bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fault Diagnosis Method under Data Imbalance Based on Generative Adversarial Network and Long Short-Term Memory Algorithms for Aircraft Hydraulic System
Authors: Shen Kenan , Zhao Dongbiao
Published: February 2023

Safe and stable operation of the aircraft hydraulic system is of great significance to the flight safety of an aircraft. Any fault may be a threat to flight safety and may lead to enormous economic losses and even human casualties. Hence, the normal status of the aircraft hydraulic system is large, but very few data samples relate to the fault status. This causes a data imbalance in the fault diagnosis of the aircraft hydraulic system, which directly affects the accuracy of aircraft fault diagnosis. To solve the data imbalance problem in the fault diagnosis of the aircraft hydraulic system, this paper proposes an improved GAN-LSTM algorithm by using the improved GAN method, which can stably and accurately generate high-quality simulated fault samples using a small number of fault data. First, the model of the aircraft hydraulic system was built using AMESim software, and the imbalanced fault data and normal status data were acquired. Then, the imbalanced data were used to train the GAN model until the system reached a Nash equilibrium. By comparing the time domain and frequency signal, it was found that the quality of the generated sample was highly similar to the real sample. Moreover, LSTM (long short-term memory) and some other data-driven intelligent fault diagnosis methods were used as classifiers. The accuracy of these fault diagnosis methods increased steadily when the number of fault samples was gradually increased until it reached a balance with the normal sample. Meanwhile, three different sample generation methods were compared and analyzed to find the method with the best data generation ability. Finally, the anti-noise performance of the LSTM-GAN method was analyzed; this model has superior noise immunity.
Effects of LED Lights with Defined Spectral Proportion on Growth and Reproduction of Indigenous Beijing-You Chickens
Authors: Sun Yanyan , Li Yunlei , Ma Shumei , Shi Lei , Chen Chao , Li Dongli , Guo Jiangpeng , Ma Hui , Yuan Jingwei , Chen Jilan
Published: February 2023

Light presents an important exogenous factor for poultry. This study examined effects of LED lights with different defined spectrums on growth and reproduction of indigenous Beijing-You chickens. A total of 576 one-day old female chicks were divided into 16 rooms, and each were exposed to four different lights: LED A (21% green light, 30% blue light, 24% yellow light, and 25% red light), B (35%, 35%, 18%, and 12%), C (27%, 30%, 22%, and 21%), or compact fluorescent lamps (CFL, 15%, 28%, 41%, and 16%). Results showed that feed intake and feed conversion ratio were comparable among treatments throughout the 17 week rearing period (p > 0.05). LED C showed similar body weight gain with CFL, but higher than LED A and B. The CFL birds start to lay on 132.25 d, while LED B did not lay until 148.25 d. The age at 50% egg production did not vary among groups (p = 0.12). Total egg number until 43 week of LED B was higher than others (p < 0.05). Therefore, LED lights with defined spectral proportion have different effects on chickens’ growth and reproduction. The LED C promotes the prepubertal growth, and the LED B provides proper sexual maturation age and better egg-laying persistence.
Automated Virtual Fencing Can Effectively Contain Sheep: Field Trials and Prospects
Authors: Campbell Dana L. M. , Belson Sue , Lea Jim M. , Ouzman Jackie , Lee Caroline , Kalinowski Troy , Mowat Damian , Llewellyn Rick S.
Published: February 2023

Virtual fencing technology uses on-animal devices to communicate boundaries via a warning audio tone and electrical pulse signals. There is currently limited validation work on sheep. This study used modified cattle eShepherd® virtual fencing neckbands on reduced-wool sheep with clipped necks to enable automated trials with small groups across both day and night. The first 5-day trial with six Dorper crossbred sheep was conducted in an experimental paddock setting, with a second 5-day trial conducted with 10 Ultra White sheep on a commercial farm. The animals across both trials were contained in the inclusion zone for 99.8% and 92.2% of the trial period, with a mean percentage (±SD) of total audio cues as audio only (i.e., not followed by an electrical pulse) being 74.9% ± 4.6 in the first trial, and 83.3% ± 20.6 for the second trial. In the second trial, sheep crossed over into the exclusion zone on the third night and remained there until they were walked out for their daily yard check in the morning. These preliminary trial results are promising for the use of automated technology on sheep, but suitable devices and algorithms still need to be designed specifically for sheep in the long term.
Meta-Regression to Develop Predictive Equations for Urinary Nitrogen Excretion of Lactating Dairy Cows
Authors: Beck Matthew , Marshall Cameron , Garrett Konagh , Campbell Terra , Foote Andrew , Vibart Ronaldo , Pacheco David , Gregorini Pablo
Published: February 2023

