bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Surface-Based Smoothing Methods for Topology Optimization Results
Authors: Sotola Martin , Marsalek Pavel , Rybansky David , Kopacka Jan , Gabriel Dusan , Jezek Ondrej , Kovar Ludek , Tejc Josef , Pasek Miloslav , Halama Radim , Barnovsky Michal
Published: July 2024

Topology optimization (TO) is becoming an essential part of designing new or modifying current parts to improve their properties. A typical problem of TO in structural applications is minimizing compliance with volume (mass) constraints. TO is often complemented by additive manufacturing which allows the printing of complex geometries. Resulting geometries are dependent on the used method, most of the time it is the finite element method. The exported geometry from the optimization procedure, however, tends to have a lot of sharp edges, which causes problems with stress distribution, aesthetics and manufacturing (even if it is additive manufactured). The aim of this paper is to review, apply smoothing techniques on the surface of bodies, Laplacian and Taubin smoothing, and compare the results of smoothing. To fulfill this aim, we developed a smoothing procedure and evaluated the criteria of smoothed-out polymer geometries.
Mechanical Behavior of Frozen Soil Subjected to Freeze–Thaw Cycle Under Cyclic Impact Load and Passive Confining Pressure
Authors: Zhao Wangqi , Zhu Zhiwu , Li Bin
Published: July 2024

In this study, the effects of freeze–thaw cycles and cyclic impacts on frozen soil were systematically investigated. With an increase in the number of freeze–thaw cycles, the peak stress of frozen soil decreased until a stable state was achieved. Moreover, subjecting frozen soil to an increased number of cyclic impacts led to notable alterations in mechanical characteristics, including peak stress, critical strain and dynamic elasticity modulus. Both the freeze–thaw cycles and cyclic impacts were identified as primary damage mechanisms in understanding frozen soil degradation processes. Damage resulting from these impacts conformed to the Weibull distribution pattern. Damages induced by freeze–thaw cycles, individual impacts and cyclic impacts were integrated into the Zhu–Wang–Tang viscoelastic model (ZWT model). Relying on principles of elastic mechanics, the role of confining pressure on frozen soil was examined and subsequently integrated into an improved ZWT model. To evaluate the model’s effectiveness, its predictions were compared with experimental results.
Exploiting Nonlinearities of Electrostatic MEMS Resonators for Tunable Low Pressure Sensing
Authors: Alattar Basil , Ghommem Mehdi
Published: July 2024

In this paper, we demonstrate the potential functionalization of inherent nonlinearities associated with electrostatic MEMS resonators for low air pressure applications, with operating ranges as low as 0.65-295 mbar. The proposed pressure sensor is made of a polysilicon microplate subject to electrostatic actuation via an underneath electrode and attached to two cantilever microbeams. The pressure sensing mechanism relies on the motion-induced current method, a transduction mechanism that converts the dynamic alteration of the microplate due to pressure variations into an electrical signal detected via a lock-in amplifier. The experimental study showed evidence of the possible tunability of the pressure sensor via the deployment of different detection mechanisms to achieve superior performance in terms of sensitivity and low pressure operating range. These mechanisms rely on nonlinear dynamic features that result from the strong coupling between the microplate and the surrounding fluid along with the electrostatic actuation. These include dynamic pull-in instability, bifurcation and softening behavior associated with the elastic effect of the squeeze-film damping. The experimental results revealed that tracking the bifurcation frequency allows for the detection of low pressure levels, in the range of a few millibars. This capability is not provided by the resonance frequency shift method, which, while offering higher sensitivity, does not achieve the same low-pressure detection.
Dynamic Topology Optimization with Multiple Materials Based on Impedance Mismatching of Wave
Authors: Zhang Xin , Wu Fan , Xue Pu
Published: July 2024

Topology optimization with multiple materials studies were commonly adopted to address the issues of complex structures and dynamic loading cases. However, the perturbation excited from the transient load will be propagated and change the local stress level in the structure. Therefore, it is indispensable to consider impedance mismatching of waves at the interfaces of multi-materials layers in the optimization model. In this work, the wave impedance will be regarded as constraint conditions and assessment indicators in the optimization design. Firstly, a multi-material interpolation model using SIMP models is established based on the variable density method. Secondly, the optimization process is applied by combining using Newmark-[Formula: see text] method which is used to solve the dynamic response, an adjoint variable method for sensitivity study, and an optimization criterion method employed to update the design variables. Finally, the simulation examples are used to analyze the influence of impedance mismatching and volume fraction for multilayer dielectric on response. The results indicate that the position and content of the Polymethyl Methacrylate (PMMA) plays a key role in reducing vibration and buffering action.
Development and Implementation of a New Computational Strategy for the Prediction of Elastoplastic Buckling
Authors: BelHadjAmor M. , Bettaieb M. Ben , Mezlini S. , Abed-Meraim F.
Published: July 2024

