bluuebunny/crossref_metadata_2025 huggingface dataset:
Divers as Citizen Scientists: Response Time, Accuracy and Precision of Water Temperature Measurement Using Dive Computers
Authors: Marlowe Celia , Hyder Kieran , Sayer Martin D. J. , Kaiser Jan
Published: March 2021

There is a lack of depth-resolved temperature data, especially in coastal areas, which are often commonly dived by SCUBA divers. Many case studies have demonstrated that citizen science can provide high quality data, although users require more confidence in the accuracy of these data. This study examined the response time, accuracy and precision of water temperature measurement in 28 dive computers plus three underwater cameras, from 12 models. A total of 239 temperature response times (τ) were collected from 29 devices over 11 chamber dives. Mean τ by device ranged from (17 ± 6) to (341 ± 69) s, with significant between-model differences found for τ across all models. Clear differences were found in τ by pressure sensor location and material, but not by size. Two models had comparable τ to designed-for-purpose aquatic temperature loggers. 337 mean data points were collected from equilibrated temperatures in hyperbaric chamber (n = 185) and sea (n = 152) dives, compared with baseline mean temperature from Castaway CTDs over the same time period. Mean bias, defined as mean device temperature minus baseline temperature, by model ranged from (0.0 ± 0.5) to (−1.4 ± 2.1) °C and by device from (0.0 ± 0.6) to (−3.4 ± 1.0) °C. Nine of the twelve models were found to have “good” accuracy (≤0.5 °C) overall. Irrespective of model, the overall mean bias of (−0.2 ± 1.1) °C is comparable with existing commonly used coastal temperature data sets, and within global ocean observing system accuracy requirements for in situ temperature. Our research shows that the quality of temperature data in dive computers could be improved, but, with collection of appropriate metadata to allow assessment of data quality, some models of dive computers have a role in future oceanographic monitoring.
Drivers of Marine Heatwaves in the Northwest Atlantic: The Role of Air–Sea Interaction During Onset and Decline
Authors: Schlegel Robert W. , Oliver Eric C. J. , Chen Ke
Published: March 2021

Marine heatwaves (MHWs) are increasing in duration and intensity at a global scale and are projected to continue to increase due to the anthropogenic warming of the climate. Because MHWs may have drastic impacts on fisheries and other marine goods and services, there is a growing interest in understanding the predictability and developing practical predictions of these events. A necessary step toward prediction is to develop a better understanding of the drivers and processes responsible for the development of MHWs. Prior research has shown that air–sea heat flux and ocean advection across sharp thermal gradients are common physical processes governing these anomalous events. In this study we apply various statistical analyses and employ the self-organizing map (SOM) technique to determine specifically which of the many candidate physical processes, informed by a theoretical mixed-layer heat budget, have the most pronounced effect on the onset and/or decline of MHWs on the Northwest Atlantic continental shelf. It was found that latent heat flux is the most common driver of the onset of MHWs. Mixed layer depth (MLD) also strongly modulates the onset of MHWs. During the decay of MHWs, atmospheric forcing does not explain the evolution of the MHWs well, suggesting that oceanic processes are important in the decay of MHWs. The SOM analysis revealed three primary synoptic scale patterns during MHWs: low-pressure cyclonic Autumn-Winter systems, high-pressure anti-cyclonic Spring-Summer blocking, and mild but long-lasting Summer blocking. Our results show that nearly half of past MHWs on the Northwest Atlantic shelf are initiated by positive heat flux anomaly into the ocean, but less than one fifth of MHWs decay due to this process, suggesting that oceanic processes, e.g., advection and mixing are the primary driver for the decay of most MHWs.
Hyperoxia and Lungs: What We Have Learned From Animal Models
Authors: Amarelle Luciano , Quintela Lucía , Hurtado Javier , Malacrida Leonel
Published: March 2021

