bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the protective efficiency of an autogenous Vibrio anguillarum vaccine in lumpfish (Cyclopterus lumpus) under controlled and field conditions in Atlantic Canada
Authors: Onireti Oluwatoyin B. , Cao Trung , Vasquez Ignacio , Chukwu-Osazuwa Joy , Gnanagobal Hajarooba , Hossain Ahmed , Machimbirike Vimbai I. , Hernandez-Reyes Yenney , Khoury Antoine , Khoury Andre , O’Brien Nicole , George Sheldon , Swanson Andrew , Gendron Robert L. , Kwabiah Rebecca , Tucker Denise , Monk Jennifer , Porter Jillian , Boyce Danny , Santander Javier
Published: December 2023

Lumpfish (Cyclopterus lumpus) have become the predominant cleaner fish species used in North American salmon aquaculture. Vibrio anguillarum is a frequent pathogen of lumpfish in Atlantic Canada, and current vaccines against local isolates conferred low to moderate efficacy. This study evaluated the safety and efficiency of a V. anguillarum autogenous vaccine under controlled and field conditions. Two safety trials were conducted following the Canadian Food Inspection Agency (CFIA) regulations before field trial testing. The first safety trial was a common garden assay, and 250 PIT-tsgged lumpfish were used for five treatments per tank (PBS-negative control, Lab vaccine-positive control, autogenous intraperitoneal (IP) vaccine, autogenous dip vaccine, autogenous dip-IP boosted vaccine) in triplicates. Weight, gross pathology, and IgM titers were evaluated to determine the vaccine’s safety. After 10 weeks post-vaccination (wpv), lumpfish were bath-challenged with a lethal dose (1.24 x 106 CFU/mL) of V. anguillarum serotype O2. Survival rate, IgM titers, memory immune response, and cross-immune protection were evaluated. The second safety trial was conducted using a double vaccine dose in two groups, PBS and autogenous IP. The gross pathology score indicated a normal immune response without tissue damage, and no mortality nor fish health issues were observed in the immunized animals. The IP route of administration conferred the highest protection against the V. anguillarum challenge. The autogenous vaccine conferred long-term immunity but did not confer cross-protection against V. anguillarum serotype O1. To evaluate the efficiency of the autogenous vaccine under field conditions, 58,976 naïve lumpfish (8-10 g) were IP immunized with either the autogenous vaccine or the commercial Forte micro IV vaccine. After 7 wpv, the lumpfish were equally distributed into eight sea cages and co-cultivated with Atlantic salmon smolts (60,000 per cage). Lumpfish IgM titers, tissue bacterial loads, mortality, and sea lice count on salmon were monitored. The autogenous vaccine and Forte vaccine confer acceptable protection to the lumpfish in sea cages. No significant difference was observed between lumpfish vaccinated with autogenous and commercial vaccines under field conditions.
Improving fluorescence lifetime imaging microscopy phasor accuracy using convolutional neural networks
Authors: Mannam Varun , P. Brandt Jacob , Smith Cody J. , Yuan Xiaotong , Howard Scott
Published: December 2023

Introduction: Although a powerful biological imaging technique, fluorescence lifetime imaging microscopy (FLIM) faces challenges such as a slow acquisition rate, a low signal-to-noise ratio (SNR), and high cost and complexity. To address the fundamental problem of low SNR in FLIM images, we demonstrate how to use pre-trained convolutional neural networks (CNNs) to reduce noise in FLIM measurements.

Methods: Our approach uses pre-learned models that have been previously validated on large datasets with different distributions than the training datasets, such as sample structures, noise distributions, and microscopy modalities in fluorescence microscopy, to eliminate the need to train a neural network from scratch or to acquire a large training dataset to denoise FLIM data. In addition, we are using the pre-trained networks in the inference stage, where the computation time is in milliseconds and accuracy is better than traditional denoising methods. To separate different fluorophores in lifetime images, the denoised images are then run through an unsupervised machine learning technique named “K-means clustering”.

Results and Discussion: The results of the experiments carried out on in vivo mouse kidney tissue, Bovine pulmonary artery endothelial (BPAE) fixed cells that have been fluorescently labeled, and mouse kidney fixed samples that have been fluorescently labeled show that our demonstrated method can effectively remove noise from FLIM images and improve segmentation accuracy. Additionally, the performance of our method on out-of-distribution highly scattering in vivo plant samples shows that it can also improve SNR in challenging imaging conditions. Our proposed method provides a fast and accurate way to segment fluorescence lifetime images captured using any FLIM system. It is especially effective for separating fluorophores in noisy FLIM images, which is common in in vivo imaging where averaging is not applicable. Our approach significantly improves the identification of vital biologically relevant structures in biomedical imaging applications.
Development of ZnCdSe/ZnS quantum dot-based fluorescence immunochromatographic assay for the rapid visual and quantitative detection 25⁃hydroxyvitamins D in human serum
Authors: Wang Jianfa , Sun Guoshao , Li Fang , Zhu Zhi , Sun Lei , Lv Pengju , Yue Han
Published: December 2023

