bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Association Between Immune-Related Adverse Events and Treatment Efficacy in Non-Small Cell Lung Cancer Patients Treated with Nivolumab plus Ipilimumab-Based Therapy
Authors: Ebi Noriyuki , Inoue Hiroyuki , Igata Fumiyasu , Okuma Rei , Kinoshita Eriko , Kawabata Toshiaki , Tan Ibun , Osaki Yusuke , Ikeda Takato , Nakao Akira , Shundo Yuki , Hamada Naoki , Fujita Masaki
Published: January 2024

Nivolumab and ipilimumab combination therapy, explored for advanced non-small cell lung cancer (NSCLC) in trials like CheckMate 227 and CheckMate 9LA, raises questions about the relationship between immune-related adverse events (irAEs) and treatment efficacy in real-world settings. In our retrospective analysis of 28 advanced or recurrent NSCLC patients treated with nivolumab plus ipilimumab (with/without platinum-doublet chemotherapy) from February 2021 to January 2023, we aimed to understand the clinical association between irAEs and treatment efficacy. Among the 28 patients, 22 (78.6%) experienced irAEs. Patients with irAEs demonstrated significantly longer median progression-free survival (PFS) and overall survival (OS) than those without (P = 0.0158 and P = 0.000394, respectively). irAE severity did not significantly influence PFS or OS. The objective response rate was higher in patients with irAEs than those without (50.0% versus 0.0%, P = 0.0549). Multivariate analysis identified irAE occurrence as an independent factor for PFS (hazard ratio = 0.2084, P = 0.01383) and OS (hazard ratio = 0.0857, P = 0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. In conclusion, advanced NSCLC patients experiencing irAEs demonstrated superior clinical outcomes with nivolumab plus ipilimumab-based therapy, though interstitial lung disease may be less linked with PFS and OS than other irAE profiles.
A heart derived-soluble factor which controls kidney and cardiovascular function after acute cardiorenal syndrome
Authors: Hutchens Michael , Funahashi Yoshio , Hebert Jessica , Munhall Adam , Burfeind Kevin , Nguyen Elizabeth , Groat Tahnee , Nickerson Megan , Eiwaz Mahaba , Andeen Nicole , Yanagita Motoko , Gurley Susan
Published: January 2024

Heart and kidney are bi-directionally interacting organs. Because heart and kidney disease are amongst the most common human diseases, investigating disease-causing interactions is important. Here, we identified a new heart-derived endocrine mediator of kidney function, cardiac cysteine-and-glycine-rich protein 3 (CSRP3). We determined CSRP3's stimulus for release from the heart, plasma transit, and kidney disease-causing mechanism. We found that cardiac CSRP3 was upregulated after cardiac injury (modeled using cardiac arrest and cardiopulmonary resuscitation in the mouse), and released into the systemic circulation, subsequently undergoing megalin-dependent endocytosis in the renal proximal tubule and changing kidney cell phenotype. Administration of CSRP3 to mice experiencing focal kidney injury reproduced the kidney phenotype observed in cardiac arrest-exposed mice. Genetic deletion of cardiac CSRP3 or renal megalin ameliorated cardiac injury-induced chronic kidney injury. Lastly, pharmacologic megalin inhibition ameliorated CSRP3-mediated chronic renal injury. We describe the role of cardiac CSRP3 in a heart-kidney interaction which directs specific renal dysfunction and renovascular remodeling after injury. We describe a novel mechanism of the intricate coupling of heart and kidney which determines renal function. These investigations may eventually lead to novel therapy for heart-induced kidney disease.
KU60019 induced ATM blockage regulates GPR91/has-miR-576-3p to inhibit ovarian cancer progression
Authors: Zhou Yangyang , Guo Xiaolei , Dang Rongjing , Cong Lin , Zhao Xin
Published: January 2024

Ataxia telangiectasia mutated (ATM) protein play a key role in the DNA damage response and sustain genomic stability, targeting which has been widely studied in different types of cancer as a potential therapeutic strategy for antitumor therapies. However, the mechanism of targeting ATM in ovarian cancer has not been fully elaborated. In the current study, we explore the influence of GPR91 on ovarian cancer cells in the context of ATM blockage in vitro. We identified that GPR91 might be a potential target of miR-576-3p in ovarian cancer cells upon KU60019 treatment. KU60019 induced cell apoptosis by downregulating GPR91 level. Inhibition of miR-576-3p reversed KU60019 induced cell apoptosis by upregulating GPR91 in vitro. Our results revealed cellular and molecular pathways in KU60019 induced cell death as well as identified a novel potential target for antitumor research.
Empirical formula model and process parameter optimization of two-dimensional ultrasonic assisted grinding force based on 2.5D-Cf/SiC fiber orientation
Authors: Wang Yashuai , Xin Bo , Li Jiangtao , Zhu Lida
Published: January 2024

Due to the anisotropic characteristic of carbon fiber-reinforced silicon carbide ceramics, the fiber orientation angle significantly affects the grinding force. Therefore, it is important to study the influence rule of different fiber orientations on the grinding force of 2.5D-Cf/SiC composites. To study the comprehensive influence of machine tool parameters and the anisotropy of carbon fiber reinforced ceramic matrix composites on the grinding force, two-dimensional ultrasonic plane grinding was studied by orthogonal test and single factor experiment. Based on the multi-exponential fitting analysis method of multiple linear regression equation, the empirical equations of power exponential grinding force prediction model of 2D ultrasonic assisted grinding and conventional grinding 2.5D-Cf/SiC composites at 0°, 45°, 90° fiber orientation and considering fiber orientation and ultrasonic amplitude were established respectively. To verify the empirical formula model in predicting the grinding force of 2.5D-Cf/SiC composites under various fiber orientation angles, the regression equation and regression coefficient of the model were examined. The influence of 2.5D-Cf/SiC grinding parameters on the grinding force was analyzed. The parameters of the grinding force model were optimized based on range analysis and variance analysis, and the optimal process parameter combination was obtained. The results show that the grinding force is negatively correlated with the linear speed, and positively correlated with the feed speed and grinding depth within the range of experimental parameters. The maximum reduction of the normal grinding force is 29.78% when the line speed is 10.48m/s, the feed speed is 100 mm/min, the grinding depth is 50µm, and along the 45° fiber direction. The optimal grinding parameter combination is a line speed of 23.60m/s, feed speed of 5mm/min, and grinding depth of 10µm along the 0° fiber orientation.
Unlocking Growth: A Comprehensive Analysis of Indian Exports through ARDL Methodology and the Catalytic Role of Advanced Technology in Enhancing Exports and GDP.
Authors: Singh Vipul
Published: January 2024

This study examines the relationship between exports, export instability, foreign currency reserves, and economic growth in India from 2001 to 2021. The Autoregressive Distributed Lag model is used to analyze the data, while Granger causality analysis is utilized to determine the causative relationships among the variables and additionally, explain how new technology will help to boost trade and economic growth. The data used in this study was sourced from reputable academic publications, including the Handbook of Statistics on Indian Economy published by the Reserve Bank of India (RBI), the World Integrated Trade Solution (WITS) database, and many editions of the Economic Survey. This study also examines several statistical tests such as Autocorrelation, Heteroskedasticity, and Normality tests. The finding of the study shows the Error Correction Term (ECT) had a statistically significant effect with a p-value of 0.00. The rate of adjustment is at a level of 33 percent. The findings of the Granger Causality test indicate the existence of a bidirectional relationship between exports and GDP, as well as a unidirectional relationship between export instability and economic growth. Export instability has been shown to have a positive impact on economic growth. However, it has been observed that economic growth does not have a causal effect on export instability. Furthermore, there is no association between foreign currency reserves and GDP.
Downscaling daily fine Particulate Matter (PM2.5) concentration maps for Ho Chi Minh City
Authors: Nguyen Phuong D.M. , Phan An H. , Ngo Truong X. , Ho Bang Q. , Pham Vu T. , Nguyen Thanh T.N.
Published: January 2024

The problem of PM2.5 pollution is a major concern in both Vietnam and around the world, with adverse effects on human health, animals, and the environment. It is crucial to monitor PM2.5 levels regularly on a large scale to assess air pollution and develop effective solutions. Besides, fine particulate matter (PM2.5) mapping at high resolution can have significance in studying pollution at a small scale. Nevertheless, most current researches on high-resolution PM2.5 mapping depend on high-resolution aerosol optical depth products. In this study, we propose a method to enhance the spatial resolution of low-resolution (3km) PM2.5 products and improve the quality of model output. The proposed method utilized a machine learning-based downscaling approach to generate high-resolution (1km) PM2.5 maps for Ho Chi Minh City in 2021. We also incorporated additional data sources such as meteorological data and land use information to improve the accuracy of the products. The proposed method was evaluated through numerical experiments, and the results showed a significant enhancement of the spatial resolution of PM2.5 products, from 3km to 1km and improved the accuracy of the output. Four models were trained and validated using data collected from 2018 to 2021. Catboost model yielded the best results in terms of predictive power with a Pearson R of 0.80, RMSE of 6.46 µg/m3, and MRE of 0.21 out of 2891 samples. The aggregated monthly and annual average maps of PM2.5 concentration in Ho Chi Minh City in 2021 exhibited exceptional quality compared to the 3km-resolution PM2.5 product. These concentration maps effectively depicted the spatial distribution and seasonal variations of PM2.5 in Ho Chi Minh City.
Machine Learning-Aided Molecular Dynamics Simulation for Prediction of Binding Kinetics
Authors: Shahbazi Fatemeh , Esfahani Mohammad Nasr , Keshmiri Amir , Jabbari Masoud
Published: January 2024

Chemical sensors provide new solutions to address some of the world’s biggest challenges, including climate change, energy and healthcare. Understanding molecule binding kinetics and thermodynamics is essential in enhancing the design and functionality of chemical sensors. To contribute to this field, we have developed a numerical framework to predict the binding kinetics without requiring experimental inputs. Once the target molecules and fictional surface are identified, the details alongside the environment and mass transport are included as input to this code. The output would be the predictive model of target molecule behaviour passing by the surface. This framework comprises an all-atom molecular dynamics model and a Bayesian machine learning model for predicting affinity. Different predictive models have been trained, and the Bayesian-based Gaussian process regression (GPR) best predicts the binding reaction amongst them all. The predictive model is validated for an aluminium-based platform. The proposed numerical framework has the potential to be generalised and, therefore, contribute to future low-cost binding reaction estimations, providing a valuable tool for industry and experimentalists.
Optimization of Culture Conditions and Batch-Process Control for the Augmented Production of Bacteriocin by Bacillus Species
Authors: Elazzazy Ahmed M. , Mobarki Mona O. , Baghdadi Afra M. , Bataweel Noor M. , Alhejin Ahmed
Published: January 2024

Background: The rise of antibiotic-resistant microorganisms is a major global health concern. This study explores the potential of soil-derived bacterial isolates in combating such pathogens, focusing on their antimicrobial properties.
Results: Fifteen bacterial isolates from agricultural and polluted soils in Jizan and Jeddah were screened for their ability to inhibit common human pathogens. Two Bacillus strains, Bacillus atrophaeus and Bacillus amyloliquaefacins, were identified via 16S rDNA analysis. These strains showed notable antibacterial activity against various pathogens, including Methicillin-Resistant Staphylococcus aureus(MRSA) and Pseudomonas aeruginosa. Optimizing production conditions for their bacteriocin revealed that nutrient and Muller Hinton broths were ideal media, with optimal production observed at 37°C and pH levels of 7 and 8 for Bacillus atrophaeus and Bacillus amyloliquaefacins, respectively. Enhanced production was achieved in a 10-L bioreactor with controlled pH, doubling bacteriocin yield. The study monitored growth, substrate utilization, pH variation, and bacteriocin production over time.
Conclusions: The isolated Bacillus strains show promise as sources of potent antimicrobials against antibiotic-resistant bacteria. The optimization of culture conditions significantly boosts bacteriocin production, highlighting the potential of these strains in developing new antimicrobial agents.
Quantile Transformation Gabor and Edge Techniques for Brain Tumour Segmentation in MRI Images
Authors: G shruthi , M krishna raj P
Published: January 2024

The segmentation of a brain tumor is an exciting and exigent research task in the field of medical image analysis. An early finding of a brain tumor aids to obtain effective treatment and boosting the survival time of the patients. The brain tumor segmentation segregates the abnormal tissues region from the normal tissues region. The major challenges are the complex structure, size, and location of the tumor region. In this proposed methodology, quantile transformation, Gabor filter, and various edge techniques are implemented to segment the tumor tissues in the MRI brain images. The quantile transformation computes the Gaussian probability distribution values to increase the semantic gap between tumor region and the non-tumor region. Gabor technique analyses the texture information for identifying specific frequency contents in the brain image. Various edge techniques such as Canny, Robert, Scharr, Prewitt, and Sobel edges are applied to extract the actual location and effective boundary regions. Gaussian low pass filter and median filter concept is applied to eliminate the external factors like unwanted noise. At last, the collected properties are then fed into the Random Forest classifier to isolate tumor tissue regions from the brain MRI images. Accuracy, precision, recall, and f-measures are used to estimate the performance of the proposed methodology. The results of the experiments reveal that our proposed strategy produced better outcomes.
Diallel analysis for seed yield and yield-related traits in tepary bean (Phaseolus acutifolius A. Gray) under non-stress and drought-stress conditions
Authors: Mwale Saul Eric , Shimelis Hussein , Nkhata Wilson , Sefasi Abel , Fandika Isaac , Mashilo Jacob
Published: January 2024

Tepary bean (Phaseolus acutifolius A. Gray) cultivation is not expansive in Southern Africa due to the unavailability of high-yielding and locally adapted varieties. To deliver well-adapted and new-generation tepary beans in Africa, pre-breeding and breeding of drought tolerant and high-yielding varieties is a critical need. Therefore, the objective of this study was to determine the combining ability effects and genetic components for seed yield and yield-related traits in selected tepary bean genotypes under non-stressed (NS) and drought-stressed (DS) conditions. Seven parents and 21 F2 progenies derived from a half-diallel design were evaluated at two sites in Malawi under NS and DS conditions using a 4 × 7 lattice design with three replications. The genotype × location interaction effect was significant (p < 0.05) for days to 50% flowering (DTF), number of pods per plant (NPP), and seed yield (SY) traits under both NS and DS conditions, implying a differential performance of genotypes across the two locations. The specific combining ability (SCA) × Location interaction effect was significant (p < 0.05) for DTF, NPP, and SY under both water regimes, implying the genetic effects of crosses were affected by test locations. General combining ability (GCA) and SCA mean squares were significant for number of seeds per pod (NSP) and SY under DS condition, indicating additive and non-additive gene effects controlled these traits. Baker’s ratio (BR) > 0.50 for NPP and NSP under DS condition, suggested the preponderance of additive gene effects. The narrow-sense heritability estimates of > 0.60 for NSP under DS condition suggested relatively better trait transmissibility from parents to offspring. G40145, G40148, and G40150 were good general combiners for NPP and SY under both NS and DS conditions. F2 families Zimbabwe landrace x G40138, Zimbabwe landrace × G40150, G40059 × G40145, G40059 × G40148, G40138 × G40150, and G40145 × G40150 were best-specific combiners with enhanced SY of 1.67 tons/ha under DS condition. The selected parents are valuable genetic resources for breeding programs to enhance the NPP and SY. High-performing early-generation families are recommended for genetic advancement and selection across representative growing environments for variety release and commercialization.
Suicidal Ideation, Psychological Distress and Depression in Medical Students of Pakistan: Surviving or Thriving
Authors: Sarwar Anum , Waris Hira , Khan Hina , Umar Muhammad Hamza , Karmani Vikash kumar
Published: January 2024

Background: In recent years, psychological stress has lead to increase in suicide cases readily among medical students of many countries. This study aims determine the prevalence of psychological stress, major depressive disorder, and suicidal ideation in Bachelor of Medicine and Bachelor of Surgery (MBBS) students of a government setup medical university in Pakistan.
Methods: The data was gathered using a valid questionnaire containing 10 items Kessler psychological distress scale. The scale consists of the severity of the psychological distress from well, mild, moderate, and severe. Physical health questionnaire 2(PHQ2) was used for identifying the students with major depressive illness. Suicidal ideation was assessed using item no. 9 from PHQ9 questionnaire.11,17
Results: The overall prevalence of suicidal ideation, distress and major depression among 353 students of MBBS was 22.9%, 63.1%, 27.8% respectively. The students with major depression and moderate/severe distress are more probable to think about suicide. Moreover, Students who choose medicine under the family influence are more likely to have suicidal ideation. Besides this, we found that particularly females experience higher psychological distress as compared to males.
Conclusion: In the overall study, it is identified that suicidal ideation is strongly correlated to depression and distress. However, controlling these factors at an early stage can prevent the suicidal thoughts, which inevitably can reduce the suicide attempts not only in medical students but could also be valuable for students of different fields.
Quantum Chemical Investigation of (E)-2-(2-hydroxy-5- methoxybenzylidene)hydrazinecarbothioamide and its N-methyl Variant by Using DFT Methods
Authors: Srisha K. , Ravindranath L. , Ramesh Gaddam. , Praveena D. , V Sunil kumar , Kumar Danikonda. Suresh , Muthu S. , Rao G. Ramana
Published: January 2024

Geometry optimization for 2-(2-hydroxy-5-methoxybenzylidene)hydrazinecarbothioamide (HMHC) and 2-(2-hydroxy-5methoxybenzylidene)-N-methylhydrazinecarbothioamide (HMNHC) was attempted using DFT/B3LYP/6-311 + + G(d,p) formalism. The computations identified the existence of both intra-molecular and bifurcated intra-molecular hydrogen bonds in both the molecules. Time-dependent density functional theory (TD-DFT) was employed to simulate Ultra-Violet spectra for both HMHC and HMNHC in order to substantiate experimental spectra in a solution of dimethyl formamide. For the two compounds under investigation, specific global reactivity descriptors were estimated with the help of frontier molecular orbital (FMO) analysis to understand the origin of UV-Vis spectra. Nonlinear optical (NLO) profile, for each of the two molecules, was computed, with in the frame work of the DFT/B3LYP/6-311 + + G(d,p) formalism to determine their utility for NLO applications. NBO analysis of hyper conjugate interactions made it possible to interpret the molecules NLO behavior in terms of intramolecular charge transfer (ICT). The reactive sites around the molecules were identified using Fukui function investigations and Molecular Electrostatic Potential (MEP).
Trends and Incidence of Reported Events Associated with Ureteral Stents: An Analysis of the Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) Database
Authors: Lombardo Riccardo , Guidotti Alessio , Turchi Beatrice , Franco Giorgio , Tubaro Andrea , De Nunzio Cosimo
Published: January 2024

