bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?
Authors: D'Addabbo Pietro , Frezza Domenico , Sulentic Courtney E.W.
Published: February 2023

One gene, the immunoglobulin heavy chain (IgH) gene, is responsible for the expression of all the different antibody isotypes. Transcriptional regulation of the IgH gene is complex and involves several regulatory elements including a large element at the 3’ end of the IgH gene locus (3’RR). Animal models have demonstrated an essential role of the 3’RR in the ability of B cells to express high affinity antibodies and to express different antibody classes. Additionally, environmental chemicals such as aryl hydrocarbon receptor (AhR) ligands modulate mouse 3’RR activity that mirrors the effects of these chemicals on antibody production and immunocompetence in mouse models. Although first discovered as a mediator of the toxicity induced by the high affinity ligand 2,3,7,8-tetracholordibenzo-p-dioxin (dioxin), understanding of the AhR has expanded to a physiological role in preserving homeostasis and maintaining immunocompetence. We posit that the AhR also plays a role in human antibody production and that the 3’RR is not only an IgH regulatory node but also an environmental sensor receiving signals through intrinsic and extrinsic pathways, including the AhR. This review will 1) highlight the emerging role of the AhR as a key transducer between environmental signals and altered immune function; 2) examine the current state of knowledge regarding IgH gene regulation and the role of the AhR in modulation of Ig production; 3) describe the evolution of the IgH gene that resulted in species and population differences; and 4) explore the evidence supporting the environmental sensing capacity of the 3’RR and the AhR as a transducer of these cues. This review will also underscore the need for studies focused on human models due to the premise that understanding genetic differences in the human population and the signaling pathways that converge at the 3’RR will provide valuable insight into individual sensitivities to environmental factors and antibody-mediated disease conditions, including emerging infections such as SARS-CoV-2.
Effect of DIN and DON sources on the nitrogen uptake of the seagrass Zostera japonica and the macroalgae Ulva pertusa previously grown in different light levels
Authors: Han Qiuying , Qiu Chongyu , Zeng Wenxuan , Chen Yu , Zhao Muqiu , Shi Yunfeng , Zheng Fengying
Published: February 2023

This study quantified the absorption ability of the seagrass Zostera japonica and the macroalgae Ulva pertusa for dissolved inorganic nitrogen (DIN) (ammonium and nitrate) and dissolved organic nitrogen (DON) (urea and glycine) under different light conditions. The plants were cultured in filtered seawater (31‰, 25°C) for 2 weeks under three light levels. Macroalgae and the above- and belowground parts of seagrasses were separately placed into four different manmade seawater solutions with DIN (ammonium and nitrate) and DON (urea and glycine) stable isotopes for 1 h. The results showed that macroalgae had higher absorption rates for ammonium and nitrate after higher light (14.67 ± 2.50 and 1.29 ± 0.16 mg−1 dry weight (DW) h−1) than after lower light (4.52 ± 0.95 and 0.18 ± 0.12 mg−1 DW h−1) treatments. Compared to the belowground seagrass portions that had previously been grown in high and low light conditions, the seagrass leaves assimilated ammonium more quickly. Z. japonica preferred glycine to nitrate and urea after the high- and low-light treatments; that is, the absorption rates of the belowground seagrass parts for glycine were 14.71 ± 1.85 and 6.38 ± 0.52 mg−1 DW h−1 after the high- and low-light treatments, respectively, which were higher than those of ammonium, nitrate, and urea. The absorption rates of algae were lower than those for ammonium previously grown under medium- and low-light treatments. These results indicate that light reduction can impact the assimilation of DIN by Z. japonica and U. pertusa, and both have the ability to directly assimilate DON. This study provides information that could help reduce the negative effects of eutrophication on macroalgae and seagrasses in order to protect seagrass meadows.
15N tracing reveals preference for different nitrogen forms of Fusarium oxysporum f. sp. cubense tropical race 4
Authors: He Chen , Jia Zhongjun , Fan Pingshan , Ruan Yunze , Liang Ye , Ma Jingjing , Li Jinku
Published: February 2023

Plant uptake of nitrogen is often associated with increased incidence of banana Fusarium wilt, a disease caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4). However, the nitrogen metabolic preferences of Foc TR4 pathogens remain unknown. In this study, we investigated the ecophysiological patterns of Foc TR4 grown on different combinations of organic and inorganic nitrogen. Potato Dextrose Agar (PDA) and Rose Bengal Medium (RBM) were used as an organic nitrogen source, which was sequentially replaced with inorganic N (0, 50% or 90%) in the form 15NH4NO3 or NH415NO3 to reveal preferential assimilation of ammonium or nitrate. The results showed that mycelium biomass and nitrogen content decreased significantly, while the carbon content and C:N ratio increased in Foc TR4 grown on media containing inorganic nitrogen sources. Mycelium biomass was negatively correlated with C:N ratio. Mycelium 15N abundance increased significantly between the PDA50 + A50/RBM50 + A50 treatments (50% organic nitrogen+50%15NH4NO3) and the PDA10 + A90/RBM10 + A90 treatments (10% organic nitrogen+90%15NH4NO3). These results indicate that the higher C:N ratio reduced mycelium growth by reducing its biomass and diameter and showed that Foc TR4 preferred to use ammonium nitrogen to promote the growth. These findings suggest that treating banana crops with a combination of organic and inorganic (i.e., nitrate) nitrogen could be a better way to defend against Fusarium wilt of banana.
Local and systemic immune responses induced by intranasal immunization with biomineralized foot-and-mouth disease virus-like particles
Authors: Li Shuo , Zhao Ruichong , Song Hetao , Pan Songjia , Zhang Yun , Dong Hu , Bai Manyuan , Sun Shiqi , Guo Huichen , Yin Shuanghui
Published: February 2023

