bluuebunny/crossref_metadata_2025 huggingface dataset:
“Shrimp Watching” Ecotourism in Thailand: Toward Sustainable Management Policy
Authors: Hongjamrassilp Watcharapong , Traiyasut Prapun , Blumstein Daniel T.
Published: January 2021

Interest in wildlife ecotourism is increasing but many studies have identified detrimental effects making it unsustainable in the long run. We discuss a relatively new wildlife ecotourism event where tourists visit Ubon Ratchathani, Thailand to witness a mass migration of freshwater shrimp that emerge from the water and move across land known as “shrimp parading.” As this has been developed into a tourist event, the number of migrating shrimp have declined, suggesting that it may be unsustainable as currently practiced. We used a questionnaire to ask how locals, tourists, and stakeholders value the shrimp and their willingness to change their behavior to mitigate anthropogenic impacts. We found that three groups of participants were not aware of potential negative impacts to the shrimp from tourism. Locals valued the tourism in terms of the economy, culture, and environment less than tourists and stakeholders. The local government applied a top-down approach to manage this tourism without a fundamental understanding of the shrimp's biology, impacts of tourists on the shrimp, or the various stakeholder perceptions. We discuss the problems and possible solutions that may be employed to help sustain this fascinating biological and cultural event and propose a framework to develop a sustainable wildlife ecotourism management plan. This case study serves as a model for others developing wildlife watching ecotourism, especially in developing countries.
Assessing Raspberry Shake and Boom Sensors for Recording African Elephant Acoustic Vocalizations
Authors: Lamb Oliver D. , Shore Michael J. , Lees Jonathan M. , Lee Stephen J. , Hensman Sean M.
Published: January 2021

Acoustic sensors are increasingly being used in ecological and conservation research, but the choice of sensor can be fraught with trade-offs. In this work we assess the performance of the Raspberry Shake and Boom (RS&B) sensor package for detecting and monitoring African elephants (Loxodonta africana). This is the first documented test of this particular unit for recording animal behavior; the unit was originally designed for detecting tectonic earthquakes and low frequency (<50 Hz) atmospheric acoustics. During a four day deployment in South Africa we tested five RS&B units for recording acoustic and seismic vocalizations generated by a group of African elephants. Our results highlight a varied degree of success in detecting the signals of interest. The acoustic microphone recorded fundamental frequencies of low-frequency (<50 Hz) harmonic vocalizations that were not clearly recorded by more sensitive instruments, but was not able to record higher frequency harmonics due to the low sampling rate (100 Hz). The geophone was not able to consistently record clear seismic waves generated by vocalizations but was able to record higher harmonics. In addition, seismic signals were detected from footsteps of elephants at <50 m distance. We conclude that the RS&B unit currently shows limited potential as a monitoring tool for African elephants and we propose several future directions and deployment strategies to improve the sensitivity of the sensor package.
Identifying Expert and Novice Visual Scanpath Patterns and Their Relationship to Assessing Learning-Relevant Student Characteristics
Authors: Kosel Christian , Holzberger Doris , Seidel Tina
Published: January 2021

The paper addresses cognitive processes during a teacher's professional task of assessing learning-relevant student characteristics. We explore how eye-movement patterns (scanpaths) differ across expert and novice teachers during an assessment situation. In an eye-tracking experiment, participants watched an authentic video of a classroom lesson and were subsequently asked to assess five different students. Instead of using typically reported averaged gaze data (e.g., number of fixations), we used gaze patterns as an indicator for visual behavior. We extracted scanpath patterns, compared them qualitatively (common sub-pattern) and quantitatively (scanpath entropy) between experts and novices, and related teachers' visual behavior to their assessment competence. Results show that teachers' scanpaths were idiosyncratic and more similar to teachers of the same expertise group. Moreover, experts monitored all target students more regularly and made recurring scans to re-adjust their assessment. Lastly, this behavior was quantified using Shannon's entropy score. Results indicate that experts' scanpaths were more complex, involved more frequent revisits of all students, and that experts transferred their attention between all students with equal probability. Experts' visual behavior was also statistically related to higher judgment accuracy.
Genetic and Epigenetic Causes of Pituitary Adenomas
Authors: Chang Mengqi , Yang Chengxian , Bao Xinjie , Wang Renzhi
Published: January 2021

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel–Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (AIP) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (GNAS) and G protein-coupled receptor 101 (GPR101) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene USP8, USP48, and BRAF mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.
Primary Neuroendocrine Neoplasms of the Breast: Still Open Issues
Authors: Gallo Marco , Campione Severo , Di Vito Valentina , Fortunati Nicoletta , Lo Calzo Fabio , Messina Erika , Ruggeri Rosaria Maddalena , Faggiano Antongiulio , Colao Annamaria Anita Livia
Published: January 2021

Neuroendocrine breast tumors represent a rare subtype of breast cancer, accounting for less than 1% of all neuroendocrine neoplasms. Starting from their pathology definition, and going through their prevalence, prognosis and treatment, our knowledge is still really uncertain. In the present short review of the medical literature on this topic, we have evaluated in details their epidemiology, risk factors, pathogenesis, pathology, clinical presentation, radiographic aspects, prognosis, and therapy. We have thus been able to identify a number of open issues regarding primary neuroendocrine neoplasms of the breast that need to be clarified. Our ultimate aim was actually to try to understand whether neuroendocrine neoplasms of the breast can be considered a definite clinical entity and if neuroendocrine differentiation of breast tumors has a really clinical relevance.
Integrated Weighted Gene Co-expression Network Analysis Identified That TLR2 and CD14 Are Related to Coronary Artery Disease
Authors: Qi Bin , Chen Jian-Hong , Tao Lin , Zhu Chuan-Meng , Wang Yong , Deng Guo-Xiong , Miao Liu
Published: January 2021

The current research attempted to identify possible hub genes and pathways of coronary artery disease (CAD) and to detect the possible mechanisms. Array data from GSE90074 were downloaded from the Gene Expression Omnibus (GEO) database. Integrated weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene module and clinical characteristics. Gene Ontology annotation (GO), Disease Ontology (DO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by clusterProfiler and the DOSE package in R. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection (MCODE) to identify hub genes. Then, further functional validation of hub genes in other microarrays and population samples was performed, and survival analysis was performed to investigate the prognosis. A total of 660 genes were located in three modules and associated with CAD. GO functions identified 484 biological processes, 39 cellular components, and 22 molecular functions with an adjusted P < 0.05. In total, 38 pathways were enriched in KEGG pathway analysis, and 147 DO items were identified with an adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). There was a total of four modules with a score > 10 after PPI network analysis using the MCODE app, and two hub genes (TLR2 and CD14) were identified. Then, we validated the information from the GSE60993 dataset using the GSE59867 dataset and population samples, and we found that these two genes were associated with plaque vulnerability. These two genes varied at different time points after myocardial infarction, and both of them had the lowest prognosis of heart failure when they were expressed at low levels. We performed an integrated WGCNA and validated that TLR2 and CD14 were closely associated with the severity of coronary artery disease, plaque instability and the prognosis of heart failure after myocardial infarction.
Dysbacteriosis of the Intestinal Flora Is an Important Reason for the Death of Adult House Flies Caused by Beauveria bassiana
Authors: Zhang Ruiling , Feng Shuo , Xie Xiaochen , Huang Zhendong , Wan Qing , Wang Shumin , Zhang Zhong
Published: January 2021

Beauveria bassiana is one of the most widespread insect pathogens and can be used in the biological control of agricultural, forestry and medical pests. The mechanisms by which B. bassiana leads to mortality in different host insects are also different. For house flies, B. bassiana has strong virulence, but its microecological mechanism is not clear. In this paper, the virulence of three strains of B. bassiana (TB, CB and BB) isolated from different hosts to house flies was studied. The results showed that the three strains of B. bassiana had strong pathogenicity to house fly adults. Specifically, TB was the strongest, CB was the second strongest, and BB was the weakest, with maximum lethal effects on house fly populations 5, 6, and 7 days after infection, respectively. Further study showed that the intestinal flora of house flies was disordered 3, 4, and 5 days after B. bassiana TB, CB and BB strain infection, respectively. Intestinal flora dysbacteriosis may be an important reason for the death of house flies caused by B. bassiana. After infection, the negative interaction ratio of bacteria in the house fly intestine decreased, and the stronger the virulence was, the lower the negative interaction ratio was. The time from B. bassiana infection to intestinal flora dysbacteriosis was not fixed. We named this period the “spring stage”. The stronger the virulence of the B. bassiana strain was, the shorter the “spring stage” was. Therefore, the “spring stage” can be used as a virulence marker for evaluating the pathogenicity of different B. bassiana strains.
Myeloid Ezh2 Deficiency Limits Atherosclerosis Development
Authors: Neele Annette E. , Chen Hung-Jen , Gijbels Marion J. J. , van der Velden Saskia , Hoeksema Marten A. , Boshuizen Marieke C. S. , Van den Bossche Jan , Tool Anton T. , Matlung Hanke L. , van den Berg Timo K. , Lutgens Esther , de Winther Menno P. J.
Published: January 2021

Macrophages define a key component of immune cells present in atherosclerotic lesions and are central regulators of the disease. Since epigenetic processes are important in controlling macrophage function, interfering with epigenetic pathways in macrophages might be a novel approach to combat atherosclerosis. Histone H3K27 trimethylation is a repressive histone mark catalyzed by polycomb repressive complex with EZH2 as the catalytic subunit. EZH2 is described to increase macrophage inflammatory responses by supressing the suppressor of cytokine signaling, Socs3. We previously showed that myeloid deletion of Kdm6b, an enzymes that in contrast to EZH2 removes repressive histone H3K27me3 marks, results in advanced atherosclerosis. Because of its opposing function and importance of EZH2 in macrophage inflammatory responses, we here studied the role of myeloid EZH2 in atherosclerosis. A myeloid-specific Ezh2 deficient mouse strain (Ezh2del) was generated (LysM-cre+ x Ezh2fl/fl) and bone marrow from Ezh2del or Ezh2wt mice was transplanted to Ldlr-/- mice which were fed a high fat diet for 9 weeks to study atherosclerosis. Atherosclerotic lesion size was significantly decreased in Ezh2del transplanted mice compared to control. The percentage of macrophages in the atherosclerotic lesion was similar, however neutrophil numbers were lower in Ezh2del transplanted mice. Correspondingly, the migratory capacity of neutrophils was decreased in Ezh2del mice. Moreover, peritoneal Ezh2del foam cells showed a reduction in the inflammatory response with reduced production of nitric oxide, IL-6 and IL-12. In Conclusion, myeloid Ezh2 deficiency impairs neutrophil migration and reduces macrophage foam cell inflammatory responses, both contributing to reduced atherosclerosis.
Spatio-Temporal Variations of Winter Phytoplankton Blooms Northwest of the Luzon Island in the South China Sea
Authors: Gao Hui , Zhao Hui , Han Guoqi , Dong Changming
Published: January 2021

