bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle-Mimetic Nanovesicles Loaded with Chemotherapeutics
Authors: Brezgin Sergey , Kostyusheva Anastasiya , Ponomareva Natalia , Bayurova Ekaterina , Frolova Anastasia , Slatinskaya Olga , Fatkhutdinova Landysh , Maksimov Georgy , Zyuzin Mikhail , Gordeychuk Ilya , Makarov Sergey , Ivanov Alexander V. , Zamyatnin Andrey , Chulanov Vladimir , Parodi Alessandro , Kostyushev Dmitry
Published: December 2022

Because of their high biocompatibility, stability, ability to negotiate biological barrier passage, and functionalization properties, biological nanoparticles have been actively investigated for many medical applications. Biological nanoparticles, including natural extracellular vesicles (EVs) and synthetic extracellular vesicle-mimetic nanovesicles (EMNVs) represent novel drug delivery vehicles that can accommodate different payloads. In this study, we investigated EVs and EMNVs for their physical, biological and delivery properties and we showed that EMNVs have similar delivery properties compared to EVs. In addition, these nanotherapeutics were analyzed for their cytostatic properties in combination with the FDA-approved drug hydroxychloroquine (HCQ), which increased their cytostatic thanks to its lysosome-destabilizing properties. Altogether, these data demonstrated that, at least in vitro, the use of synthetic biomimetic particles is comparable to the natural counterparts, while their synthesis is significantly faster and more cost effective. In addition, we highlighted the benefits of combining biological nanoparticles with a lysosome destabilizing agent that increased the delivery properties of the particles.
Approximation of differential operators with boundary conditions
Authors: Varin Victor Petrovich
Published: December 2022

The use of spectral methods for solution of boundary value problems is very effective but involves great technical difficulties associated with the implementation of the boundary conditions. There exist several methods of such an implementation, but they are either very cumbersome or require a preliminary analysis of the problem and its reduction to an integral form. We propose a universal means of implementation of the boundary conditions for linear differential operators on a finite interval, which is very simple in its realization. The use of the rational arithmetic allows to assess the effectiveness of this method without interference of the round-off errors. We apply this approach for computation of rational approximations for some fundamental constants. We obtained approximations that in a number of cases are better than those that are given by convergents of regular continued fractions of these constants.
Jobsheet Sebagai Pemantik Pembelajaran Interaktif dalam Praktikum
Authors: Pariyono Ahmad , Budiyanto Cucuk Wawan , Lestari Muji
Published: December 2022

Learning in the digital age requires upskilling and reskilling in the application to the efficacy of learner-centered learning. Every time that goes by and becomes a new era to always accompany the development of the times, especially in the world of education. So with the development of this Era, it is hoped that educators will be able to adjust to welcoming the learning of the Eras and Their Eras. So that true learning is created with enthusiasm and happiness will be obtained by students and educators to carry out meaningful learning activities according to the environmental conditions of each school. So it is necessary to hold a shift starting from reorganizing the mindset of learning puzzles, the mindset of fierce teachers, assertive teachers, teachers commanding, and learning focusing on the teacher that we must be aware of, so that students also have the space and time to grow in accordance with the era of their time. Most importantly learners get enough love and material for them to process to discover the natural potesntion that exists in each – each unique individual.
Karst y fractales
Authors: Pardo Igúzquiza Eulogio
Published: December 2022

¿Qué tienen en común la distribución de galaxias en el universo, la red del metro de Madrid y la estrategia de caza de la tribu de los Hadza en el norte de Tanzania? La respuesta es que las tres están conectadas con el karst, tal y como se describe en este trabajo, a través del carácter fractal del mismo. En efecto, el karst presenta un comportamiento fractal tanto en superficie como en el subsuelo. En superficie, tanto la topografía kárstica como las depresiones cerradas (dolinas) que caracterizan el paisaje kárstico son fractales. En el karst subterráneo, la red de conductos kársticos (cuevas) presenta asimismo un comportamiento fractal.
Formation of Orthogonal Components of Input Signals in Digital Measuring Protection Elements with Correction of Dynamic Errors
Authors: Romaniuk F. A. , Rumiantsev Yu. V. , Rumiantsev V. Yu.
Published: December 2022