Vitamin D deficiency is associated with various diseases such as obesity, digestive problems, osteoporosis, depression, and infections, and has therefore emerged as a topic of great interest in public healthcare. The quantitative assessment of 25-hydroxyvitamin D (25-OH VD) in human serum may accurately reflect the nutritional status of vitamin D in the human body, which is significant for the prevention and treatment of vitamin D-deficient patients. In this study, we developed an assay for quantitative detection of 25-OH VD based on the 25-OH VD monoclonal antibody (mAb), and identified the optimal process parameters. The following process settings were found to be suitable for the test strips: pH of 7.6, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) ratio of 1:2000, and the anti-25-OH VD mAb ratio was 1:8. The equilibration time of the immune dynamic assay was 15 min. Under optimal conditions, the quantum dot nanoparticle-based fluorescent immunochromatographic assay (QDs-FICA) exhibited dynamic linear detection of 25-OH VD in PBS, from 5 ng/mL to 100 ng/mL, and the strip quantitative curve could be represented by the following regression equation: y = −0.02088 logx)+1.444 (R2 = 0.9050). The IC50 of the QDs-FICA was 39.6 ± 1.33 ng/mL. The specificity of the QDs-FICA was evaluated by running several structurally related analogues, including 25-OH VD2, 25-OH VD3, 1,25-OH2VD3, 1,25-OH2VD2, VD2, and VD3. The coefficients of variation were all below 10%. The shelf life of the test strips in this study was about 160 days at room temperature. Briefly, this study is the first to perform QDs-FICA for the rapid visual and quantitative detection of 25-OH VD, with great potential significance for clinical diagnosis of vitamin D-associated diseases.
Stability, biomechanics and biocompatibility analysis following different preparation strategies of hierarchical zeolite coatings on titanium alloy surfaces
Authors: Liu Chang , Zhang Jiaxin , Zhao Xin , Xu Mingwei , Liu He , Zhou Hongming
Published: December 2023

Traditional titanium alloy implant surfaces are inherently smooth and often lack effective osteoinductive properties. To overcome these limitations, coating technologies are frequently employed to enhance the efficiency of bone integration at the implant–host bone interface. Hierarchical zeolites, characterized by their chemical stability, can be applied to 3D-printed porous titanium alloy (pTi) surfaces as coating. The resulting novel implants with a “microporous-mesoporous-macroporous” spatial gradient structure can influence the behavior of adjacent cells; thereby, promoting the integration of bone at the implant interface. Consequently, a thorough exploration of various preparation methods is warranted for hierarchical zeolite coatings with respect to biocompatibility, coating stability, and osteogenesis. In this study, we employed three methods: in situ crystal growth, secondary growth, and layer-by-layer assembly, to construct hierarchical zeolite coatings on pTi, resulting in the development of a gradient structure. The findings of this investigation unequivocally demonstrated that the LBL-coating method consistently produced coatings characterized by superior uniformity, heightened surface roughness, and increased hydrophilicity, as well as increased biomechanical properties. These advantages considerably amplified cell adhesion, spreading, osteogenic differentiation, and mineralization of MC3T3-E1 cells, presenting superior biological functionality when compared to alternative coating methods. The outcomes of this research provide a solid theoretical basis for the clinical translation of hierarchical zeolite coatings in surface modifications for orthopedic implants.
Doxorubicin-sensitive and -resistant colorectal cancer spheroid models: assessing tumor microenvironment features for therapeutic modulation
Authors: Valente Ruben , Cordeiro Sandra , Luz André , Melo Maria C. , Rodrigues Catarina Roma , Baptista Pedro V. , Fernandes Alexandra R.
Published: December 2023

Introduction: The research on tumor microenvironment (TME) has recently been gaining attention due to its important role in tumor growth, progression, and response to therapy. Because of this, the development of three-dimensional cancer models that mimic the interactions in the TME and the tumor structure and complexity is of great relevance to cancer research and drug development.

Methods: This study aimed to characterize colorectal cancer spheroids overtime and assess how the susceptibility or resistance to doxorubicin (Dox) or the inclusion of fibroblasts in heterotypic spheroids influence and modulate their secretory activity, namely the release of extracellular vesicles (EVs), and the response to Dox-mediated chemotherapy. Different characteristics were assessed over time, namely spheroid growth, viability, presence of hypoxia, expression of hypoxia and inflammation-associated genes and proteins. Due to the importance of EVs in biomarker discovery with impact on early diagnostics, prognostics and response to treatment, proteomic profiling of the EVs released by the different 3D spheroid models was also assessed. Response to treatment was also monitored by assessing Dox internalization and its effects on the different 3D spheroid structures and on the cell viability.