Aim of this study is to summarize medical device reports (MDRs) between 2012 and 2022 relating to ureteral stents within the Manufacturer and User Facility Device Experience (MAUDE) database maintained by The Food and Drug Administration (FDA). The MAUDE database was analyzed for all MDRs relating to each FDA-approved ureteral stent. Event descriptions were reviewed and characterized into specific event types. Outcome measures include specific ureteral stent and reported events as detailed by the MDRs. All data is de-identified and in compliance with the Health Insurance Portability and Accountability Act (HIPAA). Data is presented as number of specific event/total events. Pooled Relative risk was used to compare data. Overall, 2652 reports were retrieved in 10 years and a progressive rise in reported events was recorded (Fig. 1). 831/2652 (31%) were reported as injury while 1810/2652 (68%) as malfunction of the ureteral stent and 4 events of death. The most frequently reported adverse events (AEs) were stent break (627/2652: 23%); material problems (384/2652: 14%); calcification (222/2652: 8%); difficulty to insert, advance or remove the device (155/2652: 6%). Bard stents were associated with most material problems (19%), Resonance stents were associated with most difficulty to insert, advance or remove the device (9%) and calcification (15%) while filiform double pigtail stent set were associated with most breakage reports (56%) when compared to the other stents (PRR > 1, p < 0,05) (Table 1, 2, 3). According to MAUDE database the most frequent complications related to ureteral stents are breakage, material problems, calcification and difficulty to insert, advance or remove the device. As well Resonance ureteral stents seem to be associated with a higher risk of device problems.
The double Burden of Stressful Life Events among professional nurses: public mass shootings during the COVID-19 Pandemic
Authors: Imkome Ek-uma
Published: January 2024

Background
Stress is a significant consequence of frontline care. Nurses have recently been at the forefront of care for victims of both public mass shootings and the coronavirus disease 2019 (COVID-19) pandemic. They have been coping with stressful life events, fearing potential infection and the possibility of transmitting the virus to their patients and families, experiencing heavy workloads, high patient-nurse ratios, and extended shifts—all of which lead to exhaustion and stress. Nurses’ perceptions of mass shooting events during the COVID-19 pandemic should be explored to ensure that these professionals receive more efficient support to deliver high-quality care. This study explored nurses’ perceptions in the era of mass shootings and the COVID-19 pandemic.
Methods
This phenomenological-hermeneutic research was performed to examine the perspectives of 16 nurses caring for patients who were either injured during a public mass shooting or infected with COVID-19. Participants were selected through purposeful sampling. Data were collected using semi-structured questionnaires during online interviews using Microsoft Teams. Themes derived from structural understanding illuminated participant nurses' perceptions of patient care during the COVID-19 pandemic.
Results
Qualitative data analysis revealed five main themes: stressful life events, flashbulb memories, service-oriented mindset, team collaboration key, and professional needs. The theoretical interpretation points to the multidimensional perceptions of nurses and the need to confirm these perceptions and reconcile them with the psychological impact of stressful life events, making future adjustments and adaptations possible.
Conclusions
Interested stakeholders must consider service-oriented mindsets, team collaboration is key, and the professional needs of nurses to support and prepare novice to expert nurses for the delivery of optimal care during public health crises.
Molecular mechanism of N-acetylcysteine regulating proliferation and hormone secretion of granulosa cells in sheep
Authors: Wang Jine , Ma Junyuan , Li Yang , yang yahua , Yang Chongfa , Hu Songming , Huo Shengdong , Yang Yanmei , 扎 西英派 , Luo Wenxue
Published: January 2024

Granulosa cells are not only important supporting cells in follicular development, but also the main cells secreting steroids. The proliferation of GCs and steroid hormone synthesis play a key role in follicular development and atresia. In this experiment, GCs were isolated by follicular fluid aspiration, and identified by immunofluorescence technique. The effects of different concentrations of NAC (50, 100, 500, 1000 µmol/L) on sheep GCs with regards to the antioxidant levels, proliferation, apoptosis, and steroid hormone secretion were investigated. PI3K/AKT inhibitor LY294002 was used to explore the molecular mechanism of NAC on GCs proliferation and steroid hormone secretion in sheep. The results showed that in sheep GCs, all concentration of NAC group could promote the proliferation of GCs and inhibit their apoptosis. Among them, 100 µmol/L NAC had the most significant promote on the proliferation of sheep GCs for 48 h. The expression of CCND1, CDK4 and Bcl-2 in all NAC concentration group was significantly increased, and the expression of Bax was significantly decreased. All concentrations of NAC significantly decreased reactive oxygen species (ROS) concentration and increased the expression of CAT and SOD1. NAC significantly increased the expression of CYP19A1, 3β-HSD and the secretion of estradiol (E2) and progesterone (P4) in GCs. In conclusion, NAC activates the PI3K/AKT signaling pathway to promote the proliferation of GCs, E2 and P4 secretion of sheep GCs in vitro.
Determination of the Expression Levels of Hym, AmNrx1, and CYP9Q3 Genes in the Anatolian Honey Bee (Apis mellifera anatoliaca)
Authors: Kabakcı Dilek , Karataş Ümit , Tunca Rahşan Ivgin , Çankaya Murat , Karabağ Kemal , Akdeniz Gökhan , Kuzucu Mehmet
Published: January 2024

The Varroa destructor poses a significant threat to honey bees, leading to substantial yield losses and colony declines. Defence behaviour (such as grooming behavior: auto and allogrooming) in honey bees serves as a crucial mechanism against Varroa infestations, but the many genes responsible for this behavior remain unidentified. This study focuses on the expression levels of hymenoptaecin (Hym), neurexin-1 (AmNrx1), and CYP9Q3 which could be associated with defence behavior, in Muğla honey bee ecotype (Apis mellifera anatoliaca) colonies subjected to a against Varroa selection program. Using the qPCR method, researchers analyzed worker bees from 23 control groups and 23 colonies under the selection program. The results revealed a remarkable increase in the expression levels of Hym, AmNrx1, and CYP9Q3 genes in the selected group, with respective fold changes of 2.9, 2.95, and 3.26 compared to the control group (p < 0.01). This finding suggests that selection against Varroa infestations induces alterations in gene expression linked to behaviour related to exposure of Varroa in honey bees. These outcomes propose the potential use of Hym, AmNrx1, and CYP9Q3 genes in preselection for future Varroa-resistant programs in honey bees. The genes used in the study that may be related to this behavior are supported by other studies in the future, they may help create an initial population with advanced defence behaviours (such as autogrooming and allogrooming).
Error analysis of blade milling considering surface features and deformation
Authors: Wu Shi , Chunfeng Wang , Xianli Liu , Yupeng Wang , Yong Zhang
Published: January 2024

Thin-walled impeller blade curvature changes in the milling process, low stiffness and other reasons lead to large milling processing error, in order to compensate for online blade milling processing error,A milling machining error prediction method is proposed by considering the curved surface features and deformation of the blade. First, based on the tool-worker contact relationship of blade curvature and machining deformation individually, the undeformed and deformation chip thickness models considering curvature and deformation are constructed to analyze influence law of curvature change and deformation on the chip thickness individually; Then, change amount of the chip thickness considering undeformed and deformed in the tool coordinate system is converted to the surface coordinate system. The surface normal vector of variation is taken as the predicted machining error; Finally, corresponding experiments are conducted on five-axis machine to indicate that the error between the predicted and the experimentally measured machining error during stable milling falls within 21%.
Glottis recognition software development using artificial intelligence
Authors: マスモリ ヤスシ , いのue 宗一郎 , セイノ ユウスケ , 小西 マモル , 西川 ヒロユキ
Published: January 2024

Purpose
The use of video laryngoscopes has enhanced visualization of the vocal cords, thereby improving the accessibility of tracheal intubation. Employing artificial intelligence (AI) to recognize images obtained through video laryngoscopy, particularly when marking the epiglottis and vocal cords, may elucidate anatomical structures and enhance anatomical comprehension. This study investigated the ability of an AI model to accurately identify the glottis on video laryngoscopy images captured from a human anatomical model.
Methods
Tracheal intubation was conducted on a human anatomical model using a bronchoscope with recording capabilities, and image data of the glottis were gathered to create an AI model. Data preprocessing and annotation of the vocal cords, epiglottis, and glottis were performed. Based on the AI determinations, anatomical structures were color-coded for identification.
Results
The accuracy of the AI model was 0.9516, which exceeded 95%. AI successfully marked the glottis, epiglottis, and vocal cords during tracheal intubation. These markings aided in the visual identification of the respective structures with an accuracy of more than 95%.
Conclusion
AI demonstrated the ability to recognize the epiglottis, vocal cords, and glottis using an image recognition model of a human anatomical model.
Spatial distribution and health risks assessment of heavy metals in e-waste dumping sites from Pakistan
Authors: Hashmi Muhammad Zaffar , Khan Sohaib , Hasnain Ahmad , Shakil Sidra , Wang Shuhong , Ahmed Zulkifl
Published: January 2024

The current research work is done to determine the concentration of heavy metals (Cu, Pb, Zn, Cd, Hg, Cr) in the surface soil of recycling centres located in different provinces of Pakistan and to quantify and compare the environmental risk by using different geostatistical techniques. The impact of recycling activities on the soil microbial community is also investigated through soil enzyme activities and microbial community profiles. Recycling activities increased the levels of pH, EC, and decreased the levels of K, N, P, and organic matter compared to the soil without recycling activities. The Cr at all sites whereas Hg at only two sites (AL and AM) exceeds the World Health Organization standards (WHO) for soil. A fluctuating soil enzyme activity trend was observed among all the sites but the maximum enzyme activity was observed for urease followed by phosphatase and catalase. Contamination factor (Cf), Pollution load index (PLI), and geo-accumulation index (Igeo) results showed all the recycling sites are highly contaminated with Cu, Cd, and Pb. No non-carcinogenic health risk was observed for both children and adults as HI is less than 1. There was a strong probability of adverse health effects among children and adults living near recycling centers due to Cu and Cr poisoning (1.59 ×10− 5 to 4.28 × 10− 5). Therefore, there is a dire need to introduce sustainable e-waste recycling techniques as well as to make stringent e-waste management policies to reduce further environmental contamination.
Low-temperature oxidation of methane mediated by Al-doped ZnO cluster and nanowire: A first-principles investigation
Authors: Esrafili Mehdi D.
Published: January 2024