Digital measuring elements in microprocessor protections of electrical installations are implemented mainly with the use of orthogonal components of input signals. To form orthogonal components in microprocessor protections, digital Fourier filters are most widely used, the action of which is al-ways inertial in transient modes. As a result, a dynamic error appears, changing over time and completely disappearing when a steady-state regime occurs. The dynamic error consists of amplitude and phase errors, which can significantly affect the functioning of digital measuring elements and create conditions for their excessive triggering during external short circuits and deceleration of triggering during internal short circuits. Therefore, it is advisable to compensate for the dynamic error, for which it is proposed to determine the amplitude and phase of the fundamental harmonic signal by specially formed orthogonal components. The proposed method of forming orthogonal components of the signal with compensation of dynamic amplitude and phase errors is based on the use of orthogonal components of the digital Fourier filter, followed by the determination of their samples of the final orthogonal components that coincide with the orthogonal components of Fourier in steady-state mode and shifted in phase relative to the latter in transient mode. The amplitude and phase of the signal with minimal dynamic phase errors are calculated from the samples of the final orthogonal components in the digital measuring element. In the dynamic modeling environment of MATLAB-Simulink-SimPowerSystems, a digital model is implemented, which includes a power system, a three-phase group of current transformers, a load, a short-circuit block, as well as a model of a digital measuring element implemented on the basis of the final orthogonal components. The operation of the digital model was checked using two types of test effects, viz. a sinusoidal signal with a frequency of 50 Hz, and a signal close to the real secondary current of a short-circuit current transformer. As a result of the calculations, it was found that digital measuring elements made on the basis of the proposed methodology made it possible to reduce the relative dynamic amplitude and phase errors by three to four times, as compared with the Fourier measuring element taken as a reference.
A Semi-Analytical Model of an Off-Center Multi-Wing Fractured Well in a Low-Permeability Gas Reservoir
Authors: Yang Sihan , Li Xiaoping , Liu Qiguo , Xu Youjie
Published: December 2022

Since there are several hydraulic fractures around a wellbore after a large-scale hydraulic fracturing and the well is not in the center of the reservoir, no corresponding semianalytical model for wellbore pressure analysis has been proposed. To bridge this gap, this paper aims to present a semianalytical model of the off-center multiwing fractured well. With consideration of permeability stress sensitivity, the reservoir model and hydraulic fracture model are established, respectively. The coupling approach of the reservoir model and hydraulic fracture model is used to obtain the wellbore pressure solution. Meanwhile, the off-center multiwing fractured well is verified with a numerical solution. The seven flow regimes can be distinguished according to the characteristics of the pressure derivative curve. Furthermore, the effect of different fracture distributions on wellbore pressure and the derivative curve is discussed and analyzed. Assuming that the fracture wing number is equal to the average length of all fracture wings, the wellbore pressure is lowest before the radial flow regime when the fracture wing has a uniform distribution around the angle and all fracture wings are equal in length. Besides, the influence of other important parameters (fracture wing number, off-center distance, etc.) is discussed. According to the analysis, we conclude that fracture wing number has a significant influence on the pressure and derivative curves before the radial flow regime. The off-center distance has no influence on the pressure and derivative curve before the radial flow regime, but it has an obvious influence on arc boundary reaction time. Finally, the advantages of the semianalytical solution are fast calculation speed and high calculation accuracy (especially in the early flow regime).
Multiplex Immunohistochemistry protocol in formalin-fixed, paraffin embedded Colorectal Liver Metastases patient tissues and Machine Learning- based Tissue Segmentation and Cell Phenotyping analysis 
Authors: Vallejo-Ardila Dora L. , Tutuka Candani S. A. , Fifis Theodora , Walsh Katrina A. , Muralidharan Vijayaragavan , Christophi Christopher , Perini Marcos V.
Published: December 2022

Colorectal cancer liver metastasis (CLM) is the most of common cause of death in patients with colorectal cancer (CRC) worldwide. There are various immune-suppressive and tumor-promoting mechanisms, which contribute to the unresponsiveness associated with current check point immunotherapy in CRC. Techniques such as Multiplex immunohistochemistry (mIHC) and automated image quantitation analysis, enable a deeper understanding of the diversity of the host’s anti-tumor immune response and could identify potential targets for immunotherapy. Herein, we present a 7-plex OPALTM protocol used to assess the composition and spatial distribution of T cell markers CD3, CD8, Foxp3 and CD103 and the epithelial to mesenchymal transition (EMT) markers alpha smooth muscle actin (α-SMA) and E-cadherin. The protocol has been manually optimized and validated in two independent cohorts of formalin-fixed, paraffin embedded CLM patient tissues (n=42) using well-established antibodies, single spectral library, negative controls and biological controls for corroborating staining pattern of α-SMA+ (sclerosed hemangioma samples) and T-cell infiltrates (benign liver). The accurate profiling of T- cell composition, location and phenotypic characterization could reveal important insights about the influence of T lymphocytes on prognosis after liver metastasectomy.
Stem cell-derived mouse embryos develop within an extra-embryonic yolk sac to form anterior brain regions and a beating heart-like structure.
Authors: Amadei Gianluca , Handford Charlotte E. , Glover David , Zernicka-Goetz Magdalena
Published: December 2022

Mouse embryos are an invaluable tool to study mammalian development but establishment of novel transgenic mouse lines is a costly and time-consuming endeavour. Stem cell models, on the other hand, lend themselves to quick genetic manipulation and are easily scalable, yet they do not successfully capture morphogenesis.Here, we report stem cell-based structures called ETiX-embryoids that can recapitulate mouse post-implantation morphogenesis. ETiX-embryoids form by aggregating embryonic and trophoblast stem cells to embryonic stem cells transiently expressing Gata4. Over the course of 4 days, these structures develop like mouse post-implantation egg cylinders; they then undertake and complete gastrulation on day 5 and 6, respectively. On day 7, ETiX-embryoids undergo neural induction and form the mouse anterior-posterior axis from neural folds to tail bud by movements of convergent extension. On day 8 they form a brain, establish a beating heart-like structure and a gut tube, as they develop inside extraembryonic membranes equivalent to amnion and yolk sac. We detail here the experimental set up and procedure required to generate ETiX-embryoids, and anticipate that they will establish themselves as a novel, powerful tool to study mammalian development without generating a novel mouse lines.
Shifting consumers towards sustainable food consumption and avoiding food waste: Protocol for a machine-learning assisted systematic review and meta-analysis of demand-side interventions
Authors: Lohmann Paul M. , Pizzo Alice , Carvalho Bruna , Bauer Jan Michael , Reisch Lucia A.
Published: December 2022

It is now widely accepted that a significant portion of emissions reductions required to meet net zero targets must come from individual behaviour change. Shifting consumers towards more sustainable food consumption and avoiding food waste and loss (FWL) have been identified as two key levers to tackle climate change at the individual and household level. While the IPCC estimates substantial “technical potential” to reduce emissions via changes in diets and reductions in FWL, there is a lack of learning on which climate solutions can best harness this potential. The purpose of this systematic review and meta-analysis is to synthesise the empirical literature reporting on demand-side interventions targeting sustainble food consumption and food waste behaviours of individuals and households. The review encompasses empirical research evaluating a wide range of policy interventions targeted at changing actual food consumption and waste behaviours, which have the potential to contribute towards climate change mitigation. The review forms part of an ‘ecosystem of reviews’, a large-scale evidence synthesis initiative seeking to provide a comprehensive analysis of household-scale interventions and their emissions reduction potential. The reviews within the ecosystem utilise state-of-the-art AI-assisted screening procedures and follow a set of harmonised inclusion criteria.
Single-Cell B-cell Sequencing to Generate Natively-paired scFab Yeast Surface Display Libraries
Authors: Pascual Nathaniel , Belecciu Theodore , Schmidt Sam , Nakisa Athar , Huang Xuefei , Woldring Daniel
Published: December 2022

The immune cell profiling capabilities of single-cell RNA sequencing (scRNA-seq) are powerful tools that can be applied to the design of theranostic monoclonal antibodies (mAbs). Using scRNA-seq to determine natively-paired B-cell receptor (BCR) sequences of immunized mice as a starting point for design, this method outlines a simplified workflow to express single-chain antibody fragments (scFabs) on the surface of yeast for high-throughput characterization and further refinement with directed evolution experiments. While not extensively detailed in this chapter, this method easily accommodates the implementation of a growing body of in silico tools that improve affinity and stability among a range of other developability criteria (e.g., solubility, immunogenicity).
A Cross- sectional Study on Bovine Tuberculosis in Small holder Intensive Dairy Farms at Assosa District, Western Ethiopia
Authors: Disassa Haimanot , Mekonnen Nega
Published: December 2022

Background: Bovine tuberculosis (BTB) is a contagious chronic and debilitating disease of cattle that can infect humans, other domestic animal and some wild life. Assosa district is one of the remote settings in Ethiopia where information on neglected tropical disease like BTB is not well documented. Hence this study aimed to estimate the prevalence of bovine tuberculosis at Assosa District, Western Ethiopia.
Results: For the current study, 224 dairy cows were sampled and screened for bovine tuberculosis. Among which 18 (8.04%) cows were found positive for bovine tuberculosis where as the rest were negative for the screening test. The effects of different associated risk factors (like age, breed type, and body condition score) for the occurrence of BTB were investigated. The difference in reactivity to the CIDT test among the study participants in different age groups, breed types and body condition were found statistically significant (P-value = 0.034, 0.002 and 0.000) respectively showing higher risk of BTB in older animals when compared to the younger ones (OR=6.42, 95% CI, .01-0.20), exotic breeds (OR=7.49, 95% CI, 2.10-26.78) and poor body condition scored animals (OR=16.75, 95% CI, 5.41-51.8).
Conclusion: The prevalence reported in the current study only using CIDT test revealed that BTB is present and is well-established in small holder dairy farms in the district. The farm owners in the study areas are usually in close contact with their animals and also consume raw milk regularly which may predispose them for the disease. Thus, the livestock agency of the district and the researchers should give awareness creation to the farm owners on the relevance of screening test for BTB before purchasing the animals. Moreover, further detailed epidemiological as well as molecular studies should be done to investigate the link between bovine and human tuberculosis in the study area in order to design appropriate strategic prevention and control measures.
WITHDRAWN: Pulmonary nodules and the psychological distress they can cause: A scoping review
Authors: Milano Nicole , Bulman William A. , Hillyer Grace Clarke
Published: December 2022