Although oxygen (O2) is essential for aerobic life, it can also be an important source of cellular damage. Supra-physiological levels of O2 determine toxicity due to exacerbated reactive oxygen species (ROS) production, impairing the homeostatic balance of several cellular processes. Furthermore, injured cells activate inflammation cascades, amplifying the tissue damage. The lung is the first (but not the only) organ affected by this condition. Critically ill patients are often exposed to several insults, such as mechanical ventilation, infections, hypo-perfusion, systemic inflammation, and drug toxicity. In this scenario, it is not easy to dissect the effect of oxygen toxicity. Translational investigations with animal models are essential to explore injuring stimuli in controlled experimental conditions, and are milestones in understanding pathological mechanisms and developing therapeutic strategies. Animal models can resemble what happens in critical care or anesthesia patients under mechanical ventilation and hyperoxia, but are also critical to explore the effect of O2 on lung development and the role of hyperoxic damage on bronchopulmonary dysplasia. Here, we set out to review the hyperoxia effects on lung pathology, contributing to the field by describing and analyzing animal experimentation's main aspects and its implications on human lung diseases.
A Comparative Study for License Application Regulations on Proprietary Chinese Medicines in Hong Kong and Canada
Authors: Zhong Linda L. D. , Lam Wai Ching , Lu Fang , Tang Xu Dong , Lyu Aiping , Bian Zhaoxiang , Boon Heather
Published: March 2021

Ethnopharmacological Relevance: Chinese Medicine plays a symbolic role among traditional medicines. As Chinese Medicine products are widely used around the globe, regulations for Chinese Medicine products are often used as models for the efficient regulation of natural products that are safe, and high-quality.

Aim of the Study: We aimed to compare the regulatory registration requirements for Proprietary Chinese Medicines in Hong Kong and Canada.

Materials and Methods: We compared registration requirements for Proprietary Chinese Medicine in Hong Kong and Canada based on publicly available information provided by the respective Regulators. A marketed product, Zhizhu Kuanzhong Capsule (SFDA approval number Z20020003; NPN approval number 80104354), was used as a case study to demonstrate the similarities and differences of the requirements in both Hong Kong and Canada.

Results: There were similarities and differences between the two regulatory systems in terms of the quality, safety and efficacy requirements. Despite the superficial appearance of similar categories and groups/classes, Hong Kong requires significantly more primary test data compared to Canada's reliance on attestation to manufacturing according the standards outlined in approved reference pharmacopeias/texts.

Conclusion: Improved understand of the similarity and differences will enable applicants to plan appropriate strategies for gaining product approval. Exploring ways to harmonize the regulatory process has the potential to benefit manufacturers, regulators, and patients by increasing efficiency and decreasing costs.
A Psychometric Platform to Collect Somatosensory Sensations for Neuroprosthetic Use
Authors: Valle Giacomo , Iberite Francesco , Strauss Ivo , D'Anna Edoardo , Granata Giuseppe , Di Iorio Riccardo , Stieglitz Thomas , Raspopovic Stanisa , Petrini Francesco M. , Rossini Paolo M. , Micera Silvestro
Published: March 2021

Somatosensory neuroprostheses exploit invasive and non-invasive feedback technologies to restore sensorimotor functions lost to disease or trauma. These devices use electrical stimulation to communicate sensory information to the brain. A sensation characterization procedure is thus necessary to determine the appropriate stimulation parameters and to establish a clear personalized map of the sensations that can be restored. Several questionnaires have been described in the literature to collect the quality, type, location, and intensity of the evoked sensations, but there is still no standard psychometric platform. Here, we propose a new psychometric system containing previously validated questionnaires on evoked sensations, which can be applied to any kind of somatosensory neuroprosthesis. The platform collects stimulation parameters used to elicit sensations and records subjects' percepts in terms of sensation location, type, quality, perceptual threshold, and intensity. It further collects data using standardized assessment questionnaires and scales, performs measurements over time, and collects phantom limb pain syndrome data. The psychometric platform is user-friendly and provides clinicians with all the information needed to assess the sensory feedback. The psychometric platform was validated with three trans-radial amputees. The platform was used to assess intraneural sensory feedback provided through implanted peripheral nerve interfaces. The proposed platform could act as a new standardized assessment toolbox to homogenize the reporting of results obtained with different technologies in the field of somatosensory neuroprosthetics.
Impacts of Urbanization Undermine Nestedness of the Plant–Arbuscular Mycorrhizal Fungal Network
Authors: Lin Litao , Chen Yun , Xu Guorui , Zhang Yuxin , Zhang Shuang , Ma Keming
Published: March 2021

Cities are prone to ecological problems, yet the impacts of rapid global urbanization on the feedback between above- and belowground subsystems remain largely unknown. We sampled the roots of 8 common herbaceous plants within the Fifth Ring (urban areas) and in Jiufeng National Forest Park (rural areas) in Beijing (China) to assess the impacts of urbanization on the network of plant-arbuscular mycorrhizal (AM) fungal associations. Using Illumina MiSeq sequencing, 81 AM fungal OTUs were identified in 78 herb root samples. The Shannon, Simpson, and Pielou indices of root AM fungi in urban areas were significantly higher than those in rural areas. In this study, a significantly nested mycorrhizal association network was observed in rural areas (NODF = 64.68), whereas a non-nested pattern was observed in urban areas (NODF = 55.50). The competition index C-score (0.0769) of AM fungi in urban areas was slightly lower than that in rural areas (0.1431), and the species specialization (d’) of 8 host plants and fungal dissimilarity among 8 host plants in urban areas were significantly lower than those in rural areas. Convergent associations among hosts may be an important factor influencing this non-nested pattern of the plant-AM fungi network in urban areas. Generalists, rather than specialists, were enhanced during the establishment of mycorrhizal associations in urban areas. Our results suggest that reduced selectivity of host plants, and generalist promotion and specialist reduction of AM fungi during urbanization may contribute to the non-nested network of plant-AM fungal associations.
Fresh Crab Plays an Important Role as a Nutrient Reservoir for the Rapid Propagation of Vibrio vulnificus
Authors: Kim Suyeon , Chung Han Young , Kwon Joon-Gi , Choi Sang Ho , Lee Ju-Hoon
Published: March 2021

Vibrio vulnificusis a well-known opportunistic pathogen causing food-borne illnesses by ingestion of contaminated seafood. A new strain ofV. vulnificusFORC_016 was isolated from a patient’s blood sample in South Korea. The genome consists of two circular DNA chromosomes: chromosome I (3,234,424 bp with a G + C contents of 46.60% containing 2,889 ORFs, 106 tRNA genes, and 31 rRNA genes) and chromosome II (1,837,945 bp with a GC content of 47.00% containing 1,572 ORFs, 13 tRNA genes, and 3 rRNA genes). In addition, chromosome I has a super integron (SI) containing 209 ORFs, which is probably associated with various additional functions including antibiotic resistance and pathogenicity. Pan-genome analysis with otherV. vulnificusgenomes revealed that core genome regions contain most of the important virulence factors. However, accessory genome regions are located in the SI region and contain unique genes regarding cell wall biosynthesis and generation of host cell protecting capsule, suggesting possible resistance ability against environmental stresses. Comparative RNA-Seq analysis of samples between contact and no contact to the crab conditions showed that expressions of amino acid/peptide and carbohydrate transport and utilization genes were down-regulated, but expressions of cell division and growth-related genes were up-regulated, suggesting that the crab may be a nutrition reservoir for rapid propagation ofV. vulnificus. Therefore, consumption of the contaminated fresh crab would provide a large number ofV. vulnificusto humans, which may be more dangerous. Consequently, biocontrol ofV. vulnificusmay be critical to ensure the safety in seafood consumption.
Inonotus rickii (Agaricomycetes, Hymenochaetaceae) in Brazilian Cerrado: Expanding Its Geographic Distribution and Host List
Authors: Leonardo-Silva Lucas , Abdel-Azeem Ahmed M. , Xavier-Santos Solange
Published: March 2021

Inonotus rickii(Pat.) Reid (Agaricomycetes: Hymenochaetaceae) is a poroid fungus characterized by the expressive production of chlamydospores,in vivoandin vitro, especially during its anamorphic stage. The species plays important ecological roles, standing out as a phytopathogen, affecting several species of ornamental and wild trees, mainly in tropical and subtropical regions. The infected trees develop canker and white rot of the wood, showing symptoms of reduced vegetative vigor and decline of leaves and branches which causes death in some cases. The first record ofI. rickiifor the Cerrado biome (Brazilian Savanna) and the first record as causal agent of canker inSchinus molleL. in Brazil is reported here. In addition, we present a checklist of its worldwide geographical distribution and known hosts, from an extensive bibliographic search in Google Scholar, SciELO, Scopus, and Web of Science databases. The species is widespread in tropical and subtropical zones; common in the American continent, especially in Central and South America and the Mediterranean region, and rare in temperate zones. We found specimens growing in both living and dead hosts, totalizing 70 species of hosts, distributed in 43 genera and 22 families. Of these,Acer negundoL. (10.5%),Celtis australisL. (6.5%), andPlatanus acerifolia(Aiton) Willd. (4.8%), and the Fabaceae (30%), Fagaceae (10%), and Sapindaceae (8.6%) families were the most frequent. We present morphological descriptions and illustrations, as well as the growth characteristics in culture medium. Our study expands the known geographical distribution ofI. rickii, including the Cerrado biome, as well as its structural, physiological characteristics, and its hosts.
Optimized Detection of Acute MHV68 Infection With a Reporter System Identifies Large Peritoneal Macrophages as a Dominant Target of Primary Infection
Authors: Riggs Julianne B. , Medina Eva M. , Perrenoud Loni J. , Bonilla Diana L. , Clambey Eric T. , van Dyk Linda F. , Berg Leslie J.
Published: March 2021

Investigating the dynamics of virus-host interactions in vivo remains an important challenge, often limited by the ability to directly identify virally infected cells. Here, we utilize a beta-lactamase activated fluorescent substrate to identify primary targets of murine gammaherpesvirus 68 (MHV68) infection in the peritoneal cavity. By optimizing substrate and detection conditions, we were able to achieve multiparameter characterization of infected cells and the ensuing host response. MHV68 infection leads to a pronounced increase in immune cells, with CD8+ T cells increasing by 3 days, and total infiltrate peaking around 8 days post-infection. MHV68 infection results in near elimination of large peritoneal macrophages (LPMs) by 8 days post-infection, and a concordant increase in small peritoneal macrophages (SPMs) and monocytes. Infection is associated with prolonged changes to myeloid cells, with a distinct population of MHC IIhigh LPMs emerging by 14 days. Targets of MHV68 infection could be readily detected. Between 1 and 3 days post-infection, MHV68 infects ∼5–10% of peritoneal cells, with >75% being LPMs. By 8 days post-infection, the frequency of MHV68 infection is reduced at least 10-fold, with infection primarily in SPMs, with few infected dendritic cells and B cells. Importantly, limiting dilution analysis indicates that at 3 days post-infection, the majority of MHV68-infected cells harbor latent rather than lytic virus at frequencies consistent with those identified based on reporter gene expression. Our findings demonstrate the utility of the beta-lactamase MHV68 reporter system for high throughput single-cell analysis and identify dynamic changes during primary gammaherpesvirus infection.
Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort
Authors: Hayden Zsófia , Bóné Beáta , Orsi Gergely , Szots Monika , Nagy Ferenc , Csépány Tünde , Mezei Zsolt , Rajda Cecília , Simon Diána , Najbauer József , Illes Zsolt , Berki Timea
Published: March 2021

Background: In our previous single-center study of autoimmune encephalitis (AE) related autoantibody test results we found positivity in 60 patients out of 1,034 with suspected AE from 2012 through 2018 as part of a Hungarian nationwide program. In our current multicenter retrospective study, we analyzed the clinical characteristics and outcome of AE patients with positive neuronal cell surface autoantibody test results.

Methods: A standard online questionnaire was used to collect demographic and clinical characteristics, laboratory and imaging data, therapy and prognosis of 30 definitive AE patients in four major clinical centers of the region.

Results: In our study, 19 patients were positive for anti-NMDAR (63%), 6 patients (20%) for anti-LGI1, 3 patients for anti-GABABR (10%) and 3 patients for anti-Caspr2 (10%) autoantibodies. Most common prodromal symptoms were fever or flu-like symptoms (10/30, 33%). Main clinical features included psychiatric symptoms (83%), epileptic seizures (73%) and memory loss (50%). 19 patients (63%) presented with signs of central nervous system (CNS) inflammation, which occurred more frequently in elder individuals (p = 0.024), although no significant differences were observed in sex, tumor association, time to diagnosis, prognosis and immunotherapy compared to AE patients without CNS inflammatory markers. Anti-NMDAR encephalitis patients were in more severe condition at the disease onset (p = 0.028), although no significant correlation between mRS score, age, sex and immunotherapy was found. 27% of patients (n = 8) with associated tumors had worse outcome (p = 0.045) than patients without tumor. In most cases, immunotherapy led to clinical improvement of AE patients (80%) who achieved a good outcome (mRS ≤ 2; median follow-up 33 months).

Conclusion: Our study confirms previous publications describing characteristics of AE patients, however, differences were observed in anti-NMDAR encephalitis that showed no association with ovarian teratoma and occurred more frequently among young males. One-third of AE patients lacked signs of inflammation in both CSF and brain MRI, which emphasizes the importance of clinical symptoms and autoantibody testing in diagnostic workflow for early introduction of immunotherapy, which can lead to favorable outcome in AE patients.
N-Oleoylglycine and N-Oleoylalanine Do Not Modify Tolerance to Nociception, Hyperthermia, and Suppression of Activity Produced by Morphine
Authors: Rock Erin M. , Limebeer Cheryl L. , Sullivan Megan T. , DeVuono Marieka V. , Lichtman Aron H. , Di Marzo Vincenzo , Mechoulam Raphael , Parker Linda A.
Published: March 2021