Introduction

Foot-and-mouth disease virus (FMDV) infects the host by invading mucosal epithelial cells of the respiratory or digestive tract. Therefore, establishing a specific antiviral mucosal immune barrier can effectively block viral invasion.

Methods

We evaluated local mucosal and systemic immune responses elicited by intranasal immunization of mice with foot-and-mouth disease (FMD) calcium phosphate mineralized virus-like particles (CaP-VLPs) and tested whether three commercial mucosal adjuvants enhanced the immunogenicity of the antigen. The biosafety of the vaccine was verified through gross observation and pathological analysis of the lungs.

Results

CaP-VLPs effectively induced secretion of IgA (sIgA) from multiple sites in mouse mucosa and produced anti-FMD-specific IgG in the serum. Splenic lymphocytes specifically proliferated and secreted IFN-γ following antigen stimulation, indicating the vaccine can induce a certain level of cellular immune response. Finally, the pathological examination confirmed that CaP-VLPs did not cause substantial damage to the lungs of animals after immunization via mucosal administration. Notably, the vaccine mixed with S adjuvant increased the content of sIgA and serum IgG, and the high level of IgG in serum was maintained at least 7 weeks.

Discussion

Overall, this study reveals that FMD CaP-VLPs can induce good local mucosal immune and systemic immune response through intranasal immunization, and the immune response was specifically enhanced by S adjuvant. These data support that CaP-VLPs-S as a candidate mucosal vaccine for the prevention of FMD vaccine infection.
Performance control study of interleaved meltblown non-woven materials based on statistical analysis and predictive modeling
Authors: Xu Hao , Xu Ji-Wei , Yi Long-Xiang , Yuan Yu-Ting , Cai Zheng-Qun
Published: February 2023

Meltblown nonwoven materials have gained attention due to their excellent filtration performance. The research on the performance of the intercalation meltblown preparation process is complex and a current research focus in the field of chemical production. Based on data related to intercalated and unintercalated meltblown materials under given process conditions, a product performance prediction model of intercalated meltblown materials was established under different process parameters (receiving distance, hot air velocity). The structural variables (thickness, porosity, and compressive resilience), the change in product performance, and the relationship between structural variables and product performance (filtration resistance, efficiency, air permeability) after intercalation were studied. Multiple regression analysis was used to analyze the structural variables, and evaluation of the regression results were made using R2, MSE, SSR, and SST. A BP neural network prediction model for product performance was established. The BP neural network model was used to find the maximum filtration efficiency. The study provides theoretical support for regulating product performance by solving the maximum filtration efficiency using BP neural network model.
Inter-rater reliability of functional MRI data quality control assessments: A standardised protocol and practical guide using pyfMRIqc
Authors: Williams Brendan , Hedger Nicholas , McNabb Carolyn B. , Rossetti Gabriella M. K. , Christakou Anastasia
Published: February 2023

Quality control is a critical step in the processing and analysis of functional magnetic resonance imaging data. Its purpose is to remove problematic data that could otherwise lead to downstream errors in the analysis and reporting of results. The manual inspection of data can be a laborious and error-prone process that is susceptible to human error. The development of automated tools aims to mitigate these issues. One such tool is pyfMRIqc, which we previously developed as a user-friendly method for assessing data quality. Yet, these methods still generate output that requires subjective interpretations about whether the quality of a given dataset meets an acceptable standard for further analysis. Here we present a quality control protocol using pyfMRIqc and assess the inter-rater reliability of four independent raters using this protocol for data from the fMRI Open QC project (https://osf.io/qaesm/). Data were classified by raters as either “include,” “uncertain,” or “exclude.” There was moderate to substantial agreement between raters for “include” and “exclude,” but little to no agreement for “uncertain.” In most cases only a single rater used the “uncertain” classification for a given participant’s data, with the remaining raters showing agreement for “include”/“exclude” decisions in all but one case. We suggest several approaches to increase rater agreement and reduce disagreement for “uncertain” cases, aiding classification consistency.
Double osseous flaps for simultaneous midfacial and mandible reconstruction: Automation in surgical complexity within an entirely computerized workflow
Authors: Tel Alessandro , Bagatto Daniele , Sembronio Salvatore , Ferrari Silvano , Robiony Massimo
Published: February 2023

Introduction

Broad maxillofacial surgical resections involving both the midface and the mandible represent a challenge in terms of reconstruction. Although several papers have explored the possibility of simultaneously using two microsurgical flaps, reports on the implementation of a dual osseous flap strategy are limited, and mainly addressed to static anatomical reconstruction, regardless of functional implications. In particular, there is a lack in the literature of a unifying protocol which illustrates how technology including virtual planning, statistical shape modeling, virtual occlusion, 3D-printing and patient-specific implants can address the functional and accuracy needs required for an optimal reconstruction.

