bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Learning Strategies for Biodiversity Science
Authors: Chodkowski Nicole , O’Grady Patrick M. , Specht Chelsea D. , Zamudio Kelly R.
Published: April 2022

Organismal courses are inherently integrative, incorporating concepts from genetics, physiology, ecology and other disciplines linked through a comparative and phylogenetic framework. In a comprehensive organismal course, the organisms themselves are a lens through which students view and learn major concepts in evolutionary biology. Here, we present the learning goals of five core concepts (phylogenetics, biogeography, biodiversity, evo-devo, and key traits) we are using to transform organismal courses. We argue that by focusing on organismal knowledge and authentic examples, students learn foundational concepts and investigate biological hypotheses through the content that is unique to individual organismal groups. By using active learning strategies to teach core concepts, instructors can promote an inclusive classroom designed to engage students from diverse backgrounds and facilitate mastery and retention to test understanding of core biological concepts. This paper provides justification for why organismal biology needs to be kept as part of the biology curriculum, outlines the framework we are using to transform organismal courses, and provides examples of different ways instructors can incorporate active learning strategies and in-class activities in organismal courses in ways that enable their application to further investigation of both foundational and translational sciences for students.
Transmission Electron Microscopy Study on the Effect of Thermal and Electrical Stimuli on Ge2Te3 Based Memristor Devices
Authors: Shallcross Austin , Mahalingam Krishnamurthy , Shin Eunsung , Subramanyam Guru , Alam Md Shahanur , Taha Tarek , Ganguli Sabyasachi , Bowers Cynthia , Athey Benson , Hilton Albert , Roy Ajit , Dhall Rohan
Published: April 2022

Memristor devices fabricated using the chalcogenide Ge2Te3 phase change thin films in a metal-insulator-metal structure are characterized using thermal and electrical stimuli in this study. Once the thermal and electrical stimuli are applied, cross-sectional transmission electron microscopy (TEM) and X-ray energy-dispersive spectroscopy (XEDS) analyses are performed to determine structural and compositional changes in the devices. Electrical measurements on these devices showed a need for increasing compliance current between cycles to initiate switching from low resistance state (LRS) to high resistance state (HRS). The measured resistance in HRS also exhibited a steady decrease with increase in the compliance current. High resolution TEM studies on devices in HRS showed the presence of residual crystalline phase at the top-electrode/dielectric interface, which may explain the observed dependence on compliance current. XEDS study revealed diffusion related processes at dielectric-electrode interface characterized, by the separation of Ge2Te3 into Ge- and Te- enriched interfacial layers. This was also accompanied by spikes in O level at these regions. Furthermore, in-situ heating experiments on as-grown thin films revealed a deleterious effect of Ti adhesive layer, wherein the in-diffusion of Ti leads to further degradation of the dielectric layer. This experimental physics-based study shows that the large HRS/LRS ratio below the current compliance limit of 1 mA and the ability to control the HRS and LRS by varying the compliance current are attractive for memristor and neuromorphic computing applications.
Investigation and Application of Risk Factors of Macrosomia Based on 10,396 Chinese Pregnant Women
Authors: Yuan Xiaosong , Han Xiaoya , Jia Chenbo , Long Wei , Wang Huiyan , Yu Bin , Zhou Jun
Published: April 2022

Objective

The objective of this study was to examine the association of fetal macrosomia with maternal D-dimer and blood lipid levels, and explore whether D-dimer and blood lipids, either alone or in combination with traditional risk factors at hospital birth, could be used to predict subsequent delivery of macrosomia.

Methods

From April 2016 to March 2017, 10,396 women with singleton pregnancy giving birth at around 28–41 weeks of gestation were recruited into the present study. D-dimer and blood lipid levels were measured at hospital admission; and data on birth outcomes were obtained from hospital records.

Results

Multivariate logistic regression analysis showed that D-dimer, triglyceride and HDL-C levels were significantly associated with risk of macrosomia independent of traditional risk factors (for D-dimer: adjusted OR: 1.33, 95% CI, 1.23–1.43; for triglyceride: adjusted OR: 1.14, 95% CI, 1.05–1.23; for HDL-C: adjusted OR: 0.35, 95% CI, 0.24–0.51, all P <0.01). More importantly, incorporating D-dimer and blood lipids into the traditional model significantly increased the area under curve (AUC) for prediction of macrosomia (0.783 vs. 0.811; P <0.01).

Conclusion

Our study demonstrates that maternal D-dimer, triglyceride, and HDL-C levels before hospital birth could be significant and independent of risk factors of fetal macrosomia. Therefore, combining D-dimer and blood lipid levels with traditional risk factors might improve the ability to predict macrosomia in gestational diabetes mellitus and normal pregnancies.
Upper-Extremity Musculoskeletal Disorders and Their Associated Factors Among Diabetes Mellitus Patients Attending at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia: Cross-Sectional Study
Authors: Muluneh Assefa Gebeyehu , Adem Kedir Sany , Dawud Jemal Suleyman , Kibret Alemu Kassaw , Yitayal Melisew Mekie , Eriku Getachew Azeze
Published: April 2022

Background

Globally, diabetes mellitus (DM) is a major public health, causing functional disability among those affected. Among the common diabetes mellitus-related complications, musculoskeletal disorders had a significant negative impact on the social health quality of life and productivity of individuals. Evidence in this regard, however, is scarce in Ethiopia. Therefore, this study aimed at determining the prevalence of musculoskeletal disorders and identifying factors associated in people with diabetes in Felege Hiwot Comprehensive Specialized Hospital, northwest Ethiopia.