The endogenous amide N-Oleoylglycine (OlGly) and its analog N-Oleoylalanine (OlAla), have been shown to interfere with the affective and somatic responses to acute naloxone-precipitated MWD in male rats. Here we evaluated the potential of a single dose (5 mg/kg, ip) which alleviates withdrawal of these endogenous fatty acid amides to modify tolerance to anti-nociception, hyperthermia, and suppression of locomotion produced by morphine in male Sprague-Dawley rats. Although rats did develop tolerance to the hypolocomotor and analgesic effects of morphine, they did not develop tolerance to the hyperthermic effects of this substance. Administration of neither OlGly nor OlAla interfered with the establishment of morphine tolerance, nor did they modify behavioral responses elicited by morphine on any trial. These results suggest that the effects of OlGly and OlAla on opiate dependence may be limited to naloxone-precipitated withdrawal effects.
Fish Protein Ingestion Induces Neural, but Not Muscular Adaptations, Following Resistance Training in Young Adults
Authors: Watanabe Kohei , Holobar Aleš , Uchida Kenji , Mita Yukiko
Published: March 2021

Purpose: Nutritional supplementation in conjunction with exercise is of interest for the prevention or improvement of declines in motor performances in older adults. An understanding of the effects on both young and older adults contributes to its effective application. We investigated the effect of fish protein ingestion with resistance training on neural and muscular adaptations in young adults using interventions and assessments that have already been tested in older adults.

Methods: Eighteen young adults underwent 8 weeks of isometric knee extension training. During the intervention, nine participants ingested 5 g of fish protein (n = 9, Alaska pollack protein, APP), and the other nine participants ingested casein as a control (n = 9, CAS) in addition to daily meals. Before, during, and after the intervention, the isometric knee extension force, lower extremity muscle mass, and motor unit firing pattern of knee extensor muscles were measured.

Results: Maximum voluntary contraction (MVC) was significantly increased in both APP and CAS groups from 0 weeks to 4, 6, and 8 weeks of intervention (p < 0.001), but there were no significant differences between the groups (p = 0.546–0.931). Muscle mass was not significantly changed during the intervention in either group (p = 0.250–0.698). Significant changes in motor unit firing rates (p = 0.02 and 0.029 for motor units recruited at 20–40% of MVC and at 40–60%) were observed following the intervention in the APP but not CAS (p = 0.120–0.751) group.

Conclusions: These results suggest that dietary fish protein ingestion changes motor unit adaptations following resistance training in young adults.
The Impact of Antarctic Ice Microalgae Polysaccharides on D-Galactose-Induced Oxidative Damage in Mice
Authors: Yi Ruokun , Deng Lei , Mu Jianfei , Li Chong , Tan Fang , Zhao Xin
Published: March 2021

Antarctic ice microalgae (Chlamydomonas sp.) are a polysaccharide-rich natural marine resource. In this study, we evaluated the impact of Antarctic ice microalgae polysaccharides (AIMP) on D-galactose-induced oxidation in mice. We conducted biological and biochemical tests on tissue and serum samples from mice treated with AIMP. We found that AIMP administration was associated with improved thymus, brain, heart, liver, spleen, and kidney index values. We also found that AIMP treatment inhibited the reduced aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase, glutathione peroxidase, and glutathione levels as well as the increased serum, splenic, and hepatic nitric oxide and malondialdehyde levels arising from oxidation in these animals. Pathological examination revealed that AIMP also inhibited D-galactose-induced oxidative damage to the spleen, liver, and skin of these animals. AIMP was additionally found to promote the upregulation of neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc-superoxide dismutase, manganese superoxide dismutase, catalase, heme oxygenase-1, nuclear factor erythroid 2-related factor 2, γ-glutamylcysteine synthetase, and NAD(P)H dehydrogenase [quinone] 1 as well as the downregulation of inducible nitric oxide synthase in these animals. High-performance liquid chromatography analysis revealed AIMP to be composed of five monosaccharides (mannitol, ribose, anhydrous glucose, xylose, and fucose). Together, these results suggest that AIMP can effectively inhibit oxidative damage more readily than vitamin C in mice with D-galactose-induced oxidative damage, which underscores the value of developing AIMP derivatives for food purposes.
HLC Pair Suppression as a Risk Factor for Bacterial Bloodstream Infections and Early Mortality in Newly Diagnosed Intact Immunoglobulin Multiple Myeloma Patients
Authors: Garcia de Veas Silva Jose Luis , Gonzalez Cejudo Maria Trinidad , Garcia Perojil Jimenez Alberto , Garcia Lopez Velez Maria del Señor , Garcia Rios Tamayo Rafael , Garcia Bermudo Guitarte Carmen , Garcia De Haro Muñoz Tomas
Published: March 2021

Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system’ attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a “real world” setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.
Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD
Authors: Miao Ti-wei , Du Long-yi , Xiao Wei , Mao Bing , Wang Yan , Fu Juan-juan
Published: March 2021

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD.