Phytoplankton is a key component of marine ecosystems. Winter phytoplankton blooms are frequently observed northwest of Luzon Island in the South China Sea. In this study, with the multi-satellite merged ocean color remote sensing data from November 1999 to February 2015, we examine the spatial and temporal changes of chlorophyll-a (Chl-a) concentration and further investigate its response to physical environment parameters including wind speed, Ekman transport, Ekman pumping velocity, sea surface temperature, and sea level anomalies in the region northwest of Luzon Island. The main factors affecting the distribution of Chl-a are discussed by using the partial correlation analysis and multiple stepwise linear regression analysis. The results show that centers of winter Chl-a blooms northwest of Luzon Island often occur near 119.5°E, 19.5°N. The significant multiple correlation (r = 0.76, p < 0.01) between Chl-a and oceanic conditions indicates that both the wind component parallel to the coastline and the wind stress curls enhance the winter upwelling in the study area, consistent with previous studies. A novel finding in the present study is that the winter bloom center is located north of the upwelling center, attributed to the advection effect of the northward background coastal flow.
Regional Diversity of Maritime Antarctic Soil Fungi and Predicted Responses of Guilds and Growth Forms to Climate Change
Authors: Newsham Kevin K. , Davey Marie L. , Hopkins David W. , Dennis Paul G.
Published: January 2021

We report a metabarcoding study documenting the fungal taxa in 29 barren fellfield soils sampled from along a 1,650 km transect encompassing almost the entire maritime Antarctic (60–72°S) and the environmental factors structuring the richness, relative abundance, and taxonomic composition of three guilds and growth forms. The richness of the lichenised fungal guild, which accounted for 19% of the total fungal community, was positively associated with mean annual surface air temperature (MASAT), with an increase of 1.7 operational taxonomic units (OTUs) of lichenised fungi per degree Celsius rise in air temperature. Soil Mn concentration, MASAT, C:N ratio, and pH value determined the taxonomic composition of the lichenised guild, and the relative abundance of the guild was best predicted by soil Mn concentration. There was a 3% decrease in the relative abundance of the saprotrophic fungal guild in the total community for each degree Celsius rise in air temperature, and the OTU richness of the guild, which accounted for 39% of the community, was negatively associated with Mn concentration. The taxonomic composition of the saprotrophic guild varied with MASAT, pH value, and Mn, NH4+-N, and SO42−concentrations. The richness of the yeast community, which comprised 3% of the total fungal community, was positively associated with soil K concentration, with its composition being determined by C:N ratio. In contrast with a similar study in the Arctic, the relative abundance and richness of lichenised fungi declined between 60°S and 69°S, with those of saprotrophic Agaricales also declining sharply in soils beyond 63°S. Basidiomycota, which accounted for 4% of reads, were much less frequent than in vegetated soils at lower latitudes, with the Ascomycota (70% of reads) being the dominant phylum. We conclude that the richness, relative abundance, and taxonomic composition of guilds and growth forms of maritime Antarctic soil fungi are influenced by air temperature and edaphic factors, with implications for the soils of the region as its climate changes during the 21st century.
Flavor Composition and Microbial Community Structure of Mianning Ham
Authors: Chen Lin , Wang Zhengli , Ji Lili , Zhang Jiamin , Zhao Zhiping , Zhang Rui , Bai Ting , Hou Bo , Wang Wei
Published: January 2021

Mianning ham, a traditional Chinese dry-cured ham, is protected by national geographical indications. To understand the surface and internal flavor composition and microbial community structure of Mianning ham, solid phase microextraction-gas chromatography (SPME-GC-MS) technology and Illumina high-throughput sequencing were utilized. The results showed that a total of 60 flavor substances were identified in the hams. Forty-nine kinds of flavorings were identified on the surface, including 14 aldehydes, 6 ketones, 10 alcohols, 5 esters, 7 hydrocarbons, 5 acids, and 2 other compounds. Thirty-six kinds of internal flavorings were identified, including 13 aldehydes, 4 ketones, 6 alcohols, 3 esters, 5 hydrocarbons, 4 acids and 1 other type. Decanal (34.91 μg/g) was the most prevalent compound on the surface, followed by n-hexanol (24.99 μg/g), n-hexanal (20.20 μg/g), and n-octyl (16.14 μg/g). n-Hexanal (20.74 μg/g) was the most common compound internally, followed by non-aldehyde (5.70 μg/g), 1-octene-3-alcohol (3.54 μg/g), and inverse-2-octenal (2.77 μg/g). Penicillium lanosum, Penicillium nalgiovense, Debaryomyces hansenii, Staphylococcus equorum, and Erwinia tasmaniensis were isolated from the surfaces of the hams by the traditional culture method. By Illumina high-throughput sequencing, three fungal phyla were identified. Ascomycota was the dominant phylum followed by Basidiomycota. At the genus level, 11 fungi were identified, of which Aspergillus was the dominant fungus, followed by Penicillium and Wallemia. These findings provide fundamental knowledge regarding the microorganisms and flavor compounds in Mianning ham, which will help industrial processors develop effective strategies for standardizing quality parameters.
The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors
Authors: Rohde Kyle H. , Sorci Leonardo
Published: January 2021

Given the upsurge of drug-resistant tuberculosis worldwide, there is much focus on developing novel drug combinations allowing shorter treatment duration and a lower toxicity profile. Nicotinamide adenine dinucleotide (NAD) biosynthesis targeting is acknowledged as a promising strategy to combat drug-susceptible, drug-resistant, and latent tuberculosis (TB) infections. In this review, we describe the potential synergy of NAD biosynthesis inhibitors with several TB-drugs in prospective novel combination therapy. Despite not directly targeting the essential NAD cofactor’s biosynthesis, several TB prodrugs either require a NAD biosynthesis enzyme to be activated or form a toxic chemical adduct with NAD(H) itself. For example, pyrazinamide requires the action of nicotinamidase (PncA), often referred to as pyrazinamidase, to be converted into its active form. PncA is an essential player in NAD salvage and recycling. Since most pyrazinamide-resistant strains are PncA-defective, a combination with downstream NAD-blocking molecules may enhance pyrazinamide activity and possibly overcome the resistance mechanism. Isoniazid, ethionamide, and delamanid form NAD adducts in their active form, partly perturbing the redox cofactor metabolism. Indeed, NAD depletion has been observed in Mycobacterium tuberculosis (Mtb) during isoniazid treatment, and activation of the intracellular NAD phosphorylase MbcT toxin potentiates its effect. Due to the NAD cofactor’s crucial role in cellular energy production, additional synergistic correlations of NAD biosynthesis blockade can be envisioned with bedaquiline and other drugs targeting energy-metabolism in mycobacteria. In conclusion, future strategies targeting NAD metabolism in Mtb should consider its potential synergy with current and other forthcoming TB-drugs.
The Biological Characteristics of Novel H5N6 Highly Pathogenic Avian Influenza Virus and Its Pathogenesis in Ducks
Authors: Huang Jianni , Wu Siyu , Wu Wenbo , Liang Yiwen , Zhuang Haibin , Ye Zhiyu , Qu Xiaoyun , Liao Ming , Jiao Peirong
Published: January 2021

Clade 2.3.4.4 H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused outbreaks in poultry in the world. Some of these viruses acquired internal genes from other subtype avian influenza viruses (AIVs) such as H9 and H6 for the generation of novel reassortant viruses and continually circulated in poultry. Here, we applied a duck-origin virus DK87 and a chicken-origin virus CK66 to assess the biological characteristics of novel reassortant H5N6 HPAIVs and its pathogenesis in ducks. A genetic analysis indicated that the HA genes of the two H5N6 HPAIVs were closely related to the H5 viruses of clade 2.3.4.4 circulating in Eastern Asia and classified into H5 AIV/Eastern Asia (EA)-like lineage. Their NA genes fell into Eurasian lineage had close relationship with those of H5N6 viruses circulating in China, Laos, Vietnam, Japan, and Korea. All internal genes of DK87 were aggregated closely with H5 AIV/EA-like viruses. The internal genes (PB1, PA, NP, M, and NS) of CK66 were derived from H9N2 AIV/SH98-like viruses and the PB2 were derived from H5 AIV/EA-like viruses. These results indicate that clade 2.3.4.4 H5N6 AIVs have continually evolved and recombined with the H9N2 viruses circulating in Southern China. Pathogenicity test showed that the two viruses displayed a broader tissue distribution in ducks and caused no clinical signs. These results indicated that ducks were permissive for the replication of the chicken-origin reassortant virus CK66 without prior adaptation, but the duck-origin virus DK87-inoculated ducks showed significantly higher viral titers in some organs than the CK66-inoculated ducks at 5 day post-inoculated (DPI). The recovery of viruses from oropharyngea and cloacal swabs of contacted ducks indicated that they transmitted in native ducks by direct contact. Quantitative reverse transcription PCR (qRT-PCR) results revealed that the immune-relative genes (PRRs, IFNs, Mx-1, IL-6, and IL-8) in the lungs of inoculated ducks were expressed regardless of virus origin, but the expression of these genes was significantly higher in response to infection with the DK87 virus compared to the CK66 virus at 3 DPI. Overall, we should provide further insights into how clade 2.3.4.4 H5N6 AIVs undergo genetic and pathogenic variations to prevent outbreaks of this disease.
Pre-exercise Caffeine Intake Enhances Bench Press Strength Training Adaptations
Authors: Giráldez-Costas Verónica , Ruíz-Moreno Carlos , González-García Jaime , Lara Beatriz , Del Coso Juan , Salinero Juan José
Published: January 2021