Methods

A cross-sectional study design was employed at Felege Hiwot Comprehensive Specialized Hospital from June 01 to August 30, 2020, among 413 participants. A systematic random sampling was employed to select the study participants. A structured, pretested questionnaire was used to collect data on socio-demographic, clinical, and lifestyle characteristics. Musculoskeletal disorders were assessed through clinical and physical examination. A logistic regression model was used to explore factors associated with musculoskeletal disorders.

Result

The prevalence of musculoskeletal disorders among diabetes mellitus patients was 24% (95% CI 20, 28.3). In logistic regression, factors such as being female, older age, occupation (farmer, merchant, and retired), and long duration of diabetes were significantly associated with musculoskeletal disorders.

Conclusion

Nearly one quarter of the study participants had musculoskeletal disorders. Special attention should be given for those individuals living with diabetes mellitus, particularly for those who are female, are older, and had a prolonged history of diabetes mellitus.
Application of the Material Balance Equation Based on the BET Multimolecular Fractal Theory in a Shale Gas Reservoir
Authors: Qiu Tingting , Hu Shuyong , Zhang Jiayi
Published: April 2022

During shale gas reservoir development, obtaining actual formation pressure is challenging; therefore, it is challenging to obtain a single well production allocation using the current formation pressure based on a productivity equation. Different shale gas reservoirs with different rock adsorption properties and the traditional Langmuir isotherm adsorption equations are not accurate in describing the adsorption properties of shale gas reservoirs, causing significant errors. BET multimolecular adsorption, considering the shale gas surface fractal dimension theory to describe the adsorption properties, can describe the adsorption surface as a multimolecular layer and regard adsorption using a fractal dimension, describing the adsorption property of shale gas more accurately. According to the core adsorption test data and theory, the actual BET multimolecular adsorption is established by considering the shale gas surface fractal dimension. Therefore, the actual material balance equation was obtained using the theory, establishing the relationship between the formation pressure and cumulative shale gas production. A time-independent distribution and cumulative gas production chart were formed using the productivity equation. Consequently, the material balance equation, which takes advantage of the BET multimolecular fractal theory, was conducted. This allocation production method obtained from the material balance equation has significant importance in shale gas development.
State-Space Modeling, Stability Analysis, and Controller Design of Grid-Forming Converters With Distributed Virtual Inertia
Authors: Deng Han , Fang Jingyang
Published: April 2022

The ever-increasing integration of power converter-coupled renewable energy sources reduces carbon footprints yet weakens power system inertia due to the retirement of synchronous generators. Inertia shortage makes modern power systems sensitive to frequency variations, thereby leading to undesirable load shedding, cascading failures, or even large-scale blackouts. To address the inertia concern, distributed virtual inertia from grid-tied power converters is emerging as an attractive solution. On top of that, there are upcoming standards of grid-tied power converters, such as PV inverters, that require grid formulation. As such, this paper proposes flexible distributed virtual inertia delivered by grid-forming converters without additional energy storage units. It is revealed that virtual inertia control may possibly cause stability problems. Through the derived state-space model and sensitivity analysis, the mechanism of instability is disclosed. Although droop control may stabilize converters, it inevitably necessitates extra energy storage, and is hence not cost-effective. Instead, a lead compensator, together with its design procedure, is proposed. Finally, simulation and experimental results validate the correctness and effectiveness of the proposed model and compensator. Moreover, the results demonstrate that the proposed grid-forming converters allow significant improvements in inertia and frequency regulation.
RETRACTED: Public Spending, Green Finance, and Zero Carbon for Sustainable Development: A Case of Top 10 Emitting Countries
Authors: Han Feng , Farooq Muhammad Umar , Nadeem Muhammad , Noor Malaika
Published: April 2022

In general, the public expenditure on schooling, science, and research and development (R&D) is thought to have a positive effect on the development and sustainability of an economy, but such evidence is lacking in the developing and developed countries, especially in the top 10 CO2-emitting countries. This study investigates the impact of public spending and green finance on environmental sustainability, using the ordinary least square method and data envelopment analysis, which uses the panel data from selected countries from 2008 to 2018. Results reveal a fluctuating green economic growth index, which was due to the non-serious existence of government policies. More precisely, a 1% increase in gross domestic product (GDP) growth increases the carbon emissions by about 0.40%, whereas the rise in coal consumption decreases environmental efficiency by about 0.88%. We also concluded that 0.95% GDP growth and economic development significantly enhance environmental emissions, whereas 0.5% of renewable energy consumption decreases the negative impact of environmental pollution. Furthermore, a 1% growth in renewable energy consumption improved environmental efficiency by 0.58%. Furthermore, the analysis demonstrates that the public expenditure on human capital and renewable energy (R&D) leads to a productive green economy through labor, and technically advance developmental practices, with varying consequences in distinctive countries.
Assessing the Potential Prognostic and Immunological Role of TK1 in Prostate Cancer
Authors: Xie Hui , Guo Linpei , Wang Zhun , Peng Shuanghe , Ma Qianwang , Yang Zhao , Shang Zhiqun , Niu Yuanjie
Published: April 2022

Background: It has been reported that thymidine kinase 1 (TK1) was up-regulated in multiple malignancies and participated in the regulation of tumor malignant behavior. However, its specific role in prostate cancer (PCa) remains unclear.