Method: RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature.

Results: Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and Staphylococcus aureus infection. A survival-associated gene signature consisting of CEACAM5, RASAL1, CSTL1, CNGB1, and SLC4A3 was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group (P < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram–predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort.

Conclusion: Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.
miR-4461 Regulates the Proliferation and Metastasis of Ovarian Cancer Cells and Cisplatin Resistance
Authors: Dou Lei , Zhang Yi
Published: March 2021

microRNAs (miRNAs) are of great significance in cancer treatment, which may have a desirable result on the regulation of tumorigenesis, progression, recurrence, and chemo-resistance of ovarian cancer. However, the research on the further potential application of miR-4461 in ovarian cancer is little and limited. Therefore, the study in this paper focus on the investigation of the of miR-4461 in ovarian cancer progression and chemo-resistance. The phenomenon that the proliferation and metastasis of ovarian cancer cells can be promoted by miR4461 is revealed in functional assays. Through the bioinformatics and luciferase reporter analysis, the PTEN is validated to be the direct target of miR-4461 in ovarian. The association between the expression of miR-4461 and PTEN is negative in in human ovarian cancer tissues. The distinction of growth and metastasis capacity between miR-4461 knockdown ovarian cancer cells and control cells is partially abolished by si-PTEN. Moreover, it was found that cisplatin treatment has obvious effect on the miR-4461 knockdown ovarian cancer cells. In summary, the data given in this paper indicate that the miR-4461 can be regarded as a potential onco-miRNA in ovarian cancer by targeting PTEN.
Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series
Authors: Alves Marclesson , Borges Daniela de Paula , Kimberly Aline , Martins Neto Francisco , Oliveira Ana Claudia , Sousa Juliana Cordeiro de , Nogueira Cleto D. , Carneiro Benedito A. , Tavora Fabio
Published: March 2021

Background

Glycogen Synthase Kinase-3 beta (GSK-3β) regulates diverse cell functions including metabolic activity, signaling and structural proteins. GSK-3β phosphorylates target pro-oncogenes and regulates programmed cell death-ligand 1 (PD-L1). This study investigated the correlation between GSK-3β expression and clinically relevant molecular features of lung adenocarcinoma (PDL1 score, PTEN expression and driver mutations).

Methods

We evaluated 95 lung cancer specimens from biopsies and surgical resections. Immunohistochemistry was performed to analyze the expression of GSK-3β, PTEN, and PDL1. Epidemiological data, molecular characteristics and staging were evaluated from medical records. The histologic classification was performed by an experienced pulmonary pathologist.

Results

Most patients were female (52.6%) and the majority had a positive smoking history. The median age was 68.3 years, with individuals over 60 years accounting for 82.1%. The predominant histological subtype was adenocarcinoma (69.5%), followed by squamous cell carcinoma (20.0%). GSK-3β expression in tumors was cytoplasmic with a dotted pattern and perinuclear concentration, with associated membranous staining. Seven (7.3%) tumors had associated nuclear expression localization. Seventy-seven patients (81.1%) had advanced clinical-stage tumors. GSK-3β was positive in 75 tumors (78%) and GSK3-positive tumors tended to be diagnosed at advanced stages. Among stage III/IV tumors, 84% showed GSK3 positivity (p= 0.007). We identified a statistically significant association between GSK-3β and PTEN in the qualitative analysis (p 0.021); and when comparing PTEN to GSK-3β intensity 2+ (p 0.001) or 3+ expression (> 50%) – p 0.013. GSK-3β positive tumors with a high histological score had a worse overall survival.