Background: More than 1.5 million solitary pulmonary nodules are diagnosed in the United States each year. While the majority prove to be benign, there is evidence to suggest that any incidental and lung cancer screening-detected pulmonary nodules cause patients psychological distress/anxiety.
Purpose: To identify the nature and extent of the evidence, we conducted a scoping review of the literature related to patient nodule-specific psychological distress/anxiety.
Findings: Of the eight studies identified, five assessed nodule-specific anxiety quantitatively and three qualitatively. Quantitative anxiety constructs included nodule-specific distress (n=3; Impact of Events Scale), anxiety alone (n = 1; Generalized Anxiety Disorder-7 measure); and anxiety and depression combined (n = 2; Hospital Anxiety and Depression Scale). Constructs examined qualitatively included emotional distress (n = 2) and anxiety, fear, and worry (n = 1). Most studies evaluated other factors such as lung cancer risk perceptions and quality of patient/provider communication. Pulmonary nodule-specific anxiety was recorded in >50% of the participants (mild 23%-27%; moderate to severe 16%-24%). Anxiety was associated with financial concerns related to a possible cancer diagnosis, fear/worry about cancer, lack of understanding of pulmonary nodules, and pre-existing depression or PTSD. Anxiety was diffused with better patient/provider communication and active coping strategies and tended to decline to the subclinical level over time.
Conclusions: Our review suggests that many patients experience nodule-specific anxiety. These findings serve as a call to action forthe development of interventions to mitigate nodule-specific anxiety andto improve the quality of the patient experience when pulmonary nodules are discovered.
How environmental conditions impact seed germination and consequently the invasion strategy of glossy buckthorn (Frangula alnus (Mill)) in Eastern Canada
Authors: Custodio Tiana Mara , Houle Daniel , Girard François
Published: December 2022

Identifying the environmental factors that control germination is essential to understanding seed traits and their effect on fitness. Glossy buckthorn ( Frangula alnus ) is a shrub or small tree from Eurasia that has become invasive in North America, and which has negative impacts on plant communities and ecosystems. In this study, we analyzed the germination response of glossy buckthorn seeds to different temperatures, various stratification lengths and scarification conditions to measure the impact on breaking seed dormancy, as well as the effect of light in triggering germination. Survival analysis was performed utilizing a Kaplan-Meier estimator and Cox proportional hazard model. Glossy buckthorn seeds exhibited physiological dormancy and required cold stratification to germinate. Germination starts at the end of spring when temperatures reach 12°C and reach a peak later in the season with a germination rate of 70% at 20°C. At warmer temperatures, germination declines, and seeds are induced into dormancy again. Ungerminated seeds will form persistent seed banks that will ensure the survival of F. alnus over time and space as well as enhance its chances of a successful establishment and invasion. Due to climate change, increases in temperatures might impact seeds buried in the soil, shorten the length of stratification periods in some areas of North America and consequently affect the timing of germination resulting in a shift of its germination period.
Computational analysis of missense variant CYP4F2*3 (V433M) in association with human CYP4F2 dysfunction: A functional and structural impact
Authors: Dehkordi Mahvash Farajzadeh , Mafakher Ladan , Samiee-Rad Fatemeh , Rahmani Babak
Published: December 2022

Background
Cytochrome P450 4F2 (CYP4F2) enzyme is one of the CYP4 family responsible for the metabolism of fatty acids, therapeutic drugs, and signaling molecules, such as arachidonic acid, tocopherols, and vitamin K. Several reports have demonstrated that missense variant CYP4F2*3 (V433M) cause decreased activity of CYP4F2 and inter-individual variations in warfarin dose in different ethnic groups. However, the molecular pathogenicity mechanism of missense V433M on the CYP4F2 protein at the atomic level has not yet been completely elucidated.
Methods and results
In the current study, we evaluate the effect of V433M substitution on the CYP4F2 enzyme through 11 different bioinformatics tools. Further molecular dynamics (MD) simulation was applied to assess the impact of V433M mutation on CYP4F2 protein structure, stability, and dynamics. Also, the molecular docking method was performed to illustrate the effect of V433M on its interaction with vitamin K. Based on our results, the CYP4F2*3 variant is a damaging polymorphism with destabilizing nature. Simulation results presented that missense V433M affects the dynamics and stability of CYP4F2 by reducing its compactness and stability, which means its tendency to change the overall structural conformation and flexibility of CYP4F2. The docking result showed that the CYP4F2*3 variant decreased binding affinity between vitamin K1 and CYP4F2 enzyme, which caused less activity of CYP4F2*3 compared to native CYP4F2.
Conclusions
This investigation determined the molecular pathogenicity mechanism of the CYP4F2*3 variant on the human CYP4F2 protein and supplied new information for comprehending the structure-function relationship in CYP4F2 and other CYP4 enzymes. These findings will help to develop effective drugs and individual treatment options.
Environmentally Friendly Concrete Block Production: Valorization of Civil Construction and Chemical Industry Waste
Authors: Junkes Valderice H , Fuziki Maria Eduarda K , Tusset Angelo Marcelo , Rodrigues Paulo Henrique , Lenzi Giane Gonçalves
Published: December 2022

