bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of romosozumab in postmenopausal women with osteoporosis who used antiresorptive osteoporosis drugs: a prospective observational study
Authors: Yamamoto Misa , Sawada Kenjiro , Ikenaga Yuka , Yamamoto Gaku , Oride Tadashi , Oi Yukako , Kuruma Airi , Bun Michiko , Yagi Taro , Kinose Yasuto , Kodama Michiko , Kimura Tadashi 
Published: January 2024

Abstract

Background: Globally there has been an increase in the number of patients receiving long-term antiresorptive drugs for the treatment of postmenopausal osteoporosis; however, there is little evidence to guide decisions regarding when and how to stop or switch antiresorptive drugs. In this prospective observational study, we investigated the efficacy of romosozumab in women treated with conventional antiresorptive osteoporosis drugs for more than 3 years.
Methods: Despite more than 36 months of treatment with conventional antiresorptive drugs for postmenopausal osteoporosis, postmenopausal women with lumbar and femoral neck bone mineral density (BMD) of less than -2.5 SD by the DXA method were recruited. Patients who provided written informed consent were treated with romosozumab for 12 months, and its efficacy and safety were closely monitored by periodically measuring the lumbar and femoral neck BMD as well as the bone turnover markers, including serum P1NP and I-CTP.
Results: A total of 21 patients were enrolled in this study. The median age was 73 years, and the median observation period was 833 (range: 378–1141) days. The median BMD before romosozumab treatment was 0.771 g/cm2 at the lumbar spine (T score: -2.0) and 0.488 g/cm2 at the femoral neck (T score: -2.8). After 12 months of treatment, the percent change in BMD was significantly increased to 6.18% in the lumbar spine (P < 0.001); however, it remained unchanged in the femoral neck (P = 0.46). The P1NP values increased significantly from baseline to 455.8% (P < 0.001) and I-CTP values increased significantly to 30.3% (P < 0.001). One patient presented with periodontitis and a vertebral fracture during treatment. Multiple regression analysis revealed that the factors affecting changes in the lumbar BMD at 12 months were the baseline BMD (partial regression coefficient = -1.39, P < 0.001) and P1NP values (partial regression coefficient = 0.00015, P < 0.05).
Conclusions: Romosozumab treatment significantly increased the lumbar BMD and bone turnover markers in patients previously treated with conventional antiresorptive osteoporosis drugs, and switching the therapy to romosozumab can be considered a treatment option.
Trial registration: This study was registered in the Japan Registry of Clinical Trials (No. jRCT1051210070) on 23 July, 2019.
Metastatic non-small cell lung cancer (NSCLC) and brain edema: a topographical and clinicopathological investigation utilizing deep learning-based artificial intelligence (DLBAI)
Authors: Yun Jonathan , Kurker Kristina , Maragkos Georgios , Kumar Jeyan , Sutherland Grant , Farzad Faraz , Sukumar Rohit , Feng Xue , Yener Ulas , Patel Sohil , Schiff David , Lopes Beatriz , Mut Melike 
Published: January 2024

Abstract

Tumor-associated vasogenic brain edema is a well-known contributor of morbidity and mortality in patients with metastatic disease to the brain. It is widely accepted that brain metastases (BM) is associated with extensive edema and can cause increased symptomatology such as pain, neurologic deficit, and elevated intracranial pressure depending on extent and location. We present a proof-of-concept retrospective analysis utilizing DLBAI to segment and detect radiological and topographical patterns of peritumoral edema and assess for clinicopathological correlates in 84 patients with NSCLC and BM who underwent surgical resection and were not previously on steroids. We found that overall, tumors in all locations demonstrated a mean 10:1 edema to tumor ratio (ETR) and an occipital tumor location was associated with a significantly elevated ETR. Within our cohort there were no other factors that were significantly associated with ETR. This study demonstrates a proof-of-concept that DLBAI is an efficient and accurate method of radiographic analysis that can be applied to detect and potentially predict clinicopathological data and prognostic determinants. Clinically, we demonstrate that NSCLC is associated with significant peritumoral edema and that topographical factors may be associated with increased extent of edema.
Dual Activities of an X-family DNA Polymerase Regulate CRISPR-Induced Insertional Mutagenesis Across Species
Authors: Zhang Feng , Weiss Trevor , Kumar Jitesh , Chen Chuan , Schlegel Oliver , Lutterman John , Ling Kun 
Published: January 2024