Conclusion

We identified the histological patterns of GSK-3β expression and evaluated its potential as marker for overall survival, establishing a simple histological score to measure the evaluated status in resected tissues. The use of GSK-3β expression as an immune response biomarker remains a challenge. Future studies will seek to explain the role of its interaction with PTEN.
Artificial Convolutional Neural Network in Object Detection and Semantic Segmentation for Medical Imaging Analysis
Authors: Yang Ruixin , Yu Yingyan
Published: March 2021

In the era of digital medicine, a vast number of medical images are produced every day. There is a great demand for intelligent equipment for adjuvant diagnosis to assist medical doctors with different disciplines. With the development of artificial intelligence, the algorithms of convolutional neural network (CNN) progressed rapidly. CNN and its extension algorithms play important roles on medical imaging classification, object detection, and semantic segmentation. While medical imaging classification has been widely reported, the object detection and semantic segmentation of imaging are rarely described. In this review article, we introduce the progression of object detection and semantic segmentation in medical imaging study. We also discuss how to accurately define the location and boundary of diseases.
Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients
Authors: Guo Jin-Cheng , Wei Qing-Shuang , Dong Lei , Fang Shuang-Sang , Li Feng , Zhao Yi
Published: March 2021

Background: Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed.

Methods: Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan–Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed.

Results: Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group (n = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank P < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis (n = 431, Log Rank P < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis.

Conclusions: We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.
Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats
Authors: Lv Linyan , Chang Yajie , Li Yanqing , Chen Haicheng , Yao Jiahui , Xie Yun , Liang Xiaoyan , Yang Xing , Zhang Min , Liu Guihua
Published: March 2021

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.
Role of PI3K in the Progression and Regression of Atherosclerosis
Authors: Zhao Yunyun , Qian Yongjiang , Sun Zhen , Shen Xinyi , Cai Yaoyao , Li Lihua , Wang Zhongqun
Published: March 2021

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.
Maize Ethylene Response Factor ZmERF061 Is Required for Resistance to Exserohilum turcicum
Authors: Zang Zhenyuan , Wang Zhen , Zhao Fuxing , Yang Wei , Ci Jiabin , Ren Xuejiao , Jiang Liangyu , Yang Weiguang
Published: March 2021

Plants have evolved a series of sophisticated defense mechanisms to help them from harm. Ethylene Response Factor (ERF) plays pivotal roles in plant immune reactions, however, its underlying mechanism in maize with a defensive function to Exserohilum turcicum (E. turcicum) remains poorly understood. Here, we isolated and characterized a novel ERF transcription factor, designated ZmERF061, from maize. Phylogenetic analysis revealed that ZmERF061 is a member of B3 group in the ERF family. qRT-PCR assays showed that the expression of ZmERF061 is significantly induced by E. turcicum inoculation and hormone treatments with salicylic acid (SA) and methyl jasmonate (MeJA). ZmERF061 was proved to function as a nucleus-localized transcription activator and specifically bind to the GCC-box element. zmerf061 mutant lines resulted in enhanced susceptibility to E. turcicum via decreasing the expression of ZmPR10.1 and ZmPR10.2 and the activity of antioxidant defense system. zmerf061 mutant lines increased the expression of the SA signaling-related gene ZmPR1a and decreased the expression of the jasmonic acid (JA) signaling-related gene ZmLox1 after infection with E. turcicum. In addition, ZmERF061 could interact with ZmMPK6-1. These results suggested that ZmERF061 plays an important role in response to E. turcicum and may be useful in genetic engineering breeding.
Cultivating Affective Resilience: Proof-of-Principle Evidence of Translational Benefits From a Novel Cognitive-Emotional Training Intervention
Authors: Dolcos Sanda , Hu Yifan , Williams Christian , Bogdan Paul C. , Hohl Kelly , Berenbaum Howard , Dolcos Florin
Published: March 2021

Available evidence highlights the importance of emotion regulation (ER) in psychological well-being. However, translation of the beneficial effects of ER from laboratory to real-life remains scarce. Here, we present proof-of-principle evidence from a novel cognitive-emotional training intervention targeting the development of ER skills aimed at increasing resilience against emotional distress. This pilot intervention involved training military veterans over 5–8 weeks in applying two effective ER strategies [Focused Attention (FA) and Cognitive Reappraisal (CR)] to scenarios presenting emotional conflicts (constructed with both external and internal cues). Training was preceded and followed by neuropsychological, personality, and clinical assessments, and resting-state functional MRI data were also collected from a subsample of the participants. Results show enhanced executive function and psychological well-being following training, reflected in increased working memory (WM), post-traumatic growth (PTG), and general self-efficacy (GSE). Brain imaging results showed evidence of diminished bottom-up influences from emotional and perceptual brain regions, along with evidence of normalized functional connectivity in the large-scale functional networks following training. The latter was reflected in increased connectivity among cognitive and emotion control regions and across regions of self-referential and control networks. Overall, our results provide proof-of-concept evidence that resilience and well-being can be learned through ER training, and that training-related improvements manifested in both behavioral change and neuroplasticity can translate into real-life benefits.
Digital Fabrication and Theater: Developing Social Skills in Young Adults With Autism Spectrum Disorder
Authors: Sandoval Poveda Alicia , Hernández Montoya Diana
Published: March 2021