Previous research has identified acute caffeine intake as an effective ergogenic aid to enhance velocity and power during bench press exercise. However, no previous investigation has analyzed the effects of chronic intake of caffeine on training adaptations induced by bench press strength training. Thus, the aim of this investigation was to determine the effects of pre-exercise caffeine intake on training adaptations induced by a bench press training protocol. Using a double-blind, randomized experimental design, 16 healthy participants underwent a bench press training protocol for 4 weeks (12 sessions). Seven participants ingested a placebo and nine participants ingested 3 mg/kg/BM of caffeine before each training session. Three days before, and 3 days after the completion of the training protocol, participants performed a one-repetition maximum (1RM) bench press and force-velocity test (from 10 to 100% 1RM). From comparable pre-training values, the strength training similarly increased 1RM in the caffeine and placebo groups (+13.5 ± 7.8% vs. +11.3 ± 5.3%, respectively; p = 0.53). In the caffeine group, the strength training induced a higher mean velocity at 40%, (0.81 ± 0.08 vs. 0.90 ± 0.14 m/s), 60% (0.60 ± 0.06 vs. 0.65 ± 0.06 m/s), 70% (0.47 ± 0.05 vs. 0.55 ± 0.06 m/s), 80% (0.37 ± 0.06 vs. 0.45 ± 0.05 m/s), 90% (0.26 ± 0.07 vs. 0.34 ± 0.06 m/s), and 100% 1RM (0.14 ± 0.04 vs. 0.25 ± 0.05 m/s; p < 0.05) while the increases in the placebo group were evident only at 30 (0.95 ± 0.06 vs. 1.03 ± 0.07 m/s), 70% (0.51 ± 0.03 vs. 0.57 ± 0.05 m/s) and 80% 1RM (0.37 ± 0.06 vs. 0.45 ± 0.05 m/s) (p < 0.05). The placebo group only increased peak velocity at 60 and 70% 1RM (p < 0.05) while peak velocity increased at 10%, and from 30 to 100% 1RM in the caffeine group (p < 0.05). The use of 3 mg/kg/BM of caffeine before exercise did not modify improvements in 1RM obtained during a 4 week bench press strength training program but induced more muscle performance adaptations over a wider range of load.
MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3
Authors: Zhou Xinxin , He Jiayuan , Wang Qingyuan , Ma Teng
Published: January 2021

The functions of non-coding RNA, including microRNA (miRNA), have attracted considerable attention in the field of oncology, In this report, we examined the roles and molecular mechanisms of miR-128-3p, as related to the biological behaviors of malignant melanoma (MM). We found that miR-128-3p was expressed in low levels in these MM cells and may serve as a tumor suppressor by inhibiting proliferation, migration, and invasion, as well as inducing apoptosis in these MM cells. Moreover, neurotrophin receptor 3 (NTRK3), which serves as an oncogene that can enhance malignant behaviors of MM cells, was up-regulated in MM cells. Our current survey disclosed a complementary binding between miR-128-3p and the NTRK3 3′ untranslated regions (3′-UTR), while luciferase activities of NTRK3 3′-UTR were restrained by miR-128-3p in 293T cells. The effects of pre-miR-128-3p and sh-NTRK3 as well as anti-miR-128-3p and NTRK3(+) appeared to function synergistically in producing malignant progression. Moreover, there were possible to have counteracted effects for pre-miR-128-3p and NTRK3(+) in malignant progression. These findings established that miR-128-3p can function as a tumor suppressor by inhibiting carcinogenesis of the oncogene, NTRK3. Collectively, miR-128-3p and NTRK3 genes participate in modulating the malignant behavior of MM, and may represent new therapeutic targets for MM.
The Era of Radiogenomics in Precision Medicine: An Emerging Approach to Support Diagnosis, Treatment Decisions, and Prognostication in Oncology
Authors: Shui Lin , Ren Haoyu , Yang Xi , Li Jian , Chen Ziwei , Yi Cheng , Zhu Hong , Shui Pixian
Published: January 2021

With the rapid development of new technologies, including artificial intelligence and genome sequencing, radiogenomics has emerged as a state-of-the-art science in the field of individualized medicine. Radiogenomics combines a large volume of quantitative data extracted from medical images with individual genomic phenotypes and constructs a prediction model through deep learning to stratify patients, guide therapeutic strategies, and evaluate clinical outcomes. Recent studies of various types of tumors demonstrate the predictive value of radiogenomics. And some of the issues in the radiogenomic analysis and the solutions from prior works are presented. Although the workflow criteria and international agreed guidelines for statistical methods need to be confirmed, radiogenomics represents a repeatable and cost-effective approach for the detection of continuous changes and is a promising surrogate for invasive interventions. Therefore, radiogenomics could facilitate computer-aided diagnosis, treatment, and prediction of the prognosis in patients with tumors in the routine clinical setting. Here, we summarize the integrated process of radiogenomics and introduce the crucial strategies and statistical algorithms involved in current studies.
Basal Cell Carcinoma of the External Genitalia: A Population-Based Analysis
Authors: Chen Xi , Hou Yulong , Chen Can , Jiang Guan
Published: January 2021

Introduction

Basal cell carcinoma (BCC) located on the genitalia is rare; data on the clinicopathologic features and survival outcomes are only available through case reports and small case series studies.