Results and Discussion: The results show that distinct features are affected by both Dox resistance and the presence of fibroblasts. Fibroblasts can stabilize spheroid models, through the modulation of their growth, viability, hypoxia and inflammation levels, as well as the expressions of its associated transcripts/proteins, and promotes alterations in the protein profile exhibit by EVs. Summarily, fibroblasts can increase cell-cell and cell-extracellular matrix interactions, making the heterotypic spheroids a great model to study TME and understand TME role in chemotherapies resistance. Dox resistance induction is shown to influence the internalization of Dox, especially in homotypic spheroids, and it is also shown to influence cell viability and consequently the chemoresistance of those spheroids when exposed to Dox. Taken together these results highlight the importance of finding and characterizing different 3D models resembling more closely the in vivo interactions of tumors with their microenvironment as well as modulating drug resistance.
The effect of problem-based learning on cognitive skills in solving geometric construction problems: a case study in Kazakhstan
Authors: Tursynkulova Elmira , Madiyarov Nurlybay , Sultanbek Turlybek , Duysebayeva Peruza
Published: December 2023

Introduction

This study aims to investigate the impact of a Problem-Based Learning (PBL) course on cognitive skills (i.e., Critical Thinking, Problem-Solving, Logical Reasoning, Creativity, and Decision-Making) in the context of solving geometric construction problems.

Methods

The research utilized a quasi-experimental design involving a control group and an experimental group to assess the effects of the PBL intervention. Cognitive skills were measured using a custom-designed questionnaire. Additionally, Structural Equation Modeling (SEM) was employed in a subsequent phase to scrutinize the causal interrelationships among these cognitive skills.

Results

In the initial phase, the findings revealed that the PBL intervention had a statistically significant positive impact on problem-solving and creativity skills. However, the effects on critical thinking, logical reasoning, and decision-making skills did not reach statistical significance. In the subsequent phase employing SEM, the analysis demonstrated significant positive relationships, particularly between critical thinking and problem-solving, critical thinking and logical reasoning, logical reasoning and problem-solving, and logical reasoning and creativity. Notably, creativity also exhibited a significant positive effect on problem-solving.

Discussion

This study underscores the nuanced impact of PBL on different cognitive skills, with clear enhancements observed in problem-solving and creativity. However, the study suggests that the effects may not be uniform across all cognitive skills. These findings offer valuable insights for educators and curriculum designers, emphasizing the need for tailored approaches when integrating PBL to foster cognitive skill development.
The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice
Authors: Van Loh Brooke M. , Yaw Alexandra M. , Breuer Joseph A. , Jackson Brooke , Nguyen Duong , Jang Krystal , Ramos Fabiola , Ho Emily V. , Cui Laura J. , Gillette Dominique L. M. , Sempere Lorenzo F. , Gorman Michael R. , Tonsfeldt Karen J. , Mellon Pamela L. , Hoffmann Hanne M.
Published: December 2023

Background

The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function.

Methods

To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre).

Results

We found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2. Interestingly, Vax1Vip females presented with increased expression of arginine vasopressin (Avp) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo. We found that GnRH neurons in Vax1Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1Vip mice were fertile and generated litters comparable in size and frequency to controls.

Conclusion

Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.
Advancements in super-resolution methods for smart meter data
Authors: Iversen Malin , Khan Mehak , Miraki Amir , Arghandeh Reza
Published: December 2023

This paper presents a comprehensive review of super-resolution methods for smart meter data analysis. Smart meters provide valuable insights into household electricity consumption, but their low-frequency data limits the ability to capture detailed patterns. Super-resolution techniques address this challenge through the reconstruction of high-resolution data from low-resolution measurements. The review covers both non-machine learning-based methods (interpolation, signal processing, and statistics) and machine learning-based methods (CNNs, GANs). Four selected methods are discussed in detail, highlighting their principles, advantages, and limitations. These methods demonstrate superior accuracy in enhancing data completeness, capturing complex relationships, and improving resolution. The review contributes to the advancement of super-resolution techniques for smart meter data analysis, providing researchers and practitioners with valuable insights for efficient energy management and forecasting.
Effects of rural collective economy policy on the common prosperity in China: based on the mediating effect of farmland transfer
Authors: Jiang Fan , Jiang Yadan , Peng Jiquan , Lv Yangqin , Wang Weiwei , Zhou Ziming
Published: December 2023

The rural collective economy plays a crucial role in achieving the common prosperity of farmers, revitalizing the countryside, and modernizing agriculture in China. This paper analyses the impact and internal mechanism of the policy on the level of common prosperity, using provincial panel data from China from 2011 to 2020. Additionally, it investigates whether the rapid development of the rural collective economy takes into account both economic growth and income distribution. The findings demonstrate that the policy significantly enhances the common prosperity of farmers and rural areas. These conclusions remain valid even after considering the endogeneity problem and conducting robustness tests using the time-varying difference-in-differences model. Furthermore, the intermediary effect model reveals that the increase in the rate of farmland transfer and the proportion of scale operation play crucial roles in transmitting the benefits of the policy to achieve common prosperity. The result of the heterogeneity analysis indicates that the marginal decline of policy effect has a greater impact on the enhancement of rural collective economy in the less developed provinces of the central and western regions in China, compared to the developed provinces of the eastern region. These findings have targeted policy significance for promoting the sustainable development of agricultural and rural areas.
ATF5 promotes malignant T cell survival through the PI3K/AKT/mTOR pathway in cutaneous T cell lymphoma
Authors: Cao Mengzhou , Lai Pan , Liu Xiangjun , Liu Fengjie , Qin Yao , Tu Ping , Wang Yang
Published: December 2023

Backgrounds

Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma characterized by skin infiltration of malignant T cells. The biological overlap between malignant T cells and their normal counterparts has brought obstacles in identifying tumor-specific features and mechanisms, limiting current knowledge of CTCL pathogenesis. Transcriptional dysregulation leading to abnormal gene expression profiles contributes to the initiation, progression and drug resistance of cancer. Therefore, we aimed to identify tumor-specific transcription factor underlying CTCL pathology.

Methods

We analyzed and validated the differentially expressed genes (DEGs) in malignant T cells based on single-cell sequencing data. Clinical relevance was evaluated based on progression-free survival and time to next treatment. To determine the functional importance, lentivirus-mediated gene knockdown was conducted in two CTCL cell lines Myla and H9. Cell survival was assessed by examining cell viability, colony-forming ability, in-vivo tumor growth in xenograft models, apoptosis rate and cell-cycle distribution. RNA sequencing was employed to investigate the underlying mechanisms.

Results

Activating transcription factor 5 (ATF5) was overexpressed in malignant T cells and positively correlated with poor treatment responses in CTCL patients. Mechanistically, ATF5 promoted the survival of malignant T cells partially through the PI3K/AKT/mTOR pathway, and imparted resistance to endoplasmic reticulum (ER) stress-induced apoptosis.

Conclusions

These findings revealed the tumor-specific overexpression of the transcription factor ATF5 with its underlying mechanisms in promoting tumor survival in CTCL, providing new insight into the understanding of CTCL’s pathology.
Assessment of the cytolytic potential of a multivirus-targeted T cell therapy using a vital dye-based, flow cytometric assay
Authors: Koukoulias Kiriakos , Papayanni Penelope G. , Jones Julia , Kuvalekar Manik , Watanabe Ayumi , Velazquez Yovana , Gilmore Sarah , Papadopoulou Anastasia , Leen Ann M. , Vasileiou Spyridoula
Published: December 2023

Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (51Cr) release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects [i.e. sensitivity, short (4-6 hours) assay duration] may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses [Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr virus (EBV), and human herpes virus 6 (HHV6)] and when administered to allogeneic hematopoietic stem cell (HCT) or solid organ transplant (SOT) recipients have been associated with clinical benefit. However, despite mediating potent antiviral effects in vivo, capturing in vitro cytotoxic potential has proven difficult in a traditional 51Cr release assay. Now, in addition to cytotoxicity surrogates, including CD107a and Granzyme B, we report on an alternative, vital dye -based, flow cytometric platform in which superior sensitivity and prolonged effector:target co-culture duration enabled the reliable detection of both CD4- and CD8-mediated in vitro cytolytic activity against viral targets without non-specific effects.
Lymphodepletion – an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle
Authors: Lickefett Benno , Chu Lulu , Ortiz-Maldonado Valentin , Warmuth Linda , Barba Pere , Doglio Matteo , Henderson David , Hudecek Michael , Kremer Andreas , Markman Janet , Nauerth Magdalena , Negre Helene , Sanges Carmen , Staber Philipp B. , Tanzi Rebecca , Delgado Julio , Busch Dirk H. , Kuball Jürgen , Luu Maik , Jäger Ulrich
Published: December 2023

Lymphodepletion (LD) or conditioning is an essential step in the application of currently used autologous and allogeneic chimeric antigen receptor T-cell (CAR-T) therapies as it maximizes engraftment, efficacy and long-term survival of CAR-T. Its main modes of action are the depletion and modulation of endogenous lymphocytes, conditioning of the microenvironment for improved CAR-T expansion and persistence, and reduction of tumor load. However, most LD regimens provide a broad and fairly unspecific suppression of T-cells as well as other hematopoietic cells, which can also lead to severe side effects, particularly infections. We reviewed 1271 published studies (2011-2023) with regard to current LD strategies for approved anti-CD19 CAR-T products for large B cell lymphoma (LBCL). Fludarabine (Flu) and cyclophosphamide (Cy) (alone or in combination) were the most commonly used agents. A large number of different schemes and combinations have been reported. In the respective schemes, doses of Flu and Cy (range 75-120mg/m2 and 750-1.500mg/m2) and wash out times (range 2-5 days) differed substantially. Furthermore, combinations with other agents such as bendamustine (benda), busulfan or alemtuzumab (for allogeneic CAR-T) were described. This diversity creates a challenge but also an opportunity to investigate the impact of LD on cellular kinetics and clinical outcomes of CAR-T. Only 21 studies explicitly investigated in more detail the influence of LD on safety and efficacy. As Flu and Cy can potentially impact both the in vivo activity and toxicity of CAR-T, a more detailed analysis of LD outcomes will be needed before we are able to fully assess its impact on different T-cell subsets within the CAR-T product. The T2EVOLVE consortium propagates a strategic investigation of LD protocols for the development of optimized conditioning regimens.
Circular RNAs in inflammatory bowel disease
Authors: Lun Jie , Guo Jing , Yu Mengchao , Zhang Hongwei , Fang Jing
Published: December 2023

Inflammatory bowel disease (IBD) is a term encompassing a few chronic inflammatory disorders that leads to damage of the intestinal tract. Although much progress has been made in understanding the pathology of IBD, the precise pathogenesis is not completely understood. Circular RNAs (circRNAs) are single-stranded, covalently closed, endogenous molecules in eukaryotes with a variety of biological functions. CircRNAs have been shown to have regulatory effects in many diseases, such as cancer, cardiovascular disease, and neurological disorders. CircRNAs have also been found to play important roles in IBD, and although they are not sufficiently investigated in the context of IBD, a few circRNAs have been identified as potential biomarkers for the diagnosis and prognosis of IBD and as potential therapeutic targets for IBD. Herein, we survey recent progress in understanding the functions and roles of circRNAs in IBD and discuss their potential clinical applications.
Connecting coastal wetland microbial community characteristics with soil physicochemical properties across an estuarine salinity and vegetation gradient in Mobile Bay, AL, USA
Authors: Weingarten Eric A. , Jung Carina M. , Crocker Fiona H. , Kneer Marissa L. , Hurst Nia R. , Chappell Mark A. , Berkowitz Jacob F. , Indest Karl J.
Published: December 2023

Coastal wetlands provide a variety of ecological functions that sustain biodiverse habitats, serve as barriers to storm surge, regulate biogeochemical cycles, and yield ecosystem goods and services that benefit society. The magnitude of wetland functional delivery varies with geomorphology and landscape position, hydropattern and hydrodynamics, vegetation structure and composition, soil properties, and microbial community assemblages and activities. Here we describe soil physicochemical and microbial diversity along a vegetation and salinity gradient in the Mobile Bay estuary, AL, USA and discuss how these factors feedback on ecosystem characteristics and the delivery of ecological functions. We incorporated microbial biomass, diversity, and community composition into patterns of dominant vegetation cover type and soil properties. Stepwise model selection using permutation tests indicated that vegetation type >> soil horizon > and salinity strongly influenced microbe-soil relationships. The dominant variables governing microbial content were total sulfur concentration in surface soils and nitrate and nitrite (NOx) for subsurface soils. All biotic and abiotic variables indicated that seasonally inundated forested wetlands represented a distinct microbial biome within the Mobile Bay estuary compared to more frequently flooded and increasingly salt-tolerant Typha, tidal shrub, and Juncus wetland types. Compared with the other wetland types examined for this study, forested wetlands contained ~80% less organic carbon content, ~75% less nitrogen, ~33% less phosphorus, and ~95% less sulfur. Our results show the benefit of incorporating microbial trait data, including metataxonomics, enzymatics, and biomass, with other ecosystem properties such as vegetation and soil characterization data.
Compressive mechanical properties of cottonseed
Authors: Zheng Yuanzhao , Wang Meng , Du Xintian , Zhang Hongwen , Wang Lei , Wei Ximei , Fu Xuewen , Wang Jun
Published: December 2023

Understanding cottonseeds’ basic physical parameters and compressive mechanical properties is necessary in seed cotton packing and cottonseed processing. In this study, the basic physical parameters of three cottonseed varieties (Huiyuan 720, Xinluzao 61, and Xinluzao 74) under different moisture contents (6%, 9%, 12%, and 15%) were measured. These parameters include 1000-grain weight, triaxial dimension, and sphericity. The effects of different moisture, varieties, and compression orientation (horizontal and vertical) on the compressive mechanical properties of the cottonseed were studied, and the variance analysis of the experimental data showed that the triaxial dimension, 1000-grain weight, arithmetic mean diameter, and geometric mean diameter of cottonseeds of the same variety increased with an increase in moisture content. Extremely significant differences (p< 0.01) were found in the physical parameters among different varieties. The main factors affecting crushing force and apparent elastic modulus are moisture content, variety, and compression orientation. For deformation, the main factors are moisture content, compression orientation, and variety. Moreover, compression orientation, moisture content, and variety are the main factors affecting failure energy. The results obtained that the crushing force and apparent elastic modulus decreased, deformation increased, and failure energy decreased first and then increased with the increase in moisture content under the same cottonseed variety. The results also provided the basic physical parameters for the design parameter optimization of seed cotton harvesting and processing machinery.
Artificial intelligence-based screening for amblyopia and its risk factors: comparison with four classic stereovision tests
Authors: Csizek Zsófia , Mikó-Baráth Eszter , Budai Anna , Frigyik Andrew B. , Pusztai Ágota , Nemes Vanda A. , Závori László , Fülöp Diána , Czigler András , Szabó-Guth Kitti , Buzás Péter , Piñero David P. , Jandó Gábor
Published: December 2023

Introduction

The development of costs-effective and sensitive screening solutions to prevent amblyopia and identify its risk factors (strabismus, refractive problems or mixed) is a significant priority of pediatric ophthalmology. The main objective of our study was to compare the classification performance of various vision screening tests, including classic, stereoacuity-based tests (Lang II, TNO, Stereo Fly, and Frisby), and non-stereoacuity-based, low-density static, dynamic, and noisy anaglyphic random dot stereograms. We determined whether the combination of non-stereoacuity-based tests integrated in the simplest artificial intelligence (AI) model could be an alternative method for vision screening.

Methods

Our study, conducted in Spain and Hungary, is a non-experimental, cross-sectional diagnostic test assessment focused on pediatric eye conditions. Using convenience sampling, we enrolled 423 children aged 3.6–14 years, diagnosed with amblyopia, strabismus, or refractive errors, and compared them to age-matched emmetropic controls. Comprehensive pediatric ophthalmologic examinations ascertained diagnoses. Participants used filter glasses for stereovision tests and red-green goggles for an AI-based test over their prescribed glasses. Sensitivity, specificity, and the area under the ROC curve (AUC) were our metrics, with sensitivity being the primary endpoint. AUCs were analyzed using DeLong’s method, and binary classifications (pathologic vs. normal) were evaluated using McNemar’s matched pair and Fisher’s nonparametric tests.

Results

Four non-overlapping groups were studied: (1) amblyopia (n = 46), (2) amblyogenic (n = 55), (3) non-amblyogenic (n = 128), and (4) emmetropic (n = 194), and a fifth group that was a combination of the amblyopia and amblyogenic groups. Based on AUCs, the AI combination of non-stereoacuity-based tests showed significantly better performance 0.908, 95% CI: (0.829–0.958) for detecting amblyopia and its risk factors than most classical tests: Lang II: 0.704, (0.648–0.755), Stereo Fly: 0.780, (0.714–0.837), Frisby: 0.754 (0.688–0.812),p < 0.02,n = 91, DeLong’s method). At the optimum ROC point, McNemar’s test indicated significantly higher sensitivity in accord with AUCs. Moreover, the AI solution had significantly higher sensitivity than TNO (p = 0.046, N = 134, Fisher’s test), as well, while the specificity did not differ.

Discussion

The combination of multiple tests utilizing anaglyphic random dot stereograms with varying parameters (density, noise, dynamism) in AI leads to the most advanced and sensitive screening test for identifying amblyopia and amblyogenic conditions compared to all the other tests studied.
Probing the interaction of lysozyme with cardiac glycoside digitoxin: experimental and in silico analyses
Authors: Ali Mohd Sajid , Al-Lohedan Hamad A. , Bhati Rittik , Muthukumaran Jayaraman
Published: December 2023

Digitoxin is a cardiac glycoside used to treat heart failure and heart arrhythmia. However, its therapeutic concentration range is very narrow. High doses of digitoxin are associated with severe side effects; therefore, it is necessary to develop the delivery system which can control the plasma levels of it. In this context, the binding of lysozyme, an important protein having many applications, with digitoxin has been studied to see the ability of the former as a carrier. The studies were carried out using both experimental and computational methods. The intrinsic fluorescence of lysozyme increased on the addition of digitoxin. Fluorescence results suggested that there was a strong interaction between lysozyme and digitoxin which was favored, mainly, by hydrophobic forces. Further, digitoxin affected the secondary structure of lysozyme slightly by causing the partial unfolding of lysozyme. The preferred binding site of digitoxin within lysozyme was the large cavity of the protein. Molecular docking studies also established the principal role of hydrophobic forces in the binding with a significant support of hydrogen bonding. Frontier molecular orbitals of free digitoxin and in complexation with lysozyme were also computed and discussed. The findings from molecular dynamics simulation studies elucidate that, when contrasted with the first and third conformations of the digitoxin-bound lysozyme complex, the second conformation promotes structural stability, reduces flexibility, and enhances the compactness and folding properties of lysozyme. The overall study shows that lysozyme could act as a potential carrier for digitoxin in pharmaceutical formulations.
Genetically encoded mediators for sonogenetics and their applications in neuromodulation
Authors: Wang Hsien-Chu , Phan Thi-Nhan , Kao Chi-Ling , Yeh Chih-Kuang , Lin Yu-Chun
Published: December 2023

Sonogenetics is an emerging approach that harnesses ultrasound for the manipulation of genetically modified cells. The great penetrability of ultrasound waves enables the non-invasive application of external stimuli to deep tissues, particularly advantageous for brain stimulation. Genetically encoded ultrasound mediators, a set of proteins that respond to ultrasound-induced bio-effects, play a critical role in determining the effectiveness and applications of sonogenetics. In this context, we will provide an overview of these ultrasound-responsive mediators, delve into the molecular mechanisms governing their response to ultrasound stimulation, and summarize their applications in neuromodulation.
Neurological mechanism and efficacy of acupuncture for breast cancer-related insomnia: a study protocol for randomized clinical trial
Authors: Liu Lumin , Yin Ping , Dong Yiyue , Fan Qian , Huai Yisheng , Zhang Shijie , Lv Shunyi , Wang Xueyang , Chen Yuelai
Published: December 2023

Background

Breast cancer survivors (BCSs) are at a higher risk of developing insomnia. The negative effects of cancer-related insomnia (CRI) include depression, anxiety, fatigue, aggressive pain, impaired immune functioning, decreased quality of life, and even increased cancer mortality. Although preliminary progress has been made in the treatment of CRI with acupuncture, the evidence is insufficient and the neurological mechanism underlying the effect of acupuncture is still unclear.

Methods

The study employs a single-blinded, randomized, controlled trial design. A total of 80 participants will be randomly allocated in a 1:1 ratio to either the treatment group (n = 40) or the control group (n = 40). The former will receive acupuncture treatment, while the latter will receive sham acupuncture treatment. Both groups will receive 12 sessions over a 4-week period, three times per week (every other day), and each session will last for 30 min. Follow-up assessments will be conducted in week 8. The primary outcome will be the treatment response rate. Secondary outcomes include the change in Insomnia Severity Index (ISI), the treatment remission rate, actigraphy sleep assessment, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Core Scale (QLQ-C30), the weekly usage of remedial drugs, and functional magnetic resonance imaging (fMRI) analysis. Data for the outcomes will be collected at week 0 (the baseline), week 1 (the intervention period), week 4 (the post-treatment period), and week 8 (the follow-up period).

Discussion

The objective of this study is to assess the efficacy of acupuncture for patients with CRI in comparison with sham acupuncture. Additionally, the research aims to explore the neuropathological mechanisms of CRI and provide the first evidence on the characteristics of acupuncture treatment using fMRI. We expect that the results of this study will provide valuable scientific evidence of acupuncture treatment for CRI.

Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2300070349: https://www.chictr.org.cn/showproj.html?proj=188677.
Neuropathological findings in COVID-19 vs. non-COVID-19 acute respiratory distress syndrome—A case-control study
Authors: Humayun Mariyam , Zhang Lucy , Zaikos Thomas D. , Kannapadi Nivedha , Suarez Jose I. , Hager David N. , Troncoso Juan C. , Cho Sung-Min
Published: December 2023

Acute brain injury (ABI) and neuroinflammation is reported in COVID-19 and acute respiratory distress syndrome (ARDS). It remains unclear if COVID-19 plays an independent role in development of ABI compared to those with non-COVID-19 ARDS. We aimed to evaluate if COVID-19 ARDS is associated with higher risk and specific patterns of ABI compared to non-COVID-19 ARDS. We conducted an age and sex matched case-control autopsy study at a tertiary academic center. Ten patients with COVID-19 ARDS were matched to 20 non-COVID-19 ARDS patients. Baseline demographics were comparable between the two groups including severity of ARDS (p = 0.3). The frequency of overall ABI (70 vs. 60%), infratentorial ABI (40 vs. 25%), ischemic infarct (40 vs. 25%), intracranial hemorrhage (30 vs. 35%), and hypoxic-ischemic brain injury (30 vs. 35%) was similar between COVID-19 and non-COVID-19 ARDS patients, respectively (p > 0.05). Intracapillary megakaryocytes were exclusively seen in 30% of COVID-19 patients. Overall, frequency and pattern of ABI in COVID-19 ARDS was comparable to non-COVID-19.
New insight on microglia activation in neurodegenerative diseases and therapeutics
Authors: Xu Yucong , Gao Wei , Sun Yingnan , Wu Minghua
Published: December 2023

Microglia are immune cells within the central nervous system (CNS) closely linked to brain health and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In response to changes in the surrounding environment, microglia activate and change their state and function. Several factors, example for circadian rhythm disruption and the development of neurodegenerative diseases, influence microglia activation. In this review, we explore microglia’s function and the associated neural mechanisms. We elucidate that circadian rhythms are essential factors influencing microglia activation and function. Circadian rhythm disruption affects microglia activation and, consequently, neurodegenerative diseases. In addition, we found that abnormal microglia activation is a common feature of neurodegenerative diseases and an essential factor of disease development. Here we highlight the importance of microglia activation in neurodegenerative diseases. Targeting microglia for neurodegenerative disease treatment is a promising direction. We introduce the progress of methods targeting microglia for the treatment of neurodegenerative diseases and summarize the progress of drugs developed with microglia as targets, hoping to provide new ideas for treating neurodegenerative diseases.
Fabp5 is a common gene between a high-cholesterol diet and acute pancreatitis
Authors: Qiu Minhao , Cai Fangfang , Huang Yining , Sun Liang , Li Jianmin , Wang Wei , Basharat Zarrin , Zippi Maddalena , Goyal Hemant , Pan Jingye , Hong Wandong
Published: December 2023

Background and aims

Hypercholesterolemia has been identified as risk factor for severe acute pancreatitis (AP). We aimed to identify the common differentially expressed genes (DEGs) between a high-cholesterol diet and AP.

Methods

We retrived gene expression profiles from the GEO database. DEGs were assessed using GEO2R. For AP hub genes, we conducted functional enrichment analysis and protein–protein interaction (PPI) analysis. GeneMANIA and correlation analysis were employed to predict potential DEG mechanisms. Validation was done across various healthy human tissues, pancreatic adenocarcinoma, peripheral blood in AP patients, and Sprague–Dawley rats with AP.

Results

The gene “Fabp5” emerged as the sole common DEG shared by a high-cholesterol diet and AP. Using the 12 topological analysis methods in PPI network analysis, Rela, Actb, Cdh1, and Vcl were identified as hub DEGs. GeneMANIA revealed 77.6% physical interactions among Fabp5, TLR4, and Rela, while genetic correlation analysis indicated moderate associations among them. Peripheral blood analysis yielded area under the ROC curve (AUC) values of 0.71, 0.63, 0.74, 0.64, and 0.91 for Fabp5, TLR4, Actb, Cdh1 genes, and artificial neural network (ANN) model respectively, in predicting severe AP. In vivo immunohistochemical analysis demonstrated higher Fabp5 expression in the hyperlipidemia-associated AP group compared to the AP and control groups.