The oxidation of methane over aluminum (Al)-doped Zn12O12 cluster and (Zn12O12)2 nanowire is investigated using first-principles calculations. The impact of Al impurity on the geometry, electronic structure and surface reactivity of Zn12O12 and (Zn12O12)2 are thoroughly studied. It is found that N2O is highly activated on these systems to provide an activated *O species. Though, the oxidation of CH4 is almost impossible over pristine ZnO counterparts due to less activation of N2O or CH4 over these systems, however, the addition of an Al atom helps the dissociation of N‒O bond of N2O. The conversion of CH4 into CH3OH over AlZn11O12 and (AlZn11O12)2 requires an activation energy of 0.45 and 0.29 eV, respectively, indicating it can be easily performed at normal temperatures. Besides, the overoxidation of methanol into formaldehyde cannot take place over the AlZn11O12 and (AlZn11O12)2, due to the high energy barrier needed to dissociate C-H bond of the CH3O intermediate.
Numerical study on the dynamic response of gas explosion in uneven coal mine tunnels using LS DYNA CESE reaction dynamics model
Authors: Du Jiaqi , Chen Jian , Zhu Lingqi , Guo Liwen , Wang Fusheng , Hu Xiangming
Published: January 2024

A numerical simulation method combining detailed chemical reaction mechanism of methane deflagration with approximate real tunnel structure was proposed to confirm whether the unevenness of the tunnel wall during coal mine gas explosion can be ignored. The approximate real tunnel model and smooth wall tunnel model were developed using 3D modeling methods. The propagation and attenuation processes of shock waves in the two tunnel models, as well as the different dynamic responses of the two tunnel walls, are compared and analyzed. Research results show that the non-uniformity of the tunnel wall decreases the shock wave overpressure and propagation velocity. the peak overpressure reduction value of the shock wave reached 81.91 kPa, and the shock wave overpressure reaches its peak at an extended maximum time of 7.4 ms. The stress distribution on the approximate real tunnel wall is discontinuous, the propagation speed of stress waves in the bend tunnel is slower, and the duration of high load is relatively low. The displacement of the approximate real tunnel after gas explosion is lower than that of tunnels with smooth walls, and the displacement of most measuring points on the tunnel on the right is only 1/3–1/2 that of the smooth tunnel.
Prediction of PD-L1 tumor positive score in lung squamous cell carcinoma with H&E staining whole slide images and deep learning
Authors: Wang Qiushi , Deng Xixiang , Huang Pan , Ma Qiang , Zhao Lianhua , Feng Yangyang , Wang Yiying , Zhao Yuan , Chen Yan , Zhong Peng , He Peng , Feng Peng , Xiao Hualiang
Published: January 2024

Purpose
Detecting programmed death ligand 1 (PD-L1) expression based on immunohistochemical (IHC) staining is an important guide for the treatment of lung cancer with immune checkpoint inhibitors. However, this method has problems such as high staining costs, tumor heterogeneity, and subjective differences among pathologists. Therefore, the application of deep learning models to segment and quantitatively predict PD-L1 expression in digital sections of Hematoxylin and eosin (H&E) stained lung squamous cell carcinoma is of great significance.
Materials and Methods
We constructed a dataset comprising H&E-stained digital sections of lung squamous cell carcinoma and used a Transformer Unet (TransUnet) deep learning network with an encoder-decoder design to segment PD-L1 negative and positive regions and quantitatively predict the tumor cell positive score (TPS).
Results
The results showed that the dice similarity coefficient (DSC) and intersection overunion(IoU) of deep learning for PD-L1 expression segmentation of H&E-stained digital slides of lung squamous cell carcinoma were 80% and 72%, respectively, which were better than the other seven cutting-edge segmentation models. The root mean square error (RMSE) of quantitative prediction TPS was 26.8, and the intra-group correlation coefficients with the gold standard was 0.92 (95% CI: 0.90–0.93), which was better than the consistency between the results of five pathologists and the gold standard.
Conclusion
The deep learning model is capable of segmenting and quantitatively predicting PD-L1 expression in H&E-stained digital sections of lung squamous cell carcinoma, which has significant implications for the application and guidance of immune checkpoint inhibitor treatments.
Efficacy and Safety of Orlistat in Patients With Overweight/Obese and Hyperuricemia: Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Liu Shuang , Lin Xiaojing , Chen Qi , Sun Hang , Han Yali , Yang Shaoling , Gao Yining , Qu Shen , Chen Haibing
Published: January 2024

Background Obesity is associated with elevated serum uric acid (SUA) and frequent gout flares. Losing weight can lower SUA and reduce gout flares. The effect of orlistat on SUA and gout flares in patients with overweight/obese and hyperuricemia (HUA) has not been extensively studied. In this study, we investigated the effects of orlistat on SUA and gout flares compared to placebo in overweight or obese patients with HUA. Methods A total of 72 Chinese patients with overweight/obese and HUA were randomly divided into placebo group and orlistat group for 12 weeks. The primary endpoints were relative changes in body weight and SUA, as well as gout flares. Results 72 patients with overweight/obesity and HUA were randomly assigned to placebo group (35, 48.61%) and orlistat group (37, 51.39%). Orlistat was associated with a lower proportion of patients with gout flares (log-rank p = 0.023, hazard rate = 0.31, 95% CI 0.11–0.85). There was no significant difference in SUA level between the two groups. The average weight loss of orlistat group was 2.85kg, which was significantly better than that of control group (P < 0.05). Conclusions This study is the first to demonstrate that orlistat has no direct effect on SUA levels in patients with overweight/obese and HUA. The value of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized. Trial registration: Clinicaltrials.gov NCT05496075
Efficacy of Pericapsular Nerve Group (PENG) Block in Preoperative Rehabilitation (Prehabilitation) for Patients with Femoral Neck Fractures: Study Protocol for a Randomized, Placebo-controlled, Double-blinded Trial
Authors: Jin Zhuan , Sugiyama Daisuke , Higo Fumiya , Hirata Takahiro , Kobayashi Osamu , Morimatsu Hiroshi , Ueda Kenichi
Published: January 2024

Background
Despite surgery intervention for femoral neck fractures is recommended within 48 hours of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty.
Methods
This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 hours of admission and those undergoing surgery more than 48 hours of admission.
Discussion
This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period.
Trial registration
jRCT1031220294
RNA-Sequencing Reveals Candidate Genes/Pathways Associated with Resistance to MDM2 Antagonist Idasanutlin in TP53 Wild-Type Chronic Lymphocytic Leukemia
Authors: Lunec John , Aptullahoglu Erhan , Nakjang Sirintra , Wallis Jonathan , Marr Helen , Marshall Scott , Willmore Elaine
Published: January 2024

There is a growing body of investigation currently underway on MDM2 inhibitors in clinical trials, reflecting the increasing interest in including these drugs in cancer treatment regimens. One of the developed compounds, idasanutlin (RG7388), has shown promise in early-stage clinical trials. It is a second-generation MDM2-p53 binding antagonist with enhanced potency, selectivity, and bioavailability. In addition toTP53status, which is an important determinant of the response, we have shown in our previous studies thatSF3B1mutational status is also an independent predictive biomarker ofex vivoCLL patient sample treatment response to RG7388. The objective of this study was to identify novel biomarkers associated with resistance to RG7388. Gene set enrichment analysis of differentially expressed genes (DEGs) between RG7388-sensitive and resistant CLL samples showed that the increased p53 activity led to upregulation of pro-apoptosis pathway genes while DNA damage response pathway genes were additionally up-regulated in resistant samples. Furthermore, differential expression of certain genes was detected, which could serve as the backbone for novel combination treatment approaches. This research provides preclinical data to guide the exploration of drug combination strategies with MDM2 inhibitors, leading to future clinical trials and associated biomarkers to improve outcome for CLL patients.
Endoscopic ultrasound-guided tissue acquisition using Fork-tip needle for subepithelial lesions: A single-center validation study
Authors: Watanabe Masafumi , Okuwaki Kosuke , Iwai Tomohisa , Kida Mitsuhiro , Imaizumi Hiroshi , Adachi Kai , Tamaki Akihiro , Ishizaki Junro , Hanaoka Taro , Kusano Chika
Published: January 2024

Background
The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm).
Aim
We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle.
Methods
Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher’s exact tests.
Results
The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred.
Conclusions
EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.
SocialCU: Integrating Commonalities and Uniqueness of Users and Items for Social Recommendation
Authors: Li Shuo , Gan Mingxin
Published: January 2024

Social recommendation (SR) based on Graph Neural Networks (GNN) presents a promising avenue to significantly improve user experience by leveraging historical behavior and social data, which benefits from capturing user preferences through higher-order relationships. Although two socially connected users will prefer certain specific items, their preferences in other items are likely to be inconsistent. We argue that current GNN-based social recommendation methods only focus on the commonalities of user preferences, but ignore the uniqueness. In addition, GNN also suffers from the data sparsity problem commonly observed in recommender system. To address these limitations, we propose the Integrating Commonalities and Uniqueness of users and items method, namely SocialCU, which combines GNN and contrastive learning to gain commonalities and uniqueness for SR. To be specific, we firstly model the original data as the user-item interaction graph and user-user social graph and use GNN to obtain the commonalities of nodes (users or items). Then, we design the adaptive data augmentation to build dual contrastive learning to refine the uniqueness of nodes and mitigate data sparsity by extracting supervised signals. We have conducted extensive experiments on three real-world datasets to demonstrate the performance advantages of SocialCU over current state-of-the-art recommendation methods and the rationality of the model design.