Materials and methods

In this paper, the Authors present their preliminary experience in a two-center study, showing how broad maxillofacial defects, requiring a simultaneous reconstruction in both the mandible and the midface, can be successfully reconstructed using the combination of two osseous flaps in an automated sequence in which all steps are anticipately defined in a virtual plan, accounting for the optimal alignment of temporomandibular joint, predicting the final occlusion and defining a mandibular shape according to a statistical shape model.

Results

Average RMSE for the iliac bone crest flap was of 3.2 ± 0.36 mm; for the fibula flap, RMSE value was of 2.3 ± 0.65 mm, for patient-specific implants, for mandibular prostheses the average RMSE was 2.46 mm with 0.76 mm standard deviation. Temporomandibular joint function increased when a TMJ prosthesis was placed.

Conclusions

Double bone free flap is a valuable resource to reconstruct wide defects that simultaneously involve two thirds of the cranio-maxillo-facial skeleton, but a careful virtual planning study should be always performed before approaching this surgical option.
Multilevel feature cooperative alignment and fusion for unsupervised domain adaptation smoke detection
Authors: Zhou Fangrong , Wen Gang , Ma Yi , Wang Yifan , Ma Yutang , Wang Guofang , Pan Hao , Wang Kaizheng
Published: February 2023

Early smoke detection using Digital Image Processing technology is an important research field, which has great applications in reducing fire hazards and protecting the ecological environment. Due to the complex changes of color, shape and size of smoke with time, it is challenging to accurately recognize smoke from a given image. In addition, limited by domain shift, the trained detector is difficult to adapt to the smoke in real scenes, resulting in a sharp drop in detection performance. In order to solve this problem, an unsupervised domain adaptive smoke detection algorithm rely on Multilevel feature Cooperative Alignment and Fusion (MCAF) was proposed in this paper. Firstly, the cooperative domain alignment is performed on the features of different scales obtained by the feature extraction network to reduce the domain difference and enhance the generalization ability of the model. Secondly, multilevel feature fusion modules were embedded at different depths of the network to enhance the representation ability of small targets. The proposed method is evaluated on multiple datasets, and the results show the effectiveness of the method.
Charring-induced morphological changes of Chinese “Five Grains”: An experimental study
Authors: Liu Yang , Xi Yang , Zhang Fei , Wang Zhenzhen , Wang Can , Yu Shiyong , Chen Xuexiang
Published: February 2023

Introduction

Charring process affects the preservation potential of seeds, resulting in limited perceptions of crop assemblages recovered from archaeological layers. Therefore, the specifics of the charring process deserve further investigation. Colloquially referred to as the “Five Grains” (五谷), bread wheat (Triticum aestivum), foxtail millet (Setaria italica), broomcorn millet (Panicum miliaceum), rice (Oryza sativa), and soybean (Glycine max) represent a set of four major cultivated cereals and a pulse constituting crucial staple food in Chinese history and the most frequently discovered crops at archaeological sites in China

Methods

This paper aims to understand the changes in size, volume, and weight loss of grains under variable aerobic charring conditions. The size and weight were measured for the untreated specimens and the specimens heated at different temperatures and over different time-periods.

Results

We found that temperature and exposure time directly affected the grain size. Specifically, the grains of most species shrank at lower temperatures and expanded rapidly at higher temperatures.

Discussion

Among the “Five Grains”, soybean was the type least affected by charring, followed by wheat, rice, and millet. Volume and weight can be used as conversion factors to minimize the bias in quantitative representation due to varied charring preservation potential. For rice, wheat and soybean, the variation in volume is smaller. For millet, both volume and weight can be used as the control to understand the consequences of charring for the assemblage. Further experiments and comparisons of ancient samples are needed in future studies to investigate other factors that affect the preservation of charred plant remains.
A “Motivation” model of couple support for digital technology use among rural older adults
Authors: Ma Jiaojiao , Cui Jie , Zhang Qi
Published: February 2023

Although recent research has demonstrated spouse support for technology use among older adults, by treating them as a homogeneous group, it has overlooked differences caused by socio-demographic dimensions in their digital engagement. Following the approach of the grounded theory and interviewing 15 couples in a developing aging region (Wuzhi County, Henan, China), this study paints a fuller picture of couple support for technology adoption among older adults in terms of their psychological motivations by dividing older adults into two categories: technology supports and technology recipients. The resulting concepts of motivation (e.g., social norms, benefit driven, perceptual elements, and value satisfaction), particularly limiting motivational factors (e.g.,individual status) reveal the psychological mechanisms behind this process and are conceptualized as a “motivation” model of couple support for digital technology use among rural older adults. Our study has strong implications for active and healthy aging, as policymakers can stimulate external motivation for technology adoption among older adults by fostering a sense of family responsibility and social ethos that encourages couples to help each other. In addition, local communities as stakeholders can educate older adults about the usefulness, ease of use, and risk-averse means of digital technology, and satisfy their altruistic and egoistic psychological needs to increase the inner value satisfaction they gain from the couple support process. By doing this, motivation and engagement are thereby increased, and ultimately, technology adoption in disadvantaged socioeconomic groups may be improved.
Impact of a controlling coaching style on athletes’ fear of failure: Chain mediating effects of basic psychological needs and sport commitment
Authors: Hu Qing , Li Peng , Jiang Bo , Liu Bo
Published: February 2023

