bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin-dependent protein kinases and cell cycle regulation in biology and disease
Authors: Pellarin Ilenia , Dall’Acqua Alessandra , Favero Andrea , Segatto Ilenia , Rossi Valentina , Crestan Nicole , Karimbayli Javad , Belletti Barbara , Baldassarre Gustavo 
Published: January 2025

Abstract
Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified as the kinases able to drive cell division. In reality, the human genome contains 20 different CDKs, which can be divided in at least three different sub-family with different functions, mechanisms of regulation, expression patterns and subcellular localization. Most of these kinases play fundamental roles the normal physiology of eucaryotic cells; therefore, their deregulation is associated with the onset and/or progression of multiple human disease including but not limited to neoplastic and neurodegenerative conditions. Here, we describe the functions of CDKs, categorized into the three main functional groups in which they are classified, highlighting the most relevant pathways that drive their expression and functions. We then discuss the potential roles and deregulation of CDKs in human pathologies, with a particular focus on cancer, the human disease in which CDKs have been most extensively studied and explored as therapeutic targets. Finally, we discuss how CDKs inhibitors have become standard therapies in selected human cancers and propose novel ways of investigation to export their targeting from cancer to other relevant chronic diseases. We hope that the effort we made in collecting all available information on both the prominent and lesser-known CDK family members will help in identify and develop novel areas of research to improve the lives of patients affected by debilitating chronic diseases.
A multicenter, randomized, double-blind, placebo-controlled phase 3 study of Socazolimab or placebo combined with carboplatin and etoposide in the first-line treatment of extensive-stage small cell lung cancer
Authors: Chen Zhiwei , Chen Jianhua , Huang Dingzhi , Zhang Wei , Wu Lin , Yi Tienan , Wang Qiming , Han Liang , Tan Liping , Li Yinyin , Zhang Zhihong , Li Na , li Jie , Zhang Tongmei , Hu Ying , Sun Hongmei , Wu Youhua , He Zhiyong , Yang Runxiang , Cheng Peng , Li Xingya , Shi Jianhua , Yu Guohua , Ma Daiyuan , Li Benjamin Xiaoyi , Dai Xiangrong , Wong Michael , Li Yujie , Yu Xiaohui , Lu Shun ,   for the Socazolimab Study Group, Li Benjamin Xiaoyi , Dai Xiangrong , Wong Michael , Li Yujie , Yu Xiaohui 
Published: January 2025

Abstract
This is a randomized, double-blind, placebo-controlled phase 3 clinical trial (ClinicalTrials.gov, NCT04878016) conducted in 54 hospitals in China. Adults who were histologically diagnosed and never treated for extensive-stage small cell lung cancer (ES-SCLC) were enrolled. Eligible Patients were randomly assigned (1:1) to receive four cycles (21 days as one cycle) of intravenous carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m² of body-surface area, on days 1–3 of each cycle) with either socazolimab (5 mg/kg, day 1 of each cycle) or matching placebo, following maintenance therapy with socazolimab or placebo. From July 15, 2021, to May 12, 2022, 498 eligible patients were randomly assigned to receive socazolimab (250 patients) or placebo (248 patients) combined with chemotherapy. As of October 13, 2023, patients treated with socazolimab presented significant overall survival (OS) benefit (13.90 months) compared with the placebo plus EC group (11.58 months) (hazard ratio for death, 0.799; 95% CI, 0.652–0.979; p = 0.0158). The median progression free survival (PFS) was 5.55 months in the socazolimab plus EC group, prolonging disease progression or death by nearly 1.2 months (5.55 months vs 4.37 months, hazard ratio for progression or death, 0.569; 95% CI, 0.457–0.708; p < 0.0001). 200 (80.3%) patients in the socazolimab plus EC group experienced ≥ grade 3 treatment-related adverse events and 187 (75.7%) patients occurred in the placebo plus EC group. Socazolimab combined with standard EC regimen chemotherapy for first-line treatment of ES-SCLC significantly prolonged overall survival and did not increase the safety risk of treatment.
Deep imaging of LepR+ stromal cells in optically cleared murine bone hemisections
Authors: Ni Yuehan , Wu Jiamiao , Liu Fengqi , Yi Yating , Meng Xiangjiao , Gao Xiang , Xiao Luyi , Zhou Weiwei , Chen Zexi , Chu Peng , Xing Dan , Yuan Ye , Ding Donghui , Shen Ge , Yang Min , Wu Ronjie , Wang Ling , Melo Luiza Martins Nascentes , Lin Sien , Cheng Xiaoguang , Li Gang , Tasdogan Alpaslan , Ubellacker Jessalyn M. , Zhao Hu , Fang Shentong , Shen Bo 
Published: January 2025

Abstract
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR+) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR+ stromal cells, within optically cleared bone hemisections. Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae. The protocol entails tissue fixation, decalcification, and cryosectioning to reveal the marrow cavity. Completed within approximately 12 days, this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals. The bone hemisections are compatible with diverse antibody labeling strategies. Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software, assessing a spectrum of parameters. With proper storage, the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months. This protocol is robust, straightforward to implement, and highly reproducible, offering a valuable tool for tissue architecture and cellular interaction studies.
METTL3 inhibition promotes radiosensitivity in hepatocellular carcinoma through regulation of SLC7A11 expression
Authors: Zhang Chen , Yang Tianpeng , Chen Hanbin , Ding Xiaofeng , Chen Huajian , Liang Zhenzhen , Zhao Yinlong , Ma Shumei , Liu Xiaodong 
Published: January 2025

AbstractRadiotherapy is one of the main treatment modalities for advanced hepatocellular carcinoma (HCC). Ferroptosis has been shown to promote the radiosensitivity of HCC cells, but it remains unclear whether epigenetic regulations function in this process. In this study, we found that the overexpression of METTL3 was associated with poor prognosis. Knockdown of METTL3 promoted radiosensitivity of HCC by inducing ferroptosis. Mechanistically, METTL3 targeted adenine (+1795) on the SLC7A11 mRNA, and the m6A reader IGF2BP2 promoted SLC7A11 mRNA stability by recognizing and binding to the m6A site. Additionally, METTL3 decreased the ubiquitination of SLC7A11 protein through the m6A/YTHDF2/SOCS2 axis. Furthermore, in vivo studies showed that HCC models with low METTL3/IGF2BP2 expression have higher radiosensitivity. In conclusion, our study suggests that METTL3 regulates the stability of SLC7A11 mRNA in an m6A/IGF2BP2-dependent manner and the ubiquitination of SLC7A11 protein through the m6A/YTHDF2/SOCS2 pathway, both of which require the m6A methyltransferase activity of METTL3. METTL3 or IGF2BP2 may be promising targets for radiotherapy of HCC.
Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology
