli, such as infectious pathogens or malignant cells. The resulting persistent immune system stimulation drives hypercytokinemia, ultimately leading to severe tissue inflammation and end-organ damage. Traditionally, a diagnosis of FHLH requires the identification of biallelic loss-of-function mutations in one of these degranulation pathway genes. However, this narrow definition fails to encompass patients with other genetic mechanisms underlying degranulation pathway dysfunction. In particular, mounting clinical evidence supports a potential digenic mode of inheritance of FHLH in which single loss-of-function mutations in two different degranulation pathway genes cooperate to impair pathway activity. Here, we review the functions of the FHLH-associated genes within the degranulation pathway and summarize clinical evidence supporting a model in which cumulative defects along this mechanistic pathway may underlie HLH.
Salinity and Water Temperature as Predictors of Bottlenose Dolphin (Tursiops truncatus) Encounter Rates in Upper Galveston Bay, Texas
Authors: Mintzer Vanessa J. , Fazioli Kristi L.
Published: November 2021

Bottlenose dolphins (Tursiops truncatus) that inhabit urban estuaries like Galveston Bay, Texas, are exposed to cumulative stressors including pollution, fisheries, shipping, freshwater inflows, and construction operations. With continuing development, it is imperative to understand the key environmental variables that make the Galveston Bay estuary suitable habitat for this protected species. The Galveston Bay Dolphin Research Program conducted monthly photo identification surveys of bottlenose dolphins in a previously understudied 186 km2 area in upper Galveston Bay (UGB). To understand occurrence patterns in this region, we calculated monthly encounter rates of dolphins (dolphins/km) for four consecutive years (2016–2019). Using multiple linear regression models, we investigated the relationship between encounter rates, and water temperature and salinity. Monthly encounter rates ranged from 0.00 to 1.23 dolphins/km with an average of 0.34 dolphins/km (SE = 0.05). Over 80% of the variance was explained by the predictor variables water temperature and salinity (R2 = 0.820). Water temperature had a positive linear effect on encounter rates at over 23.37°C (SE = 1.42). Accordingly, higher encounter rates occurred during months with warm temperatures (May–September) compared to cooler months (November–April), indicating a predictable yearly movement pattern. Moreover, salinity was a highly significant predictor variable, with encounter rates dropping linearly with decreases in salinity. Higher numbers of dolphins are found in UGB during summer, but an exodus of dolphins occurs with low salinity levels, regardless of the time of year and water temperature. These findings should be considered during infrastructure projects (i.e., flood gate system) that may alter dolphin habitat and prey availability.
Bridging the Gap: The Critical Role of Regulatory Affairs and Clinical Affairs in the Total Product Life Cycle of Pathology Imaging Devices and Software
Authors: Kearney Staci J. , Lowe Amanda , Lennerz Jochen K. , Parwani Anil , Bui Marilyn M. , Wack Katy , Giannini Gina , Abels Esther
Published: November 2021

Manufacturers of pathology imaging devices and associated software engage regulatory affairs and clinical affairs (RACA) throughout the Total Product Life Cycle (TPLC) of regulated products. A number of manufacturers, pathologists, and end users are not familiar with how RACA involvement benefits each stage of the TPLC. RACA professionals are important contributors to product development and deployment strategies because these professionals maintain an understanding of the scientific, technical, and clinical aspects of biomedical product regulation, as well as the relevant knowledge of regulatory requirements, policies, and market trends for both local and global regulations and standards. Defining a regulatory and clinical strategy at the beginning of product design enables early evaluation of risks and provides assurance that the collected evidence supports the product's clinical claims (e.g., in a marketing application), its safe and effective use, and potential reimbursement strategies. It is recommended to involve RACA early and throughout the TPLC to assist with navigating changes in the regulatory environment and dynamic diagnostic market. Here we outline how various stakeholders can utilize RACA to navigate the nuanced landscape behind the development and use of clinical diagnostic products. Collectively, this work emphasizes the critical importance of RACA as an integral part of product development and, thereby, sustained innovation.
Genetic and Phenotypic Diversity of Morganella morganii Isolated From Cheese
Authors: Ryser Lorenz Timo , Arias-Roth Emmanuelle , Perreten Vincent , Irmler Stefan , Bruggmann Rémy
Published: November 2021