Controlling coaching style is a key predictor of athletes’ fear of failure, but the mediating mechanisms underlying this relationship require further exploration. Based on the self-determination theory (SDT) and the hierarchical model of intrinsic and extrinsic motivation (HMIEM), this study investigated the effect of a controlling coaching style on athletes’ fear of failure, as well as the chain mediating effects of basic psychological needs and sport commitment. A questionnaire survey of 252 active athletes was administrated using scales for fear of failure, controlling coaching style, sport commitment, and basic psychological needs. The results indicated that a controlling coaching style was negatively correlated with basic psychological needs and indirectly affected athletes’ fear of failure via basic psychological needs and constrained commitment. The chain mediating effect of basic psychological needs on enthusiastic commitment was not significant, but it was for constrained commitment. In conclusion, the impact of a controlling coaching style on athletes’ fear of failure via basic psychological needs is manifested through the strengthening of constrained commitment rather than the weakening of enthusiastic commitment. These findings contribute to a deeper understanding of why and how a controlling coaching style influences athletes’ fear of failure. Coaches should seek more scientific and effective ways to instruct their athletes.
How do anxiety and stress impact the performance of Chinese doctoral students through self-regulated learning?—A multi-group analysis
Authors: Li Zhen , Huang Jinyan , Hussain Shahbaz , Shu Tiantian
Published: February 2023

Introduction

Highly accomplished doctoral students may suffer when they cannot manage their performance due to the crippling effects of anxiety and stress. This is even more likely to occur in the highly charged setting of competitive research. Using a structural equation modeling approach, this study examined how anxiety and stress impact the performance of Chinese doctoral students through self-regulated learning.

Methods

A total of 491 doctoral students and recent completers representing 112 universities in China participated in this study. A 42-item five-point Likert scale survey was used to measure participants’ perceived anxiety (emotional and physical reactions), stress (study- and research-related stress), self-regulated learning, and performance (task and contextual performance) in their doctoral studies. Specifically, the extent to which participants’ self-regulated learning mediated the influence of anxiety and stress on their task performance and contextual performance in their doctoral studies, as well as significant structural equation modeling differences across demographic variables of gender (i.e., male versus female), major (i.e., arts versus sciences), status (i.e., individuals pursuing a doctoral degree versus recent completers), and age (i.e., 30 and younger versus over 30) were examined.

Results and Discussion

The results indicated that self-regulated learning considerably affected task and contextual performance; stress had a considerable direct effect on task and contextual performance; the indirect influence of stress on task and contextual performance via self-regulated learning was significant; and there was a significant structural equation modeling difference between arts and sciences doctoral students. Educational implications are discussed.
Evolving conceptions of silvopasture among farmers and natural resource professionals in Wisconsin, USA
Authors: Mayerfeld Diane , Keeley Keefe O. , Rickenbach Mark , Rissman Adena , Ventura Stephen J.
Published: February 2023

Silvopasture has gained attention as an agroecological practice that may simultaneously meet farmer goals and provide environmental benefits, including climate change mitigation. At the same time there are significant concerns about the potential for livestock to damage trees and forest soils. Like other innovative agroecological systems, silvopasture combines management complexity with limited research knowledge. Unlike annual crops, the effects of silvopasture management can take decades to assess and require forestry as well as agronomic expertise. We conducted mixed-methods research on silvopasture attitudes and knowledge among farmers, agricultural advisors, and foresters in Wisconsin between 2014 and 2019. We asked: (1) How do farmers who practice grazing, agricultural advisors, and foresters perceive silvopasture? and (2) How did coverage of silvopasture change between 2009 and 2019 in a popular grazing publication? Perceptions of silvopasture were influenced by recent weather history, markets for forest and agricultural products, existing land uses, and other contextual factors. Some farmers and agricultural advisors were committed to silvopasture despite significant obstacles to implementing the practice. Over the course of the study period agricultural advisors increased their willingness to provide silvopasture advice to farmers and professional colleagues, and coverage of silvopasture increased in a popular grazing publication. Finally, a multi-county supportive community of practice was associated with greater enthusiasm for the practice. The greater acceptance of silvopasture among resource professionals follows an increase in silvopasture research and outreach in the region. This interest in silvopasture suggests both a need for, and openness to, greater collaboration among forestry and agricultural professionals and farmers to develop sustainable silvopasture standards.
Thunderstorm Ground Enhancements Measured on Aragats and Progress of High-Energy Physics in the Atmosphere
Authors: Chilingarian Ashot
Published: February 2023