Methods: TK1 expression in PCa patients and cell lines was identified via crossover analysis of the public datasets. A series of in vitro experiments and in vivo models was applied to investigate the function of TK1 in PCa. Functional enrichment analyses were further conducted to explore the underlying mechanism. Additionally, TISIDB was applied to explore the correlation between TK1 expression and tumor-infiltrating lymphocytes, immune subtypes, and immune regulatory factors.

Results: TK1 expression was significantly up-regulated in PCa patients and cell lines. TK1 ablation inhibited tumor cell proliferation and migration potential, and in vivo experiments showed that TK1 inactivation can significantly restrain tumor growth. Functional enrichment analysis revealed TK1-related hub genes (AURKB, CCNB2, CDC20, CDCA5, CDK1, CENPA, CENPM, KIF2C, NDC80, NUF2, PLK1, SKA1, SPC25, ZWINT), and found that TK1 was closely involved in the regulation of cell cycle. Moreover, elevated mRNA expression of TK1 was related with higher Gleason score, higher clinical stage, higher pathological stage, higher lymph node stage, shorter overall survival, and DFS in PCa patients. Particularly, TK1 represented attenuated expression in C3 PCa and was related with infiltration of CD4+, CD8+ T cells, and dendritic cells as well as immunomodulator expression.

Conclusion: Our study indicates that TK1 is a prognostic predictor correlated with poor outcomes of PCa patients, and for the first time represented that TK1 can promote the progression of PCa. Therefore, TK1 may be a potential diagnostic and prognostic biomarker, as well as a therapeutic target for PCa.
An Ensemble-Based Deep Convolutional Neural Network for Computer-Aided Polyps Identification From Colonoscopy
Authors: Sharma Pallabi , Balabantaray Bunil Kumar , Bora Kangkana , Mallik Saurav , Kasugai Kunio , Zhao Zhongming
Published: April 2022

Colorectal cancer (CRC) is the third leading cause of cancer death globally. Early detection and removal of precancerous polyps can significantly reduce the chance of CRC patient death. Currently, the polyp detection rate mainly depends on the skill and expertise of gastroenterologists. Over time, unidentified polyps can develop into cancer. Machine learning has recently emerged as a powerful method in assisting clinical diagnosis. Several classification models have been proposed to identify polyps, but their performance has not been comparable to an expert endoscopist yet. Here, we propose a multiple classifier consultation strategy to create an effective and powerful classifier for polyp identification. This strategy benefits from recent findings that different classification models can better learn and extract various information within the image. Therefore, our Ensemble classifier can derive a more consequential decision than each individual classifier. The extracted combined information inherits the ResNet’s advantage of residual connection, while it also extracts objects when covered by occlusions through depth-wise separable convolution layer of the Xception model. Here, we applied our strategy to still frames extracted from a colonoscopy video. It outperformed other state-of-the-art techniques with a performance measure greater than 95% in each of the algorithm parameters. Our method will help researchers and gastroenterologists develop clinically applicable, computational-guided tools for colonoscopy screening. It may be extended to other clinical diagnoses that rely on image.
Novel GBS-Based SNP Markers for Finger Millet and Their Use in Genetic Diversity Analyses
Authors: Brhane Haftom , Haileselassie Teklehaimanot , Tesfaye Kassahun , Ortiz Rodomiro , Hammenhag Cecilia , Abreha Kibrom B. , Geleta Mulatu
Published: April 2022

Eleusine coracana (L.) Gaertn., commonly known as finger millet, is a multipurpose crop used for food and feed. Genomic tools are required for the characterization of crop gene pools and their genomics-led breeding. High-throughput sequencing-based characterization of finger millet germplasm representing diverse agro-ecologies was considered an effective method for determining its genetic diversity, thereby suggesting potential candidates for breeding. In this study, the genotyping-by-sequencing (GBS) method was used to simultaneously identify novel single nucleotide polymorphism (SNP) markers and genotype 288 finger millet accessions collected from Ethiopia and Zimbabwe. The accessions were characterized at individual and group levels using 5,226 bi-allelic SNPs, with a minimum allele frequency (MAF) of above 0.05, distributed across 2,500 scaffolds of the finger millet reference genome. The polymorphism information content (PIC) of the SNPs was 0.23 on average, and a quarter of them have PIC values over 0.32, making them highly informative. The grouping of the 288 accessions into seven populations based on geographic proximity and the potential for germplasm exchange revealed a narrow range of observed heterozygosity (Ho; 0.09–0.11) and expected heterozygosity (He) that ranged over twofold, from 0.11 to 0.26. Alleles unique to the different groups were also identified, which merit further investigation for their potential association with desirable traits. The analysis of molecular variance (AMOVA) revealed a highly significant genetic differentiation among groups of accessions classified based on the geographic region, country of origin, days to flowering, panicle type, and Al tolerance (p < 0.01). The high genetic differentiation between Ethiopian and Zimbabwean accessions was evident in the AMOVA, cluster, principal coordinate, and population structure analyses. The level of genetic diversity of finger millet accessions varies moderately among locations within Ethiopia, with accessions from the northern region having the lowest level. In the neighbor-joining cluster analysis, most of the improved cultivars included in this study were closely clustered, probably because they were developed using genetically less diverse germplasm and/or selected for similar traits, such as grain yield. The recombination of alleles via crossbreeding genetically distinct accessions from different regions of the two countries can potentially lead to the development of superior cultivars.
Anti-POSTN and Anti-TIMP1 Autoantibodies as Diagnostic Markers in Esophageal Squamous Cell Carcinoma
Authors: Xie Weihong , Sun Guiying , Zhu Jicun , Wang Huimin , Han Zhuo , Wang Peng
Published: April 2022