The bacterium Morganella morganii can produce the biogenic amines (BA) cadaverine, putrescine, and histamine in vitro and is responsible for high histamine concentrations in fish products. These BA can have toxic effects upon ingestion and are undesired in food. The purpose of this study was to characterize the phenotype and genotype of 11 M. morganii isolated from cheese in regard to the BA formation. In addition, we investigated the phylogeny, trehalose fermentation ability, and antibiotic resistance of the cheese isolates. To do so, we sequenced their genomes using both long and short read technologies. Due to the presence of the trehalose operon and the ability to ferment trehalose, the cheese isolates can be assigned to the subsp. sibonii. Comparative genomics with public available M. morganii genomes shows that the genomes of the cheese isolates cluster together with other subsp. sibonii genomes. All genomes between subsp. morganii and subsp. sibonii are separated by an average nucleotide identity (ANI) of less than 95.0%. Therefore, the subspecies could represent two distinct species. Nine of the strains decarboxylated lysine yielding cadaverine in vitro. This metabolic activity is linked to a previously unknown gene cluster comprising genes encoding a lysine-tRNA ligase (lysS), an HTH-transcriptional regulator (argP), a cadaverine-lysine antiporter (cadB), and a lysine decarboxylase (cadA). The formation of putrescine is linked to the speF gene encoding an ornithine decarboxylase. The gene is disrupted in five strains by an insertion sequence, and these strains only exhibit a weak putrescine production. Antimicrobial susceptibility profiling revealed that all cheese strains are resistant to tetracycline, chloramphenicol, tigecycline, colistin, and ampicillin. These phenotypes, except for colistin which is intrinsic, could be linked to antimicrobial resistance genes located on the chromosome.
Lateralized Contributions of Medial Prefrontal Cortex Network to Episodic Memory Deficits in Subjects With Amnestic Mild Cognitive Impairment
Authors: Ye Qing , Chen Haifeng , Liu Renyuan , Qin Ruomeng , Luo Caimei , Li Mengchun , Xu Yun , Zhao Hui , Bai Feng
Published: November 2021

Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans. Hippocampal networks and medial prefrontal cortex (MPFC) networks were identified based on resting-sate functional MRI (fMRI) data. AMCI subjects displayed lower episodic memory scores and executive function scores than control subjects, and the episodic memory scores were positively correlated with the executive function scores in aMCI subjects. Brain network analyses showed an interaction between the hippocampal networks and the MPFC networks, and the interaction was significantly associated with the episodic memory scores and the executive function scores. Notably, aMCI subjects displayed higher functional connectivity (FC) of the right hippocampal network with the right prefrontal cortex than did control subjects, but this difference disappeared when controlling for the MPFC networks. Furthermore, the effects of the MPFC networks on the hippocampal networks were significantly associated with the episodic memory scores in aMCI subjects. The present findings suggested that the episodic memory deficits in aMCI subjects could be partially underpinned by the modulation of the MPFC networks on the hippocampal networks.
Study on the Application of Super-Resolution Ultrasound for Cerebral Vessel Imaging in Rhesus Monkeys
Authors: Yan Li , Bai Chen , Zheng Yu , Zhou Xiaodong , Wan Mingxi , Zong Yujin , Chen Shanshan , Zhou Yin
Published: November 2021

Background: Ultrasound is ideal for displaying intracranial great vessels but not intracranial microvessels and terminal vessels. Even with contrast agents, the imaging effect is still unsatisfactory. In recent years, significant theoretical advances have been achieved in super-resolution imaging. The latest commonly used ultrafast plane-wave ultrasound Doppler imaging of the brain and microbubble-based super-resolution ultrasound imaging have been applied to the imaging of cerebral microvessels and blood flow in small animals such as mice but have not been applied to in vivo imaging of the cerebral microvessels in monkeys and larger animals. In China, preliminary research results have been obtained using super-resolution imaging in certain fields but rarely in fundamental and clinical experiments on large animals. In recent years, we have conducted a joint study with the Xi'an Jiaotong University to explore the application and performance of this new technique in the diagnosis of cerebrovascular diseases in large animals.

Objective: To explore the characteristics and advantages of microbubble-based super-resolution ultrasound imaging of intracranial vessels in rhesus monkeys compared with conventional transcranial ultrasound.

Methods: First, the effectiveness and feasibility of the super-resolution imaging technique were verified by modular simulation experiments. Then, the imaging parameters were adjusted based on in vitro experiments. Finally, two rhesus monkeys were used for in vivo experiments of intracranial microvessel imaging.

Results: Compared with conventional plane-wave imaging, super-resolution imaging could measure the inner diameters of cerebral microvessels at a resolution of 1 mm or even 0.7 mm and extract blood flow information. In addition, it has a better signal-to-noise ratio (5.625 dB higher) and higher resolution (~30-fold higher). The results of the experiments with rhesus monkeys showed that microbubble-based super-resolution ultrasound imaging can achieve an optimal resolution at the micron level and an imaging depth >35 mm.

Conclusion: Super-resolution imaging can realize the monitoring imaging of high-resolution and fast calculation of microbubbles in the process of tissue damage, providing an important experimental basis for the clinical application of non-invasive transcranial ultrasound.
Electroencephalogram-Based Motor Imagery Classification Using Deep Residual Convolutional Networks
Authors: Huang Jing-Shan , Liu Wan-Shan , Yao Bin , Wang Zhan-Xiang , Chen Si-Fang , Sun Wei-Fang
Published: November 2021

The classification of electroencephalogram (EEG) signals is of significant importance in brain-computer interface (BCI) systems. Aiming to achieve intelligent classification of motor imagery EEG types with high accuracy, a classification methodology using the wavelet packet decomposition (WPD) and the proposed deep residual convolutional networks (DRes-CNN) is proposed. Firstly, EEG waveforms are segmented into sub-signals. Then the EEG signal features are obtained through the WPD algorithm, and some selected wavelet coefficients are retained and reconstructed into EEG signals in their respective frequency bands. Subsequently, the reconstructed EEG signals were utilized as input of the proposed deep residual convolutional networks to classify EEG signals. Finally, EEG types of motor imagination are classified by the DRes-CNN classifier intelligently. The datasets from BCI Competition were used to test the performance of the proposed deep learning classifier. Classification experiments show that the average recognition accuracy of this method reaches 98.76%. The proposed method can be further applied to the BCI system of motor imagination control.
LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex
Authors: Wei Sisi , Dai Suli , Zhang Cong , Zhao Ruinian , Zhao Zitong , Song Yongmei , Shan Baoen , Zhao Lianmei
Published: November 2021

Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
Authors: Jiao Peng-Fei , Tang Pei-jun , Chu Dan , Li Ya-meng , Xu Wei-hua , Ren Gao-Fei
Published: November 2021

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.
Mixed-Beam Approach for High-Risk Prostate Cancer Carbon-Ion Boost Followed by Photon Intensity-Modulated Radiotherapy: Preliminary Results of Phase II Trial AIRC-IG-14300
Authors: Marvaso Giulia , Vischioni Barbara , Pepa Matteo , Zaffaroni Mattia , Volpe Stefania , Patti Filippo , Bellerba Federica , Gandini Sara , Comi Stefania , Corrao Giulia , Zerini Dario , Augugliaro Matteo , Fodor Cristiana , Russo Stefania , Molinelli Silvia , Ciocca Mario , Ricotti Rosalinda , Valvo Francesca , Giandini Tommaso , Avuzzi Barbara , Valdagni Riccardo , De Cobelli Ottavio , Cattani Federica , Orlandi Ester , Jereczek-Fossa Barbara Alicja , Orecchia Roberto
Published: November 2021

Purpose

This study represents a descriptive analysis of preliminary results of a Phase II trial on a novel mixed beam radiotherapy (RT) approach, consisting of carbon ions RT (CIRT) followed by intensity-modulated photon RT, in combination with hormonal therapy, for high-risk prostate cancer (HR PCa) with a special focus on acute toxicity.

