bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Multi-hop backhaul free new Massive MIMO Cell Deployment Model for Future Wireless Networks
Authors: Kausar Raabia , Sheikh Javaid A. , Gupta Akhil
Published: December 2024

Small cell deployment is considered as a sophisticated approach for enhancing capacity to the future wireless system. However, each additional cell increases the interference in the system particularly in a non-noise limited system. This paper investigates and overcomes the problem by solving the delinquent of path selection and rate allocation in the interference environment for mm-wave massive MIMO future wireless networks. Enabling mm-wave transmissions raises a potential issue of increased latency, and thus, this work aims at addressing the fundamental concerns such as selection of the best path and rate allocation over these paths subject to low latency, less channel fading, high signal-to-noise ratio (SNR), least path loss, and low transmission power through different scenarios. We propose a new model which simulates the movement of users within a network area. The parameters such as number of users, regions, network dimensions, number of columns and rows (nocx and nocy), total number of nodes (n), and other relevant variables have been considered and initialized in the proposed model. The model also uses a coverage set calculation to determine the coverage area of each user and identifies the path for data transmission. The communication fading channel modelling has been investigated using Rayleigh fading with a given maximum Doppler frequency shift (fd). The investigation calculates the Signal-to-Noise Ratio (SNR) and determines the path loss and transmission power. For each generated route, the model calculates performance metrics such as SINR (Signal-to-Interference-plus-Noise Ratio), packet delivery rate (PDR), packet loss rate, and end-to-end delay. On comparing the system model with these proposed-parameters and techniques with the previously published work the efficiency using these techniques has been observed to perform better as compared to existing ones.
Selective magnetoelectric stimulation antagonizes GABAA receptors subunit in the left prelimbic cortex neurons to alleviate schizophrenia-like behaviors
Authors: Hu Yunshan , Wang Zixu , Fang Jin , Zhang Shaotong , Li Yan , Wu Chaoran , Wang Yu , Ling Yuru , Cai Renliang , Xu Yue , Fang Xinyu , Zhou Chao , Xu Dandan , Liu Mengyu , Zhang Zhijun , Zhang Xiangrong
Published: December 2024

Schizophrenia (SCZ) is a prevalent and disabling mental disorder. Clinically, its complex symptoms, including negative symptoms and cognitive impairments, can be ameliorated using electromagnetic techniques such as repetitive transcranial magnetic stimulation (rTMS). To investigate the neural mechanisms of magnetic stimulation and identify selective therapeutic targets, we employed a combined magnetic stimulation system treatment (c-MSST). Targeting the mouse left prelimbic cortex (PrL) with c-MSST reversed SCZ-like behaviors and dendritic spine density reductions induced by MK-801 injection. SCZ-like mice showed a region-specific increase in Gabre (gamma-aminobutyric acid type A receptor subunit epsilon) in the left PrL, normalized by c-MSST. Specific Gabre knockdown in the left PrL reversed SCZ-like behaviors induced by MK-801. Additionally, the transgenic mouse with Gabre knock-in specific to the PrL exhibited SCZ-like behaviors and synaptic plasticity deficits, both reversed by c-MSST. Overexpression of the p62 gene disrupted Gabarap and Gabarapl1 binding, reducing Gabre surface expression. Our findings suggest Gabre and related circuits as promising targets for schizophrenia treatment.
Exosomal miR-125b-5p derived from mesenchymal stem cells enhances anti-PD-1 therapy in mouse colon cancer model
Authors: Jiang Mengmeng , Liu Jia , Hu Shengquan , Yan Xueqin , Cao Yongkai , Wu Zhengzhi
Published: December 2024

Background
There is compelling evidence that FoxP3+ regulatory T cells (Tregs) play a critical role in promoting tumor immune evasion. Our prior research demonstrated that the expression of miR-125b-5p directly inhibits Tregs by targeting TNFR2 and FoxP3. Given the significant therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-EXO) in cancer treatment, the potential role of MSC-EXO in augmenting anti-tumor immunotherapy through the delivery of miR-125b-5p remains unexplored.
Methods
Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were employed to characterize exosomes derived from mesenchymal stem cell (MSC). Flow cytometry analysis was conducted to investigate the function of exosomal miR-125b-5p both in vitro and in vivo. Mouse MC38 tumor models were administrated MSC-derived exosomes containing miR-125b-5p via tail vein injection, with or without the concurrent administration of anti-PD-1 antibodies.
Results
Our results indicated that exosomal miR-125b-5p derived from MSC significantly inhibited the expansion, proliferation and suppressive function of Tregs in vitro. Moreover, we observed a marked reduction in tumor growth in mice treated with exosomal miR-125b-5p. Notably, while anti-PD-1 therapy alone achieved a cure rate of approximately 30% in a mouse model of colon cancer, the combined administration of exosomal miR-125b-5p significantly enhanced the therapeutic efficacy, resulting in a more than two- to three-fold increase in tumor regression in approximately 80% of the treated mice. The underlying cellular mechanism was closely associated with the reduction of tumor-infiltrating Tregs. and the increase of CD8+ cytotoxic T lymphocytes (CTLs).
Conclusions
In summary, our findings suggest that exosomal miR-125b-5p derived from MSC exerts prominent potential in advancing anti-PD-1 therapy by modulating tumor immune environment. This property of miR-125b-5p may be therapeutically harnessed in human cancers to enhance the efficacy of immunotherapy.
General intelligent imaging and uncertainty quantification by deterministic diffusion model
Authors: Liao Yiyi , Fan Weiru , Tang Xiaobin , Wang Da-Wei
Published: December 2024