This study proposes an innovative computational strategy to predict the initiation of elastoplastic buckling in shell structures. This strategy is developed in connection with ABAQUS/Standard Finite Element (FE) code. Toward this objective, two constitutive frameworks are implemented as User MATerial subroutines (UMATs) into this FE code; namely, the incremental flow theory of plasticity and the total deformation theory. These frameworks are formulated under the plane-stress condition, which is particularly suitable for modeling sheet structures and which enhances computational efficiency. Elastoplastic buckling is detected by the Hill loss of uniqueness criterion, which establishes that buckling occurs when the global stiffness matrix, derived from the finite element computations, becomes singular. To determine this matrix and investigate its singularity, a Python script is developed and combined to the ABAQUS computations. The reliability and accuracy of this computational strategy are assessed through various representative numerical examples. The effect of some geometric and material parameters on the onset of elastoplastic buckling in both thin and thick plates, as well as cruciform columns, is investigated and compared to reference results from the literature. The findings of the present contribution can serve as useful reference guidelines for ABAQUS/Standard users, offering valuable insights for predicting the occurrence of elastoplastic buckling, even in metallic structures characterized by complex mechanical behavior and geometric configurations.
Carbon Quantum Dots as Drug Carriers of Methylene Blue: Preparation and Properties Study
Authors: Chen Yiqing , Lv Yingbin , Chen Jingyan , Li Peiyuan
Published: July 2024

Photodynamic therapy (PDT) has long been considered an effective way to tackle antibiotic resistance. Here, Methylene blue (MB) as photosensitizer was combined with carbon quantum dots (CQDs) as drug carriers to make a compound antibacterial agent. The fluorescent CQDs were prepared by hydrothermal method with citric acid (CA) and neutral red (NR) as raw materials. The CQDs can emit 640[Formula: see text]nm red fluorescence under 520[Formula: see text]nm laser irradiation. In the antibacterial experiment, CQDs-MB was irradiated with 660[Formula: see text]nm light. The results showed that CQDs-MB had ideal antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with 100% antibacterial concentration of 5[Formula: see text][Formula: see text]M and 10[Formula: see text][Formula: see text]M, respectively. The combination of CQDs and MB enhanced singlet oxygen (1O2) generation and the PDT activity of MB, which significantly increased the phototoxicity of MB to bacteria.
Synthesis of CuO Thin Film Incorporated with Nanostructured Nd2O3 Deposited by Pulsed Laser Deposition for Ammonia Sensing Applications
Authors: Mohammed Enad Abeer , Rzaij Jamal M.
Published: July 2024

This study involved depositing thin films of copper oxide (CuO) and copper oxide films incorporated with neodymium oxide (Nd2O3) in various weight ratios using the pulsed laser deposition technique to fabricate an ammonia gas sensor. The characteristics of the developed films were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and photoluminescence spectroscopy (PL) techniques. The study investigated the impact of incorporating Nd2O3 into the CuO film on its sensing characteristics. The X-ray analysis revealed a polycrystalline structure of CuO with a crystal size of 19 nanometers. Furthermore, incorporating CuO and Nd2O3 formed a mixed phase comprised of both CuO and Nd2O3. The average crystallite size varied with the Nd2O3 incorporation rate from 19[Formula: see text]nm to 14.7[Formula: see text]nm. With increasing Nd2O3 incorporation ratios, the surface morphology changed from smooth to spherical-like nanostructures, and the average particle sizes varied from 28[Formula: see text]nm to 130[Formula: see text]nm. The PL spectrum analysis results confirmed that the incorporation of Nd2O3 resulted in a change in the peak intensity of the PL spectrum, with a significant increase in the peak associated with oxygen vacancies, contributing to the improvement of the sensor response. The incorporation of Nd2O3 greatly enhanced the sensitivity of the as-deposited CuO film. The sample with 5 wt.% Nd2O3 exhibited the maximum sensitivity, reaching 180% against 79 ppm NH3 at a working temperature of 50[Formula: see text]C.
Efficiency improvement of antimony selenide solar cells based on S-doped SnO2 buffer layer
Authors: Geng Kangjun , Feng Zhengdong , Zhang Tingyu , Huang Shan , Zhu Honcheng , Shen Bangzhi , Dong Boning , Yan Yan , Jiang Sai , Qiu Jianhua , Guo Huafei
Published: July 2024