Methods

Primary endpoint was the evaluation of safety in terms of acute toxicity. Secondary endpoints were early and long-term tolerability of treatment, quality of life (QoL), and efficacy. Data on acute and late toxicities were collected according to RTOG/EORTC. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and sexual activity by IIEF-5.

Results

Twenty-six patients were enrolled in the study, but only 15 completed so far the RT course and were included. Immediately after CIRT, no patients experienced GI/GU toxicity. At 1 and 3 months from the whole course RT completion, no GI/GU toxicities greater than grade 2 were observed. QoL scores were overall satisfactory.

Conclusions

The feasibility of the proposed mixed treatment schedule was assessed, and an excellent acute toxicity profile was recorded. Such findings instil confidence in the continuation of this mixed approach, with evaluation of long-term tolerability and efficacy.
The Effects of the COVID-19 Pandemic on Health and Well-Being of Children and Youth in Nova Scotia: Youth and Parent Perspectives
Authors: Caldwell Hilary A. T. , Hancock Friesen Camille L. , Kirk Sara F. L.
Published: November 2021

Objectives: The COVID-19 pandemic led to school closures, cancellations of major events, and loss of in-person social interactions for children and youth. These restrictions undoubtedly impacted the lives of children and youth. This study describes the well-being of children and youth in Nova Scotia during the COVID-19 pandemic and their thoughts and feelings about the return to school, from the perspectives of both youth and parents.

Methods: A province-wide survey was conducted in August 2020 with parents of school-age children and youth and youth to measure youth well-being since the pandemic began.

Results: Parents of children and youth in grades pre-primary to 12 (n = 699; 53% girls) and youth in grades 3–12 (n = 279; 69% girls) completed the online survey. Perceptions of parents about children's emotions during the pandemic were: bored, safe, lonely, happy, and anxious. Youth reported feeling bored, relaxed, depressed, safe, and worried. Sixty-three percent of youth and 72% of parents reported that they/their child felt they were missing important life events. Parents reported that being with parents, being physically active and being with friends made their child feel positive. Youth reported that being with friends, pets and watching TV made them feel good during this time. Seventy-six percent of parents and 62% of youth reported they/their child were getting more screen time than before the pandemic. With schools closed, participants most frequently shared that they missed friends and social interactions, in-person learning, and extra-curricular activities. Youth and parents expressed worries about COVID-19 outbreaks and related restrictions when schools re-opened to in-person learning.

Conclusion: The well-being of children and youth in Nova Scotia was greatly impacted by the COVID-19 pandemic and related school closures in 2020. It is essential that pandemic recovery plans prioritize the health and well-being of children and youth.
Monoamine Oxidase-B Inhibitor Reduction in Pro-Inflammatory Cytokines Mediated by Inhibition of cAMP-PKA/EPAC Signaling
Authors: Putnins Edward E. , Goebeler Verena , Ostadkarampour Mahyar
Published: November 2021

Mucosal epithelial cell integrity is an important component of innate immunity and it protects the host from an environment rich in microorganisms. Virulence factors from Gram-negative bacteria [e.g. lipopolysaccharide (LPS)] induce significant pro-inflammatory cytokine expression. Monoamine oxidase (MAO) inhibitors reduce cytokine expression in a variety of inflammatory models and may therefore have therapeutic potential for a number of inflammatory diseases. We tested the anti-inflammatory therapeutic potential of a recently developed reversible MAO-B inhibitor (RG0216) with reduced transport across the blood–brain barrier. In an epithelial cell culture model, RG0216 significantly decreased LPS-induced interleukin (IL)-6 and IL-1β gene and protein expression and was as effective as equimolar concentrations of deprenyl (an existing irreversible MAO-B inhibitor). Hydrogen peroxide and modulating dopamine receptor signaling had no effect on cytokine expression. We showed that LPS-induced expression of IL-6 and IL-1β was cAMP dependent, that IL-6 and IL-1β expression were induced by direct cAMP activation (forskolin) and that RG0216 and deprenyl effectively reduced cAMP-mediated cytokine expression. Targeted protein kinase A (PKA) and Exchange Protein Activated by cAMP (EPAC) activation regulated IL-6 and IL-1β expression, albeit in different ways, but both cytokines were effectively decreased with RG0216. RG0216 reduction of LPS-induced cytokine expression occurred by acting downstream of the cAMP-PKA/EPAC signaling cascade. This represents a novel mechanism by which MAO-B selective inhibitors regulate LPS-induced IL-6 and IL-1β expression.
Fetal Undernutrition Programming, Sympathetic Nerve Activity, and Arterial Hypertension Development
Authors: Mariano Vinícius Schiavinatto , Boer Patrícia Aline , Gontijo José Antônio Rocha
Published: November 2021

A wealth of evidence showed that low birth weight is associated with environmental disruption during gestation, triggering embryotic or fetal adaptations and increasing the susceptibility of progeny to non-communicable diseases, including metabolic and cardiovascular diseases, obesity, and arterial hypertension. In addition, dietary disturbance during pregnancy in animal models has highlighted mechanisms that involve the genesis of arterial hypertension, particularly severe maternal low-protein intake (LP). Functional studies demonstrated that maternal low-protein intake leads to the renal decrease of sodium excretion and the dysfunction of the renin-angiotensin-aldosterone system signaling of LP offspring. The antinatriuretic effect is accentuated by a reduced number of nephron units and glomerulosclerosis, which are critical in establishing arterial hypertension phenotype. Also, in this way, studies have shown that the overactivity of the central and peripheral sympathetic nervous system occurs due to reduced sensory (afferent) renal nerve activity. As a result of this reciprocal and abnormal renorenal reflex, there is an enhanced tubule sodium proximal sodium reabsorption, which, at least in part, contributes directly to arterial hypertension development in some of the programmed models. A recent study has observed that significant changes in adrenal medulla secretion could be involved in the pathophysiological process of increasing blood pressure. Thus, this review aims to compile studies that link the central and peripheral sympathetic system activity mechanisms on water and salt handle and blood pressure control in the maternal protein-restricted offspring. Besides, these pathophysiological mechanisms mainly may involve the modulation of neurokinins and catecholamines pathways.
Primary Cell Wall Modifying Proteins Regulate Wall Mechanics to Steer Plant Morphogenesis
Authors: Qiu Dengying , Xu Shouling , Wang Yi , Zhou Ming , Hong Lilan
Published: November 2021

Plant morphogenesis involves multiple biochemical and physical processes inside the cell wall. With the continuous progress in biomechanics field, extensive studies have elucidated that mechanical forces may be the most direct physical signals that control the morphology of cells and organs. The extensibility of the cell wall is the main restrictive parameter of cell expansion. The control of cell wall mechanical properties largely determines plant cell morphogenesis. Here, we summarize how cell wall modifying proteins modulate the mechanical properties of cell walls and consequently influence plant morphogenesis.
Investigation and Genome-Wide Association Analysis of Fusarium Seedling Blight Resistance in Chinese Elite Wheat Lines
Authors: Liu Yike , Zhu Guang , Zhu Zhangwang , Chen Lin , Niu Hongli , He Weijie , Tong Hanwen , Song Jinghan , Zhang Yuqing , Ma Dongfang , Gao Chunbao
Published: November 2021