Dairy cows’ urinary nitrogen (N) excretion (UN; g/d) represents a significant environmental concern due to their contribution to nitrate leaching, nitrous oxide (a potent greenhouse gas), and ammonia emissions (contributor to N deposition). The first objective of the current study was to determine the adequacy of existing models to predict UN from total mixed ration (TMR)-fed and fresh forage (FF)-fed cows. Next, we aimed to develop equations to predict UN based on animal factors [milk urea nitrogen (MUN; mg/dL) and body weight (BW, kg)] and to explore how these equations are improved when dietary factors, such as diet type, dry matter intake (DMI), or dietary characteristics [neutral detergent fiber (NDF) and crude protein (CP) content], are considered. A dataset was obtained from 51 published experiments composed of 174 treatment means. The whole dataset was used to evaluate the mean and linear biases of three existing equations including diet type as an interaction term; all models had significant linear and mean biases and two of the three models had poor predictive capabilities as indicated by their large relative prediction error (RPE; root mean square error of prediction as a percent of the observed mean). Next, the complete data set was split into training and test sets, which were used to develop and to evaluate new models, respectively. The first model included MUN and BW, and there was a significant interaction between diet type and the coefficients. This model had the worst 1:1 agreement [Lin’s concordance correlation coefficient (CCC) = 0.50] and largest RPE (24.7%). Models that included both animal and dietary factors performed the best, and when included in the model, the effect of diet type was no longer significant (p > 0.10). These models all had very good agreement (CCC ≥ 0.86) and relatively low RPE (≤13.1%). This meta-analysis developed precise and accurate equations to predict UN from dairy cows in both confined and pasture-based systems.
Inspiratory–Expiratory Muscle Training Improved Respiratory Muscle Strength in Dialysis Patients: A Pilot Randomised Trial
Authors: Lamberti Nicola , Piva Giovanni , Battaglia Yuri , Franchi Michele , Pizzolato Matteo , Argentoni Antonio , Gandolfi Giorgio , Gozzi Giulia , Lembo Margherita , Lavisci Pietro , Storari Alda , Rinaldo Natascia , Manfredini Fabio , Cogo Annalisa
Published: February 2023

End-stage kidney disease (ESKD) exposes patients to progressive physical deconditioning involving the respiratory muscles. The aim of this pilot randomized controlled trial was to determine the feasibility and effectiveness of low-intensity respiratory muscle training (RMT) learned at the hospital and performed at home. A group of ESKD patients (n = 22) were randomized into RMT or usual care (control group, CON) in a 1:1 ratio. The respiratory training was performed at home with an inspiratory–expiratory system for a total of 5 min of breathing exercises in a precise rhythm (8 breaths per minute) interspersed with 1 min of rest, two times per day on nondialysis days for a total of 4 weeks, with the air resistance progressively increasing. Outcome measures were carried out every 4 weeks for 3 consecutive months, with the training executed from the 5th to the 8th week. Primary outcomes were maximal inspiratory and expiratory pressure (MIP, MEP), while secondary outcomes were lung capacity (FEV1, FVC, MVV). Nineteen patients without baseline between-group differences completed the trial (T: n = 10; Age: 63 ± 10; Males: n = 12). Both MIP and MEP significantly improved at the end of training in the T group only, with a significant difference of MEP of 23 cmH2O in favor of the RMT group (p = 0.008). No significant variations were obtained for FVC, FEV1 or MVV in either group, but there was a greater decreasing trend over time for the CON group, particularly for FVC (t = −2.00; p = 0.046). Low-fatiguing home-based RMT, with a simple device involving both inspiratory and expiratory muscles, may significantly increase respiratory muscle strength.
High Spatial Resolution Emission Inventory of Air Pollutants and Carbon in China’s Independent Coking Industry
Authors: Chen Xiaochun , Li Jianhui , Jia Min , Chen Shaobo , Zhang Shangxuan , Bo Xin , Feng Xue , Dong Guangxia
Published: February 2023

China is the largest producer and exporter of coke globally, which means that it is very important to understand the characteristics of air pollutants and carbon emissions from China’s independent coking industry. This study was the first to establish a bottom-up inventory of the air pollutants and carbon emissions of China’s independent coking industry during 2001–2018 based on continuous emission monitoring system online monitoring data and unit-based corporate information. Based on the developed emission inventory, four scenarios were established to analyze potential emissions reduction of air pollutants and carbon dioxide (CO2) in future. The emissions of particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), black carbon (BC) and organic carbon (OC) decreased by 62.11%, 63.41%, 72.85%, 63.41% and 63.41%, respectively. CO2, carbon monoxide (CO), volatile organic compounds (VOCs) and nitrogen oxides (NOX) emissions increased by 355.51%, 355.51%, 355.51% and 99.74%, respectively. In 2018, PM10, PM2.5, SO2, NOx, BC, OC, CO, VOCs and CO2 emissions were, respectively. 45.20, 16.91, 63.84, 117.71, 5.07, 5.92, 554.91, 1026.58 Gg, and 176.88 Tg. Shanxi province made the greatest contributions to the total emissions of air pollutants and CO2 from this industry by 25.01%. The emission source that contributed most to PM2.5 (SO2 and NOX) emissions was coke pushing (quenching and the coke oven chimney respectively) in 2018. Under the ULE scenario (2018–2035), PM2.5 and SO2 emissions will reduce by more than 30%. Under the PCP scenario, PM2.5 and SO2 emissions will reduce by more than 55%. Under the CBP scenario, CO2 emissions will peak at 197.99 Tg in 2025 and decrease to 70% of the peak in 2035. The results showed the emission characteristics of air pollutants and CO2, future emission with several scenarios and cooperative reduction potential in China’s independent coking industry, which provides scientific support for the development of pollution control strategies.
Highly Lithiophilic Three-Dimension Framework of Vertical CuO Nanorod Arrays Decorated Carbon Cloth for Dendrite-Free Li Metal Anode
Authors: Wang Kang , Liu Derong , Yu Ping , Gong Hongyu , Jiang Xiaoping , Gao Meng , Li Dongwei
Published: February 2023

An Li metal anode has been proposed as a promising candidate for high energy density electrode material. However, the direct use of Li metal can lead to uncontrollable dendrite growth and massive volume expansion, which generates severe safety hazards and hinders practical application. Herein, we developed a novel Li anode by thermal infusion into three-dimensional (3D) carbon cloth (CC) modified with lithiophilic CuO nanorod arrays (denoted as Li@CuO−CC). The 3D CC offers sufficient space for Li storage and adequate electrolyte/electrode contact for fast charge transfer. The uniformly distributed CuO nanorod arrays can improve the lithiophilicity of CC and redistribute the Li-ion flux on the substrate, leading to uniform Li stripping/plating behavior. As a result, the Li@CuO−CC electrode exhibits a dendrite-free feature and superior cycling performance over 1000 h with low overpotential (12 mV) at a current density of 1 mA cm−2 in the symmetrical cell without significant fluctuations. When coupled with an LiFePO4 cathode, the full cell displays high specific capacity (133.8 mAh g−1 at 1 C), outstanding rate performance, and cycle stability (78.7% capacity retention after 600 cycles at 1 C). This work opens a new approach for the development of construction of an advanced anode for Li metal batteries.
The Application of Porous Scaffolds for Cardiovascular Tissues
Authors: Watanabe Tatsuya , Sassi Salha , Ulziibayar Anudari , Hama Rikako , Kitsuka Takahiro , Shinoka Toshiharu
Published: February 2023

As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability of the artificial organs. Therefore, tissue engineering has attracted significant attention as a tissue regeneration therapy in this area. Porous scaffolds are one of the effective methods for tissue engineering. However, it could be better, and its effectiveness varies depending on the tissue application. This paper will address the challenges presented by various materials and their combinations. We will also describe some of the latest methods for tissue engineering.
Regulation of Renin Expression by Β1-Integrin in As4.1 Juxtaglomerular Line Cells
Authors: Saito Nobumichi , Toyoda Masao , Kondo Masumi , Abe Makiko , Sanechika Noriyuki , Kimura Moritsugu , Sawada Kaichiro , Fukagawa Masafumi
Published: February 2023

(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that β1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of β1-integrin phosphorylation/dephosphorylation; knockdown of β1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of β1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. β1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of β1-integrin. (4) Conclusions: β1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that β1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane.
Transforming Cross-Linked Cyclic Dimers of KR-12 into Stable and Potent Antimicrobial Drug Leads
Authors: Muhammad Taj , Strömstedt Adam A. , Gunasekera Sunithi , Göransson Ulf
Published: February 2023