Esophageal cancer is one of the most commonly diagnosed malignant gastrointestinal tumors. The aim of the study was to explore the diagnostic values of anti-POSTN and anti-TIMP1 autoantibodies in esophageal squamous cell carcinoma (ESCC). Differentially expressed genes (DEGs) associated with esophageal cancer were screened out by the LIMMA method in the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the protein–protein interaction (PPI) based on highly DEGs. The candidate hub genes were the intersection genes calculated based on degree and Maximal Clique Centrality (MCC) algorithms via Cytoscape. A total of 370 participants including 185 ESCC patients and 185 matched normal controls were enrolled in enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of autoantibodies corresponding to POSTN and TIMP1 proteins. A total of 375 DEGs with high expression were obtained in esophageal cancer. A total of 20 hub genes were acquired using the cytoHubba plugin by degree and MCC algorithms. The expression levels of anti-POSTN and anti-TIMP1 autoantibodies were higher in the sera of ESCC patients (p < 0.05). Anti-POSTN autoantibody can diagnose ESCC patients with an AUC of 0.638 at the specificity of 90.27% and sensitivity of 27.57%, and anti-TIMP1 autoantibody can diagnose ESCC patients with an AUC of 0.585 at the specificity of 90.27% and sensitivity of 20.54% (p < 0.05). In addition, anti-POSTN and anti-TIMP1 autoantibodies can distinguish ESCC patients from normal controls in most clinical subgroups (p < 0.05). In conclusion, anti-POSTN and anti-TIMP1 autoantibodies may be considered the potential biomarkers in the clinical diagnosis of ESCC.
Comparative Transcriptome Analysis Revealed the Freezing Tolerance Signaling Events in Winter Rapeseed (Brassica rapa L.)
Authors: Wu Wangze , Yang Haobo , Xing Peng , Dong Yun , Shen Juan , Wu Guofan , Zheng Sheng , Da Lingling , He Jiangtao , Wu Yujun
Published: April 2022

Winter rapeseed (Brassica rapa L.) is an important oilseed crop in northwest China. Freezing stress severely limits its production and geographical distribution, and frequent extreme freezing events caused by climate change are increasing the chances of winter freeze-injury. However, the underlying mechanism of B. rapa response to freezing stress remains elusive. Here, B. rapa genome (v3.0) was used as a reference for the comparative transcriptomic analysis of Longyou 6 and Tianyou 2 (strong and weak cold tolerance, respectively) under different freezing stress. Before and after freezing stress, 5,982 and 11,630 unique differentially expressed genes (DEGs) between two cultivars were identified, respectively. After freezing stress, the GO terms in Tianyou 2 were mainly involved in “macromolecule biosynthetic process”, and those in Longyou 6 were involved in “response to stimulus” and “oxidoreductase activity”. Morphological and physiological results indicated that Longyou 6 retained a higher basal freezing resistance than Tinayou 2, and that cold acclimation could strengthen the basal freezing resistance. Freezing stress could activate the MAPK signal cascades, and the phosphorylation level of Longyou 6 showed a higher increase in response to freezing treatment than Tianyou 2. Based on our findings, it was speculated that the cell membrane of B. rapa perceives external signals under freezing stress, which are then transmitted to the nucleus through the cold-activated MAPK cascades and Ca2+-related protein kinase pathway, thus leading to activation of downstream target genes to enhance the freezing resistance of B. rapa.
Brain Epitranscriptomic Analysis Revealed Altered A-to-I RNA Editing in Septic Patients
Authors: Zhang Jing-Qian , Pan Jia-Qi , Wei Zhi-Yuan , Ren Chun-Yan , Ru Fu-Xia , Xia Shou-Yue , He Yu-Shan , Lin Kaisheng , Chen Jian-Huan
Published: April 2022