Fusarium seedling blight (FSB) is an important disease of wheat occurring as part of the Fusarium disease complex consisting also of Fusarium head blight (FHB). 240 Chinese elite cultivars and lines were evaluated in greenhouse experiments for FSB resistance and genotyped using the wheat 90 K single nucleotide polymorphism arrays. Among them, 23 accessions had an average lesion length of less than 0.6 cm, exhibiting potential for breeding for FSB resistance in wheat. Jingfumai 1 and Yangmai 11 had a relatively high resistance to both FSB and FHB simultaneously. Six relatively stable quantitative trait loci (QTLs) were detected on chromosome arms 1DL, 3AS, 3BL, 6BL, 7AL, and Un using the mixed linear model approach, interpreting 4.83–7.53% of phenotypic variation. There was a negative correlation between the average FSB lesion length and the BLUE FHB index with a low coefficient, and resistance to both diseases appeared to be conferred by different QTLs across the same population. Four KASP markers were detected on 1DL, 3AS, 3BL, and 6BL in QTLs to facilitate marker-assisted selection. Combined with transcriptome data analysis, eight defense-related genes were considered as candidates for mapping QTLs. The resistant elite germplasm, mapped QTLs, and KASP markers developed in this study are useful resources for enhancing Fusarium seedling blight in wheat breeding.
Acute Maternal Stress Disrupts Infant Regulation of the Autonomic Nervous System and Behavior: A CASP Study
Authors: Mueller Isabelle , Snidman Nancy , DiCorcia Jennifer A. , Tronick Ed
Published: November 2021

Exposure to maternal stress is assumed to influence infant health and development across the lifespan. The autonomic nervous system (ANS) is especially sensitive to the effects of the early caregiving environment and linked to predictors of later mental health. Understanding how exposure to maternal stress adversely affects the developing ANS could inform prevention. However, there is no agreed upon definition of maternal stress making its study difficult. Here we use the Caretaker Acute Stress Paradigm (CASP) to study the effects of maternal stress in an experimentally controlled laboratory setting. The CASP has 5 episodes, a natural play, followed by a caretaker stressor (or control) condition, another play, a classic still face episode, followed by another play. A total of 104 4-months-old infants and their mothers were randomly assigned to either the caretaker-stress or caretaker-control condition. Changes in behavior, heart rate (HR), and respiratory sinus arrhythmia (RSA) before and after the introduction of the stressor (or control condition) were recorded and compared. Infants in the maternal stress condition showed significantly more behavioral distress [X2= (1,N= 104) = 4.662,p= 0.031]. Moreover, infants whose mothers were in the stress condition showed an significant increase in heart rate after the caretaker condition [F(1, 102)= 9.81,p= 0.002]. Finally we observed a trend to faster RSA recovery in infants of the control condition [F(1, 75)= 3.539,p= 0.064]. Results indicate that exposure to acute maternal stress affects infant regulation of the autonomic nervous system and behavior.
Factors Influencing Residents' Psychological Status During Standardized Training in COVID-19
Authors: Xiang Dongfang , Liang Bao , Wang Yongyi , Li Biao , Peng Juan , Zhang Sheng , Chen Bei , Yan Chuandong , Xu Chao
Published: November 2021

Objectives: To explore the influencing factors of residents' psychological status during standardized training in COVID-19 for finding ways to promote their mental health.

Methods: A total of 760 residents were surveyed with a structured questionnaire. Correlation analysis was used to analyze the influencing factors of psychological status of the residents, and a mediation model was constructed to verify the mediating role of satisfaction.

Results: Age, willingness to study medicine, and satisfaction were positively correlated with negative psychological status (P < 0.05). And gender, only child or not, and annual household income (RMB) were negatively correlated with negative psychological status (P < 0.01). Residents' satisfaction with standardized training mode plays a complete mediating role between annual household income and negative psychological status.

Conclusions: Our findings emphasize the importance of concentrating on resident's psychological status and family economic situation. And relative departments should take action to optimize the standardized training mode to improve the satisfaction.
Manufacturing of Plant-Based Bioactive Peptides Using Enzymatic Methods to Meet Health and Sustainability Targets of the Sustainable Development Goals
Authors: Ying Xin , Agyei Dominic , Udenigwe Chibuike , Adhikari Benu , Wang Bo
Published: November 2021

Due to the rapid growth in the global population, the consumption of animal-based food products/food compounds has been associated with negative implications for food sustainability/security. As a result, there is an increasing demand for the development of plant-based food and compounds as alternatives. Meanwhile, a growing number of studies report the health benefits of food protein-based peptides prepared via enzymatic hydrolysis and exhibiting biological properties such as antioxidant, antihypertensive, anti-thrombotic, and antidiabetic activities. However, the inherent bitterness of some peptides hinders their application in food products as ingredients. This article aims to provide the latest findings on plant-based bioactive peptides, particularly their health benefits, manufacturing methods, detection and qualification of their bitterness properties, as well as debittering methods to reduce or eliminate this negative sensory characteristic. However, there is still a paucity of research on the biological property of debittered peptides. Therefore, the role of plant protein-derived bioactive peptides to meet the health targets of the Sustainable Development Goals can only be realised if advances are made in the industrial-scale bioprocessing and debittering of these peptides.
The Effect of Antibiotic Treatment on the Bacterial Community of the Brown Planthopper and Its Correlation with Rice Virulence
Authors: Xu Xiaorong , Chen Liang , Zhou Hantao , Tang Ming
Published: November 2021

The prevention and control of planthoppers represent important issues for rice production. Current long-term control methods rely on pesticides, which raise concerns about environmental pollution. Recently, evidence has suggested that bacterial symbionts are important factors influencing the formation of Hemiptera insect biotypes and the selection of host plants for insects, which suggesting that targeting bacterial communities may be an effective alternative method for planthopper control. In this study, we perturbed the bacterial communities of the brown planthopper, Nilaparvata lugens, by feeding antibiotic-treated rice and used RNA-seq to examine the transcriptome of normal rice fed with perturbed BPHs by RNA-seq. Our results showed that the composition of the bacterial communities significantly changed after the perturbation, which was accompanied by changes in distinct biological processes of rice, especially the phenylpropanoid biosynthesis pathway, compared with the effect of the BPH feeding on rice without bacterial communities perturbation. Our work establishes a protocol for bacterial communities perturbation in BPH, demonstrating the link between bacterial community and the responses to BPH feeding and providing new insights into the interaction between BPH and rice.
Ex-Vivo Adhesion of Enterococcus faecalis and Enterococcus faecium to the Intestinal Mucosa of Healthy Beagles
Authors: Hanifeh Mohsen , Spillmann Thomas , Huhtinen Mirja , Sclivagnotis Yannes S. , Grönthal Thomas , Hynönen Ulla
Published: November 2021

Some Enterococcus faecalis and E. faecium strains are used as probiotics or feed additives. Adherence to the intestinal mucosa is considered a crucial step for intestinal bacteria to colonize and further interact with the host epithelium and the immune system. In dogs, there are no studies investigating the adhesion of E. faecalis and E. faecium to paraffin-embedded intestinal mucosa. Therefore, we aimed to investigate the adhesion of E. faecalis and E. faecium to the intestinal mucosa of six healthy beagles using bacteria derived from dogs and chickens. In addition, we aimed to validate a method to test the adhesion of Alexa Fluor-labeled bacteria to paraffin-embedded canine intestinal mucosa. The results of our study show that both canine- and chicken-derived E. faecalis strains adhered significantly better than E. faecium to the duodenal mucosa of healthy beagles (p = 0.002). In addition, canine E. faecalis and E. faecium adhered in higher numbers to canine duodenal mucosa, compared to chicken-derived strains of the same species (p = 0.015 for E. faecalis and p = 0.002 for E. faecium). The determination of the hydrophobicity of bacteria revealed that canine E. faecalis had the highest hydrophobicity level (36.6%), followed by chicken E. faecalis (20.4%), while canine E. faecium (5.7%) and chicken E. faecium (4.5%) had the lowest levels. Our results suggest that both the bacterial species and the host origin of the strain may influence mucosal adhesion.