Abstract

The canonical non-homologous end joining (c-NHEJ) repair pathway has generally been considered a highly efficient and stochastic repair process. Yet recent studies indicated that c-NHEJ-mediated CRISPR-Cas9 mutagenesis, primarily leading to 1-bp insertions and small deletions, may be highly predictable. This observation has spurred the development of in-silico programs with remarkable accuracy in various animal species. Nevertheless, the predictability of CRISPR-induced mutation profiles across species and the associated mechanisms remained elusive. Through comparison of CRISPR-Cas9 repair outcomes between human and plant species, we discovered significant differences in 1-bp insertion profiles across species, governed by an X-family DNA polymerase, DNA Pol λ. The high predictability observed in human cells seemed linked to the template-dependent activity of human DNA Pol λ. However, this predictability cannot be directly extended to plants due to the dual activities of the plant homolog, capable of generating 1-bp insertions through both templated and non-templated manners. While knocking out DNA Pol λ led to deletion-only mutations, its overexpression enhanced 1-bp insertion by 1.2 - 2 folds at multiple target sites in plants. These findings unveiled the underlying mechanism dictating unique CRISPR-Cas9-induced insertion profiles across species and presented new strategies for achieving predictable and precise genome editing through c-NHEJ.
A solution-processable natural crystal with giant optical anisotropy for efficient manipulation of light polarization
Authors: Zhao Sangen , Zhou Yang , Guo Zhengfeng , Gu Honggang , Li Yanqiang , Song Yi Peng , Liu Shiyuan , Hong Mao-Chun , Luo Junhua 
Published: January 2024

Abstract

Optical anisotropy (e.g., birefringence and dichroism), a light-matter interaction phenomenon observed three centuries ago in natural Iceland crystal, is paramount for manipulating light polarization in modern optics. To date, various natural birefringent crystals are widely used, but their birefringence is limited to < 0.3. Here, we demonstrate a solution-processable natural crystal C3H8N3I6·3H2O with giant birefringence up to 2.8 from visible to infrared spectral region, which hits a new high among natural crystals. Combining critical point analysis and the first-principles calculations, we reveal that this giant optical anisotropy mainly comes from the linear (I3)- structural units in a parallel arrangement, which maximizes the difference of polarizability along the different crystallographic axes. This work highlights the potential of natural polyiodide crystals as an outstanding platform to satisfy the increasing demand for next-generation polarized photonic applications in optical communication, 3D imaging, ultra-high-resolution sensing, etc.
Urban green spaces with high connectivity and complex vegetation promote occupancy and richness of birds in a tropical megacity
Authors: Oropeza-Sánchez Marco T. , Solano-Zavaleta Israel , Cuandón-Hernández Wendy Lizett , Martínez-Villegas Jorge Arturo , Palomera-Hernández Vianey , Zúñiga-Vega J. Jaime 
Published: January 2024

Abstract

The growth of urban areas promotes land-use change, resulting in the loss of biodiversity and human benefits. In urban zones, green areas facilitate physicochemical processes, undertake multiple gains to human beings, and support numerous vertebrate populations, including birds. In tropics, the capacity of green spaces to maintain bird populations is regulated by characteristics of these areas (e.g., vegetation structure) and environmental seasonality. To generate proposals that address the negative effects of Mexico City's growth, in this study (1) we defined the park characteristics that most influence the detection and occupation probabilities of birds by season and (2) evaluated bird richness in green areas between seasons. From four sampling seasons between 2021 and 2022, detection records of 108 bird species were obtained in 101 green areas. We estimate that air temperature (in the second season) and sampling time (in the other three) explained the detection for most birds. In the first and fourth seasons, the occupancy and bird richness was higher in parks close to other green areas. The occupation and richness of birds increased with tree richness in the second and fourth seasons. Flower abundance explained the occupancy and richness in the third season. In both years, we estimated differences in species richness between seasons. In 2021, we estimated the highest richness during the dry season, and in 2022, the highest richness was estimated during the rainy season. With these results, we aim to promote responsible management practices for green areas, bird conservation and, their benefits for the urban ecosystems.
Anomalous Ambiguity Detection Between Reference Stations Based on Box-Cox Transformation of Tropospheric Residual Estimation
Authors: Zhang Zeyu , Pan Shuguo , Gao Wang , Wang Chengfei , Tao Xianlu , Liu Hao 
Published: January 2024

Abstract
With the increasing scale and complexity of network RTK, the reliability of ambiguity resolution becomes particularly crucial. Undetected fixed errors may trigger a chain reaction in subsequent atmospheric delay extraction and fitting stages, thereby affecting the reliability of user positioning services. Current methods for checking abnormal ambiguities suffer from issues such as inflexible threshold selection, excessive exclusion, and overlooking observational anomalies. Addressing these concerns, this paper proposes a reference station-based abnormal ambiguity detection method utilizing tropospheric residual estimation, named Chi-Square Test combining Box-Cox Transformation and Secondary Screening (BS-CT). By unitizing the residual estimates of zenith tropospheric values obtained through ambiguity resolution and applying Box-Cox transformation for standard normalization, they become suitable for chi-square testing, thereby eliminating satellites with fixed ambiguity anomalies. The integration of secondary screening strategy further ensures the reliable fixation of the ambiguity quantity. Experimental results demonstrate that the BS-CT method, compared to Ordinary Chi-Square Test (O-CT), Partial Ambiguity Resolution (PAR) methods and a method utilizing a decision function g for enhanced fixed fraction and variance strategy, exhibits lower false alarm rates and comparable missed detection rates to PAR method. Thus, the BS-CT method demonstrates robust abnormal ambiguity detection while ensuring a reliable quantity of fixed ambiguities.
How Does University Education Pay Off? – A Time-Series Analysis of Individual Life-Cycle Earnings
Authors: Qi Haodong , Kolk Martin 
Published: January 2024

Abstract

Relying on a 45-year-long panel data, we estimated a model which integrates heterogeneous income profile (HIP) into Mincer's human capital earnings function. Specifically, our model treats each person's earning stream as individual time-series, and exploits its temporal variation.With this approach, we examined how heterogeneity in life-cycle earning dynamics constitutes income premiums for university graduates. The results revealed notable gendered mechanisms. For men, university education increases post-school human capital investments (e.g., on-the-job learning and training), which leads to a higher lifetime earning. For highly educated women, the income premium is driven primarily by a greater earning capacity at age 25, and secondarily by a lower childbearing cost.
JEL Classification I24, I26, J24
Exploring the role of obesity-induced extracellular vesicles secretion and associated oncogenic proteins in endometrial cancer pathogenesis.
Authors: Selvendiran Karuppaiyah , Sakaue Takahiko , Zingarelli Roman , Dorayappan Kalpana Deepa Priya , Khadraoui Wafa , Anbalgan Muralidharan , Wallbillich John , Kalaiyarasan Deeoika , Cosgrove Casey , Suarez Adrian , Koga Hironori , Maxwell Larry , O"Malley David , Cohn David E. 
Published: January 2024

Abstract

Endometrial cancer (EC) is the leading gynecologic malignancy in the United States with obesity implicated in 57% of cases. This research delves into the molecular complexities of extracellular vesicle (EV) secretion as carriers of oncogenic protein expression and their involvement in obesity-mediated EC. An understanding of these mechanisms is pivotal for unraveling pathways relevant to obesity-associated EC, thereby guiding the development of innovative prevention and treatment strategies. Our investigation revealed a significant increase in EV secretion carrying oncogenic proteins (TMEM205, STAT5, and FAS) in adipose and uterine tissues/serum samples from obese EC patients compared to their non-obese counterparts. We identified alterations in EV-regulating proteins (Rab7, Rab11, and Rab27a) in obesity-mediated EC patient adipose and uterine samples. Through a 24-week analysis of the effects of a 45% kcal high-fat diet (HFD) on mice, we observed heightened body weight, increased adipose tissue, enlarged uterine horns, and heightened inflammation in the HFD group. This correlated with elevated levels of EV secretion and increased expression of oncogenic proteins TMEM205, FAS, and STAT5, while the tumor suppressor gene PIAS3 was downregulated in adipose and uterine tissues in HFD treated mice. Furthermore, our study confirmed that adipocyte derived EVs increased EC cell proliferation and migration. Additionally, we identified that the small molecule inhibitors (HO-3867) or Metformin inhibited EV secretion in vitro and in vivo, demonstrating significant inhibition of high glucose or adipocyte-mediated EC cell proliferation and a reduction in body weight and adipose tissue accumulation when administered to HFD mice. Moreover, HO-3867 or Metformin treatment inhibits HFD induced hyperplasia by altered the expression of EV-regulated proteins (Rab7, Rab11, and Rab27a) and decreased oncogenic protein expression (TMEM205, FAS and STAT5) levels. This study provides critical insights into the mechanisms supporting obesity-mediated EV secretion with oncogenic protein expression, shedding light on their role in EC pathogenesis. Additionally, it offers pre-clinical evidence supporting the initiation of novel studies for EV-targeted therapies aimed at preventing obesity-mediated EC.
Master-slave Multi-chain with Risk Assessment based Access Control Model for Zero Trust Network
Authors: Shao Sisi , Gu Tiansheng , Yang Qian , Du HongYu , Liang Wei , Sun Zhen , Liu Shangdong , Jiang Fei , Ji Yimu 
Published: January 2024

Abstract
Zero trust aims to enable users in untrusted network areas to access trusted areas through authentication and policy control. When entering a zero trust network, no entity is inherently trusted, and resources are subject to continuous and dynamic evaluation during access. However, challenges such as dynamic access control decisions, multi-domain polymorphic access subjects, and continuous assessment of access behavior highlight the limitations of conventional zero trust networks in meeting evolving user demands for network security. In response to these challenges, we propose the master-slave multi-chain with risk assessment based access control (MMR-AC) model for zero trust network. This model introduces a unified identity management strategy through the design of access control contracts, facilitating seamless cross-domain access between different identity management systems. Additionally, the model leverages a master-slave multi-chain architecture to establish an Attribute-Based Access Control (ABAC) mechanism. To achieve continuous assessment of the access subject, the model utilizes the historical access records of the access subject as training data. Furthermore, it introduces an access risk assessment method using LightGBM. Experimental results with the proposed MMR-AC model demonstrate its capability to achieve a continuous and accurate assessment of user access risks.
Tailoring the Mechanical Strength and Corrosion Resistance of Aluminum Matrix Composites throughBiochar Reinforcement at Varied Weight Percentages
Authors: Alnaser Ibrahim A. 
Published: January 2024

Abstract

This study introduces an innovative approach to fabricate aluminum matrix composites strengthened with biochar, derived from renewable biomass sources. A systematic investigation of varying biochar weight percentages (0, 2.5, 5, 7.5, and 10 wt%) reveals substantial improvements in mechanical properties and corrosion resistance. Mechanical assessments, including compressive strength and hardness, demonstrate a significant enhancement in mechanical strength with biochar incorporation. In this study, it was discovered that the composite with 7.5 wt% biochar exhibits an optimal balance, displaying an 8.83% increase in compressive strength and a 15.15% rise in hardness compared to the base aluminum matrix. The study further evaluates corrosion behavior through electrochemical analyses and immersion tests in 3.5% NaCl corrosive environments, highlighting the superior corrosion resistance of biochar-reinforced composites. Corrosion rates decrease by 73% in the composite with 10 wt% biochar for the 24hrs immersion time, affirming its protective barrier against corrosive agents. This research provides quantitative insights into tailoring mechanical and corrosion properties in aluminum matrix composites through biochar reinforcement, offering a promising avenue for sustainable material development. The resulting materials exhibit not only an 8.83% increase in mechanical strength but also a 73% reduction in corrosion rates, offering valuable uses in industries that need strong, eco-friendly solutions.
Mapping karst depressions and sinkholes in anthropogenically influenced areas
Authors: Fuchs Michael , Reinartz Hermann , Torizin Jewgenij , Balzer Dirk , Kuhn Dirk , Schüßler Nick , Hahne Kai , Nix Thomas , Gunkel Claudia 
Published: January 2024

Abstract

A comprehensive sinkhole inventory is crucial for accurately assessing sinkhole susceptibility. The presented study introduces a semi-automatic approach for mapping potential sinkholes through a geomorphometric analysis of digital elevation models complemented by statistical analysis. This approach aims to augment current sinkhole inventories in quantity and quality. We chose the distinct karst terrain along the southwestern edge of the Harz Mountains in Lower Saxony as our focal area. The genesis of most sinkholes in this area is linked to subrosion processes within the evaporitic Zechstein Group, predominantly driven by the hydration of anhydrite to gypsum followed by its steady dissolution. The region exhibits diverse karst formations, ranging from bare and slightly covered karst to a fold-block landscape where resilient strata overlay subrosion zones. Human influence has also significantly reshaped this landscape over the past millennium, introducing numerous artificial structures and posing challenges to fully automated sinkhole detection. We employed a statistically refined landform classification based on geomorphons to identify localities of potential sinkhole formations, followed by a masking process to refine our results. In analyzing the distribution of these potential sinkholes, we took into account various geological and environmental factors, such as different types of karst, fault lines, and land cover, while purposefully excluding anthropogenic features from our analysis. The results revealed previously undocumented sinkholes in areas where the overburden layers, particularly in the Buntsandstein formation, are increasingly thick. The proposed approach proves to be particularly adept at detecting sinkholes in regions where they are isolated or have not been extensively surveyed yet.
A Mean Field Game Model of Staking Systemand A Reinforcement Learning Framework for Parameter Optimization
Authors: Guo Jinyan , Guo Qevan , Mou Chenchen , Zhang Jingguo 
Published: January 2024

Abstract
In this paper, we present a Mean Field Game (MFG) approach to model thestaking system in crypto industry and propose a reinforcement learning frame-work for parameter optimization. Under log utility, we derive the optimal stakingstrategy for miners. Then we develop the dynamics of staking reward rate andstaking ratio using the MFG fixed point condition. Based on our MFG model, wepropose a reinforcement learning framework to optimally decide the inflation rateof the staking system, aiming to increase the staking ratio or market cap of theblockchain project. We provide a few numerical experiments incorporating realstatistical data from IoTeX to validate our approach. Our proposed model andframework offer a brand new robust method for parameter optimization in thestaking system, contributing to the fields of tokenomics design in crypto industry.
Alpha-Hederin induces incomplete autophagic injury in non-small cell lung cancer by interfering with the lysosomal acidification
Authors: Jin Feng , Ni Xiaochen , Jiang Xiaomin , Yu Shilong , Wu Feng , Shi Xinlin , Mao Defang , Wang Haibo , Shi Qingtong , Liu Yanqing , Xu Qin 
Published: January 2024

Abstract

Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.