In the present work, a study was carried out on the dosage of wastes from civil construction (concrete and plaster) and chemical industry (tannery sludge) in mixtures for the production of concrete blocks. The characterization of the materials used was performed employing X-ray diffractometry (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The influence of the different residues in the blocks properties was evaluated from the tests of compressive strength, traction in bending, water absorption and leaching test. The results indicated that the concrete blocks produced for paving with addition of residues did not obtain gains in the values of mechanical resistance to compression and traction in bending when compared with blocks made with standard raw material. However, the blocks produced with construction waste obtained satisfactory results for use in street paving after 7 days of concrete curing, reaching values between 36.54 MPa and 44.6 MPa for the mentioned properties. It was also observed that these values increase to 21.4% within 28 days of cure. The blocks produced with plaster showed values between 37.03MPa and 39.85MPa after 28 days of curing, allowing their use for paving streets. On the other hand, the blocks produced with residues from the chemical industry had lower strengths, reaching a maximum power of 29.36MPa after 28 days of curing. In addition, it was also noted that the blocks produced with recycled concrete showed an improvement in performance with a recycled quantity 50%.
Development and validation of a Japanese language questionnaire to screen for tension-type headaches and migraines
Authors: Tanobe Kaho , Machida Minori , Motoya Ryo , Takeoka Astushi , Danno Daisuke , Miyahara Junichi , Takeshima Takao , Kumano Hiroaki , Tayama Jun
Published: December 2022

Background Tension-type headaches and migraines are prevalent conditions; however, no reliable biological markers have been identified for screening. A validated screening tool for epidemiological studies would aid in carrying out large-scale epidemiological studies. Therefore, there is a need to develop a screening tool in the Japanese language based on the International Classification of Headache Criteria, which can be used in epidemiological studies. In this study, we aimed to develop a Japanese-language tool that can be used to screen patients for migraine, tension-type headaches, and mixed migraine/tension-type headaches. Consequently, our objective was to develop a questionnaire based on the 3rd edition of the International Classification of Headache Disorders (ICHD-3) using screening items for each type of headache and to examine its validity.
Methods The questionnaire consisted of 29 questions based on the ICHD-3 diagnostic criteria. It comprised 10 screening items for migraine, eight for tension-type headache, and five for mixed migraine/tension-type headache. The screening results of the questionnaire were compared with the diagnoses of three neurologists, which were used as the gold standard reference.
Results The study population comprised 69 patients (mean age ± standard deviation, 55.0 ± 18.7 years) aged 19–89 years who were visiting the Tominaga Hospital of the Kotobukai Social Medical Corporation. According to the neurologists’ diagnoses, twenty-two patients had migraine, 30 had tension-type headaches, and 17 had mixed migraine/tension-type headaches. The sensitivity and specificity were as follows: migraine, 72.7% and 86.7%; tension-type headache, 50.0% and 86.4%; and mixed migraine/tension-type headache, 70.6% and 67.3%, respectively.
Conclusions The screening tool developed in this study has sufficient validity except for tension-type headache. The questionnaire developed in this study is a rapid and sensitive tool for determining migraine, tension-type headache, and mixed migraine/tension-type headache in persons with headache symptoms.
XPF-ERCC1 blocker improves the therapeutic efficacy of 5-FU- and oxaliplatin-based chemoradiotherapy in rectal cancer
Authors: Huang Ming-Yii , Huang Yi-Jung , Cheng Tian-Lu , Jhang Wun-Ya , Ke Chien Chih , Chen Yi-Ting , Kuo Shih-Hsun , Lin I-Ling , Huang Yu-Hsiang , Chuang Chih-Hung
Published: December 2022

5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced rectal cancer (RC). However, patients with high expression of ERCC1 have worse prognosis than those with low expression. In this study, we investigated the effect of XPF-ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in rectal cancer cell lines. We investigated half maximal inhibitory concentration (IC50) of 5-FU, OXA, XPF-ERCC1 blocker, and XPF-ERCC1 blocker and 5-FU or OXA combined, and analyzed the effect of XPF-ERCC1 blocker on 5-FU-based CRT and oxaliplatin-based CRT. Furthermore, the expression of XPF and γ-H2AX in rectal cells was analyzed. In animal models, we combined XPF-ERCC1 blocker with 5-FU and OXA to investigate the effects of RC, and finally combined XPF-ERCC1 blocker with 5-FU- and oxaliplatin-based CRT. In the IC50 analysis of each compound, the cytotoxicity of the XPF-ERCC1 blocker was lower than that of 5-FU and OXA. In addition, XPF-ERCC1 blocker combined with 5-FU or OXA enhanced the cytotoxicity of the chemotherapy drugs in rectal cells. Furthermore, the XPF-ERCC1 blocker also increased the cytotoxicity of 5-FU-based CRT and OXA -based CRT by inhibiting the XPD product DNA locus. In vivo, the XPF-ERCC1 blocker was confirmed to enhance 5-FU, OXA, 5-FU-based CRT, and OXA CRT. These findings show that XPF-ERCC1 blockers cannot only increase the toxicity of chemotherapy drugs, but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF-ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.
The average gonadotrophin dosage per follicle is predictive of ovarian response and cumulative live birth chances after in vitro fertilization: a retrospective cohort study
Authors: Liu Shan , Ma Shuai , Li Yuan
Published: December 2022