An action research project was carried out, using theater workshops and basic digital fabrication technology workshops to improve social skills—such as the expression of emotions, communication, self-control, and teamwork—in a group of 10 young individuals with autism spectrum disorder (ASD). This article focuses on the digital fabrication workshops, where participants worked on the fundamentals of electronics and programming, as well as 3D design and printing, to make props that were later used on stage in the theatrical performances in which they participated. These workshops were systematized through observation guides. According to the results, it was evident that the participants not only enjoyed and gained technological knowledge, but that their social skill development needs were addressed. Professionals from the Special Education Faculty and the Fab Lab Kä Träre, both from Universidad Estatal a Distancia in Costa Rica, were in charge of the study during its first phase, executed in 2016 and 2017.
Development of Burnout Syndrome in Non-university Teachers: Influence of Demand and Resource Variables
Authors: Llorca-Pellicer Marta , Soto-Rubio Ana , Gil-Monte Pedro R.
Published: March 2021

Psychosocial risks at work are an important occupational problem since they can have an impact on workers' health, productivity, absenteeism, and company profits. Among their consequences, burnout stands out for its prevalence and associated consequences. This problem is particularly noteworthy in the case of teachers. The aim of the study was to analyze the influence of some psychosocial factors (demand and resource variables) and risks in burnout development, taking into consideration the levels of burnout according to the Spanish Burnout Inventory (SBI). This paper contributes to advancing knowledge on this issue by analyzing the influence of work characteristics and personal characteristics on the progress of burnout. The sample consisted of 8,235 non-university teachers (2,268 men 27.5% and 5,967 women 72.5%), aged 22 to 70 (M= 45.16,SD= 9.18). For this purpose, statistical modeling by logistic regression was used. The results of this study showed that No burnout level was positively related with resources variables and negatively with demand variables. In the Medium-High levels and the higher levels of burnout (i.e., Profile 1 and Profile 2), there is a positive relation with demand variables and a negative one with resource variables. In conclusion, demand variables cause an increase in the burnout levels, influencing positively the movements between the levels of No burnout to Medium-High levels of burnout and Medium-High levels to Profile 1. At the same time, resource variables had a negative influence on burnout. However, the results in the movement between Profile 1 and Profile 2 were not expected. The variable Imbalance had a negative relationship with the movement between Profile 1 to Profile 2, and Social support and Autonomy at work had a positive relationship with this movement. Therefore, when professionals feel higher levels of burnout, lack of imbalance together with social support and autonomy could contribute to increased feelings of guilt and risk of higher burnout.
The Use of Digitally Assessed Stress Levels to Model Change Processes in CBT - A Feasibility Study on Seven Case Examples
Authors: Hehlmann Miriam I. , Schwartz Brian , Lutz Teresa , Gómez Penedo Juan Martín , Rubel Julian A. , Lutz Wolfgang
Published: March 2021

In psychotherapy research, the measurement of treatment processes and outcome are predominantly based on self-reports. However, given new technological developments, other potential sources can be considered to improve measurements. In a feasibility study, we examined whether Ecological Momentary Assessments (EMA) using digital phenotyping (stress level) can be a valuable tool to investigate change processes during cognitive behavioral therapy (CBT). Seven outpatients undergoing psychological treatment were assessed using EMA. Continuous stress levels (heart rate variability) were assessed via fitness trackers (Garmin) every 3 min over a 2-week time period (6,720 measurements per patient). Time-varying change point autoregressive (TVCP-AR) models were employed to detect both gradual and abrupt changes in stress levels. Results for seven case examples indicate differential patterns of change processes in stress. More precisely, inertia of stress level changed gradually over time in one of the participants, whereas the other participants showed both gradual and abrupt changes. This feasibility study demonstrates that intensive longitudinal assessments enriched by digitally assessed stress levels have the potential to investigate intra- and interindividual differences in treatment change processes and their relations to treatment outcome. Further, implementation issues and implications for future research and developments using digital phenotyping are discussed.