High-energy physics in the atmosphere (HEPA) has undergone an intense reformation in the last decade. Correlated measurements of particle fluxes modulated by strong atmospheric electric fields, simultaneous measurements of the disturbances of the near-surface electric fields and lightning location, and registration of various meteorological parameters on the Earth have led to a better understanding of the complex processes in the terrestrial atmosphere. The cooperation of cosmic rays and atmospheric physics has led to the development of models for the origin of particle bursts recorded on the Earth’s surface, estimation of vertical and horizontal profiles of electric fields in the lower atmosphere, recovery of electron and gamma ray energy spectra, the muon deceleration effect, etc. The main goal of this review is to demonstrate how the measurements performed at the Aragats cosmic ray observatory led to new results in atmospheric physics. We monitored particle fluxes around the clock using synchronized networks of advanced sensors that recorded and stored multidimensional data in databases with open, fast, and reliable access. Visualization and statistical analysis of particle data from hundreds of measurement channels disclosed the structure and strength of the atmospheric electric fields and explained observed particle bursts. Consequent solving of direct and inverse problems of cosmic rays revealed the modulation effects that the atmospheric electric field has on cosmic ray fluxes.
Assessment of High-Resolution Surface Soil Moisture Products over the Qinghai–Tibet Plateau for 2009–2017
Authors: Lin Dongjun , Yuan Xing , Jia Binghao , Ji Peng
Published: February 2023

The surface soil moisture over the Qinghai–Tibet Plateau (QTP) has an important impact on the weather and climate of East Asia. Under climate warming, the imbalance of solid–liquid water of QTP has become a research hotspot, but the surface soil moisture dynamics over QTP are not clear owing to the lack of precise measurements over a large scale. In this paper, the quality of gridded surface soil moisture products including CSSPv2 high-resolution (6 km) simulation, ESA CCI satellite retrieval, ERA5 land-atmosphere coupled reanalysis, and GLDAS2.1 land reanalysis products (Noah, Catchment, VIC) is analyzed over QTP by comparison with the in situ measurements at 140 stations during 2009–2017. We find that the CSSPv2 product shows a higher correlation than the global satellite and reanalysis products, with correlation increased by 7.7%–115.6%. The root mean squared error of the CSSPv2 product is lower than that of other products, with the error decreased by 13.4%–46.3%. The triple collocation analysis using high-resolution simulation, global reanalysis, and satellite retrieval products over the entire plateau shows that the error of CSSPv2 is the lowest, followed by ESA CCI, while ERA5 is the highest. The soil moisture products of ESA CCI, ERA5, and CSSPv2 all show an increasing trend from April to September of 2009 to 2017, with wetting in the west and drying in the east. This study indicates that the CSSPv2 high-resolution surface soil moisture product has better performance over QTP than other global products, and the global satellite and reanalysis products may overestimate the surface soil moisture dynamics.
MRI-Based Radiomics Combined with Deep Learning for Distinguishing IDH-Mutant WHO Grade 4 Astrocytomas from IDH-Wild-Type Glioblastomas
Authors: Hosseini Seyyed , Hosseini Elahe , Hajianfar Ghasem , Shiri Isaac , Servaes Stijn , Rosa-Neto Pedro , Godoy Laiz , Nasrallah MacLean , O’Rourke Donald , Mohan Suyash , Chawla Sanjeev
Published: February 2023

This study aimed to investigate the potential of quantitative radiomic data extracted from conventional MR images in discriminating IDH-mutant grade 4 astrocytomas from IDH-wild-type glioblastomas (GBMs). A cohort of 57 treatment-naïve patients with IDH-mutant grade 4 astrocytomas (n = 23) and IDH-wild-type GBMs (n = 34) underwent anatomical imaging on a 3T MR system with standard parameters. Post-contrast T1-weighted and T2-FLAIR images were co-registered. A semi-automatic segmentation approach was used to generate regions of interest (ROIs) from different tissue components of neoplasms. A total of 1050 radiomic features were extracted from each image. The data were split randomly into training and testing sets. A deep learning-based data augmentation method (CTGAN) was implemented to synthesize 200 datasets from the training sets. A total of 18 classifiers were used to distinguish two genotypes of grade 4 astrocytomas. From generated data using 80% training set, the best discriminatory power was obtained from core tumor regions overlaid on post-contrast T1 using the K-best feature selection algorithm and a Gaussian naïve Bayes classifier (AUC = 0.93, accuracy = 0.92, sensitivity = 1, specificity = 0.86, PR_AUC = 0.92). Similarly, high diagnostic performances were obtained from original and generated data using 50% and 30% training sets. Our findings suggest that conventional MR imaging-based radiomic features combined with machine/deep learning methods may be valuable in discriminating IDH-mutant grade 4 astrocytomas from IDH-wild-type GBMs.
ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization
Authors: Lyon Anastasia , Tripathi Rakshamani , Meeks Christina , He Daheng , Wu Yuanyuan , Liu Jinpeng , Wang Chi , Chen Jing , Zhu Haining , Mukherjee Sujata , Ganguly Saptadwipa , Plattner Rina
Published: February 2023