Computational imaging is crucial in many disciplines from autonomous driving to life sciences. However, traditional model-driven and iterative methods consume large computational power and lack scalability for imaging. Deep learning (DL) is effective in processing local-to-local patterns, but it struggles with handling universal global-to-local (nonlocal) patterns under current frameworks. To bridge this gap, we propose a novel DL framework that employs a progressive denoising strategy, named the deterministic diffusion model (DDM), to facilitate general computational imaging at a low cost. We experimentally demonstrate the efficient and faithful image reconstruction capabilities of DDM from nonlocal patterns, such as speckles from multimode fiber and intensity patterns of second harmonic generation, surpassing the capability of previous state-of-the-art DL algorithms. By embedding Bayesian inference into DDM, we establish a theoretical framework and provide experimental proof of its uncertainty quantification. This advancement ensures the predictive reliability of DDM, avoiding misjudgment in high-stakes scenarios. This versatile and integrable DDM framework can readily extend and improve the efficacy of existing DL-based imaging applications.
TeacherEye: An AI-Powered System forMonitoring Student Engagement in OnlineEducation
Authors: Abdelhadi Zainab , Naseif Mohammed , Alhejali Waad , Elhayek Ahmed
Published: December 2024

In online education, maintaining student engagement and academic integrity poses significant challenges. While multiple solutions have been introduced, none have provided a comprehensive system. We introduce TeacherEye, an Artificial Intelligence (AI) powered system for monitoring student behavior and engagement in virtual classrooms and exams. TeacherEye integrates State-Of-The-Art (SOTA) AI models to analyze video data from the webcam stream and audio data from the microphone in real time. The system first verifies students through face detection and identification. It then monitors behavior using advanced vision features like sleep detection, multi-person detection, phone usage detection, focus tracking, and emotion recognition. Audio is simultaneously converted to text and analyzed by a Large Language Model (LLM) to detect suspicious behavior, enhancing online exam proctoring. If irregularities are found, a Vision-Language Model (VLM) suggests actions to the teacher, while all detected behavior is logged for review. TeacherEye presents a comprehensive solution for improving engagement and ensuring integrity in online education.
Research on the impact of spatial and temporal changes in Ecological product value in Hebei Province based on land use changes
Authors: Gao Minna , Hu Yong-Xiang , Shang Guo-Fei , Li Wei
Published: December 2024

Analyze the changes in land use and the spatial evolution characteristics of ecological product value in Hebei Province, understand the driving factors that affect the value of ecological products, and aim to promote the sustainable use of land resources and promote local economic development. This paper investigated the changes in land use and landscape patterns in Hebei Province from 2010 to 2022, and used the improved equivalent factor to account for the value of ecological products, used the global Moran’s I index, Getis-Ord General G index, and Getis-OrdG* index to explore the characteristics of spatial and temporal changes in the value of ecosystem services in different districts and counties of the study area, and finally used a geoprobe to explore the influence factors of land use change on the spatial and temporal changes in the value of ecological products in Hebei Province. value of ecological products in Hebei Province. The following conclusions were drawn: (1) Land use in Hebei Province is dominated by farmland, forests, grasslands and impervious surfaces, accounting for about 95% of the area of Hebei Province. (2) From the accounting results, the value of ecological products in Hebei Province during the study period shows a trend of rising, then falling and then rapidly rising, with the value of ecological products in Hebei Province amounting to 256,640,551,000,000 Yuan in 2010, and 488,748,000,000 Yuan in 2022, with a rise of close to 47.4892%. In addition, the high-value area of ecological product value is concentrated in the northern part of Hebei Province, with the city of Chengde and Zhangjiakou as the main areas of the dam plateau, and the low-value area is concentrated in the plains of Hebei Province. Damshang Plateau area, mainly in Chengde City and Zhangjiakou City, and the low-value area is concentrated in the Hebei Plain area. (3) When exploring the factors influencing the spatial and temporal changes of ecological product values in Hebei Province due to land use changes, population density, slope and elevation with large q-values are the main factors influencing the ecological product values in Hebei Province. In addition, in terms of factor interactions, there are two types of two-factor enhancement and nonlinear enhancement in the interaction of factors influencing the high and low values of ecological products in Hebei Province as a result of land use change. From 2010 to 2022, the land use and landscape patterns in Hebei Province have changed significantly, and the value of ecological products has also changed continuously. It is necessary to put forward a strategy to improve the value of ecological products based on the change of land use in Hebei Province, to promote the transformation of the economic development in the direction of ecologically friendly and sustainable development, and to realize the benign cycle of economic growth and environmental protection.
Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain
Authors: Hoffman Gabriel , Zeng Biao , Yang Hui , N.M. Prashant , Venkatesh Sanan , Mathur Deepika , Auluck Pavan , Bennett David , Marenco Stefano , Haroutunian Vahram , Voloudakis Georgios , Lee Donghoon , Fullard John , Bendl Jaroslav , Girdhar Kiran , Roussos Panos
Published: December 2024

