bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic NHERF‐1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK‐1
Authors: Bae Yeonju , Lee Soomin , Kim Ajung , Lee Shinae , Kim Seong‐Seop , Park Sunyoung , Noh Junyeol , Ryoo Kanghyun , Yi Gwan‐Su , Park Jae‐Yong , Hwang Eun Mi 
Published: November 2024

ABSTRACTMature hippocampal astrocytes exhibit a linear current‐to‐voltage (I‐V) K+ membrane conductance called passive conductance. It is estimated to enable astrocytes to keep potassium homeostasis in the brain. We previously reported that the TWIK‐1/TREK‐1 heterodimeric channels are crucial for astrocytic passive conductance. However, the regulatory mechanism of these channels by other binding proteins remains elusive. Here, we identified Na+/H+ exchange regulator‐1 (NHERF‐1), a protein highly expressed in astrocytes, as a novel interaction partner for these channels. NHERF‐1 endogenously bound to TWIK‐1/TREK‐1 in hippocampal cultured astrocytes. When NHERF‐1 is overexpressed or silenced, surface expression and activity of TWIK‐1/TREK‐1 heterodimeric channels are inhibited or enhanced, respectively. Furthermore, we confirmed that reduced astrocytic passive conductance by NHERF‐1 overexpressing in the hippocampus increases kainic acid (KA)‐induced seizure sensitivity. Taken together, these results suggest that NHERF‐1 is a key regulator of TWIK‐1/TREK‐1 heterodimeric channels in astrocytes and suppression of TREK‐1 surface expression by NHERF‐1 increases KA‐induced seizure susceptibility via reduction of astrocytic passive conductance.
Analysis of Nirmatrelvir Entry into Pulmonary Lining Fluid in Patients with COVID‐19: A Unique Perspective to Explore and Understand the Target Plasma Concentration of 292 ng/mL in Antiviral Activity
Authors: Zhang Wenjing , Xia Lin , Yuan Zhilong , Jiao Yang , Wang Zhuo 
Published: November 2024

ABSTRACTBackgroundCurrently, the applicant has chosen a target plasma trough concentration for nirmatrelvir, which is adjusted to 292 ng/mL based on the drug's molecular weight (499.54 Daltons), its binding to human plasma proteins (69%), and the in vitro antiviral EC90 value (181 nM). However, the current exposure‐effect relationships (ER) analysis of viral load in patients enrolled in the EPIC‐HR study has not revealed clinically significant trends in the ER. Given that the lungs are the primary site of COVID‐19 infection, we aim to further understand this exposure relationship by exploring and analyzing the penetration characteristics of nirmatrelvir in the lungs.ObjectivesTo explore and understand the target plasma concentration of 292 ng/mL in antiviral activity.MethodsWe identified all critically ill patients with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment in the respiratory intensive care unit of Changhai hospital between January 2023 and October 2023. Samples of plasma and bronchoalveolar lavage fluid were obtained at pre‐dose trough concentrations after administration of nirmatrelvir (NMV). The relationship between NMV levels in plasma and the epithelial lining fluid (ELF) was assessed by determining concentrations of NMV.ResultsThere was a significant relationship between NMV levels in plasma and ELF (ELF = 0.4976*PLASMA‐ 204; R = 0.96), with a correlation whose slope (0.4976) suggested that the blood‐to‐ELF ratio of drug penetration was 2:1. A negative value from the equation indicates that NMV requires to reach baseline concentration to penetrate the ELF.ConclusionsThe relationship between NMV levels in plasma and ELF with low permeability and a negative baseline value suggests that the target plasma concentration of 292 ng/mL is insufficient for antiviral activity. This study provides a unique perspective to explore and understand no clinically meaningful trend of exposure‐response relationships in patients enrolled in EPIC‐HR.
VMC‐UNet: A Vision Mamba‐CNN U‐Net for Tumor Segmentation in Breast Ultrasound Image
Authors: Wang Dongyue , Zhao Weiyu , Cui Kaixuan , Zhu Yi 
Published: November 2024