Antimony Selenide (Sb2Se3) exhibits potential as a solar energy material owing to its optimal bandgap, lack of toxicity, and abundance of earth abundant elements. Currently, cadmium sulfide (CdS) serves as the predominant buffer layer for Sb2Se3 solar cells. However, the use of CdS hinders environmentally friendly advancement due to the toxic properties of the element cadmium. Hence, the quest for non-toxic buffer layers poses a significant challenge to the further advancement of Sb2Se3 solar cells. In prior research, tin oxide (SnO2) has been explored as a buffer layer. Nonetheless, the efficiency of SnO2/Sb2Se3 solar cells was hampered by the rough surface of SnO2 films and the poor crystallinity of Sb2Se3 films. In this investigation, we enhanced device efficiency by improving the uniformity of the SnO2 surface and enhancing the crystallinity of Sb2Se3 through spin-coating sulfur (S) onto the SnO2 film. Detailed examinations were conducted on the structure, optical, and electrical properties of the respective SnO2 and Sb2Se3 thin films. Ultimately, an efficiency of 3.38% was achieved using the spin-coated S:SnO2 film, marking an 85% enhancement compared to the baseline device.
MoC@C/RGO with nano-restricted area structure for active electrode in supercapacitor
Authors: Wang Wen , Yao Jixin , Shen Jingyu , Song Fei , Wang Xiuying , Li Shasha , Zhang Haili , Wang Lei , He Bingling , Ye Song , Li Guang
Published: July 2024

Metallic carbides are widely used as active electrodes in supercapacitors due to their excellent energy storage activity. In this study, a nano-restricted area strategy was employed to prepare a unique structured MoC@C flower sphere composite RGO active material (MoC@C/RGO). Due to the restricted area effect of RGO, MoC@C is restricted to specific areas, with advantages such as uniform dispersion, prominent active sites, high conductivity, and uniform distribution of current collectors. MoC@C/RGO, as the active electrode material of supercapacitors, was subjected to galvanostatic charge–discharge testing (GCD) tests and showed a specific capacitance value of 420 F/g. In addition, MoC@C/RGO showed a capacitance retention rate of 97.6% in 5000 cycles of GCD, indicating that the material has good electrochemical stability.
Physics-informed neural networks for parameter estimation and simulation of a two-group epidemiological model
Authors: Ouyoussef Kawtar Idhammou , El Karkri Jaafar , Tine Léon Matar , Aboulaich Rajae
Published: July 2024

This paper provides a comprehensive exploration of physics-informed neural networks and their core features. It delves into their role in tackling inverse problems inherent in ordinary differential equation-based models. Within this context, we introduce a two-group epidemiological model, elucidating its fundamental attributes. The central objective of this research is to accurately estimate the model parameters for both groups in the epidemiological model. We offer a detailed exposition of the adopted methodology, providing insights into the algorithm and the techniques employed for its implementation. Through this analysis, we illuminate the complexities of our study, contributing to the growing body of knowledge in this field, which intersects epidemiology and neural network-based parameter estimation for an enriched understanding of infectious disease dynamics.
THE ECONOMIC IMPACTS OF IMPLEMENTING NET ZERO POLICIES IN KOREA: A COMBINED TOP-DOWN AND BOTTOM-UP APPROACH
Authors: CHANG KI-BOK , KANG SUNG WON , KWON OH SANG , LEE SEOUNGHO , LEE JEONGEUN , KOO YOONMO
Published: July 2024

The South Korean government aims to achieve carbon neutrality by 2050. Here, this study analyzed the economic efforts of the net-zero policy by integrating top-down and bottom-up models; The UNIfied Climate Options Nexus (UNICON) within this study aims to create a link between the 26 sectors from the bottom-up model and the 85 sectors of the top-down model. Positive mathematical programming methods were used to ensure consistency between the top-down and bottom-up models within the base year. The study found that the total reduction rate was slightly higher in the integrated model than in the computable general equilibrium (CGE) stand-alone model. In both models, the reduction rate increased when the carbon tax increased, but the marginal reduction rate was considerably lowered, and the reduction rate did not exceed 80% even with the high level of a carbon tax. The technological change of the linked industries in the integrated model showed that the steel industry had the highest emission reduction. When estimating costs for reducing GHGs, results can vary based on the technological changes under consideration.
Statistical model for the description of ferroelectric phase transitions in BaTiO3 and KNbO3
Authors: Ivliev Michael , Andryushin Konstantin
Published: July 2024

In this paper, based on the developed statistical-thermodynamic model, which is based on data on the local structure of the compound and taking into account the striction interaction caused by the large sizes of the Ba and K cations, the formation of ferroelectric phases in BaTiO3 and KNbO3 perovskites has been studied. Based on the modified eight-minimum model, it has been possible to qualitatively identify the factors that determine the features of the thermodynamic behavior of these crystals and to reproduce the process of formation of the whole set of phase states observed in BaTiO3 and KNbO3.
Thermodynamical applications in teleparallel tachyonic model
Authors: Ahmed Wakeel , Naeem Fatima
Published: July 2024