Is it possible to enhance structural stability and biological activity of KR-12, a truncated antimicrobial peptide derived from the human host defense peptide LL-37? Based on the mapping of essential residues in KR-12, we have designed backbone-cyclized dimers, cross-linked via a disulfide bond to improve peptide stability, while at the same time improving on-target activity. Circular dichroism showed that each of the dimers adopts a primarily alpha-helical conformation (55% helical content) when bound to lyso-phosphatidylglycerol micelles, indicating that the helical propensity of the parent peptide is maintained in the new cross-linked cyclic form. Compared to KR-12, one of the cross-linked dimers showed 16-fold more potent antimicrobial activity against human pathogens Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans and 8-fold increased activity against Escherichia coli. Furthermore, these peptides retained antimicrobial activity at physiologically relevant conditions, including in the presence of salts and in human serum, and with selective Gram-negative antibacterial activity in rich growth media. In addition to giving further insight into the structure–activity relationship of KR-12, the current work demonstrates that by combining peptide stabilization strategies (dimerization, backbone cyclization, and cross-linking via a disulfide bond), KR-12 can be engineered into a potent antimicrobial peptide drug lead with potential utility in a therapeutic context.
Shifting Treatment Paradigms: Improvements in HR-Positive, HER-2- Negative Breast Cancer Care in Poland from a Clinical Perspective
Authors: Ziobro Marek , Grela-Wojewoda Aleksandra
Published: February 2023

Patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer constitute about 70% of the breast cancer population. About 35% of these patients develop distant metastases and their treatment will be palliative. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors were shown to significantly improve the outcomes of these patients. In combination with endocrine therapy, they have become the standard first-line treatment for HR-positive, HER2-negative breast cancer. In Poland, treatment with CDK4/6 inhibitors is reimbursed only for patients participating in the drug program of the Ministry of Health. However, fulfilling the eligibility criteria for the program may be challenging both for patients and for clinicians. This may lead to a delay in treatment with CDK4/6 inhibitors or a decision to use older and less effective drugs that are more widely available. The aim of this review was to compare the efficacy of first-line therapies in patients with HR-positive, HER2-negative metastatic breast cancer depending on the use of CDK4/6 inhibitors. We compared the efficacy of previous standard therapies with that of ribociclib, a CDK4/6 inhibitor, based on the median progression-free survival (PFS) as an outcome. Median PFS is not affected by the efficacy of subsequent treatment lines and is easy to interpret both for clinicians and for patients. The first-line treatment with chemotherapy or endocrine therapy (without CDK4/6 inhibitors) prolongs median PFS by several months and even to over a dozen months. The first-line treatment with endocrine therapy plus CDK4/6 inhibitors provides an opportunity to achieve a median PFS of more than 25 months and to prolong it by about 9 to 14 months.
Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study
Authors: La Gualana Francesca , Maiorca Francesca , Marrapodi Ramona , Villani Francesca , Miglionico Marzia , Santini Stefano Angelo , Pulcinelli Fabio , Gragnani Laura , Piconese Silvia , Fiorilli Massimo , Basili Stefania , Casato Milvia , Stefanini Lucia , Visentini Marcella
Published: February 2023

New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex. Here we report that vaccination with BNT162b2 led to an increase in the frequency and absolute count of CD4posCD25highCD127low putative Treg cells; in sharp contrast, vaccination with the adenovirus-vectored ChAdOx1 nCoV-19 vaccine led to a significant decrease of CD4posCD25high cells. This pilot study is very preliminary, suffers from important limitations and, frustratingly, very hardly can be refined in Italy because of the >90% vaccination coverage. Thus, the provocative perspective that BNT162b2 and MOGm1Ψ may share the capacity to promote expansion of Treg cells deserves confirmatory studies in other settings.
Epigenetic Mechanisms and Nephrotic Syndrome: A Systematic Review
Authors: Hayward Samantha , Parmesar Kevon , Welsh Gavin I. , Suderman Matthew , Saleem Moin A.
Published: February 2023

A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic marks are reversible but stable regulators of gene expression with utility as biomarkers and therapeutic targets. We aimed to identify and assess all published human studies of epigenetic mechanisms in NS. PubMed (MEDLINE) and Embase were searched for original research articles examining any epigenetic mechanism in samples collected from people with steroid resistant NS, steroid sensitive NS, focal segmental glomerulosclerosis or minimal change disease. Study quality was assessed by using the Joanna Briggs Institute critical appraisal tools. Forty-nine studies met our inclusion criteria. The majority of these examined micro-RNAs (n = 35, 71%). Study quality was low, with only 23 deemed higher quality, and most of these included fewer than 100 patients and failed to validate findings in a second cohort. However, there were some promising concordant results between the studies; higher levels of serum miR-191 and miR-30c, and urinary miR-23b-3p and miR-30a-5p were observed in NS compared to controls. We have identified that the epigenome, particularly DNA methylation and histone modifications, has been understudied in NS. Large clinical studies, which utilise the latest high-throughput technologies and analytical pipelines, should focus on addressing this critical gap in the literature.
Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability
Authors: Calluori Stephanie , Stark Rebecca , Pearson Brandon L.
Published: February 2023