Recent studies suggest that RNA editing is associated with impaired brain function and neurological and psychiatric disorders. However, the role of A-to-I RNA editing during sepsis-associated encephalopathy (SAE) remains unclear. In this study, we analyzed adenosine-to-inosine (A-to-I) RNA editing in postmortem brain tissues from septic patients and controls. A total of 3024 high-confidence A-to-I RNA editing sites were identified. In sepsis, there were fewer A-to-I RNA editing genes and editing sites than in controls. Among all A-to-I RNA editing sites, 42 genes showed significantly differential RNA editing, with 23 downregulated and 19 upregulated in sepsis compared to controls. Notably, more than 50% of these genes were highly expressed in the brain and potentially related to neurological diseases. Notably, cis-regulatory analysis showed that the level of RNA editing in six differentially edited genes was significantly correlated with the gene expression, including HAUS augmin-like complex subunit 2 (HAUS2), protein phosphatase 3 catalytic subunit beta (PPP3CB), hook microtubule tethering protein 3 (HOOK3), CUB and Sushi multiple domains 1 (CSMD1), methyltransferase-like 7A (METTL7A), and kinesin light chain 2 (KLC2). Furthermore, enrichment analysis showed that fewer gene functions and KEGG pathways were enriched by edited genes in sepsis compared to controls. These results revealed alteration of A-to-I RNA editing in the human brain associated with sepsis, thus providing an important basis for understanding its role in neuropathology in SAE.
Allopregnanolone in Postpartum Depression
Authors: Pinna Graziano , Almeida Felipe B. , Davis John M.
Published: April 2022

Postpartum depression (PPD) is a debilitating psychiatric disorder characterized by a high worldwide prevalence and serious long-term negative outcomes for both mothers and children. The lack of a specific treatment and overreliance on pharmacotherapy with limited efficacy and delayed treatment response has constituted a complication in the management of PPD. Recently, the Food and Drug Administration (FDA) in the USA approved a synthetic formulation of the GABAergic neurosteroid allopregnanolone, administered intravenously (brexanolone) for the rapid, long-lasting and effective treatment of PPD. Hereinafter, we review findings on allopregnanolone biosynthesis and GABAA receptor plasticity in the pathophysiology of PPD. We also discuss evidence supporting the efficacy of brexanolone for the treatment of PPD, which opens a promising new horizon for neurosteroid-based therapeutics for mood disorders.
Development and Validation of a Radiomics Nomogram Using Computed Tomography for Differentiating Immune Checkpoint Inhibitor-Related Pneumonitis From Radiation Pneumonitis for Patients With Non-Small Cell Lung Cancer
Authors: Qiu Qingtao , Xing Ligang , Wang Yu , Feng Alei , Wen Qiang
Published: April 2022

Background

The combination of immunotherapy and chemoradiotherapy has become the standard therapeutic strategy for patients with unresected locally advance-stage non-small cell lung cancer (NSCLC) and induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) and radiation pneumonitis (RP). The aim of this study is to differentiate between CIP and RP by pretreatment CT radiomics and clinical or radiological parameters.

Methods

A total of 126 advance-stage NSCLC patients with pneumonitis were enrolled in this retrospective study and divided into the training dataset (n =88) and the validation dataset (n = 38). A total of 837 radiomics features were extracted from regions of interest based on the lung parenchyma window of CT images. A radiomics signature was constructed on the basis of the predictive features by the least absolute shrinkage and selection operator. A logistic regression was applied to develop a radiomics nomogram. Receiver operating characteristics curve and area under the curve (AUC) were applied to evaluate the performance of pneumonitis etiology identification.

Results

There was no significant difference between the training and the validation datasets for any clinicopathological parameters in this study. The radiomics signature, named Rad-score, consisting of 11 selected radiomics features, has potential ability to differentiate between CIP and RP with the empirical and α-binormal-based AUCs of 0.891 and 0.896. These results were verified in the validation dataset with AUC = 0.901 and 0.874, respectively. The clinical and radiological parameters of bilateral changes (p < 0.001) and sharp border (p = 0.001) were associated with the identification of CIP and RP. The nomogram model showed good performance on discrimination in the training dataset (AUC = 0.953 and 0.950) and in the validation dataset (AUC = 0.947 and 0.936).

Conclusions

CT-based radiomics features have potential values for differentiating between patients with CIP and patients with RP. The addition of bilateral changes and sharp border produced superior model performance on classifying, which could be a useful method to improve related clinical decision-making.
Role of Programmed Cell Death Protein-1 and Lymphocyte Specific Protein Tyrosine Kinase in the Aryl Hydrocarbon Receptor- Mediated Impairment of the IgM Response in Human CD5+ Innate-Like B Cells
Authors: Zhou Jiajun , Blevins Lance K. , Crawford Robert B. , Kaminski Norbert E.
Published: April 2022