Conclusion

Fabp5 emerged as the common DEG connecting a high-cholesterol diet and AP. Rela was highlighted as a crucial hub gene in AP. Genetic interactions were observed among Fabp5, TLR4, and Rela. An ANN model consisting of Fabp5, TLR4, Actb, and Cdh1 was helpful in predicting severe AP.
Pathogenetic characterization of a Micrococcus luteus strain isolated from an infant
Authors: Shi Xiaolu , Qiu Shuxiang , Ji Liyin , Lu Huiqun , Wu Shuang , Chen Qiongcheng , Zou Xuan , Hu Qinghua , Feng Tiejian , Chen Shiting , Cui Wenkai , Xu Shiqin , Jiang Min , Cai Rui , Geng Yijie , Bai Qinqin , Huang Dingjie , Liu Peihui
Published: December 2023

Purpose

To explore the clinical characteristics of Micrococcus luteus bloodstream infection in an infant and characterize the phenotype and genotype of the isolated strains, as well as seek suitable infection models for assessing virulence.

Methods

Clinical data was collected from an infant patient diagnosed with M. luteus bloodstream infection. Metagenomic sequencing was performed on the isolated blood sample. The strain was isolated and underwent mass spectrometry, biochemical tests, antibiotic susceptibility assays, and whole-genome sequencing. The Galleria mellonella infection model was used to assess M. luteus virulence.

Results

Patient responded poorly to cephalosporins, but recovered after Linezolid treatment. Metagenomic sequencing identified M. luteus as the predominant species in the sample, confirming infection. They were identified as M. luteus with a high confidence level of 98.99% using mass spectrometry. The strain showed positive results for Catalase, Oxidase, and Urea tests, and negative results for Mannose, Xylose, Lactose, Mannitol, Arginine, and Galactose tests, consistent with the biochemical profile of M. luteus reference standards. M. luteus susceptibility to 15 antibiotics was demonstrated and no resistance genes were detected. Predicted virulence genes, including clpB, were associated with metabolic pathways and the type VI secretion system. The infection model demonstrated dose-dependent survival rates.

Conclusion

The infant likely developed a bloodstream infection with M. luteus due to compromised immunity. Although the isolated strain is sensitive to cephalosporin antibiotics and has low pathogenicity in infection models, clinical treatment with cephalosporins was ineffective. Linezolid proved to be effective, providing valuable guidance for future clinical management of such rare infections.
Preclinical evidence of reno-protective effect of quercetin on acute kidney injury: a meta-analysis of animal studies
Authors: Zeng Yi-Fan , Li Jing-Yu , Wei Xin-Yu , Ma Si-Qing , Wang Qiu-Guo , Qi Zhen , Duan Zhi-Cheng , Tan Ling , Tang Hao
Published: December 2023

Objective: This study evaluated the reno-protective effects of quercetin in animal models of acute kidney injury (AKI).

Methods: We conducted a systematic search of literature published before April 2023 in PubMed, Web of Science, and EMBASE databases. Methodological quality was assessed by SYRCLE’s RoB tool. Funnel plot, Egger’s test, and Begg’s test were used to determine publication bias.

Results: A total of 19 studies with 288 animals were included in this meta-analysis. The methodology quality scores of the included studies ranged from 4 to 7. The results indicated that quercetin reduced blood urea nitrogen (SMD = −4.78; 95% CI: 6.45, −3.12; p < 0.01; I2 = 84%) and serum creatinine (SMD: 2.73, 95% CI: 3.66, −1.80; p < 0.01; I2 = 80%) in AKI models. The result of sensitivity analysis was stable, while the results of funnel plot indicated asymmetric. In addition, we further analyzed inflammatory cytokines, oxidative stress levels, and kidney injury scores, and found that quercetin treatment had antioxidant and anti-inflammatory effects and improved kidney injury scores in animal models of AKI.

Conclusion: Quercetin exhibited a promising reno-protective effect in AKI animal models.

Systematic Review Registration: PROSPERO (CRD42023433333).
Evolution of nanohillocks by fullerene ion-induced localized plasma
Authors: Altuijri R. , El Maati L. Abu , Ahmad M. , Alharthi N. S. , Moslem W. M. , Elkamash I. S.
Published: December 2023

Surface nanostructures etch without chemicals; owing to this, their development is a crucial technical process. Surface nanohillocks may be created by irradiating yttrium iron garnet (YIG) with 30-MeV C60 cluster ions. The nanohillock creation mechanism is disputed. In this study, we propose that the formation mechanism is a plasma collective effect of charged particles that depends on localized rogue waves. Rogue waves will explain YIG surface nanohillock creation using a traditional hydrodynamic plasma model. Analytically solving hydrodynamic ion fluid equations and Maxwellian electron distributions yields a non-linear Schrödinger equation. Solving the latter gives us plausible rogue wave domains. Rogue waves concentrate charged ions from the surroundings into a small, confined zone, generating surface nanohillocks. The relevance of different plasma parameters is highlighted in the rogue wave profile.