Background: With the development of assisted reproduction technology (ART), many indicators have been proposed to evaluate ovarian response, and then predict pregnancy outcomes. In general, the predictive values remain limited.
Objective: To further explore the indicators to evaluate ovarian sensitivity to gonadotrophin (Gn) stimulation more accurately.
Methods: This retrospective cohort study included 330 women who underwent an entire ART cycle. We aimed to assess whether a new index, termed as average Gn dosage per follicle, could be used as a marker for ovarian response and pregnancy outcomes. It was calculated as the ratio of total Gn dose during ovarian stimulation and the number of pre-ovulatory follicles on the trigger day. Patients were divided into three subgroups according to the average Gn dosage per follicle: below the 33rd percentile (Group A), between 33rd and 67th percentiles (Group B), and above the 67th percentile (Group C). Then stimulation data, laboratory and clinical outcomes were compared among the groups.
Results: The results showed patients in Group A had the best ovarian response, the number of retrieved oocytes was significantly higher than in Group B and C. A multivariate regression analysis showed that average Gn dosage per follicle was an independent predictor of cumulative live birth rates (CLBRs) [adjusted odds ratio (OR): 0.96, 95% confidence interval (CI): 0.95-0.98, P < 0.01].
Conclusions: The present study showed that average Gn dosage per follicle appears to be a highly reliable index of ovarian response to exogenous Gn and can be useful to estimate CLBR.
Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway
Authors: Hao Junfeng , Chen Qiguang , Feng Yongmin , Jiang Qiyu , Sun Huiwei , Deng Botian , Huang Xin , Guan Jibin , Chen Qiuping , Liu Xincheng , Wang Yanjin , Cao Peng , Feng Fan , Li Xiaoyu
Published: December 2022

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells bothin vitroandin vivovia induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde, 4-hydroxynonenal, and cytosolic reactive oxygen species. In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the PI3K-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.
Effects of different methods of anesthesia on acute gastrointestinal dysfunction, postoperative cognitive impairment, and the immune status after laparoscopic radical rectal cancer surgery
Authors: He Xue , zhu xiaoquan , Wang Dacheng
Published: December 2022

Background
With an increase in the aged population in China, the annual incidence of rectal cancer is gradually increasing. This study compares the effects of two anesthesia methods on patients undergoing laparoscopic radical rectal cancer surgery.
Method
A total of 230 patients who underwent laparoscopic radical resection for rectal cancer in the Department of Anesthesiology, Huai'an First People's Hospital Affiliated to Nanjing Medical University from 2016 to 2021 were retrospectively analyzed. The general data, clinical symptoms, immune cell count, and cytokine count were collected on the first, third, and fifth postoperative days. In addition, the patients' Mini-Mental State Examination (MMSE) score was recorded, and dynamic analysis was performed to record gastrointestinal dysfunction after the operation.
Results
The postoperative awakening time (18.41 ± 2.88 vs. 23.23 ± 4.34), extubation time (27.84 ± 3.67 vs. 34.32 ± 5.73), and length of hospital stay (9.73 ± 1.32 vs. 12.32 ± 2.34) were shorter, while the postoperative MMSE score (25.43 ± 1.43 vs. 21.32 ± 2.32) was higher in patients administered general anesthesia plus epidural anesthesia than in those administered only general anesthesia. The proportion of CD4 + T lymphocytes was higher (39.45 ± 4.12 vs. 35.45 ± 4.56), and the proportion of CD8 + T lymphocytes was lower (25.34 ± 3.09 vs. 28.43 ± 3.43) in patients undergoing general anesthesia plus epidural anesthesia than in those undergoing only general anesthesia. Moreover, the count of natural killer (NK) cells was lower (0.104 ± 0.021 vs. 0.167 ± 0.024) and the level of human leukocyte antigen–DR isotype (HLA-DR) (66.43 ± 7.43 vs. 56.45 ± 6.43) was higher in patients administered general anesthesia plus epidural anesthesia. In addition, the levels of interleukin (IL)-6, IL-8, and IL-10 decreased with statistical differences (P < 0.05), and the probability of increased intra-abdominal pressure and acute gastrointestinal injury was lower (P < 0.05) in patients undergoing general anesthesia plus epidural anesthesia.
Conclusion
Addition of epidural anesthesia to general anesthesia can reduce the incidence of postoperative cognitive dysfunction, gastrointestinal injury, immunosuppression, postoperative awakening time, extubation time, and length of postoperative hospital stay.
Blast loads and variability on cylindrical shells under different charge orientations
Authors: Yin Fei , Zhi Xudong , Fan Feng , Wei Wuchen , Zheng Dianshuang
Published: December 2022