Innate-like B cells (ILBs) are a heterogeneous population B cells which participate in innate and adaptive immune responses. This diverse subset of B cells is characterized by the expression of CD5 and has been shown to secrete high levels of immunoglobulin M (IgM) in the absence of infection or vaccination. Further, CD5+ILBs have been shown to express high basal levels of lymphocyte specific protein tyrosine kinase (LCK) and programmed cell death protein-1 (PD-1), which are particularly sensitive to stimulation by interferon gamma (IFNγ). Previous studies have demonstrated that activation of the aryl hydrocarbon receptor (AHR), a cytosolic ligand-activated transcription factor, results in suppressed IgM responses and is dependent on LCK. A recent study showed that CD5+ILBs are particularly sensitive to AHR activation as evidenced by a significant suppression of the IgM response compared to CD5-B cells, which were refractory. Therefore, the objective of this study was to further investigate the role of LCK and PD-1 signaling in AHR-mediated suppression of CD5+ILBs. In addition, studies were conducted to establish whether IFNγ alters the levels of LCK and PD-1 in CD5+ILBs. We found that AHR activation led to a significant upregulation of total LCK and PD-1 proteins in CD5+ILBs, which correlated with suppression of IgM. Interestingly, treatment with recombinant IFNγ reduced LCK protein levels and reversed AHR-mediated IgM suppression in CD5+ILBs in a similar manner as LCK inhibitors. Collectively, these results support a critical role for LCK and PD-1 in AHR-mediated suppression of the IgM response in human CD5+ILBs.
Global-Scale Environmental Niche and Habitat of Blue Shark (Prionace glauca) by Size and Sex: A Pivotal Step to Improving Stock Management
Authors: Druon Jean-Noël , Campana Steven , Vandeperre Frederic , Hazin Fábio H. V. , Bowlby Heather , Coelho Rui , Queiroz Nuno , Serena Fabrizio , Abascal Francisco , Damalas Dimitrios , Musyl Michael , Lopez Jon , Block Barbara , Afonso Pedro , Dewar Heidi , Sabarros Philippe S. , Finucci Brittany , Zanzi Antonella , Bach Pascal , Senina Inna , Garibaldi Fulvio , Sims David W. , Navarro Joan , Cermeño Pablo , Leone Agostino , Diez Guzmán , Zapiain María Teresa Carreón , Deflorio Michele , Romanov Evgeny V. , Jung Armelle , Lapinski Matthieu , Francis Malcolm P. , Hazin Humberto , Travassos Paulo
Published: April 2022

Blue shark (Prionace glauca) is amongst the most abundant shark species in international trade, however this highly migratory species has little effective management and the need for spatio-temporal strategies increases, possibly involving the most vulnerable stage or sex classes. We combined 265,595 blue shark observations (capture or satellite tag) with environmental data to present the first global-scale analysis of species’ habitat preferences for five size and sex classes (small juveniles, large juvenile males and females, adult males and females). We leveraged the understanding of blue shark biotic environmental associations to develop two indicators of foraging location: productivity fronts in mesotrophic areas and mesopelagic micronekton in oligotrophic environments. Temperature (at surface and mixed layer depth plus 100 m) and sea surface height anomaly were used to exclude unsuitable abiotic environments. To capture the horizontal and vertical extent of thermal habitat for the blue shark, we defined the temperature niche relative to both sea surface temperature (SST) and the temperature 100 m below the mixed layer depth (Tmld+100). We show that the lifetime foraging niche incorporates highly diverse biotic and abiotic conditions: the blue shark tends to shift from mesotrophic and temperate surface waters during juvenile stages to more oligotrophic and warm surface waters for adults. However, low productivity limits all classes of blue shark habitat in the tropical western North Atlantic, and both low productivity and warm temperatures limit habitat in most of the equatorial Indian Ocean (except for the adult males) and tropical eastern Pacific. Large females tend to have greater habitat overlap with small juveniles than large males, more defined by temperature than productivity preferences. In particular, large juvenile females tend to extend their range into higher latitudes than large males, likely due to greater tolerance to relatively cold waters. Large juvenile and adult females also seem to avoid areas with intermediate SST (~21.7-24.0°C), resulting in separation from large males mostly in the tropical and temperate latitudes in the cold and warm seasons, respectively. The habitat requirements of sensitive size- and sex-specific stages to blue shark population dynamics are essential in management to improve conservation of this near-threatened species.
Predicting Foraging Habitat of European Shags - A Multi-Year and Multi-Colony Tracking Approach to Identify Important Areas for Marine Conservation
Authors: Dehnhard Nina , Mattisson Jenny , Tarroux Arnaud , Anker-Nilssen Tycho , Lorentsen Svein-Håkon , Christensen-Dalsgaard Signe
Published: April 2022

Human activity in the coastal zone is increasing worldwide, putting a number of seabird species under pressure. Norway is no exception to this development, and with > 35% of the NE Atlantic population of the currently declining European shag (Gulosus aristotelis) population, Norway has an international responsibility for the conservation of this species, and its important foraging habitats during breeding. We analysed tracking data from shags breeding in five colonies along the Norwegian coast spread over a latitudinal gradient of > 1700 km. We identified foraging locations and associated environmental characteristics. Using model cross-validation, we assessed the transferability of habitat models, both spatially (across colonies) and temporally (within colonies and across years), based on three modelling approaches: Training datasets consisted either of the data from one year at one colony, all years at one colony, or all years from all colonies except the testing colony. Across colonies, foraging activity was associated with shallow depths, proximity to colony, and the presence of kelp forests, while sea surface temperature and sea surface height contributed little to model fit. Transferability of habitat use across colonies was low when based on the training data from only one year and one colony and improved little when using several years of data from one colony for training the models. Transferability was very high for all colonies if the training dataset consisted of data from all years and all colonies except the one to be predicted. Our results highlight the importance of multi-year and multi-colony studies and show that it is possible to make sound fine-scale predictions of important foraging areas for breeding shags without the need to track birds in every colony. This facilitates much needed management of coastal marine ecosystems and the protection of the most important feeding areas for breeding shags.
Interferon Regulatory Factors Functioned as Activators of the Interferon Pathway in the Scallop Chlamys farreri
Authors: Hu Naina , Lian Shanshan , Zhu Xiaomei , Chen Xiaomei , Sun Fengzhi , Zhang Lingling , Wang Shi , Bao Zhenmin , Hu Jingjie
Published: April 2022

Interferon regulatory factors (IRFs) are a family of transcription factors that control many facets during innate and adaptive immune responses. Vertebrate IRFs play important roles in regulating the expression of interferons (IFNs) and IFN-stimulated genes, while only limited studies were conducted on invertebrate IRFs. In the present study, four IRF family genes (CfIRF1, CfIRF1-like, CfIRF2, and CfIRF8) were identified from Zhikong scallop (Chlamys farreri) through whole-genome scanning. CfIRFs contain a highly conserved N-terminal DNA-binding domain and a variable C-terminal regulatory domain. CfIRFs were constitutively expressed during development as well as in adult tissues, especially in hepatopancreas, hemolymph, gill, and mantle. In hemolymph, qRT-PCR analysis revealed that CfIRF1, CfIRF1-like, and CfIRF2 were significantly upregulated in response to Vibrio anguillarum infection, and their encoding proteins could translocate into nucleus. Dual-luciferase reporter assay on CfIRF1, CfIRF1-like, and CfIRF2 showed that these three proteins were capable to induce a strong activation of ISRE promoters. Notably, in comparison with CfIRF1 and CfIRF1-like, CfIRF2 showed the most sensitive responses in coping with V. anguillarum, and consistently, CfIRF2 exhibited the most significant activation on ISRE. This study would provide valuable information for the innate immune roles of the IRF gene family in bivalve molluscs.
Local Ion Densities can Influence Transition Paths of Molecular Binding
Authors: Roussey Nicole M. , Dickson Alex
Published: April 2022

Improper reaction coordinates can pose significant problems for path-based binding free energy calculations. Particularly, omission of long timescale motions can lead to over-estimation of the energetic barriers between the bound and unbound states. Many methods exist to construct the optimal reaction coordinate using a pre-defined basis set of features. Although simulations are typically conducted in explicit solvent, the solvent atoms are often excluded by these feature sets—resulting in little being known about their role in reaction coordinates, and ultimately, their role in determining (un)binding rates and free energies. In this work, analysis is done on an extensive set of host-guest unbinding trajectories, working to characterize differences between high and low probability unbinding trajectories with a focus on solvent-based features, including host-ion interactions, guest-ion interactions and location-dependent ion densities. We find that differences in ion densities as well as guest-ion interactions strongly correlate with differences in the probabilities of reactive paths that are used to determine free energies of (un)binding and play a significant role in the unbinding process.
The Role of Extracellular Matrix Remodeling in Skin Tumor Progression and Therapeutic Resistance
Authors: Fromme Julia E. , Zigrino Paola
Published: April 2022

The extracellular matrix remodeling in the skin results from a delicate balance of synthesis and degradation of matrix components, ensuring tissue homeostasis. These processes are altered during tumor invasion and growth, generating a microenvironment that supports growth, invasion, and metastasis. Apart from the cellular component, the tumor microenvironment is rich in extracellular matrix components and bound factors that provide structure and signals to the tumor and stromal cells. The continuous remodeling in the tissue compartment sustains the developing tumor during the various phases providing matrices and proteolytic enzymes. These are produced by cancer cells and stromal fibroblasts. In addition to fostering tumor growth, the expression of specific extracellular matrix proteins and proteinases supports tumor invasion after the initial therapeutic response. Lately, the expression and structural modification of matrices were also associated with therapeutic resistance. This review will focus on the significant alterations in the extracellular matrix components and the function of metalloproteinases that influence skin cancer progression and support the acquisition of therapeutic resistance.
Deep Learning-Based Multilevel Classification of Alzheimer’s Disease Using Non-invasive Functional Near-Infrared Spectroscopy
Authors: Ho Thi Kieu Khanh , Kim Minhee , Jeon Younghun , Kim Byeong C. , Kim Jae Gwan , Lee Kun Ho , Song Jong-In , Gwak Jeonghwan
Published: April 2022

The timely diagnosis of Alzheimer’s disease (AD) and its prodromal stages is critically important for the patients, who manifest different neurodegenerative severity and progression risks, to take intervention and early symptomatic treatments before the brain damage is shaped. As one of the promising techniques, functional near-infrared spectroscopy (fNIRS) has been widely employed to support early-stage AD diagnosis. This study aims to validate the capability of fNIRS coupled with Deep Learning (DL) models for AD multi-class classification. First, a comprehensive experimental design, including the resting, cognitive, memory, and verbal tasks was conducted. Second, to precisely evaluate the AD progression, we thoroughly examined the change of hemodynamic responses measured in the prefrontal cortex among four subject groups and among genders. Then, we adopted a set of DL architectures on an extremely imbalanced fNIRS dataset. The results indicated that the statistical difference between subject groups did exist during memory and verbal tasks. This presented the correlation of the level of hemoglobin activation and the degree of AD severity. There was also a gender effect on the hemoglobin changes due to the functional stimulation in our study. Moreover, we demonstrated the potential of distinguished DL models, which boosted the multi-class classification performance. The highest accuracy was achieved by Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) using the original dataset of three hemoglobin types (0.909 ± 0.012 on average). Compared to conventional machine learning algorithms, DL models produced a better classification performance. These findings demonstrated the capability of DL frameworks on the imbalanced class distribution analysis and validated the great potential of fNIRS-based approaches to be further contributed to the development of AD diagnosis systems.
Alzheimer's Disease Diagnosis With Brain Structural MRI Using Multiview-Slice Attention and 3D Convolution Neural Network
Authors: Chen Lin , Qiao Hezhe , Zhu Fan
Published: April 2022