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384 donors of diverse ancestries. Through multi-resolution analyses spanning eight major cell classes and 27 subclasses, we identify genetic regulation for 14,258 genes, with 857 showing cell type-specific regulatory effects at the class level and 981 at the subclass level. Colocalization of genetic variants associated with gene regulation and disease traits uncovers novel cell type-specific genes implicated in Alzheimer's disease, schizophrenia, and other disorders, which were not detectable in bulk tissue analyses. Analysis of dynamic genetic regulation at the single nucleus level identifies 2,073 genes with regulatory effects that vary across developmental trajectories, inferred from a broad age range of donors. We also uncover 1,655 genes with trans-regulatory effects, revealing distal regulation of gene expression. This high-resolution atlas provides unprecedented insight into the cell type-specific regulatory architecture of the human brain, and offers novel mechanistic targets for understanding the genetic basis of neuropsychiatric and neurodegenerative diseases.
Hearing threshold affects cognitive function in hearing aid non-users and long-term users
Authors: Nishiyama Takanori , Kimizuka Tomomi , Kataoka Chinatsu , Tazoe Mami , Sato Yasunori , Hosoya Makoto , Shimanuki Marie , Wakabayashi Takeshi , Ueno Masafumi , Ozawa Hiroyuki , Oishi Naoki
Published: December 2024

Hearing loss is a potential risk factor for cognitive decline, and the use of hearing aids is thought to have positive effect of preventing cognitive decline. However, the extent of hearing loss requiring hearing aid use to prevent cognitive decline is unclear. This study examined the hearing thresholds associated with cognitive decline risk in individuals with hearing impairment and analyzed the relationship between hearing thresholds and cognitive function in those who had never used hearing aids or had used hearing aids for > 3 years. This cross-sectional, prospective, cohort study was undertaken at a tertiary care center between September 2022 and September 2023. The cohort comprised 117 individuals aged ≥ 55 years with an average hearing threshold of ≥ 25 dB HL (degree of hearing loss in decibels) in their better ear, and included participants who had never used hearing aids (non-users; n = 55) and participants who had used hearing aids for > 3 years (long-term users; n = 62). The Mini-Mental State Examination and the Symbol Digit Modalities Test were used to assess cognitive function. Pure-tone and sound-field audiometry were conducted. Non-users showed a significant association (P = 0.01) between the hearing threshold and Symbol Digit Modalities Test scores, with a cutoff value of above 38.75 dB HL identified as affecting cognitive function. There were no significant associations for long-term users. A mean hearing threshold of ≥ 38.75 dB HL may be a risk factor for cognitive decline in midlife and older hearing aid non-users. The long-term use of hearing aids may reduce this risk.
Comparison of ciprofol versus propofol for the induction of patients with valve stenosis undergoing valve surgery: A prospective, randomized, controlled trial
Authors: Li Shurong , Li Lingyao , Li Xiang , Lin Duomao , Zhai Siqi , Gao Junwei , jun Ma
Published: December 2024

Background: Ciprofol（HSK3486）, a novel 2,6-disubstituted phenol derivative, is a new intravenous anesthetic compound with a similar chemical structure to propofol. The aim of this study was to investigate whether the induction of anesthesia with ciprofol in patients with valve stenosis with cardiac compromise has a better clinical effect than propofol, and whether it is more conducive to the maintenance of perioperative hemodynamics in valve surgery.
Methods: Between May 2022 and June 2023, 80 participants were assessed for eligibility and randomly allocated to ciprofol group and propofol group. In ciprofol group, patients received ciprofol 0.3mg/kg, sufentanil 1.5 µg/kg and rocuronium 0.6-0.9mg/kg intravenously for anesthesia induction. In propofol group, anesthesia induction was conducted with propofol 1.5mg/kg, sufentanil 1.5 µg/kg and rocuronium 0.6-0.9mg/kg. Anesthesia maintenance drugs were connected 10 minutes after induction. Ciprofol/Propofol combined with dexmedetomidine, sufentanil and rocuronium were used to adjust the dose of anesthetics. BIS index was maintained at 40-60, SpO2 ≥ 98% and PETCO2 at 35-40mmHg throughout the operation. The occurrence of post induction hypotension (PIH，median arterial pressure below baseline 20%) was recorded. If hypotension occurred, norepinephrine treatment was given, and the total dosage of norepinephrine and VIS score were recorded 10 minutes after induction and from induction to the beginning of surgery.
Results: The incidence of PIH is 25% in ciprofol group and 75% in propofol group ,giving an OR of 0.080(95%CI, 0.23-0.276, P<0.01). In ciprofol group ,the norepinephrine dose(μg, median)10 minutes after induction(0.00 vs 10.00)and from induction to the beginning of surgery(0.00 vs 16.10),VIS score(median)10 minutes after induction(0.00 vs 1.73)and from induction to the beginning of surgery(0.00 vs 0.61),were lower than that in propofol group(P＜0.01).The lactate level on the POD1 was lower in the ciprofol group than in the propofol group.
Conclusion: 0.3mg/kg ciprofol was better than propofol 1.5 mg/kg in patients with valve stenosis, with both drugs producing 100% anesthesia and keeping the BIS at 40-60. In addition ciprofol has a minor effect on the cardiovascular system, it can be used as a safer anesthetic for patients with valve stenosis.
Trial registration: Clinical Trials Registry ;Clinical trial number：ChiCTR2200059378
Direct-Acting Oral Anticoagulant Removal by Intraoperative Hemoadsorption in CABG and/or Single Valve Surgery: Interim Analysis of the International Safe and Timely Antithrombotic Removal (STAR) Registry
Authors: Schmoeckel Michael , Thielmann Matthias , Vitanova Keti , Eberle Thomas , Marczin Nandor , Hassan Kambiz , Liebold Andreas , Lindstedt Sandra , Mächler Georg , Matejic-Spasic Marijana , Wendt Daniel , Deliargyris Efythymios , Storey Robert
Published: December 2024