Melanomas harboring NRAS mutations are a particularly aggressive and deadly subtype. If patients cannot tolerate or the melanomas are insensitive to immune checkpoint blockade, there are no effective 2nd-line treatment options. Drugs targeting the RAF/MEK/ERK pathway, which are used for BRAF-mutant melanomas, do little to increase progression-free survival (PFS). Here, using both loss-of-function and gain-of-function approaches, we show that ABL1/2 and DDR1 are critical nodes during NRAS-mutant melanoma intrinsic and acquired MEK inhibitor (MEKi) resistance. In some acquired resistance cells, ABL1/2 and DDR1 cooperate to stabilize RAF proteins, activate ERK cytoplasmic and nuclear signaling, repress p27/KIP1 expression, and drive RAF homodimerization. In contrast, other acquired resistance cells depend solely on ABL1/2 for their survival, and are sensitive to highly specific allosteric ABL1/2 inhibitors, which prevent β-catenin nuclear localization and destabilize MYC and ETS1 in an ERK-independent manner. Significantly, targeting ABL1/2 and DDR1 with an FDA-approved anti-leukemic drug, reverses intrinsic MEKi resistance, delays acquisition of acquired resistance, and doubles the survival time in a NRAS-mutant mouse model. These data indicate that repurposing FDA-approved drugs targeting ABL1/2 and DDR1 may be a novel and effective strategy for treating patients with treatment-refractory NRAS-driven melanomas.
Changes in Expression of Tumor Suppressor Gene RKIP Impact How Cancers Interact with Their Complex Environment
Authors: Figy Christopher , Guo Anna , Fernando Veani Roshale , Furuta Saori , Al-Mulla Fahd , Yeung Kam C.
Published: February 2023

Tumor microenvironment (TME) is the immediate environment where cancer cells reside in a tumor. It is composed of multiple cell types and extracellular matrix. Microenvironments can be restrictive or conducive to the progression of cancer cells. Initially, microenvironments are suppressive in nature. Stepwise accumulation of mutations in oncogenes and tumor suppressor genes enables cancer cells to acquire the ability to reshape the microenvironment to advance their growth and metastasis. Among the many genetic events, the loss-of-function mutations in tumor suppressor genes play a pivotal role. In this review, we will discuss the changes in TME and the ramifications on metastasis upon altered expression of tumor metastasis suppressor gene RKIP in breast cancer cells.
Urinary PSA and Serum PSA for Aggressive Prostate Cancer Detection
Authors: Höti Naseruddin , Lih Tung-Shing , Dong Mingming , Zhang Zhen , Mangold Leslie , Partin Alan W. , Sokoll Lori J. , Kay Li Qing , Zhang Hui
Published: February 2023

Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained the gold standard in urological practices for the management of and intervention for prostate cancer. Based on these adopted practices, the limitations of serum PSA in identifying aggressive prostate cancer has led us to evaluate whether urinary PSA levels might have any clinical utility in prostate cancer diagnosis. Utilizing the Access Hybritech PSA assay, we evaluated a total of n = 437 urine specimens from post-DRE prostate cancer patients. In our initial cohort, PSA tests from a total of one hundred and forty-six (n = 146) urine specimens were obtained from patients with aggressive (Gleason Score ≥ 8, n = 76) and non-aggressive (Gleason Score = 6, n = 70) prostate cancer. A second cohort, with a larger set of n = 291 urine samples from patients with aggressive (GS ≥ 7, n = 168) and non-aggressive (GS = 6, n = 123) prostate cancer, was also utilized in our study. Our data demonstrated that patients with aggressive disease had lower levels of urinary PSA compared to the non-aggressive patients, while the serum PSA levels were higher in patients with aggressive prostate disease. The discordance between serum and urine PSA levels was further validated by immuno-histochemistry (IHC) assay in biopsied tumors and in metastatic lesions (n = 62). Our data demonstrated that aggressive prostate cancer was negatively correlated with the PSA in prostate cancer tissues, and, unlike serum PSA, urinary PSA might serve a better surrogate for capitulating tissue milieus to detect aggressive prostate cancer. We further explored the utility of urine PSA as a cancer biomarker, either alone and in combination with serum PSA, and their ratio (serum to urine PSA) to predict disease status. Comparing the AUCs for the urine and serum PSA alone, we found that urinary PSA had a higher predictive power (AUC= 0.732) in detecting aggressive disease. Furthermore, combining the ratios between serum to urine PSA with urine and serum assay enhanced the performance (AUC = 0.811) in predicting aggressive prostate disease. These studies support the role of urinary PSA in combination with serum for detecting aggressive prostate cancer.
Enhancer Clusters Drive Type I Interferon-Induced TRAIL Overexpression in Cancer, and Its Intracellular Protein Accumulation Fails to Induce Apoptosis
Authors: Di Benedetto Carolina , Khan Taimoor , Serrano-Saenz Santiago , Rodriguez-Lemus Anthony , Klomsiri Chananat , Beutel Tim-Mathis , Thach Alysia , Walczak Henning , Betancur Paola
Published: February 2023

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine produced and secreted by immune cells in response to an infection, often in response to interferon (IFN) stimulation. In cancer, it has also been shown that IFN stimulates the production of TRAIL, and it has been proposed that this TRAIL can induce apoptosis in an autocrine or paracrine manner in different cancer cells. Yet, the mechanism mediating TRAIL upregulation and the implications of TRAIL as an apoptotic molecule in cancer cells are still poorly understood. We show here that in certain cancer cells, TRAIL is upregulated by enhancer clusters, potent genomic regulatory regions containing densely packed enhancers that have combinatorial and additive activity and that are usually found to be associated with cancer-promoting genes. Moreover, we found that TRAIL upregulation by IFNα is mediated by these enhancer clusters in breast and lung cancer cells. Surprisingly, IFNα stimulation leads to the intracellular accumulation of TRAIL protein in these cancer cells. Consequently, this TRAIL is not capable of inducing apoptosis. Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells.
Surgery-Related Muscle Loss after Pancreatic Resection and Its Association with Postoperative Nutritional Intake
Authors: Hogenbirk Rianne N. M. , Hentzen Judith E. K. R. , van der Plas Willemijn Y. , Campmans-Kuijpers Marjo J. E. , Kruijff Schelto , Klaase Joost M.
Published: February 2023

To study the occurrence of surgery-related muscle loss (SRML) and its association with in-hospital nutritional intake, we conducted a prospective observational cohort study including patients who underwent pancreatic surgery because of (suspected) malignant diseases. Muscle diameter was measured by using bedside ultrasound 1 day prior to surgery and 7 days postoperatively. Clinically relevant SRML was defined as ≥10% muscle diameter loss in minimally one arm and leg muscle within 1 week after surgery. Protein and caloric intake was measured by nutritional diaries. The primary endpoint included the number of patients with SRML. Secondary endpoints included the association between SRML and postoperative nutritional intake. Of the 63 included patients (60.3% men; age 67.1 ± 10.2 years), a total of 24 patients (38.1%) showed SRML. No differences were observed in severe complication rate or length of hospital stay between patients with and without SRML. During the first postoperative week, patients with clinically relevant SRML experienced more days without any nutritional intake compared with the non-SRML group (1 [0–4] versus 0 [0–1] days, p = 0.007). Significantly lower nutritional intake was found in the SRML group at postoperative days 2, 3 and 5 (p < 0.05). Since this study shows that SRML occurred in 38.1% of the patients and most of the patients failed to reach internationally set nutritional goals, it is suggested that more awareness concerning direct postoperative nutritional intake is needed in our surgical community.
A Comparison of Different Sample Processing Protocols for MALDI Imaging Mass Spectrometry Analysis of Formalin-Fixed Multiple Myeloma Cells
Authors: Casadonte Rita , Kriegsmann Jörg , Kriegsmann Mark , Kriegsmann Katharina , Torcasio Roberta , Gallo Cantafio Maria Eugenia , Viglietto Giuseppe , Amodio Nicola
Published: February 2023

Sample processing of formalin-fixed specimens constitutes a major challenge in molecular profiling efforts. Pre-analytical factors such as fixative temperature, dehydration, and embedding media affect downstream analysis, generating data dependent on technical processing rather than disease state. In this study, we investigated two different sample processing methods, including the use of the cytospin sample preparation and automated sample processing apparatuses for proteomic analysis of multiple myeloma (MM) cell lines using imaging mass spectrometry (IMS). In addition, two sample-embedding instruments using different reagents and processing times were considered. Three MM cell lines fixed in 4% paraformaldehyde were either directly centrifuged onto glass slides using cytospin preparation techniques or processed to create paraffin-embedded specimens with an automatic tissue processor, and further cut onto glass slides for IMS analysis. The number of peaks obtained from paraffin-embedded samples was comparable between the two different sample processing instruments. Interestingly, spectra profiles showed enhanced ion yield in cytospin compared to paraffin-embedded samples along with high reproducibility compared to the sample replicate.
Epiploic Adipose Tissue (EPAT) in Obese Individuals Promotes Colonic Tumorigenesis: A Novel Model for EPAT-Dependent Colorectal Cancer Progression
Authors: Iftikhar Rida , Snarski Patricia , King Angelle N. , Ghimire Jenisha , Ruiz Emmanuelle , Lau Frank , Savkovic Suzana D.
Published: February 2023

The obesity epidemic is associated with increased colorectal cancer (CRC) risk and progression, the mechanisms of which remain unclear. In obese individuals, hypertrophic epiploic adipose tissue (EPAT), attached to the colon, has unique characteristics compared to other fats. We hypothesized that this understudied fat could serve as a tumor-promoting tissue and developed a novel microphysiological system (MPS) for human EPAT-dependent colorectal cancer (CRC-MPS). In CRC-MPS, obese EPAT, unlike lean EPAT, considerably attracted colon cancer HT29-GFP cells and enhanced their growth. Conditioned media (CM) from the obese CRC-MPS significantly increased the growth and migration of HT29 and HCT116 cells (p < 0.001). In HT29 cells, CM stimulated differential gene expression (hOEC867) linked to cancer, tumor morphology, and metabolism similar to those in the colon of high-fat-diet obese mice. The hOEC867 signature represented pathways found in human colon cancer. In unsupervised clustering, hOEC867 separated transcriptomes of colon cancer samples from normal with high significance (PCA, p = 9.6 × 10−11). These genes, validated in CM-treated HT29 cells (p < 0.05), regulate the cell cycle, cancer stem cells, methylation, and metastasis, and are similarly altered in human colon cancer (TCGA). These findings highlight a tumor-promoting role of EPAT in CRC facilitated with obesity and establishes a platform to explore critical mechanisms and develop effective treatments.
Hormone Receptor Expression in Meningiomas: A Systematic Review
Authors: Agopiantz Mikaël , Carnot Mélanie , Denis Constance , Martin Elena , Gauchotte Guillaume
Published: February 2023

Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature. Several studies have discussed the expression of progesterone, estrogen, androgen, and somatostatin receptors. The utility of analyzing these expressions for prognostic, theragnostic, and therapeutic purposes remains unclear. The aim of this study was to report the expression of these receptors, based on immunohistochemistry. Cochrane Collaboration guidelines and PRISMA statements were followed. We did an online search in PubMed using the MeSH database. References were selected if the investigations occurred from 1990 to 2022. 61 references were included (34 descriptive observational studies, 26 analytical observational studies, and one case report). In this review, we describe the expression of these receptors in function of age, sex, hormonal context, localization, histological subtype, grade, and recurrence.
Morphology-Dependent Near-Infrared Electrochromic Properties of Tungsten Oxide
Authors: Huang Qingyi , Liang Yi , Cao Sheng , Yang Zaishang
Published: February 2023

Vertically aligned WO3 nano-architectures on the transparent conducting substrate are produced via a hydrothermal method. The results revealed that different WO3 nano-architectures, including “nanoblocks”, “nanosheet” and “nanobelt” structures, can be obtained by adjusting the composition of the precursor solution, that shows that solvent composition plays an important role in the adjustment of the prepared material morphology. The nanostructured array films with thicknesses of about 600 nm show remarkable enhancement of the electrochromic properties in the infrared region. The obtained WO3 films have good electrochromic properties in the near-infrared range. In particular, significant optical modulation of the WO3 nanosheets (72% at 1200 nm), fast switching speed (6.5 s for colored and 8.7 s for bleached), and excellent cycling stability (maintained 90.2% of the initial optical modulation after 1000 cycles). The improved electrochromic performance is mainly due to the vertically arranged structure, which makes it easier for ions to diffuse in the nanoarray, and also provides a larger surface area for charge transfer reaction. The research results provide a certain reference value for the research of electrochromic near-infrared performance.
Structure and Properties of CrN/TiN Multi-Layer Coatings Obtained by Vacuum-Arc Plasma-Assisted Deposition Method
Authors: Leonov Andrey A. , Denisova Yuliya A. , Denisov Vladimir V. , Syrtanov Maxim S. , Shmakov Alexander N. , Savostikov Viktor M. , Teresov Anton D.
Published: February 2023

The paper presents the study results of CrN/TiN multi-layer coatings, as well as single-layer TiN and CrN coatings on Cr12MoV cold work die steel deposited by the vacuum-arc plasma-assisted method. Three CrN/TiN coatings of 8-, 16-, and 32-layers were deposited, in which the thickness of each layer was 500 nm, 250 nm and 125 nm, respectively. All of the coatings reveal a face-centered cubic structure with highly oriented (111) growth. The hardness of the CrN/TiN multi-layer coatings was about 27 GPa. Changing the architecture of CrN/TiN multi-layer coatings by reducing the thickness of the CrN and TiN layers from 500 nm to 125 nm promotes a smooth decrease in both the wear parameter and the coefficient of friction. By using an X-ray phase analysis with synchrotron radiation, it was found that 32-layer CrN/TiN coating retained thermal stability during heating in air to a temperature of 1120–1125 °C, and in a vacuum at least to a temperature of 1200 °C.
Design and Device Numerical Analysis of Lead-Free Cs2AgBiBr6 Double Perovskite Solar Cell
Authors: Alanazi Tarek I.
Published: February 2023

The advancement of lead-free double perovskite materials has drawn great interest thanks to their reduced toxicity, and superior stability. In this regard, Cs2AgBiBr6 perovskites have appeared as prospective materials for photovoltaic (PV) applications. In this work, we present design and numerical simulations, using SCAPS-1D device simulator, of Cs2AgBiBr6-based double perovskite solar cell (PSC). The initial calibrated cell is based on an experimental study in which the Cs2AgBiBr6 layer has the lowest bandgap (Eg = 1.64 eV) using hydrogenation treatment reported to date. The initial cell (whose structure is ITO/SnO2/Cs2AgBiBr6/Spiro-OMeTAD/Au) achieved a record efficiency of 6.58%. The various parameters that significantly affect cell performance are determined and thoroughly analyzed. It was found that the conduction band offset between the electron transport layer (ETL) and the Cs2AgBiBr6 layer is the most critical factor that affects the power conversion efficiency (PCE), in addition to the thickness of the absorber film. Upon engineering these important technological parameters, by proposing a double ETL SnO2/ZnO1-xSx structure with tuned absorber thickness, the PCE can be boosted to 14.23%.
Editorial to “Gender Differences in Diabetes”
Authors: Tonolo Giancarlo
Published: February 2023

Welcome to this Special Issue of Diabetology entitled “Gender Difference in Diabetes” [...]