In the framework of teleparallel tachyonic model, we explore the stability of the generalized thermodynamical law and equilibrium case at Hubble horizon together with Bekenstein entropy at present as well as past epoch for flat Friedmann–Lemaître–Robertson–Walker metric. For this purpose, we take three distinct models of Hubble parameter in terms of redshift. Also, we choose power-law correction terms and specific coupling of scalar field and take observational values from [Formula: see text] dataset and compare results of all different models.
Early Segmental Production in Thai Preschool Children Learning Mandarin
Authors: Wan I-Ping , Allassonnière-Tang Marc , Yu Pu
Published: July 2024

The research aims to conduct a corpus-based and data-driven analysis of the early-stage Mandarin learning production of 11 Thai preschool children in Bangkok, Thailand, within the interlanguage system. These children consist of 8 boys and 3 girls, with an age range of 4;1-6;5 ([Formula: see text] =5.455, SD=0.688; total tokens=36,565). Data were extracted from a spoken corpus constructed between 2018 and 2022, which was time-stamped, phone-aligned, and multi-tiered using Praat [P. Boersma and D. Weenink, Praat: Doing phonetics by computer (2022), http://www.praat.org/ ]. The data were annotated and labeled through a semi-automatic process employing various applications in Hybrid-DNN-HMM. The findings indicate the following: (1) Most sound deviations in learning do not mirror the phonetic inventory of L1; (2) Sound deviations can be influenced by L2, with marked phones exhibiting more deviations between L1 and L2; (3) Interlanguage manifests as a self-organizing and self-adaptive system. The study delves into the Contrastive Analysis Hypothesis, Markedness Differential Hypothesis and Interlanguage theory. It compares data with cross-linguistic universal trends in Mandarin acquisition and spoken corpus in Mandarin adults. Segmental similarities regarding phonological distances are quantitatively measured through Levenshtein edit distance and Hamming distance based on multivalued distinctive features.
Development of an easy and economical carbon paste electrode for fisetin detection
Authors: Mukherjee Sumani , Dasgupta Samhita , Naskar Hemanta , Firdoushi Shreya , Bhattacharya Ipshita , Ahmed A.H.M. Toufique , Das Deepak Kumar , Bandyopadhyay Rajib , Tudu Bipan
Published: July 2024

Fisetin is a crucial flavonoid that is naturally synthesized in various fruits and vegetables. It has many medicinal applications including chemotherapy, neuropathy, antiviral, anti-inflammatory, antibacterial, and antioxidant properties. A low-cost, easily fabricated carbon paste electrode (CPE) was used to examine the sensitivity of analytical-grade fisetin in PBS6 buffer solution. CPE was used as a working electrode. A reference electrode of silver–silver chloride and a platinum electrode as a counter were used to analyze the electrochemical behavior in this study. Experimental studies were achieved using cyclic voltammetry and differential pulse voltammetry (DPV) processes. The developed sensor was shown to have good linearity from 5 to 200[Formula: see text][Formula: see text]M with an identification limit of detection being 0.3[Formula: see text][Formula: see text]M. The study of repeatability, reproducibility, and stability using DPV response of the working sensor had shown a relative standard deviation of 3.56%, 3.2%, and 1.69%, respectively. The presence of fisetin in onion extract by using a selected electrode was observed. The developed sensor’s average fisetin recovery from the onion extract was 100.86%. The discrete concentration value of fisetin was analyzed using principal component analysis with a separability index of 40.66. The prepared electrochemical sensor can be helpful for the real-time detection of fisetin in any real sample solution.
The meteoritic record of Arabia
Authors: Hofmann Beda A. , Gnos Edwin
Published: July 2024

Meteorites provide a wealth of information about the origin of the Earth and the solar system. Systematic searches have proved successful in cold and hot desert areas. Meteorite finds are favoured in areas with light-coloured surfaces that have been stable over tens of thousands of years and in hyper-arid climates. The deserts of Arabia are well suited for the search for meteorites. Following the first finds by explorers in the 1930s, and during oil exploration in the 1950s, a significant number of finds have been recorded in Oman since 1999, with more than 4000 meteorites currently recorded. Exploratory searches in Saudi Arabia have also shown a significant potential for meteorite discoveries. A collaborative Omani-Swiss search project was initiated in 2001 and 23 search campaigns since then have yielded more than 7300 samples, including meteorites from the Moon and Mars and, 37 strewn fields. Arabia has the potential to become one of the key regions for meteorite recovery and future research. Only three confirmed (Wabar, Saqqar and Jebel Waqf as Suwwan), several suspected and some dubious impact structures have been reported. The Wabar impact locality in Saudi Arabia features impact craters in dune sands, shocked and melted sand, and finds of several large meteorites.
Self-Supervised EEG Representation Learning for Robust Emotion Recognition
Authors: Liu Huan , Zhang Yuzhe , Chen Xuxu , Zhang Dalin , Li Rui , Qin Tao
Published: July 2024