ABSTRACTBreast cancer remains one of the most significant health threats to women, making precise segmentation of target tumors critical for early clinical intervention and postoperative monitoring. While numerous convolutional neural networks (CNNs) and vision transformers have been developed to segment breast tumors from ultrasound images, both architectures encounter difficulties in effectively modeling long‐range dependencies, which are essential for accurate segmentation. Drawing inspiration from the Mamba architecture, we introduce the Vision Mamba‐CNN U‐Net (VMC‐UNet) for breast tumor segmentation. This innovative hybrid framework merges the long‐range dependency modeling capabilities of Mamba with the detailed local representation power of CNNs. A key feature of our approach is the implementation of a residual connection method within the U‐Net architecture, utilizing the visual state space (VSS) module to extract long‐range dependency features from convolutional feature maps effectively. Additionally, to better integrate texture and structural features, we have designed a bilinear multi‐scale attention module (BMSA), which significantly enhances the network's ability to capture and utilize intricate feature details across multiple scales. Extensive experiments conducted on three public datasets demonstrate that the proposed VMC‐UNet surpasses other state‐of‐the‐art methods in breast tumor segmentation, achieving Dice coefficients of 81.52% for BUSI, 88.00% for BUS, and 88.96% for STU. The source code is accessible at https://github.com/windywindyw/VMC‐UNet.
KGF secreted from HSCs activates PAK4/BMI1, promotes HCC stemness through PI3K/AKT pathway
Authors: Li Qinghua , Chen Qiuyang , Wang Wenchao , Xie Rongrong , Li Zhen , Chen Dawei 
Published: November 2024

AbstractIn our present study, we investigated the interaction between HSCs and HCC, also explored the molecular mechanism. Clinical samples were collected from HCC and adjacent tissue with different degree of liver fibrosis. HCC cells were co‐cultured with LX‐2 cell by Transwell system or cultured with conditioned medium (CM), which was collected from LX‐2. The tumor spheroid growth and colony formation analyses were performed to evaluate the cell stemness. Flow cytometry analysis was conducted on cell apoptosis after 5‐Fu treatment. Co‐immunoprecipitation assay confirmed the interaction between BMI1 and PAK4. Our results showed that BMI1 was highly expressed in HCC and was correlated with HCC liver fibrosis. Both co‐cultured with LX‐2 and cultured with CM promoted HCC stemness, also increased KGF level and BMI1 expression. KGF treatment had a similar effect with co‐culture with LX‐2 on HCC. BMI1 overexpression promoted HCC stemness and activated PI3K/AKT pathway, which was reversed by PI3K inhibition. PAK4 was activated by KGF, then phosphorylated S315 site and promoted protein stability of BMI1, therefore enhanced HCC stemness. BMI1 also had a promote effect on liver fibrosis. In summary, we found that KGF secreted by HSCs activated PAK4, which phosphorylated S315 and promoted protein stability of BMI1, and further promoted liver fibrosis and HCC stemness through the PI3K/AKT signaling pathway. Our present study deeply studied the interaction and mechanism between HSCs and HCC, which might provide a new insight for HCC therapy.
Reward deprivation is associated with elevated alcohol demand in emerging adults
Authors: Murphy James G. , Acuff Samuel F. , Buck Avery C. , Campbell Kevin W. , MacKillop James 
Published: November 2024

AbstractPolicies vary substantially in terms of providing sources of psychosocial enrichment. Behavioral economic models of substance use and addiction emphasize that deficits in access to substance‐free sources of reward increase substance reinforcing value and risk for addiction. The current study used an alcohol demand curve approach to test the hypothesis that various indices of reward deprivation would be associated with elevated alcohol reinforcing efficacy. We examined associations between alcohol demand indices and several facets of reward deprivation in a sample of young adults (N = 1,331; ages 19–25 years) recruited from the United States and Canada who reported recent binge drinking. Additionally, we created an index of cumulative reward deprivation that integrated the various reward facets and examined its association with alcohol demand intensity and maximum expenditure on alcohol. Our findings indicate that reward deprivation is associated with elevated alcohol demand and provide support for alcohol prevention and intervention approaches that emphasize environmental enrichment.
Assessment of bovine milk exosome preparation and lyophilized powder stability
Authors: Lu Lu , Han Chunle , Wang Miao , Du Huanqing , Chen Ning , Gao Mengya , Wang Na , Qi Dongli , Bai Wei , Yin Jianxin , Dong Fengwei , Li Tianshi , Ge Xiaohu 
Published: November 2024

AbstractExosomes are cell‐derived nanovesicles that play a crucial role in intercellular communication, presenting promising potential as biomarkers and therapeutic agents. Bovine milk exosomes (MK‐Exo) show production scalability and cost‐effectiveness, offering distinct advantages over cell‐derived exosomes. However, exosome storage and transportation are challenging owing to their unstable nature, necessitating preservation at ultralow temperatures. Research findings suggest that freeze‐drying could provide a viable solution; however, different sources of exosomes may require specific protocols. In this study, we aimed to successfully isolate high‐purity MK‐Exo and develop a specialized freeze‐drying and lyophilization method for improved long‐term preservation of MK‐Exo. Specifically, the stability of the lyophilized MK‐Exo was evaluated using storage stability tests. Notably, lyophilized MK‐Exo remained stable for at least 3 months under high temperature of 50°C and for at least 24 months under low temperatures of 2°C–8°C, preserving their physicochemical properties and biological activity. Conclusively, these findings provide a potential solution for ambient‐temperature transportation of MK‐Exo, facilitating their industrial‐scale production.
Hepatocyte‐derived extracellular vesicles regulate liver regeneration through a negative feedback mechanism
Authors: McGinn Mina , Rabender Christopher , Mikkelsen Ross , Yakovlev Vasily 
Published: November 2024

AbstractWhile significant progress has been made in understanding various aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver following massive tissue loss or injury of liver remain unknown. As it was previously shown, the loss of liver mass affects putative hepatocyte‐specific mitogenic inhibitors in the blood. Although the presence of these putative inhibitors regulating precise liver regeneration has been described in numerous publications, they have never been identified. Extracellular vesicles (EVs) are nano‐sized, membrane‐limited structures secreted by cells into the extracellular space. Their proposed role is stable intercellular carriers of proteins and RNAs, predominantly micro‐RNA, from secreted to recipient cells. Upon uptake by the recipient cells, EVs can significantly modulate their biological functions. In the present study, using in vivo and in vitro models, we demonstrate that hepatocyte proliferation and liver regeneration are regulated by EVs secreted by hepatocytes into the bloodstream. This regulation occurs through a negative feedback mechanism, which explains the precise regeneration of liver tissue after massive damage. We also demonstrate that an essential component of this mechanism is RNA carried by hepatocyte‐derived EVs. Our findings open up a new and unexplored area of liver biology regarding the mechanisms involved in the precise regulation of liver regeneration after a massive tissue loss or injury. Further study of this mechanism will have a great influence on the development of new approaches to liver transplantation, various liver pathologies, and hepatic tumors.
Outcomes and validity of risk stratification tools for endoscopic submucosal dissection of early gastric cancer in Western Australia
Authors: Judge Ciaran , Halder Abir , Pateria Puraskar , Khor Tzeng , Muwanwella Niroshan , Chin Marcus , Ragunath Krish 
Published: November 2024

AbstractBackground and AimEndoscopic submucosal dissection (ESD) has become the treatment of choice for many superficial gastric neoplasms. Clinical outcomes are increasingly comparable between Japanese and Western series; however, data are lacking on the validity of risk stratification tools in Western cohorts. We aimed to evaluate clinical outcomes, explore risk stratification, and compare our data with published Western series.MethodsWe conducted a retrospective, observational cohort study in a single tertiary referral center over a 13‐year period. Primary outcomes were rates of en bloc, complete (R0) and curative resection. Secondary outcomes included adverse events, recurrence, metachronous lesions, eCura grades, and ESGE criteria. A comparative analysis was performed with existing published series from Western centers.ResultsTotally 112 patients were included in the study cohort. 50.9% were male, 87.5% Caucasian, and median age was 75.5 years (IQR 14.3 years). Lesions were predominantly antral (36.6%) or body (35.7%); median size 20 mm (IQR 15 mm). Rates of en bloc, R0 resection, and curative resection were 96.4%, 89.3%, and 78.6% (identical between eCura and ESGE), respectively. Adverse events occurred in 5.8%, recurrence in 0%, and metachronous lesions in 9.9%. Our data compared favorably with a review existing Western series, which illustrates increasing adoption of ESD and stable outcomes over time.ConclusionESD represents a safe and effective method of treatment for gastric neoplasia in the Western setting. This study highlights the potential for excellent outcomes in a single center with a heterogeneous patient cohort and supports the use of eCura in guiding post procedural management.
Immediate improvement in patient care: Auditing adherence to the British Society for Haematology guidelines on screening and management of the long‐term consequences of multiple myeloma and treatment
Authors: Sweeney Kerrie , Niblock Aaron , Greenfield Diana , Snowden John 
Published: November 2024

AbstractAdvances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long‐term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long‐term myeloma consequences. Thereafter a screening checklist was developed to prompt the implementation of guideline recommendations, followed by a re‐audit evaluating the effectiveness of the checklist.Good baseline practice was identified relating to vaccinations, herpes prophylaxis, dental assessment, bisphosphonates, calcium/ vitamin D supplementation and holistic needs assessments. However gaps in practice included monitoring of lipids, HBA1C, NT‐pro‐BNP/ BNP, BMI, calcium/ vitamin D and parathyroid hormone in kidney disease, endocrine screening and geriatric assessments. Re‐audit demonstrated that geriatric assessment remains a gap in practice, however other standards now scored between 80 to 100% compliance, highlighting the benefits of a screening checklist, to increase adherence to recommendations.
Turtle Girdles: Comparing the Relationships Between Environment and Behavior on Forelimb Function in Loggerhead Sea Turtles (Caretta caretta) and River Cooters (Pseudemys concinna)
Authors: Mayerl Christopher J. , Capano John G. , MME Noraly van Meer , Weller Hannah I. , Kaczmarek Elska B. , Chadam Maria , Blob Richard W. , Brainerd Elizabeth L. , Wyneken Jeanette 
Published: November 2024

ABSTRACTLocomotion in water and on land impose dramatically different demands, yet many animals successfully move in both environments. Most turtle species perform both aquatic and terrestrial locomotion but vary in how they use their limbs. Freshwater turtles use anteroposterior movements of the limbs during walking and swimming with contralateral fore‐ and hindlimbs moving in synchrony. In contrast, sea turtles swim primarily with “powerstroke” movements, characterized by synchronous forelimb motions while the hindlimbs act as rudders. High‐speed video has been used to study powerstroking, but pectoral girdle movements and long‐axis rotation (LAR) of the humerus are likely both key components to turtle locomotor function and cannot be quantified from external video. Here, we used XROMM to measure pectoral girdle and humeral movements in a sea turtle (loggerhead, Caretta caretta) compared to the freshwater river cooter (Pseudemys concinna) during terrestrial and aquatic locomotion. The largest difference among species was in yaw of the pectoral girdle during swimming, with loggerheads showing almost no yaw during powerstroking whereas pectoral girdle yaw in the cooter during rowing was over 30°. The magnitude of humeral LAR was greatest during loggerhead powerstroking and the temporal pattern of supination and pronation was opposite from that of cooters. We hypothesize that these kinematic differences are driven by differences in how the limbs are used to power propulsion. Rotations at the glenoid drive the overall patterns of movement in freshwater turtles, whereas glenohumeral LAR in loggerheads is used to direct the position and orientation of the elbow, which is the joint that determines the orientation of the thrust‐generating structure (the flipper) in loggerheads.
A High Power Density Ku‐Band GaN Power Amplifier Based on Device‐Level Thermal Analysis
Authors: Zhou Jiuding , Yi Chupeng , Liu Wenliang , Lu Yang , Ma Xiaohua , Zhao Yuanfu , Hao Yue 
Published: November 2024

ABSTRACTThis paper introduces a new design method for a high‐power density GaN MMIC amplifier operating in the Ku‐band. A thermal model to investigate the thermal distribution of power amplifiers is proposed to achieve optimal performance in terms of power density, chip size, and channel temperature. The thermal distribution and channel temperature of a single device, an eight‐way parallel device combination, and the entire PA layout are obtained by finite element simulation. The thermal coupling effects of high‐power MMICs are analyzed in detail. The thermal resistances are extracted from the simulation to design a Ku‐band amplifier. Measurement results demonstrate that the designed amplifier achieves 43.0–44.2 dBm output power and 22.7%–34.5% PAE at 28 V drain voltage with a 100 μs pulse width and 10% duty cycle within 12–18 GHz. The proposed design method enables the amplifier to have a compact layout of 10.88 mm2 and a power density between 1.84 and 2.42 W/mm. This design method can offer valuable insights for future development of high‐power MMIC amplifiers.
An Elevated Influence of the Low‐Latitude Drivers on the East Asian Winter Monsoon After Around 1990
Authors: Chen Bozhou , Fang Keyan , Mei Zepeng , Ou Tinghai , Zhou Feifei , Wu Hao , Zhao Zheng , Chen Deliang 
Published: November 2024

ABSTRACTCurrent East Asian winter monsoon (EAWM) indices effectively depict the associated high‐ and low‐latitude atmospheric circulations. However, the spatial dynamics of the winter coldness within the monsoon domain are not well adequately represented by EAWM indices. We introduce a novel approach to classify winter temperatures based on both their co‐variability and their mean values. We classified the EAWM domain into three distinct modes: northern (ranging from −27°C to −15°C), central (−14°C to 5°C), and southern (6°C to 27°C). The northern mode, characterised by intense coldness, correlates with a strengthened westerlies that traps Arctic cold air masses during the positive phase of the Arctic Oscillation (AO). In contrast, the southern mode is primarily influenced by low‐latitude oceanic and atmospheric patterns, particularly for near‐coast areas. The central mode, representing an interplay of both high and low‐latitude processes, encapsulates the comprehensive characteristics of the EAWM. Our analysis reveals a notable shift in the relationships among the northern, central, and southern modes around 1990. Prior to this year, the EAWM was predominantly influenced by northern atmospheric patterns, while there is a discernible increase in the influence of low‐latitude drivers afterwards. This shift may be linked to the significant warming in the western Pacific and Indian Oceans, underscoring the heightened role of low‐latitude drivers on the EAWM.
Metabolic syndrome and spatial disparities: The role of socioeconomic deprivation and medical resource availability in the Cijin district, Taiwan
Authors: Su Pei‐Hung , Tsai Jong‐Rung , Chang Wei‐Lun , Hsieh Hui‐Min 
Published: November 2024

AbstractMetabolic syndrome (MetS) is a global health concern with spatial disparities, especially in disadvantaged neighborhoods. This study aimed to examine the association between area‐level socioeconomic deprivation, the availability of medical resources in disadvantaged areas such as the Cijin district, and the prevalence of MetS in Taiwan. We used two representative secondary cross‐sectional datasets, including physical examinations and lifestyle surveys from 2016 to 2020, sourced from the Taiwan Biobank and the Cijin District Adult Lifestyle and Health Survey. Our findings indicate that residing in the Cijin district, characterized by socioeconomic deprivation and limited medical resources, is associated with significantly higher odds of MetS (aOR = 1.45, 95% CI = 1.28–1.64, p <0.001). Additionally, living in areas with medium (aOR = 1.12, 95% CI = 1.07–1.17, p <0.001) and high area‐level socioeconomic deprivation indexes (aOR = 1.13, 95% CI = 1.01–1.25, p <0.001) is linked to a higher likelihood of MetS. Conversely, residing in high medical resource availability index areas is associated with a lower risk of MetS (aOR = 0.92, 95% CI = 0.86–0.99, p = 0.026). We found a link between socioeconomic deprivation and limited medical resources, especially in disadvantaged areas such as the Cijin district, contributing to a higher MetS risk. Residents in these areas often struggle to access healthcare and preventive care. Addressing these disparities requires comprehensive public health initiatives and targeted policy interventions to improve residents' well‐being.
Exposure, body size, and zooplankton overland dispersal capacity
Authors: Branstrator Donn K. , Smith Rebecca A. 
Published: November 2024

AbstractThe dormant life stages of freshwater zooplankton are generally resistant to environmental exposure, and this facilitates their overland dispersal. However, environmental exposure and overland dispersal are less well studied for the active life stages of freshwater zooplankton. To characterize empirically the longevity of active life stages out of water, survival time to air exposure was measured in the laboratory for seven cladoceran species using heartbeat cessation to signify survival time. Survival time increased with body dry weight with an allometric scaling exponent near 2/3 in both a single‐species model with Daphnia mendotae and a multispecies model with five bivalved species that included Bosmina longirostris, Acroperus harpae, Ceriodaphnia dubia, D. mendotae, and Daphnia magna. The 2/3 scaling exponent is consistent with Euclidean geometry and points to water loss across the surface of a spherical body as the cause. Survival time of a 6th species, Holopedium gibberum, was 618% longer than predictions based on the multispecies model, likely due to its gelatinous mantle. Survival time of a 7th species, Bythotrephes cederströmii, was 58–83% shorter than predictions based on the multispecies model, likely due to its lack of a bivalve carapace. The longest survival time of an individual was 225.4 min (H. gibberum). Results suggest that at landscape scales, body size could be a proxy for the geographic extent of overland dispersal capacity of the active life stage.