Objective
Patients on direct-acting oral anticoagulants (DOACs) are at high risk of perioperative bleeding complications. Intraoperative hemoadsorption is a novel strategy to reduce perioperative bleeding in patients on DOACs undergoing non-deferable cardiac surgery. The international STAR-registry reports real-world clinical outcomes associated with this application.
Methods
The hemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit and active for the duration of the pump run. Patients on DOACs undergoing CABG and/or single valve surgery before completing the recommended washout were included. Outcome measurements included bleeding events according to standardized definitions and 24-hour chest-tube-drainage (CTD).
Results
A total of 62 patients were included from 7 institutions in Austria, Germany, Sweden, and the UK (mean age 69.9 ± 7.5years, 71% male). Approximately half were on apixaban and the other half was split between rivaroxaban and edoxaban with 21% of patients also on aspirin. Surgery occurred at a median time of 28.9h since the last DOAC dose with single valve surgery accounting for 2/3 of cases. Mean CPB duration was 118.6 ± 46.4min. Severe bleeding (UDPB ≥ 3) occurred in 4.8%, and BARC-4 bleeding occurred in 3.2% of the patients. Only one patient (1.6%) required reoperation for bleeding control. The mean 24-hour CTD was 771.3 ± 482.79mL. No device-related adverse events were reported.
Conclusions
This interim report of the ongoing STAR-registry shows that, in patients on DOAC undergoing non-deferable CABG and/or single valve surgery, the use of intraoperative hemoadsorption is associated with low rates of severe perioperative bleeding complications.
Clinical registration number:ClinicalTrials.gov identifier: NCT05077124
Association between the triglyceride-glucose obesity-related index and risk of gallstone disease and first gallstone surgery: the NHANES 2017-2020
Authors: Zhang Yue , Duan Ruifeng , Chen Xin , Wei lijuan
Published: December 2024

Background
The triglyceride-glucose index (TyG) and its associated obesity indicators [TyG-body mass index(TyG-BMI), TyG-waist-height ratio(TyG-WHtR), and TyG-waist circumference(TyG-WC)] are emerging tools for assessing insulin resistance. This study aimed to examine the association between TyG obesity-related indicators and the risk of gallstone disease or first gallbladder surgery.
Methods
Individuals were selected from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) database. The associations between TyG, TyG-WHtR, TyG-WC, TyG-BMI, and the risk of gallstone disease and first gallbladder surgery were initially analyzed using weighted logistic regression models. Restricted cubic spline (RCS) plots and receiver operating characteristic (ROC) curves were used to analyze the relationship between TyG obesity-related indicators and gallstone disease and first gallbladder surgery. Generalized additive models, smoothed curve fitting, and linear regression were applied to assess the relationship between TyG-WC and age at first gallbladder surgery. Sensitivity analyses, including stratified and interaction analyses, were conducted to identify specific populations and assess potential interactions between covariates and TyG obesity-related indicators. Mediation analyses explored the role of ethnicity as a mediator between TyG-WHtR and first gallbladder surgery.
Results
In this study, TyG obesity-related indicators were significantly correlated with the risk of gallstone disease and first gallbladder surgery, except for TyG, which showed no significant correlation. A linear relationship was observed between TyG obesity-related indicators and the risk of gallstone disease (P-overall < 0.0001, P-nonlinear > 0.05). In addition, TyG-WC demonstrated the strongest performance in predicting the risk of first gallbladder surgery and was negatively associated with age at first gallbladder surgery (β = -0.03, 95% CI: -0.04, -0.01). Sensitivity analysis indicated that TyG-WHtR was more strongly correlated with first gallbladder surgery in other races (OR = 3.13, 95% CI: 1.67, 5.86). Mediation analyses showed that race mediated the association between TyG-WHtR and first gallbladder surgery.
CONCLUSION
TyG-WHtR, TyG- WC, and TyG-BMI were correlated and linearly associated with gallstones and first gallbladder surgery. In addition TyG- WC showed the most favourable performance in predicting the risk of first gallbladder surgery and may lead to an earlier age of first gallbladder surgery. In addition attention needs to be paid to the effect of other races between TyG-WHtR and first gallstone surgery.
CAMK2B affects the proliferation, invasion and migration of glioma cells via Ras/Raf/MEK/ERK signal pathway
Authors: Zhang Shiyang , Li Jingchen , Jin Qianxu , Zhu Siyu , Yan Hongshan , Wang Yizheng , Song Zihan , Liu Liqiang
Published: December 2024