Cylindrical shells are widely used in public buildings and military protection fields, and it has a high risk of terrorist attacks and military attacks, it is of great social benefit to carry out the anti-blast design of cylindrical shells, which needs to consider building shape and the shape of blast waves. In this paper, cylindrical charges in 5 directions were detonated on the outer ground of the scaled cylindrical shell, blast loads of the cylindrical shell were measured and blast waves were photographed. The variation of blast load is analyzed by combining the test and simulation results, the difference in peak overpressure of the blast waves on the end face between five orientations is nearly twice. The blast loads in the axial direction of cylindrical charges have a secondary peak phenomenon, and the blast loads between the axial direction and radial direction of cylindrical charges change abruptly at a specific angle. The experimental and simulation methods provide a reference for establishing a blast load database of typical buildings.
Functional investigation of five R2R3-MYB transcription factors associated with wood development in Eucalyptus using DAP-seq-ML
Authors: Takawira Lazarus Tichararama , Bachir Ines Hadj , Ployet Raphael , Tulloch Jade , Clemente Helene San , Christie Nanette , Ladouce Nathalie , Dupas Annabelle , Grima-Pettenati Jacqueline , Myburg Alexander A , Mizrachi Eshchar , Mounet Fabien , Hussey Steven Grant
Published: December 2022

A multi-tiered transcriptional network regulates xylem differentiation and secondary cell wall (SCW) formation in plants, with evidence of both conserved and lineage-specific SCW network architecture. We aimed to elucidate the roles of selected R2R3-MYB transcription factors (TFs) linked to Eucalyptus wood formation by identifying genome-wide TF binding sites and direct target genes through an improved DAP-seq protocol combined with machine learning for target gene assignment (DAP-seq-ML). We applied this to five TFs including a well-studied SCW master regulator (EgrMYB2; homolog of AtMYB83), a repressor of lignification (EgrMYB1; homolog of AtMYB4), a TF affecting SCW thickness and vessel density (EgrMYB137; homolog of PtrMYB074) and two TFs with unclear roles in SCW regulation (EgrMYB135 and EgrMYB122). Each DAP-seq TF peak set (average 12,613 peaks) was enriched for canonical R2R3-MYB binding motifs. To improve the reliability of target gene assignment to peaks, a random forest classifier was developed from ArabidopsisDAP-seq, RNA-seq, chromatin, and conserved noncoding sequence data which demonstrated significantly higher precision and recall to the baseline method of assigning genes to proximal peaks. EgrMYB1, EgrMYB2 and EgrMYB137 predicted targets showed clear enrichment for SCW-related biological processes. As validation, EgrMYB137 overexpression in transgenic Eucalyptus hairy roots increased xylem lignification, while its dominant repression in transgenic Arabidopsis and Populus reduced xylem lignification, stunted growth, and caused downregulation of SCW genes. EgrMYB137 targets overlapped significantly with those of EgrMYB2, suggesting partial functional redundancy. Our results show that DAP-seq-ML identified biologically relevant R2R3-MYB targets supported by the finding that EgrMYB137 promotes SCW lignification in planta.
Equid herpesvirus type 3 (EHV-3) synthesizes membrane-associated and secreted forms of glycoprotein G which are not required for efficient virus cell-to-cell in vitro spread
Authors: Losinno Antonella , Vissani María Aldana , Sanchez Diego , Damiani Armando
Published: December 2022

The equid alphaherpesvirus type 3 (EHV-3) ORF 70 gene encodes glycoprotein G (gG), which is conserved in the majority of alphaherpesviruses. This gG is located in the virus envelope with the characteristic of being secreted into the culture medium after proteolytic processing. Alphaherpesviruses’s gG modulate the host antiviral immune response by interacting with chemokines. The aim of this study is to identify and characterize EHV-3 gG. By constructing gG-tagged versions of the virus, gG was detectable in lysates of infected cells, its supernatants and purified virions. A 100-, 60-, and 17-kDa protein forms were detected in viral particles while a 60-kDa form was identified in supernatants of infected cells. The role of EHV-3 gG in the viral infection cycle was assessed by the construction of a gG-minus EHV-3 mutant and its gG-positive revertant. When growth characteristics in equine dermal fibroblast cell line were compared, the plaque size and the growth kinetics of the gG-minus mutant were similar to the revertant virus indicating that EHV-3 gG has not a role neither in direct cell-to-cell transmission nor virus proliferation of EHV-3 in tissue culture. The identification and characterization of EHV-3 gG presented here provides a solid background for further studies to assess whether it has a function in modulating the host immune response.
The Effect of Implant Surgical Experience on the Learning Curve of a Dynamic Navigation System: An In Vitro Study
Authors: Xu Zonghe , Zhou Lin , Zheng Ming , Lin Yanjun , Huang Wenxiu , Chen Jiang , Li Yan , Wu Dong
Published: December 2022

Background
Dynamic navigation systems have a broad application prospect in digital implanting field. This study aimed to explore and compare the dynamic navigation system learning curve of dentists with different implant surgical experience through dental models.
Methods
The nine participants were divided equally into three groups. Group 1(G1) and Group 2(G2) were dentists who had more than 5 years of implant surgical experience. G1 also had more than 3 years of experience with dynamic navigation, while G2 had no experience with dynamic navigation. Group 3(G3) consisted of dentists with no implant surgical experience and no experience with dynamic navigation. Each participant sequentially placed two implants (31 and 36) on dental models according to four practice courses (1–3, 4–6, 7–9, 10–12 exercises). The preparation time, surgery time and related implant accuracy were analyzed.
Results
Three groups placed 216 implants in four practice courses. The regressions for preparation time (F = 10.294, R2 = 0. 284), coronal deviation (F = 4.117, R2 = 0. 071), apical deviation (F = 13.016, R2 = 0. 194) and axial deviation (F = 30.736, R2 = 0.363) were statistically significant in G2. The regressions for preparation time (F = 9.544, R2 = 0. 269), surgery time (F = 45.032, R2 = 0.455), apical deviation (F = 4.295, R2 = 0. 074) and axial deviation (F = 21.656, R2 = 0.286) were statistically significant in G3. Regarding preparation and surgery time, differences were found between G1 and G3, G2 and G3. Regarding implant accuracy, differences were found in the first two practice courses between G1 and G3.
Conclusions
The operation process of dynamic navigation system is relatively simple and easy to use. There is a dynamic navigation learning curve for dentists with or without implant experience. However, dentists with implant experience learn more efficiently and have a shorter learning curve.
Developing a Model for Detection of Ethiopian Fake Banknote Using Deep Learning
Authors: Gebremeskel Gebeyehu , Tadele Tariku Asmamaw , Girmaw Dagne Walle , Salau Ayodeji Olalekan
Published: December 2022

Recently, analyzing multiple types of fake banknote recognition and detection is a key concern in finance and business. Fake detection is an increasing methodological approach with the significance and technologies in an enormous amount of banknote image data with high dimensionality and unprecedented speed, which leaves a massive data gold ore waiting to be mined. Therefore, in this paper, we proposed a deep CNN technique to differentiate between real and fake banknotes using the fake detection method by examining the computer vision features of the digital content for detecting fake banknotes using smartphone cameras in a cross-dataset environment. The proposed CNN model is used to classify and detect real and fake banknotes datasets for Ethiopian banknotes confirming that the proposed algorithm demonstrates a higher detection accuracy. The detection model sequence includes image acquisition, Image size normalization, grayscale conversation, and histogram equalization, which support to reducing the number of parameter counts in the convolutional layer in the DL framework with high performance. The proposed model architecture results in less computational complexity during hardware deployment and model training. The impact of parameter reduction on model accuracy is analyzed by evaluating the proposed Customized model. We used the percentage method to split the banknote dataset into training (80%), validation (10%), and testing (10%). After a different experimental iteration of the proposed model, we get 99.9% training accuracy, 99.4% Validation accuracy, and 97.6% testing accuracy.
Orthogonal proteomics methods warrants development of Duchenne Muscular Dystrophy biomarkers
Authors: Johansson Camilla , Hunt Helian , Signorelli Mirko , Edfors Fredrik , Hober Andreas , Svensson Anne-Sophie , Tegel Hanna , Forstström Björn , Aartsma-Rus Annemieke , Niks Erik , Spitali Pietro , Uhlén Mathias , Szigyarto Cristina Al-Khalili
Published: December 2022

Background: Molecular components in blood, like proteins, are used as biomarkers to reveal or predict disease states, guide clinical interventions and aid development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, it is generally difficult to translate them to clinical use due to lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy is developed and used to assess reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD). DMD is a monogenic incurable disease characterized by progressive muscle damage currently lacking reliable and specific disease monitoring tools.
Methods: Two technological platforms are used to detect and quantify the biomarkers in 72 longitudinally collected serum samples from DMD patients at 3 to 5 timepoints. Quantification of the biomarkers is achieved by detection of the same biomarker fragment either through interaction with validated antibodies in immuno-assays or through quantification of peptides by Multiple Reaction Monitoring Mass Spectrometry assay (PRM-MS).
Results: Out of ten previously identified biomarkers by immuno-based proteomics methods, five are confirmed using the mass spectrometry based method. Two biomarkers, carbonic anhydrase III and lactate dehydrogenase B, are quantified with two independent methods, sandwich immunoassays and PRM-MS, to a Pearson correlation of 0.92 and 0.946 respectively. The median concentration of CA3 and LDHB in DMD patients is elevated in comparison to healthy individuals to 35- and 3-fold, respectively. Levels of CA3 vary between 10.26 and 0.36 ng/ml in DMD patients whereas that of LDHB vary between 15.1 and 0.8 ng/ml.
Conclusions: These results indicate that orthogonal assays can be used to assess analytical reliability of biomarker quantification assays, providing means to facilitate translation of biomarkers to clinical practice. This strategy also warrants development of the most relevant biomarkers, markers that can be reliably quantified with different proteomics methods.