Emotion recognition based on electroencephalography (EEG) is becoming a growing concern of researchers due to its various applications and portable devices. Existing methods are mainly dedicated to EEG feature representation and have made impressive progress. However, the problem of scarce labels restricts their further promotion. In light of this, we propose a self-supervised framework with contrastive learning for robust EEG-based emotion recognition, which can effectively leverage both readily available unlabeled EEG signals and labeled ones to learn highly discriminative EEG features. Firstly, we construct a specific pretext task according to the sequential non-stationarity of emotional EEG signals for contrastive learning, which aims at extracting pseudo-label information from all EEG data. Meanwhile, we propose a novel negative segment selection algorithm to reduce the noise of unlabeled data during the contrastive learning process. Secondly, to mitigate the overfitting issue induced by a small number of labeled samples during learning, we originate a loss function with label smoothing regularization that can guide the model to learn generalizable features. Extensive experiments over three benchmark datasets demonstrate the effectiveness and superiority of our model on EEG-based emotion recognition task. Besides, the generalization and robustness of the model have also been proved through sufficient experiments.
PsyChatbot: A Psychological Counseling Agent Towards Depressed Chinese Population Based on Cognitive Behavioural Therapy
Authors: Chen Tiantian , Shen Ying , Chen Xuri , Zhang Lin
Published: July 2024

Nowadays, depression has been widely concerned due to the growing depressed population. Depression is a global mental problem, the worst case of which can lead to suicide. However, factors such as high treatment costs and social stigma prevent people from obtaining effective treatments. Chatbot technology is one of the main attempts to solve the problem. But as far as we know, existing chatbot systems designed for depressed people are still sporadic, and most of them have some non-negligible limitations. Specifically, existing systems simply guide users to release their negative emotions or provide some general advice. They cannot offer personalized advice for users’ specific problems. In addition, most of them only support English speakers, despite the fact that depressed Chinese constitute a large population. Psychological counseling systems for the depressed Chinese population with improved responsiveness are temporarily lacking. As an attempt to fill in the research gap to some extent, we design a novel Chinese psychological chatbot system, namely PsyChatbot. First, we establish a counseling dialogue framework based on Cognitive Behavioral Therapy (CBT), which guides users to reflect on themselves and helps them discover their negative perceptions. Then, we propose a retrieval-based Q&A algorithm to provide suitable suggestions for users’ specific problems. Last but not least, we construct a large-scale Chinese counseling Q&A corpus, which contains nearly 89,000 psychological Q&A triples. Experimental results have demonstrated the effectiveness of PsyChatbot. The source code and data has been released at https://github.com/slptongji/PsyChatbot.
Minimizing Recess of Cu Pad on Hybrid Bonding with SiCN via Non-selective Chemical Mechanical Polishing and Post-cleaning Steps
Authors: Nakayama Kohei , Hayama Kenta , Tanaka Fabiana Lie , La Mai Thi Ngoc , Inoue Fumihiro
Published: July 2024

Hybrid bonding has become a promising approach to realizing fine pitch interconnection via bonding for both the wafer level and die level. The morphology and cleanliness of the bonding surface are critical to ensure a high yield. Therefore, surface planarization by chemical mechanical polishing (CMP) is considered a key process. The recess on the Cu pad must be controlled to be less than 5 nm by adjusting the removal rate between the Cu, the barrier layer, and the bonding dielectric layer. Conventionally, SiO2 has served as the bonding dielectric. However, SiCN is considered a promising dielectric because of its high bonding strength, suppression of voids, and ability to function as a Cu diffusion barrier. Here, we investigated simultaneous Cu, barrier, and SiCN CMP for hybrid bonding. Post-CMP processes such as cleaning and activation were also assessed. The results revealed that the removal rate of the three materials could be adjusted by dilution of the slurry and oxidizer. Lower selectivity was achieved at a certain dilution rate in an alkaline barrier slurry. Plasma activation revealed that the Cu passivation layer formed during cleaning was removed. Therefore, residues from CMP and post-CMP processes did not affect Cu prior to the hybrid bonding.
Structure, Electronic, Optical, Magnetic and Magnetocaloric Properties of Sm2CuMnO6 Double Perovskite Nanomaterial
Authors: Saha Samarendra Nath , Barman Purna Chandra , Roy Rajdip , Singh N. Bedamani , Mondal Rajkumar , Gupta Shuvankar , Das Rakesh , Shukla Shivam , Srivastava S. K. , Anirban Sk.
Published: July 2024