Background
Glioma exhibits a high recurrence rate and unfavorable prognosis, with the mechanisms underlying the regulation of glioma cell proliferation, invasion, and migration remaining elusive. CAMK2B, a crucial kinase involved in regulating cell growth and synaptic plasticity, remains enigmatic in terms of its specific role in glioma.
Methods
This study comprehensively analyzed the correlation between the expression level of CAMK2B in gliomas and patient prognosis using immunohistochemistry, qRT-PCR, and Western Blot techniques. Furthermore, the study determined the role of CAMK2B in glioma cell proliferation, invasion, and migration through CCK8, EdU, wound healing, Transwell, and in vivo tumor xenograft assays.
Result
We observed that patients exhibiting high levels of CAMK2B exhibited superior prognostic outcomes compared to those with low levels. Furthermore, CAMK2B expression was notably lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines. Notably, overexpression of CAMK2B in glioma cells suppressed their proliferative capacity by approximately 40% and attenuated their invasive and migratory abilities by 60–70%, relative to normal glioma cell lines. Conversely, knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative, invasive, and migratory capabilities of glioma cells in both in vitro and in vivo settings, increasing these abilities by 1.5 to 3 times. Remarkably, these effects could be reversed through the application of the Ras pathway inhibitor Salirasib. Western blot analysis revealed that knockdown of CAMK2B activated the Ras/Raf/MEK/ERK signaling pathway in glioma cell lines, whereas overexpression of CAMK2B exerted inhibitory effects on this pathway.
Conclusion
CAMK2B inhibits glioma proliferation, invasion, and migration through Ras/Raf/MEK/ERK signal pathway.
Reactive Power Dispatch Method for Wind Farms Based on Dynamic Weight Adjustment of Electrical Distance and Reactive Power Capacity
Authors: Wu Guodong , Li Xiaohu , Zhang Ruixiao , Bao Guangqing , tan hongtao
Published: December 2024

To solve the problem of terminal voltage of wind turbines (WT) exceeding the limit caused by reactive power allocation in wind farms, this paper proposes a reactive power allocation method based on dynamic weight adjustment of inverter capacity and electrical distance. Firstly, the impact of WT power output on the voltage of each node in the system at different electrical distances was analyzed. Then, establish a reactive power dispatch model that takes the remaining capacity of the converter and electrical distance factors into account, and the weight coefficient between the two is dynamically adjusted based on voltage deviation by combining the idea of disturbance observation, achieve rapid distribution of reactive power commands without relying on detailed power flow modeling of the system. Finally, a 5MW*25 wind farm case is used to verify the proposed method. The results show that the proposed method can effectively reduce the voltage deviation by more than 30% under the same reactive power scheduling instruction, and can improve the reactive power dispatch range of the wind farm.
Macrophage M2 polarization with down-regulated NOX2 promotes placental angiogenesis
Authors: Zhang Ruonan , Zhang Lu , Wang Ruixue , Wubulikasimu Ayinisa , Wei Mengtian , Tian Haojun , Yang Jialu , Wei Xuanchen , Deng Xinyu , Bi Ruomeng , Duan Tao , Wang Kai
Published: December 2024

The polarised state of placental Hofbauer cells (HBCs) is frequently accompanied by alterations in inflammatory factors and marker proteins, which are crucial in normal pregnancy. NOX2, as one of NADPH oxidase, is commonly expressed in phagocytes and mediates oxidative stress. A recent paper reported that the upregulation of NOX2 in porcine placenta led to reduced angiogenesis through increased oxidative stress, which attracted our interesting. To investigate whether NOX2 expression in human placenta is the cause of reduced vascularity in placentas of Fetal growth restriction (FGR), we examined the expression and localisation of NOX2 in placental villous and analysed the expression of NOX2 in different macrophages subtypes as well as its effect on vascular endothelial function. Our results showed that NOX2 was predominantly expressed in HBCs of placental villi. Moreover M2 polarisation of macrophages were inversely associated with NOX2 expression and promoted angiogenesis. The expression of NOX2 was significantly elevated in the placenta of FGR compared with normal placentas, which might be related to the reduction of placental vasculature in FGR. These results suggested that NOX2 can be used as a marker of HBCs and as a result of M2 polarization, and is also deeply involved in the functional regulation of placental vascular endothelial cells. These evidences providing a potential target for the diagnosis and treatment of FGR.
Cytoskeleton disruption and plasma membrane damage determine methuosis of normal and malignant cells
Authors: Gao Xiuge , Dong Bin , Xiao Jing , Wang Junqi , Song Xinhao , Ji Hui , Peng Jiurong , Weng Xinru , Guo Dawei , Jiang Shanxiang
Published: December 2024

Methuosis represents a novel cell death modality characterized by catastrophic cytoplasmic vacuolization in normal and malignant cells. However, the critical role and the underlying mechanism of cytoskeleton and plasma membrane damage in methuotic cells are largely unknown. Herein, maduramicin-treated myocardial cells (H9c2) and indole chalcone-exposed glioma cells (U251) were used as methuosis model to uncover this secret. We found that cytoskeleton protein F-actin, α-tubulin, β-tubulin and filamin A/B were disrupted in a reversible-dependent manner. In addition, RhoA-ROCK1 signaling pathway mediated cytoskeleton disruption in methuotic cells. Excessive cytoplasmic vacuolization triggered cellular plasma membrane damage and the release of DAMPs, including LDH, ATP and CRT. Furthermore, at the end phase of methuotic cells, plasma membrane was damaged independent of pore-forming protein p-MLKL and GSDMD. Endosomal sorting complex required for transport (ESCRT)-Ⅲ especially its subunit CHMP3 and CHMP5 negatively regulated excessive vacuolization-induced plasma membrane damage in cells undergoing methuosis. In conclusion, for the first time, the critical role and potential mechanism of cytoskeleton and plasma membrane damage in methuotic cells are known, which would facilitate the employment of methuosis in life science and pharmacology.
Descending Inhibitory Neurons of the RVM Cause Widespread Bilateral Antinociception and Contribute to the Pain-Inhibits-Pain Phenomenon
Authors: Zeilhofer Hanns Ulrich , Ganley Robert , Sousa Marilia , Ranucci Matteo , Beccarini Camilla , Werder Kira , Pietrafesa Francesca , d'Aquin Simon , Öztürk Tugce , Hubli Michèle , Schweinhardt Petra , Hoon Mark , Wildner Hendrik
Published: December 2024