Purpose

This study aimed to explore the epidemiology and identify the prognostic factors of genital BCCs.

Methods

We queried the 18 registries of the Surveillance, Epidemiology, and End Results database for patients with primary BCCs of the genital skin from 2000 through 2017. The primary endpoint was overall survival (OS) and disease specific survival (DSS). Kaplan-Meier survival analysis was conducted to assess the impact of clinicopathological variables on OS and DSS. Multivariate Cox proportional hazards model was performed to evaluate risk factors for OS.

Results

A total of 1,607 cases of genital BCCs were identified. The cohort was composed of 1,352 women (84.1%) and 255 men (15.9%). The median (P25, P75) age of the entire cohort was 73(63–82)years. White patients accounted for 87.2% of the cases. For women and men, the most common site of involvement was the labia majora (89.6%) and scrotum (74.5%), respectively. The majority of patients with genital BCC had localized disease (75.5%). Kaplan-Meier survival analysis showed that female genital BCCs experienced better DSS than men (209.1 months vs 194.8 months); for men, BCCs located on the scrotum had better DSS and OS than those on the penis (P < 0.05 for both endpoints). All patients with distant disease died of disease-specific death, and the average survival time was 8.2 months. Multivariate analysis revealed that age, primary site, and stage were independent determinants of OS for men, while tumor size, histologic subtype, and race were not. For women, factors associated with worse OS included increasing age, tumor size more than 2 cm, and distant disease; factors associated with a decreased risk included “other” and “unknown” races.

Conclusion

The prognosis of genital BCCs is excellent, while the survival of distant disease is very poor. Despite similar clinicopathologic features and overall survival outcomes, men and women should be treated as two different entities when making survival predictions.
Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis
Authors: Yen Elizabeth , Kaneko-Tarui Tomoko , Maron Jill L.
Published: January 2021

Non-invasive techniques to monitor and diagnose neonates, particularly those born prematurely, are a long-sought out goal of Newborn Medicine. In recent years, technical advances, combined with increased assay sensitivity, have permitted the high-throughput analysis of multiple biomarkers simultaneously from a single sample source. Multiplexed transcriptomic and proteomic platforms, along with more comprehensive assays such as RNASeq, allow for interrogation of ongoing physiology and pathology in unprecedented ways. In the fragile neonatal population, saliva is an ideal biofluid to assess clinical status serially and offers many advantages over more invasively obtained blood samples. Importantly, saliva samples are amenable to analysis on emerging proteomic and transcriptomic platforms, even at quantitatively limited volumes. However, biomarker targets are often degraded in human saliva, and as a mixed source biofluid containing both human and microbial targets, saliva presents unique challenges for the investigator. Here, we provide insight into technical considerations and protocol optimizations developed in our laboratory to quantify and discover neonatal salivary biomarkers with improved reproducibility and reliability. We will detail insights learned from years of experimentation on neonatal saliva within our laboratory ranging from salivary collection techniques to processing to downstream analyses, highlighting the need for consistency in approach and a global understanding of both the potential benefits and limitations of neonatal salivary biomarker analyses. Importantly, we will highlight the need for robust and stringent research in this population to provide the field with standardized approaches and workflows to impact neonatal care successfully.
Legal and Ethical Issues Regarding Minors in the Italian Coronavirus Flu Emergency
Authors: Fedeli Piergiorgio , Cannovo Nunzia , Scendoni Roberto , Cingolani Mariano
Published: January 2021

On February 21, 2020, Italy became one of the countries hit by an epidemic of the new coronavirus that causes “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). Even a month before that, however, the Italian government began issuing a series of decrees and ordinances aimed at the containment of the virus in Italy, the first of them on January 25, 2020. The COVID 19 infection has been faced as an epidemic through measures to enforce a high degree of isolation. These regulations hold for minors, as well, with consequent difficulties for this age group. While at the moment young people appear to be the least vulnerable to the severe complications of COVID 19, the psychological problems that may be brought on by pandemic-related restrictions should be taken into serious consideration.
Non-Coding RNAs as Biomarkers and Therapeutic Targets for Diabetic Kidney Disease
Authors: Gu Yue-Yu , Lu Fu-Hua , Huang Xiao-Ru , Zhang Lei , Mao Wei , Yu Xue-Qing , Liu Xu-Sheng , Lan Hui-Yao
Published: January 2021

Diabetic kidney disease (DKD) is the most common diabetic complication and is a leading cause of end-stage kidney disease. Increasing evidence shows that DKD is regulated not only by many classical signaling pathways but also by epigenetic mechanisms involving chromatin histone modifications, DNA methylation, and non-coding RNA (ncRNAs). In this review, we focus on our current understanding of the role and mechanisms of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the pathogenesis of DKD. Of them, the regulatory role of TGF-β/Smad3-dependent miRNAs and lncRNAs in DKD is highlighted. Importantly, miRNAs and lncRNAs as biomarkers and therapeutic targets for DKD are also described, and the perspective of ncRNAs as a novel therapeutic approach for combating diabetic nephropathy is also discussed.
The Potential use of Honey as a Remedy for Allergic Diseases: A Mini Review
Authors: Aw Yong Poi Yi , Islam Fahmida , Harith Hanis Hazeera , Israf Daud Ahmad , Tan Ji Wei , Tham Chau Ling
Published: January 2021

Honey has been conventionally consumed as food. However, its therapeutic properties have also gained much attention due to its application as a traditional medicine. Therapeutic properties of honey such as anti-microbial, anti-inflammatory, anti-cancer and wound healing have been widely reported. A number of interesting studies have reported the potential use of honey in the management of allergic diseases. Allergic diseases including anaphylaxis, asthma and atopic dermatitis (AD) are threatening around 20% of the world population. Although allergic reactions are somehow controllable with different drugs such as antihistamines, corticosteroids and mast cell stabilizers, modern dietary changes linked with allergic diseases have prompted studies to assess the preventive and therapeutic merits of dietary nutrients including honey. Many scientific evidences have shown that honey is able to relieve the pathological status and regulate the recruitment of inflammatory cells in cellular and animal models of allergic diseases. Clinically, a few studies demonstrated alleviation of allergic symptoms in patients after application or consumption of honey. Therefore, the objective of this mini review is to discuss the effectiveness of honey as a treatment or preventive approach for various allergic diseases. This mini review will provide insights into the potential use of honey in the management of allergic diseases in clinical settings.
Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of Clinical Trials
Authors: Sun Yanli , Han Jie , Wang Zhanzhao , Li Xuening , Sun Yanhua , Hu Zhenbo
Published: January 2021

Background: The upregulated expression of BET proteins is closely associated with the occurrence and development of hematological malignancies and solid tumors. Several BET inhibitors have been developed, and some have been in phase I/II of clinical trials. Here, the safety, efficacy, and pharmacodynamics of ten BET inhibitors currently in clinical trials were evaluated.

Methods: We retrieved and reviewed published reports on the clinical trials of twelve BET inhibitors including AZD5153, ABBV-075, BMS-986158, CPI-0610, GSK525762, OTX-015, PLX51107, INCB054329, INCB057643, FT-1101, CC-90010, and ODM-207 for patients with hematological malignancies and solid tumors and summarized their published target genes.

Results: In the monotherapy of BET inhibitors, the most common and severe (grade ≥3) hematological adverse events (AEs) are thrombocytopenia, anemia, and neutropenia. The most common non-hematological syndromes are diarrhea, nausea, fatigue, dysgeusia, and decreased appetite, while the most severe AE is pneumonia. Additionally, Tmax of these BET inhibitors was between 0.5–6 h, but the range for T1/2 varied significantly. According to published data, the rates of SD, PD, CR and PR were 27.4%, 37.6%, 3.5%, and 5.7%, respectively, which is not very satisfactory. In addition to BRD4, oncogene MYC is another common target gene of these BET inhibitors. Ninety-seven signaling pathways may be regulated by BET inhibitors.

Conclusion: All BET inhibitors reviewed in our study exhibited exposure-dependent thrombocytopenia, which may limit their clinical application. Moreover, further efforts are necessary to explore the optimal dosing schemes and combinations to maximize the efficacy of BET inhibitors.
Understanding Multilevel Selection May Facilitate Management of Arbuscular Mycorrhizae in Sustainable Agroecosystems
Authors: Johnson Nancy Collins , Gibson Kara Skye
Published: January 2021

Studies in natural ecosystems show that adaptation of arbuscular mycorrhizal (AM) fungi and other microbial plant symbionts to local environmental conditions can help ameliorate stress and optimize plant fitness. This local adaptation arises from the process of multilevel selection, which is the simultaneous selection of a hierarchy of groups. Studies of multilevel selection in natural ecosystems may inform the creation of sustainable agroecosystems through developing strategies to effectively manage crop microbiomes including AM symbioses. Field experiments show that the species composition of AM fungal communities varies across environmental gradients, and that the biomass of AM fungi and their benefits for plants generally diminish when fertilization and irrigation eliminate nutrient and water limitations. Furthermore, pathogen protection by mycorrhizas is only important in environments prone to plant damage due to pathogens. Consequently, certain agricultural practices may inadvertently select for less beneficial root symbioses because the conventional agricultural practices of fertilization, irrigation, and use of pesticides can make these symbioses superfluous for optimizing crop performance. The purpose of this paper is to examine how multilevel selection influences the flow of matter, energy, and genetic information through mycorrhizal microbiomes in natural and agricultural ecosystems, and propose testable hypotheses about how mycorrhizae may be actively managed to increase agricultural sustainability.
The Implications of Filial Piety in Study Engagement and Study Satisfaction: A Polish-Vietnamese Comparison
Authors: Różycka-Tran Joanna , Jurek Paweł , Truong Thi Khanh Ha , Olech Michał
Published: January 2021