This study explores the structural, microstructural, optical, and magnetic characteristics of double perovskite oxide Sm2CuMnO6. The sample is prepared in the monoclinic phase with space group P21/n using the auto-combustion method. The crystal structure exhibits distortion and tilting. First-principles calculations are conducted using the density-functional theory framework, focusing on electronic structures and density of states. The average crystallite size, particle size and grain size of the sintered sample are 34.42 nm, 36.15 nm and 475 nm respectively. The sample exhibits a direct band gap energy of 1.96 eV. Analysis of the X-ray photoelectron spectra indicates the presence of Sm3+, Cu2+, and Mn3+/Mn4+ ions in the sample. The DC magnetization study reveals a Curie temperature (Tc) of 50 K for the sample. A non-metallic state resembling a spin glass is detected below 15 K, arising from the competition between antiferromagnetic and ferromagnetic interactions. The maximum value of isothermal magnetic entropy, the relative cooling power and heat capacity are 1.4 J.kg–1.K–1, 100.2 J.kg–1, and 1.35 J.kg–1.K–1 at a field change of 70 kOe respectively. The value of Temperature Averaged Entropy Change is 1.36 J.kg−1.K−1 and 1.29 J.kg−1.K−1 for a temperature span of 10 K and 40 K at a field change of 70 kOe.
PI3K Inhibitors in Hematology: When One Door Closes…
Authors: Skånland Sigrid S. , Okkenhaug Klaus , Davids Matthew S.
Published: July 2024

The PI3K signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110γ and p110δ are highly enriched in leukocytes, providing an additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kδ inhibitor idelalisib was the first of four PI3K inhibitors (PI3Ki) to receive regulatory approval for relapsed B-cell malignancies. This was followed by approvals of the pan–class I inhibitor copanlisib (2017), the dual PI3Kγ/δ inhibitor duvelisib (2018), and the PI3Kδ and casein kinase 1ε inhibitor umbralisib (2021). Copanlisib and umbralisib received accelerated approvals, whereas idelalisib and duvelisib received initial accelerated approvals followed by full approvals. The accelerated approvals were based on overall response rates; however, follow-up studies showed increased risk of death and serious side effects. Furthermore, the confirmatory trial with copanlisib failed to show an improvement in progression-free survival when compared with chemoimmunotherapy. These developments led to black box warnings for idelalisib and duvelisib and withdrawal of copanlisib and umbralisib from the market by their manufacturers. Given the uncertain future of this drug class, additional manufacturers terminated ongoing phase III trials with novel PI3Kis. In this study, we review the development and current status of PI3Kis in hematology, limitations to their use, and our perspective on whether there is a future for PI3Kis in hematology.
hnRNPAB Promotes Pancreatic Ductal Adenocarcinoma Extravasation and Liver Metastasis by Stabilizing MYC mRNA
Authors: Lei Ke , Sun Mingyue , Chen Xianghan , Wang Jia , Liu Xiaolan , Ning Ying , Ping Shuai , Gong Ruining , Zhang Yu , Qing Gong , Zhao Chenyang , Ren He
Published: July 2024

Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. hnRNPAB was highly expressed in PDAC tissues compared with normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in patients with PDAC. hnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. hnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life. hnRNPAB induced PDAC cells to secrete CXCL8 via MYC, which promoted neutrophil recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis.

Implications: hnRNPAB participates in the posttranscriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.
“Couple’s Immunotherapy”: Is CXCL13 at the Heart of the Prescription?
Authors: Cruz-Hinojoza Eduardo , Stromnes Ingunn M.
Published: July 2024

Sex differences in cancer survivorship and response to immunotherapy have been observed, with males generally displaying better outcomes to immune checkpoint blockade compared with females. In this article, by interrogating public lung cancer sequencing datasets, Brennan and colleagues uncover a chemokine axis that may contribute to disparate immunotherapy outcomes between the sexes.

See related article by Brennan et al., p. 956 (3).
Figure 1 from Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis
Authors: Verma Surbhi , Giagnocavo Stephanie D. , Curtin Meghan C. , Arumugam Menusha , Osburn-Staker Sandra M. , Wang Guoying , Atkinson Aaron , Nix David A. , Lum David H. , Cox James E. , Hilgendorf Keren I.
Published: July 2024