Acute painful stimuli applied to one body site reduce pain at other sites. The circuit basis of this “pain-inhibits-pain” phenomenon, also known as diffuse noxious inhibitory control (DNIC) in animals or conditioned pain modulation (CPM) in humans, is largely unknown. Using anatomical and optogenetic circuit tracing, we identified a population of descending inhibitory neurons of the rostral ventromedial medulla (RVM) that densely and bilaterally innervate the spinal cord along its rostrocaudal axis. Activating these neurons reduced heat and cold sensitivity widely in healthy mice and caused similarly wide-spread antihyperalgesia in chronic pain models, while their silencing evoked mechanical allodynia and spontaneous pain-like behaviors. Noxious stimuli activated subsets of these neurons in the lateral paragigantocellularis nucleus (LPGi), which inhibited nociception upon chemogenetic reactivation. Spinally projecting inhibitory RVM neurons are hence ideally positioned to function as circuit elements of DNIC and CPM, while their dysfunction may contribute to wide-spread chronic pain syndromes.
Cross-Domain Tuple and Random Collision GuidedApproach for Creative Requirement GenerationUsing LLM
Authors: Huang ZhiJian , Zhang Junyi , Jin Min , Gong HongWu , Pi Yuyan
Published: December 2024

In software engineering, creative requirements are unique features detailed in software specifications. Generating these requirements is both crucial and challenging within the field of software requirements engineering. Manual methods, which rely on limited human experience, are often time-consuming and unpredictable. Current machine learning solutions typically offer only combinatorial creation mechanisms and lack objective standards for evaluating creativity. This paper presents a novel approach for automatically generating creative software requirements using large language models (LLM). Our method utilizes cross-domain tuple random collision, where innovative requirements are produced by inputting randomly recombined and preprocessed subject-verb-object (SVO) tuples into a fine-tuned GPT-2 model. We provide a detailed discussion of strategies for recombining SVO tuples from various domains and introduce techniques to enhance creativity. To evaluate the creativity of the generated requirements, we establish the GRUEN Integrated Creativity (GIC) evaluation standard by incorporating the GRUEN model. Experimental studies across three software domains show that this fully automated approach consistently generates creative requirements. Additionally, comparisons with state-of-the-art methods and ChatGPT 4.0 highlight the unique advantages of our approach.
The Psychopathological Effects of Child Marriages and the Relationship with Sociodemographic-Obstetric Factors
Authors: Teze Saniye , Ayhan Fatma , Balsak Habip
Published: December 2024

Purpose
The aim of this study was to determine the psychopathological characteristics of child brides and to examine the relationship with sociodemographic and obstetric factors.
Method
The sample in this descriptive, cross-sectional study consisted of 92 women who had married before the age of 18 and who were contacted via snowball sampling, one of the purposive sampling methods. Data were collected using questions concerning sociodemographic and obstetric characteristics and the Brief Symptom Inventory(BSI) to determine psychopathologic characteristics.
Results
Women whose income was lower than their expenses had higher somatization scores than those whose income exceeded expenses, and those whose mothers married under the age of 18 had higher somatization scores than those whose mothers married over 18. Women who rated their marital relationship status as moderate registered higher negative self-scores than those who rated it as poor, while those who rated their marital relationship status as good exhibited lower total and somatization scores than those who rated it as poor(p < 0.05). A weak positive correlation was observed between the duration of marriage and somatization scores. A weak negative correlation was determined between the mothers' Anxiety, Depression, Hostility and total BSI scores and age at first pregnancy, and between age at birth of the first infant and BSI total and subscale scores.
Conclusion
This study emphasizes the adverse effects of factors such as low income and early marriage on mental health. The findings may contribute to a better understanding of the psychological consequences of child marriages.
Genomic Blueprint of Novel Slow-Growing Bacteria with Insights into their Potential Adaptation Mechanisms in Soil Ecosystems
Authors: Gonçalves Osiel Silva , Santana Mateus Ferreira
Published: December 2024

Slow-growing bacteria play a crucial role in soil ecosystems, yet our understanding of their persistence in complex environments remains limited. Do these organisms lack essential metabolic genes, or do they possess specific genes that enable survival under challenging conditions? Our study begins to fill this knowledge gap by analyzing the genomes of four slow-growing bacteria isolated from tropical savanna soil, providing insights into their metabolic capacities and adaptation mechanisms. Our findings revealed that these bacteria represent novel species, including new strains of Bosea, Nocardioides, Cupriavidus, and Enterobacter roggenkampii. Most genomes encoded key genes and pathways related to central metabolism, particularly in sugar and amino acid metabolism, suggesting that slow growth may be an adaptive strategy. The strains also exhibited potential contributions to vital biogeochemical processes, including carbon, nitrogen, and sulfur cycling, as well as plant growth promotion. We identified 164 defense genes across 32 defense families and at least one antimicrobial resistance (AMR) gene in each strain, with strain CER55 showing the highest number of predicted AMR genes. Additionally, twelve biosynthetic gene clusters were identified in three strains. The combination of defense mechanisms, antimicrobial resistance, and secondary metabolite production indicates that these bacteria may evolved multiple strategies to thrive in competitive microbial communities.
Perceiving Altered Reality (REALTER): Understanding the Impact of Maculopathy on Reading with Extended Reality
Authors: Barbieri Mattia , Albanese Giulia A. , Sabatini Silvio P. , Gori Monica , Facchini Valentina , Sandini Giulio
Published: December 2024