Numerous artificial intelligence (AI) based approaches have been proposed for automatic Alzheimer's disease (AD) prediction with brain structural magnetic resonance imaging (sMRI). Previous studies extract features from the whole brain or individual slices separately, ignoring the properties of multi-view slices and feature complementarity. For this reason, we present a novel AD diagnosis model based on the multiview-slice attention and 3D convolution neural network (3D-CNN). Specifically, we begin by extracting the local slice-level characteristic in various dimensions using multiple sub-networks. Then we proposed a slice-level attention mechanism to emphasize specific 2D-slices to exclude the redundancy features. After that, a 3D-CNN was employed to capture the global subject-level structural changes. Finally, all these 2D and 3D features were fused to obtain more discriminative representations. We conduct the experiments on 1,451 subjects from ADNI-1 and ADNI-2 datasets. Experimental results showed the superiority of our model over the state-of-the-art approaches regarding dementia classification. Specifically, our model achieves accuracy values of 91.1 and 80.1% on ADNI-1 for AD diagnosis and mild cognitive impairment (MCI) convention prediction, respectively.
Decreased Vessel Density in Retinal Capillary Plexus and Thinner Ganglion Cell Complex Associated With Cognitive Impairment
Authors: Yang Kai , Cui Lele , Chen Xueyu , Yang Chuang , Zheng Jingwei , Zhu Xiaoxuan , Xiao Yunfan , Su Binbin , Li Chunmei , Shi Keai , Lu Fan , Qu Jia , Li Ming
Published: April 2022

Background

To determine the association of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with cognitive impairment using optical coherence tomography angiography (OCTA).

Methods

A cross-sectional, community-based study utilizing data from the participants enrolled between August 2019 and January 2020 in the Jidong Eye Cohort Study. We assessed the vessel density in RCP and GCC thickness using OCTA, and cognitive testing using the Montreal Cognitive Assessment (MoCA). Cognitive impairment in this study was defined as MoCA score < 24. We used multivariable analysis to evaluate the association of RCP and GCC with cognitive impairment after adjusting for confounders.

Results

This study analyzed 1555 participants. The mean age of participants was 52.3 (8.4) years, and 861 (55.4%) were women. Cognitive impairment was observed in 268 (17.2%) participants. The adjusted odds ratio (OR) with 95% confidence interval (95% CI) for parafovea vessel density in the deep RCP with cognitive impairment was 1.20 (1.03–1.39). For vessel area and length density surrounding foveal avascular zone with cognitive impairment, the ORs with 95% CIs were 1.23 (1.07–1.41) and 1.30 (1.13–1.49), respectively. For thickness in the superior GCC with cognitive impairment, the OR with 95% CI was 1.16 (1.01–1.32).

Conclusion

Lower vessel density in the RCP and thinner GCC were associated with cognitive impairment. Our results suggest that alterations in the RCP and GCC could provide further evidence when assessing the cognitive function and may even be potentially useful biomarkers in the detection of cognitive impairment.
The Nature of Noradrenergic Volume Transmission From Locus Coeruleus to Brainstem Mesencephalic Trigeminal Sensory Neurons
Authors: Toyoda Hiroki , Won Jonghwa , Kim Wheedong , Kim Hayun , Davy Oscar , Saito Mitsuru , Kim Doyun , Tanaka Takuma , Kang Youngnam , Oh Seog Bae
Published: April 2022

Noradrenergic neurons in the locus coeruleus (LC) release noradrenaline (NA) that acts via volume transmission to activate extrasynaptic G-protein coupled receptors (GPCRs) in target cells throughout the brain. As the closest projection, the dorsal LC laterally adjoins the mesencephalic trigeminal nucleus (MTN), in which proprioceptive primary sensory neurons innervating muscle spindles of jaw-closing muscles are exceptionally located. MTN neurons express α2-adrenergic receptors (α2-ARs) and display hyperpolarization-activated cyclic nucleotide-gated (HCN) currents (Ihs), which is downregulated by α2-AR activation. To quantify the activity-dependent outcome of volume transmission of NA from LC to MTN, we investigated how direct LC activation inhibits Ih in MTN neurons by performing dual whole-cell recordings from LC and MTN neurons. Repetition of 20 Hz spike-train evoked with 1-s current-pulse in LC neurons every 30 s resulted in a gradual decrease in Ih evoked every 30 s, revealing a Hill-type relationship between the number of spike-trains in LC neurons and the degree of Ih inhibition in MTN neurons. On the other hand, when microstimulation was applied in LC every 30 s, an LC neuron repeatedly displayed a transient higher-frequency firing followed by a tonic firing at 5–10 Hz for 30 s. This subsequently caused a similar Hill-type inhibition of Ih in the simultaneously recorded MTN neuron, but with a smaller Hill coefficient, suggesting a lower signal transduction efficacy. In contrast, 20 Hz activity induced by a 1-s pulse applied every 5–10 s caused only a transient facilitation of Ih inhibition followed by a forced termination of Ih inhibition. Thus, the three modes of LC activities modulated the volume transmission to activate α2-adrenergic GPCR to differentially inhibit Ih in MTN neurons.