Secretome of human breast cancer cells modulates adipogenesis. A, Schematic of experimental workflow. Breast cancer cell secretomes were added only during the first 2 days of 3T3-L1 adipogenesis. B, Effect of human breast cancer cell line secretomes on 3T3-L1 adipogenesis. C and D, The secretome of TNBC cell lines MDA-MB-468 and MDA-MB-231 inhibits the differentiation of primary murine ASPCs as assessed by (C) lipid accumulation during adipogenesis and (D) expression of adipogenic genes Pparγ, Cebpα, and Adipoq. B–D, All data are mean ± SD. Data points show independent biological replicates. P values calculated using (B and D) one-way ANOVA followed by Dunnett’s multiple comparison test or (C) two-way ANOVA followed by Šidák’s multiple comparison test. (**, P < 0.01; ***, P < 0.001; ****, P < 0.0001; A, Created with BioRender.com.)
Direitos linguísticos e cooficialização da língua alemã em São João do Oeste, Santa Catarina
Authors: Frizzo Celina Eliane , Ruscheinsky Elena Wendling , Krug Marcelo Jacó
Published: July 2024

The Universal Declaration of Linguistic Rights is little known by the general population and, perhaps, by those who are most interested in it. According to this document, speakers of other languages, which are not official in a given territory, have the right to use them in their lives without suffering any kind of discrimination, exclusion and persecution. This study proposes to explain issues related to linguistic rights, linguicism and linguicide and relate them to the process of co-officialization of the German language in the municipality of São João do Oeste, Santa Catarina, Brazil, based mainly on the theoretical assumptions of Skutnabb-Kangas (2019) and Skutnabb-Kangas & Phillipson (1995; 2017) and others, in addition to historical sources about the municipality and the Law 1685/2016. The results show that, before the co-officialization in 2016, there were actions to attribute prestige to the German variety. However, when analyzing what the law postulates, we realize that this policy is aimed at attracting tourists and does little to represent the speakers or guarantee the linguistic rights of a minority group.
ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway
Authors: Tian Qi , Liu Chengli , Liao Jianming , Wang Guijun , Han Wenrui , Xiong Xiaoxing , Chen Zhibiao , Gu Lijuan , Li Mingchang
Published: July 2024

BACKGROUND:

Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis.

METHODS:

Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting
BAP1
mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH.

RESULTS:

First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome–mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH.

CONCLUSIONS:

Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.
Amana wanyuensis (Liliaceae), a new species from the Dabieshan Mountains, Anhui Province, China
Authors: SONG XIANGWEN , LI GUANGYAN , WANG WEI , SONG XIANGWEN , XU TAO , GAO XINYI , HAN BANGXING , YI SHANYONG
Published: July 2024

Amana wanyuensis is a recently discovered species from the Dabieshan Mountains, Anhui Province, China. It is like A. edulis in terms of leaves (2), bracts (2–3), flowers (1–5), and yellow anthers and round (versus oblique) stigmas, but differs most notably from A. edulis in its ovoid bulb with a glabrous interior, green leaves with white veins, bracts 3.0–5.0 cm below the flower and tepals with white streaks. Additionally, this new species forms an independent clade in the phylogenetic tree.
Revision of Matsumuraja (Hemiptera, Aphidinae, Macrosiphini) in China with two new synonyms and four new records
Authors: XU YING , CHEN JING , JIANG LIYUN , QIAO GEXIA
Published: July 2024

The genus Matsumuraja Schumacher, 1921 is an eastern Asiatic genus and was reviewed in China. After this research, M. polydactylota Qiao & Zhang syn. nov. was regarded as the synonym of M. rubicola Takahashi; and Chaetosiphon anguifragum Zhang & Qiao syn. nov. was regarded as the synonym of M. rubifoliae Takahashi. Furthermore, M. rubi (Matsumura), M. rubiphila Takahashi, M. taisetsusana Miyazaki, M. urticae Ghosh, Ghosh & Raychaudhuri were first recorded in China. Seven species of the genus are now recognized in China. A key to species of Matsumuraja in China is presented.
Two new records of the genus Idaea Treitschke, 1825 (Lepidoptera: Geometridae: Sterrhinae) for Iran
Authors: WANKE DOMINIC , SKOU PEDER , RAJAEI HOSSEIN
Published: July 2024

Two species, Idaea admiranda Hausmann, 2004 and Idaea subsericeata (Haworth, 1809) are reported as new faunal elements for Iran. Wing pattern and genitalia structures of both species are depicted and their diagnostic characters are highlighted.
An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure
Authors: Summers Jane , Baribeau Danielle , Perlman Polina , Hoang Ny , Cui Sunny , Krakowski Aneta , Ambrozewicz Patricia , Ho Ariel , Selvanayagam Thanuja , Sándor-Bajusz Kinga A. , Palad Katrina , Patel Nishi , McGaughey Sarah , Gallagher Louise , Scherer Stephen W. , Szatmari Peter , Vorstman Jacob
Published: July 2024

Background

A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary ‘genetic-diagnosis-first’ clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians.

Methods

We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians.

Results

159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement.