Central vision loss due to binocular maculopathy significantly impairs daily tasks like reading by disrupting oculomotor behavior, particularly saccadic movements. This study employed the REALTER system, an extended reality simulator, to replicate severe binocular maculopathy in eighteen healthy participants. Using the MNREAD Acuity Chart, we measured reading speed and acuity, and col- lected data on ocular movements to verify the system’s capability as a tool for accurate saccade detection. Importantly, the study highlights that the read- ing difficulties caused by maculopathy result in a decline in visual acuity and reading speed, similar to that observed in individuals actually affected by this condition. Our findings revealed significant changes in saccadic patterns, includ- ing increased frequency and amplitude, which closely mirrored those observed in actual patients. We believe that these results suggest REALTER as an effec- tive tool for studying low vision by using simulated impairments in healthy individuals. This approach avoids the need to stress real patients with macu- lopathy during the acquisition of oculomotor knowledge. Additionally, it provides valuable insights into compensatory mechanisms and enhances the training of ophthalmologists in understanding the effects of low vision.
Loss of Paneth cell contact starts a WNT differentiation timer in intestinal crypts
Authors: Zon Jeroen van , Kok Rutger , Zheng Xuan , Spoelstra Willem , Clement Tinka , de Grift Yorick van , Clevers Hans , Amerongen Renee van , Tans Sander
Published: December 2024

WNT signaling is pivotal to the renewal of many organs including the intestine. WNT gradients are thought to provide a spatial differentiation cue, and hence control the required spatial patterning of cell types. Testing this mechanism is difficult, however, as current methods are static while the underlying processes are highly dynamic. Here, we show that a ‘timer’ mechanism rather than spatial cues controls the WNT signaling decreases that drive cell differentiation. Using live-cell imaging and single-cell tracking of intestinal organoids, we find that WNT signaling in stem cells decreases immediately after loss of Paneth cell contact. This WNT signaling decrease does not depend on cell growth and division, and precedes differentiation, as shown by subsequent antibody staining and cell type propagation along lineage trees. Cells frequently regain Paneth cell contact, which in turn increases WNT signaling again, showing that differentiation is not progressive but rather repeatedly reset. Our WNT timer mechanism overturns existing spatial gradient models, explains differentiation within the intestinal crypt, and may well be more broadly relevant to WNT-mediated tissue renewal.
Genotype-integrated single-cell transcriptome analysis of a myelodysplastic neoplasm case reveals the role of DDX41 p.R525H
Authors: Matsui Hirotaka , Nagamachi Akiko , Koizumi Minori , Kudo Rei , Ajiro Masahiko , Harada Hironori , Harada Yuka , Shichino Shigeyuki , Yoshimi Akihide
Published: December 2024

DEAD-box helicase 41 (DDX41) is a key gene in germline-predisposed myeloid neoplasms, where pathogenic germline variants often lead to disease after acquiring a somatic mutation in trans. We conducted single-cell RNA sequencing combined with genotyping of the p.R525 site in a myelodysplastic neoplasm (MDS) case with germline p.R339C and somatic p.R525H variants, which enabled us to compare p.R525H cells with germline variant-only cells. p.R525H acquisition selectively induced G2/M arrest in colony-forming unit-erythroid cells along with R-loop elevation, thus impairing erythropoiesis via DNA damage accumulation. In hematopoietic stem cell (HSC) and myeloid progenitor populations, gene expression profiles were largely similar between p.R525H-positive and -negative cells; however, HSC frequencies were lower and granulocyte-monocyte progenitor frequencies were higher in p.R525H cells. Ligand-receptor and transcriptional regulation analyses suggested non-cell-autonomous influence from p.R525H cells on germline variant-only cells, driving convergence toward a shared expression profile and revealing an intricate interplay that shapes the MDS phenotype.
Cryo-EM of PMEL Amyloids Reveals Pathogenic Mechanism of Pigment Dispersion Syndrome.
Authors: Oda Toshiyuki , Yanagisawa Haruaki , Arai Harumi , Miyazawa Hideyuki , Kikkawa Masahide
Published: December 2024

PMEL amyloids provide a vital scaffold for melanin deposition in melanosomes, playing a central role in pigmentation. Despite their importance, the high-resolution structure of PMEL amyloids has remained elusive. Here, we determined near-atomic resolution structures of wild-type PMEL amyloids using cryo-electron microscopy, revealing two distinct polymorphic forms with unique structural features. We further examined the pathogenic G175S mutation linked to pigment dispersion syndrome (PDS). Structural analysis showed that the G175S mutation introduces an additional hydrogen bond, stabilizing a novel fibril conformation. In vitro assays demonstrated a fourfold increase in polymerization efficiency for the G175S mutant compared to the wild-type. This enhanced polymerization correlated with a ~70% increase in secreted amyloids in G175S-expressing cells without detectable changes in melanosome morphology or number. These findings suggest that the G175S mutation promotes amyloidogenesis within melanosomes, increasing amyloid load and contributing to PDS pathophysiology. This study provides insights into the molecular basis of PMEL amyloid formation in both physiological and pathological contexts, offering new perspectives on their structural diversity and dysregulation in pigmentation disorders.
Medien*Konstruktion
Authors: Swertz Christian
Published: December 2024