Short tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are characterized by repeat instability. Longer repeat tracts are typically associated with earlier age of onset and increased disease severity. Environmental exposures are suspected to play a role in the pathogenesis of repeat expansion diseases. Here, we review the current knowledge of mechanisms of environmentally induced repeat instability in repeat expansion diseases. The current evidence demonstrates that environmental factors modulate repeat instability via DNA damage and induction of DNA repair pathways, with distinct mechanisms for repeat expansion and contraction. Of particular note, oxidative stress is a key mediator of environmentally induced repeat instability. The preliminary evidence suggests epigenetic modifications as potential mediators of environmentally induced repeat instability. Future research incorporating an array of environmental exposures, new human cohorts, and improved model systems, with a continued focus on cell-types, tissues, and critical windows, will aid in identifying mechanisms of environmentally induced repeat instability. Identifying environmental modulators of repeat instability and their mechanisms of action will inform preventions, therapies, and public health measures.
Towards Quantum-Chemical Level Calculations of SARS-CoV-2 Spike Protein Variants of Concern by First Principles Density Functional Theory
Authors: Ching Wai-Yim , Adhikari Puja , Jawad Bahaa , Podgornik Rudolf
Published: February 2023

The spike protein (S-protein) is a crucial part of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with its many domains responsible for binding, fusion, and host cell entry. In this review we use the density functional theory (DFT) calculations to analyze the atomic-scale interactions and investigate the consequences of mutations in S-protein domains. We specifically describe the key amino acids and functions of each domain, which are essential for structural stability as well as recognition and fusion processes with the host cell; in addition, we speculate on how mutations affect these properties. Such unprecedented large-scale ab initio calculations, with up to 5000 atoms in the system, are based on the novel concept of amino acid–amino acid-bond pair unit (AABPU) that allows for an alternative description of proteins, providing valuable information on partial charge, interatomic bonding and hydrogen bond (HB) formation. In general, our results show that the S-protein mutations for different variants foster an increased positive partial charge, alter the interatomic interactions, and disrupt the HB networks. We conclude by outlining a roadmap for future computational research of biomolecular virus-related systems.
Drug-Eluting Stents: Technical and Clinical Progress
Authors: Koźlik Maciej , Harpula Jan , Chuchra Piotr J. , Nowak Magdalena , Wojakowski Wojciech , Gąsior Paweł
Published: February 2023

Drug-eluting stents (DES) demonstrated superior efficacy when compared to bare metal stents and plain-old balloon angioplasty and are nowadays used in almost all percutaneous revascularization procedures. The design of the stent platforms is constantly improving to maximize its efficacy and safety. Constant development of DES includes adoption of new materials used for scaffold production, new design types, improved overexpansion abilities, new polymers coating and, finally, improved antiproliferative agents. Especially nowadays, with the immense number of available DES platforms, it is crucial to understand how different aspects of stents impact the effect of their implantation, as subtle differences between various stent platforms could impact the most important issue—clinical outcomes. This review discusses the current status of coronary stents and the impact of stent material, strut design and coating techniques on cardiovascular outcomes.
Doping of Graphene Nanostructure with Iron, Nickel and Zinc as Selective Detector for the Toxic Gas Removal: A Density Functional Theory Study
Authors: Mollaamin Fatemeh , Monajjemi Majid
Published: February 2023

In this research, the ability of transition metals (TM)-doped graphene nanosheets to adsorb the toxic gas CO has been investigated. The Langmuir adsorption model was used, with a three-layered ONIOM, using the CAM-B3LYP functional accompanying the LANL2DZ and 6-31+G (d,p) basis sets, and using the Gaussian 16 revision C.01 program, on the complexes of CO adsorbed on (Fe, Ni, Zn)-doped graphene nanosheets. The order of the changes of charge density for the Langmuir adsorption of CO on Fe-doped, Ni-doped, and Zn-doped graphene nanosheets has been investigated. This shows the greatest change of charge density for the Ni-doped graphene nanosheet. However, based on NMR spectroscopy, sharp peaks around the Ni-doped area on the surface of the graphene nanosheet have been observed. In addition, the Ni-doped graphene nanosheet has a large effect on the bond orbitals of C-Ni in the adsorption of CO, having the maximum occupancy. The values of ΔGadso, calculated through IR, showed that ΔGads,CO→ Fe-doped GRo has the highest value, because of a charge density transfer from the oxygen atom in carbon monoxide to the Fe-doped graphene nanosheet. The frontier molecular orbitals, HOMO and LUMO, and the band energy gap accompanying some chemical reactivity parameters, have revealed the attributes of the molecular electrical transport of (Fe, Ni, Zn)-doped graphene nanosheets for the adsorption of CO. As a result, since a CO molecule interacts simultaneously with a Fe, Ni, or Zn atom and the C-C nanosheet, at first it might be separated, as in this state a CO atom constructs a physical bond with the Fe, Ni, or Zn atom, and then the other could be adsorbed chemically on the C-C nanosheet surface. Finally, our results have shown that a considerable amount of charge transfer occurs between CO molecules and TM-doped graphene nanosheets after adsorption, which suggests that TM-doped graphene is more sensitive and selective to the adsorption of CO than a pristine graphene surface.
Imaging and Histopathological Analysis of Microvascular Angiogenesis in Photodynamic Therapy for Oral Cancer
Authors: Yang Tzu-Sen , Hsiao Yen-Chang , Chiang Yu-Fan , Chang Cheng-Jen
Published: February 2023

The objective of this study is to use imaging and histopathological analysis to characterize and monitor microvascular responses to photodynamic therapy (PDT). In vivo chicken chorioallantoic membranes (CAMs) and a stimulated malignant oral lesions animal model were used to determine the blood flow and the biological activities of Photofrin® (2.5 mg/kg) exposed to different laser power densities at 630 nm. The vascular changes, the velocity of the blood flow, the speckle flow index (SFI) of fluorescence changes, and ultrastructure damage in the microvasculature before and after PDT were recorded. The subcellular localization of Photofrin® revealed satisfactory uptake throughout the cytoplasm of human red blood cells at 10 s and 20 s before PDT. The mean blood-flow velocities of the veins and arteries were 500 ± 40 and 1500 ± 100 μm/s, respectively. A significant decrease in the velocities of the blood flow in the veins and arteries was detected in the CAM model after PDT. The veins and arteries of CAMs, exposed to the power densities of 80, 100, and 120 mW/cm2, had average blood-flow velocities of 100 ± 20, 60 ± 10, and 0 μm/s and 300 ± 50, 150 ± 30, and 0 μm/s, respectively. In the stimulated malignant oral lesions animal model, the treated tumors exhibited hemorrhage and red blood cell extravasation after PDT. The oxyhemoglobin and total hemoglobin levels decreased, which resulted in a decrease in tissue oxygen saturation, while the deoxyhemoglobin levels increased. PDT using Photofrin® has the ability to cause the destruction of the targeted microvasculature under nonthermal mechanisms selectively.
Explainable AI for Estimating Pathogenicity of Genetic Variants Using Large-Scale Knowledge Graphs
Authors: Abe Shuya , Tago Shinichiro , Yokoyama Kazuaki , Ogawa Miho , Takei Tomomi , Imoto Seiya , Fuji Masaru
Published: February 2023

Background: To treat diseases caused by genetic variants, it is necessary to identify disease-causing variants in patients. However, since there are a large number of disease-causing variants, the application of AI is required. We propose AI to solve this problem and report the results of its application in identifying disease-causing variants. Methods: To assist physicians in their task of identifying disease-causing variants, we propose an explainable AI (XAI) that combines high estimation accuracy with explainability using a knowledge graph. We integrated databases for genomic medicine and constructed a large knowledge graph that was used to achieve the XAI. Results: We compared our XAI with random forests and decision trees. Conclusion: We propose an XAI that uses knowledge graphs for explanation. The proposed method achieves high estimation performance and explainability. This will support the promotion of genomic medicine.
Breast Cancer Risk Assessment Tools for Stratifying Women into Risk Groups: A Systematic Review
Authors: Velentzis Louiza S. , Freeman Victoria , Campbell Denise , Hughes Suzanne , Luo Qingwei , Steinberg Julia , Egger Sam , Mann G. Bruce , Nickson Carolyn
Published: February 2023

Background: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. Methods: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008–20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. Results: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. Conclusion: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population.
Glucose-Regulated Protein 78 Is a Potential Serum and Imaging Marker for Early Detection of Ovarian Cancer
Authors: Paris Elizabeth A. , Bahr Janice M. , Abramowicz Jacques S. , Basu Sanjib , Barua Animesh
Published: February 2023

Background: Understanding malignant transformation associated with ovarian cancer (OVCA) is important to establish early detection tests. This study examined whether expression of glucose-regulated protein 78 (GRP78, marker of cellular stress) increases during OVCA development, and whether GRP78 can be detected by targeted-transvaginal ultrasound (TVUS) imaging. Methods: Normal ovaries (n = 10), benign (n = 10) and malignant ovarian tumors at early (n = 8) and late stages (n = 16), hens with and without ovarian tumors at early and late stages (n = 10, each) were examined for GRP78 expression during OVCA development by immunohistochemistry, immunoblotting, gene expression and immunoassay. Feasibility of GRP78-targeted TVUS imaging in detecting early OVCA was examined. Results: Compared with normal ovaries and benign tumors, intensity of GRP78 expression was higher (p < 0.0001) in OVCA patients. Compared with normal (9007.76 ± 816.54 pg/mL), serum GRP78 levels were significantly higher (p < 0.05) in patients with early (12,730.59 ± 817.35 pg/mL) and late-stage OVCA (13,930.12 ± 202.35) (p < 0.01). Compared with normal (222.62 ± 181.69 pg/mL), serum GRP78 levels increased (p < 0.05) in hens with early (590.19 ± 198.18 pg/mL) and late-stage OVCA (1261.38 ± 372.85) (p < 0.01). Compared with non-targeted, GRP78-targeted imaging enhanced signal intensity of TVUS (p < 0.0001). Conclusions: Tissue and serum levels of GRP78 increase in association with OVCA. GRP78 offers a potential serum and imaging marker for early OVCA detection.
Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study
Authors: Leblanc Eric , Narducci Fabrice , Ferron Gwenaël , Mailliez Audrey , Charvolin Jean-Yves , Houssein El , Guyon Frédéric , Fourchotte Virginie , Lambaudie Eric , Crouzet Agathe , Fouche Yves , Gouy Sébastien , Collinet Pierre , Caquant Frédéric , Pomel Christophe , Golfier François , Vaini-Cowen Véronique , Fournier Isabelle , Salzet Michel , Tresch Emmanuelle , Probst Alicia , Lemaire Anne-Sophie , Deley Marie-Cécile , Hudry Delphine
Published: February 2023

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20–30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.
Erythrocyte Plasma Membrane Lipid Composition Mirrors That of Neurons and Glial Cells in Murine Experimental In Vitro and In Vivo Inflammation
Authors: Stanzani Agnese , Sansone Anna , Brenna Cinzia , Baldassarro Vito Antonio , Alastra Giuseppe , Lorenzini Luca , Chatgilialoglu Chryssostomos , Laface Ilaria , Ferreri Carla , Neri Luca Maria , Calzà Laura
Published: February 2023

Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly.
Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice
Authors: Wang Dao-Xin , Qing Sheng-Li , Miao Zhu-Wei , Luo Heng-Yu , Tian Jia-Sheng , Zhang Xiu-Ping , Wang Shu-Na , Zhang Tian-Guang , Miao Chao-Yu
Published: February 2023

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this study, hepatocyte-specific Nampt knockout (HC-Nampt-/-) mice were generated by Cre/loxP system. Nampt mRNA expression was reduced in the liver, but not in other tissues, in HC-Nampt-/- mice compared with wild-type (WT) mice. Hepatic Nampt deficiency had no effect on body weight and fasting blood glucose, and it did not induce atherosclerosis in mice under both normal chow diet (NCD) and high fat diet (HFD). At baseline state under NCD, hepatic Nampt deficiency also did not affect liver weight, liver function index, including alanine aminotransferase, aspartate aminotransferase, albumin and alkaline phosphatase, and serum levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA). However, under HFD, deficiency of hepatic Nampt resulted in increased liver weight, liver function index, and serum levels of TG, TC, HDL-C, and NEFA. Meanwhile, histopathological examination showed increased fat accumulation and fibrosis in the liver of HC-Nampt-/- mice compared with WT mice. Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.
Role of Cholesterol 25-Hydroxylase (Ch25h) in Mediating Innate Immune Responses to Streptococcus pneumoniae Infection
Authors: Cho Soo Jung , Pronko Alexander , Yang Jianjun , Pagan Kassandra , Stout-Delgado Heather
Published: February 2023

Alveolar macrophages (AM) are long-lived tissue-resident innate immune cells of the airways. AM are key effectors of recognition, initiation, and resolution of the host defense against microbes and play an essential role in mediating host responses to Streptococcus pneumoniae infection. Lipid metabolism in AM can significantly impact cellular function and biology. Dysregulated metabolism contributes to an accumulation of lipids, unfolded protein response induction, and inflammatory cytokine production. Our study was designed to investigate the impact of Ch25h on mediating innate immune responses by macrophages during S. pneumoniae infection. Using wild-type and Ch25−/− mice, we examined the role of cholesterol metabolism on inflammatory cytokine production and bacterial clearance. Our results demonstrate that Ch25h plays an important role in the initiation and intensity of cytokine and chemokine production in the lung during S. pneumoniae infection. In the absence of Ch25h, there was enhanced phagocytosis and bacterial clearance. Taken together, our findings demonstrate the important role of Ch25h in modulating host responsiveness to S. pneumoniae infection.
Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia
Authors: de Bartolomeis Andrea , Vellucci Licia , De Simone Giuseppe , Mazza Benedetta , Barone Annarita , Ciccarelli Mariateresa
Published: February 2023

Emerging evidence from genomics, post-mortem, and preclinical studies point to a potential dysregulation of molecular signaling at postsynaptic density (PSD) in schizophrenia pathophysiology. The PSD that identifies the archetypal asymmetric synapse is a structure of approximately 300 nm in diameter, localized behind the neuronal membrane in the glutamatergic synapse, and constituted by more than 1000 proteins, including receptors, adaptors, kinases, and scaffold proteins. Furthermore, using FASS (fluorescence-activated synaptosome sorting) techniques, glutamatergic synaptosomes were isolated at around 70 nm, where the receptors anchored to the PSD proteins can diffuse laterally along the PSD and were stabilized by scaffold proteins in nanodomains of 50–80 nm at a distance of 20–40 nm creating “nanocolumns” within the synaptic button. In this context, PSD was envisioned as a multimodal hub integrating multiple signaling-related intracellular functions. Dysfunctions of glutamate signaling have been postulated in schizophrenia, starting from the glutamate receptor’s interaction with scaffolding proteins involved in the N-methyl-D-aspartate receptor (NMDAR). Despite the emerging role of PSD proteins in behavioral disorders, there is currently no systematic review that integrates preclinical and clinical findings addressing dysregulated PSD signaling and translational implications for antipsychotic treatment in the aberrant postsynaptic function context. Here we reviewed a critical appraisal of the role of dysregulated PSD proteins signaling in the pathophysiology of schizophrenia, discussing how antipsychotics may affect PSD structures and synaptic plasticity in brain regions relevant to psychosis.
The Influence of Surfactants on the Deposition and Performance of Single-Walled Carbon Nanotube-Based Gas Sensors for NO2 and NH3 Detection
Authors: Orlando Antonio , Mushtaq Asma , Gaiardo Andrea , Valt Matteo , Vanzetti Lia , Costa Angeli Martina Aurora , Avancini Enrico , Shkodra Bajramshahe , Petrelli Mattia , Tosato Pietro , Krik Soufiane , Novel David , Lugli Paolo , Petti Luisa
Published: February 2023

Solid-state chemiresistive gas sensors have attracted a lot of researchers’ attention during the last half-century thanks to their ability to detect different gases with high sensitivity, low power consumption, low cost, and high portability. Among the most promising sensitive materials, carbon nanotubes (CNTs) have attracted a lot of interest due to their large active surface area (in the range of 50–1400 m2/g, depending on their composition) and the fact that they can operate at room temperature. In this study, single-walled carbon nanotube (SWCNT)-based sensing films were prepared and deposited by spray deposition for the fabrication of gas sensors. For the deposition, various SWCNTs were prepared in deionized water with the addition of specific surfactants, i.e., carboxymethyl cellulose (CMC) and sodium dodecyl sulfate (SDS), which act as dispersing agents to create a suitable ink for deposition. This study aims to elucidate the possible differences in the sensing performance of the fabricated devices due to the use of the two different surfactants. To achieve this goal, all the devices were tested versus ethanol (C2H5OH), carbon monoxide (CO), nitrogen dioxide (NO2), and ammonia (NH3). The produced devices demonstrated high selectivity towards NH3 and NO2. The different sensors, prepared with different deposition thicknesses (from 0.51 nm to 18.41 nm), were tested in dry and wet conditions (40% humidity), highlighting an enhanced response as a function of relative humidity. In addition, sensor performance was evaluated at different working temperatures, showing the best performance when heated up to 150 °C. The best sensing conditions we found were against NO2, sensors with 10 layers of deposition and an operating temperature of 150 °C; in this condition, sensors showed high responses compared those found in the literature (62.5%—SDS-based and 78.6%—CMC-based). Finally, cross-sensitivity measurements showed how the produced sensors are good candidates for the practical and selective detection of NO2, even in the presence of the most important interfering gases identified, i.e., NH3.