Even in psychological literature, which describes many determining variables related to the school domain, few studies have investigated the universal (i.e., etic) mechanism underlying parent–child relations, which is a prototype matrix for future student–teacher relations. The role of the imprinted schema of children’s obligations toward parents seems to be crucial for school functioning in classroom society. The Dual Filial Piety Model (DFPM; Yeh, 2003) is comprised of two higher-order factors that correspond to the two focal filial piety attributes: reciprocal (need of interpersonal relatedness) and authoritarian (need of social belonging and national identity), which have been shown to have distinct implications on social adaptation and individuals’ psychological functioning. In this study, we investigate the relationship between filial piety and student attitudes (study engagement and satisfaction) in a more individualistic and egalitarian culture (Poland, N = 310) and in a more collectivistic and hierarchical society (Vietnam, N = 297). The measurement invariances of three scales, i.e., the Vietnamese adaptation of DFP Scale, the Utrecht Work Engagement Scale (UWES–S9), and the Study Satisfaction Scale, were improved in the MLM analyses. Our results show that in more individualistic cultures, the RFP (reciprocal mode) is a stronger predictor of study engagement and study satisfaction; however, the AFP (authoritarian mode) is a better factor to predict study engagement in more collectivistic cultures. What is more, only RFP positively correlates with study satisfaction in individualistic culture. Our findings revealed that in different cultures, different aspects of filial piety should be emphasized by parents in the context of the future academic achievements of their children. The conclusion is that the prevention and intervention strategies or techniques intended for children with school problems should be culturally appropriate and addressed to the parents of kindergarten and later to very early-stage education teachers. The results of studies based on the DFPM may stimulate practical applications and policy development within the domain of success and failure in the academic environment.
The Role of Literal Features During Processing of Novel Verbal Metaphors
Authors: Ronderos Camilo R. , Guerra Ernesto , Knoeferle Pia
Published: January 2021

When a word is used metaphorically (for example “walrus” in the sentence “The president is a walrus”), some features of that word's meaning (“very fat,” “slow-moving”) are carried across to the metaphoric interpretation while other features (“has large tusks,” “lives near the north pole”) are not. What happens to these features that relate only to the literal meaning during processing of novel metaphors? In four experiments, the present study examined the role of the feature of physical containment during processing of verbs of physical containment. That feature is used metaphorically to signify difficulty, such as “fenced in” in the sentence “the journalist's opinion was fenced in after the change in regime.” Results of a lexical decision task showed that video clips displaying a ball being trapped by a box facilitated comprehension of verbs of physical containment when the words were presented in isolation. However, when the verbs were embedded in sentences that rendered their interpretation metaphorical in a novel way, no such facilitation was found, as evidenced by two eye-tracking reading studies. We interpret this as suggesting that features that are critical for understanding the encoded meaning of verbs but are not part of the novel metaphoric interpretation are ignored during the construction of metaphorical meaning. Results and limitations of the paradigm are discussed in relation to previous findings in the literature both on metaphor comprehension and on the interaction between language comprehension and the visual world.
Early-Life Neglect Alters Emotional and Cognitive Behavior in a Sex-Dependent Manner and Reduces Glutamatergic Neuronal Excitability in the Prefrontal Cortex
Authors: Sun Xiuping , Zhang Yu , Li Xianglei , Liu Xinmin , Qin Chuan
Published: January 2021

Early-life neglect in critical developmental periods has been associated with emotional and cognitive consequences. Maternal separation (MS) has been commonly used as a rodent model to identify the developmental effects of child neglect. However, reports have shown considerable variability in behavioral results from MS studies in both mice and rats. Difficulties in developing reliable child neglect models have impeded advances in identifying the effects of early-life stress. Accumulating evidence shows that neuronal intrinsic excitability plays an important role in information processing and storage in the brain. The prefrontal cortex (PFC) integrates information from many cortical and subcortical structures. No studies to date have examined the impact of early-life stress on glutamatergic neuronal excitability in the PFC. This study aimed to develop a reliable child neglect rat model and observe glutamatergic neuronal excitability in the PFC. An MS with early weaning (MSEW) rat model was developed. Rats were separated from the dam for 4 h per day on postnatal days (PNDs) 2–5 and for 8 h per day on PNDs 6–16 and then weaned on PND 17. A battery of behavioral tests was used to assess anxiety-like behavior, coping behavior, working memory, spatial reference memory, and fear memory. The action potentials (APs) of glutamatergic neuronal membranes were recorded. MSEW resulted in anxiety-like behavior, a passive coping strategy and increased fear memory in male rats and decreased locomotor activity in both sexes. MSEW slightly impaired working memory during non-stressful situations in female rats but did not change spatial reference memory or associative learning under stressful circumstances in either sex. MSEW reduced the number of glutamatergic neuron APs in male rats. Our findings showed that MS with early weaning induced anxiety-like behavior in male rats. The reduced glutamatergic neuronal excitability may be associated with the emotional alteration induced by MSEW in male rats. In addition, MSEW induced adaptive modification, which depended on a non-stressful context.