Im Beitrag werden monistische und dualistische medienpädagogische Kritikbegriffe differenziert. Dazu wird methodisch eine systematische Analyse verwendet, die mit der Bestimmbarkeit des Begriffs des Begriffs und der Begrenztheit des Wissens als Prämissen angesetzt und als performativen Retorsion durchgeführt wird.In der systematischen Analyse wird der Bildungsbegriff als Bewegung zwischen Sprachen und damit als Medienbildung bestimmt, mit dem dann die Kritikbegriffe diskutiert werden. Es wird gezeigt, dass Menschen, die nicht nur Gesellschaftkritik betreiben, sondern sich auch selbst bestimmen wollen, einen dualitischen Kritikbegriff verwenden.
Identifizierung der Zielgene des Transkriptionsfaktors GATA1s in der Down-Syndrom assoziierten myeloischen Leukämie
Authors:   , Ehl Charlotte
Published: December 2024

Kinder mit Down-Syndrom (DS) haben ein erhöhtes Risiko, an myeloischer Leukämie (ML-DS) zu erkranken. Bis zu 30% der Neugeborenen mit DS entwickeln eine präleukämische transiente abnormale Myelopoese (TAM). TAM ist durch Mutationen im GATA1-Gen gekennzeichnet, die zu einer verkürzten Form des Proteins (GATA1s) führen, dem die N-terminale Transaktivierungsdomäne fehlt. In dieser Studie untersuchten wir die differentielle Bindung von GATA1 und GATA1s an Zielpromotoren und ihre Wirkung auf die Gentranskription.
Zu diesem Zweck wurden GATA1 und GATA1s lentiviral in die ML-DS-Zelllinie CMK eingeführt. Nach Doxycyclin-Induktion der Transgen-Expression wurde die Bindung der Transkriptionsfaktoren an Zielgene mittels CUT&RUN analysiert und durch RNA-Sequenzierungsanalysen ergänzt. Die RNA-Sequenzierung zeigte eine unterschiedliche Aktivierung der Zielgene durch die verschiedenen Transkriptionsfaktor-Isoformen. Dies ging einher mit einer veränderten Promotorbelegung von GATA1s im Vergleich zu GATA1. Durch Kombination von CUT&RUN, RNA-Sequenzierung und Geneset-Enrichment-Analysen konnten differentiell regulierte Zielgene mit wichtigen Funktionen in Onkogenese und Tumorsuppression identifiziert werden. Des Weiteren zeigte sich eine Dysregulation von erythroiden Genen in GATA1s-Zellen. Diese Daten zeigen die Bedeutung der veränderten Chromatinbindung und Gentranskription durch die GATA1s-Isoform in der Pathogenese von ML-DS. Unsere Erkenntnisse werden Wege für die Entwicklung künftiger Therapiekonzepte ebnen.
The Products of Aziz Gardi and their Reflect Ions in Academic Research: for Example, Doctoral thesis of the Kurdish Literature Field of the University of Salahaddin (1996-2023)
Authors: Pshtiwan Asaad Kareem  , Shakawan Farhad Mohammed
Published: December 2024

Scientific production and its  reuse as a source in other scientific works are important and  valuable. The products and scientific works of Dr. Aziz Gardi have their own values and significance in the Kurdish library, andas the source is based on and depends on in the academic research process. From this point on، we have given the title of the research as: "The products of Aziz Gardi and their reflectionsin academic research. For exampledoctoral thesis of the Kurdish literature field of the University of Salah al-Din (1996-2023), in order to show the balance of his works and products. Moreover, the scope of this research is withinthe framework of the doctoral thesis in the field of literature at the University of Salah al-Din/ Erbil, and they were taken as examples between 1996 and 2023. The main task of this research is to show and identify Aziz Gardi’s products such as books, writings, researches (master’s and doctoral thesis), preparation and explanation, translation and its reflection in academic letters. Furthermore, this research would have answer to these questions: How did the products reflect? What products were used and which one had been used the most? Which pages were most used? And what are the rates? To do the task correctly and issue the rate, Descriptive-Statistical method has been followed.
When does a Fermi puddle become a Fermi sea? Emergence of pairing in two-dimensional trapped mesoscopic Fermi gases
Authors: Laird Emma , Mulkerin Brendan C. , Wang Jia , Davis Matthew J.
Published: December 2024

Pairing lies at the heart of superfluidity in fermionic systems. Motivated by recent experiments in mesoscopic Fermi gases, we study up to six fermionic atoms with equal masses and equal populations in two different spin states, confined in a quasi-two-dimensional harmonic trap. We couple a stochastic variational approach with the use of an explicitly correlated Gaussian basis set, which enables us to obtain highly accurate energies and structural properties. Utilising two-dimensional two-body scattering theory with a finite-range Gaussian interaction potential, we tune the effective range to model realistic quasi-two-dimensional scattering. We calculate the excitation spectrum, pair correlation function, and number of pairs as a function of increasing attractive interaction strength. For up to six fermions in the ground state, we find that opposite spin and momentum pairing is maximised well below the Fermi surface in momentum space. By contrast, corresponding experiments on twelve fermions have found that pairing is maximal at the Fermi surface and strongly suppressed beneath [M. Holten et al., Nature 606, 287-291 (2022)]. This suggests that the Fermi sea — which acts to suppress pairing at low momenta via Pauli blocking — emerges in the transition from six to twelve particles.