Conclusions

DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population.
Genetic and genomic analysis of Belgian Blue’s susceptibility for psoroptic mange
Authors: Meyermans Roel , Janssens Steven , Coussé Annelies , Tinel Susanne , Gorssen Wim , Lepot Fabrice , Hubin Xavier , Mayeres Patrick , Veulemans Wim , De Wilde Nathalie , Druet Tom , Georges Michel , Charlier Carole , Claerebout Edwin , Buys Nadine
Published: July 2024

Background

Psoroptic mange, caused by Psoroptes ovis mites, is affecting Belgian Blue cattle’s welfare and production potential. The Belgian Blue cattle—known for its high degree of muscling, low feed conversion ratio and high beef quality—is highly susceptible for this disease.

Results

In this study, we phenotyped 1975 Belgian Blue cattle from more than 100 different groups on commercial beef farms for their psoroptic mange susceptibility. Substantial individual differences were observed within these management groups, with lesion extent differences up to ± 15%. Animal models showed that estimated heritabilities were low for lesion extent and severe lesion extent (0.07 and 0.09, respectively) and 0.12 for the number of mites. A genome wide association study for mange susceptibility revealed signals on BTA6, BTA11, BTA15 and BTA24. In these regions, candidate genes GBA3, RAG2, and TRAF6 were identified.

Conclusions

Despite the challenges in phenotyping for psoroptic mange due to the timing of screening, the continuous evolution of lesions and different management conditions, we successfully conducted a study on the genetic susceptibility to psoroptic mange in Belgian Blue cattle. Our results clearly indicate that psoroptic mange is under polygenic control and the underlying candidate genes should be studied more thoroughly. This is the first study providing candidate genes for this complex disease. These results are already valuable for Belgian Blue breeding, however, further research is needed to unravel the architecture of this disease and to identify causal mutations.
Functional and evolutionary comparative analysis of the DIR gene family in Nicotiana tabacum L. and Solanum tuberosum L.
Authors: Li Tong , Luo Wenbin , Du Chaofan , Lin Xiaolu , Lin Guojian , Chen Rui , He Huaqin , Wang Ruiqi , Lu Libin , Xie Xiaofang
Published: July 2024

Background

The dirigent (DIR) genes encode proteins that act as crucial regulators of plant lignin biosynthesis. In Solanaceae species, members of the DIR gene family are intricately related to plant growth and development, playing a key role in responding to various biotic and abiotic stresses. It will be of great application significance to analyze the DIR gene family and expression profile under various pathogen stresses in Solanaceae species.

Results

A total of 57 tobacco NtDIRs and 33 potato StDIRs were identified based on their respective genome sequences. Phylogenetic analysis of DIR genes in tobacco, potato, eggplant and Arabidopsis thaliana revealed three distinct subgroups (DIR-a, DIR-b/d and DIR-e). Gene structure and conserved motif analysis showed that a high degree of conservation in both exon/intron organization and protein motifs among tobacco and potato DIR genes, especially within members of the same subfamily. Total 8 pairs of tandem duplication genes (3 pairs in tobacco, 5 pairs in potato) and 13 pairs of segmental duplication genes (6 pairs in tobacco, 7 pairs in potato) were identified based on the analysis of gene duplication events. Cis-regulatory elements of the DIR promoters participated in hormone response, stress responses, circadian control, endosperm expression, and meristem expression. Transcriptomic data analysis under biotic stress revealed diverse response patterns among DIR gene family members to pathogens, indicating their functional divergence. After 96 h post-inoculation with Ralstonia solanacearum L. (Ras), tobacco seedlings exhibited typical symptoms of tobacco bacterial wilt. The qRT-PCR analysis of 11 selected NtDIR genes displayed differential expression pattern in response to the bacterial pathogen Ras infection. Using line 392278 of potato as material, typical symptoms of potato late blight manifested on the seedling leaves under Phytophthora infestans infection. The qRT-PCR analysis of 5 selected StDIR genes showed up-regulation in response to pathogen infection. Notably, three clustered genes (NtDIR2, NtDIR4, StDIR3) exhibited a robust response to pathogen infection, highlighting their essential roles in disease resistance.

Conclusion

The genome-wide identification, evolutionary analysis, and expression profiling of DIR genes in response to various pathogen infection in tobacco and potato have provided valuable insights into the roles of these genes under various stress conditions. Our results could provide a basis for further functional analysis of the DIR gene family under pathogen infection conditions.
Automating incidence and prevalence analysis in open cohorts
Authors: Cockburn Neil , Hammond Ben , Gani Illin , Cusworth Samuel , Acharya Aditya , Gokhale Krishna , Thayakaran Rasiah , Crowe Francesca , Minhas Sonica , Smith William Parry , Taylor Beck , Nirantharakumar Krishnarajah , Chandan Joht Singh
Published: July 2024

Motivation

Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses.

Implementation

We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later.

General features

The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence.

Availability

The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication.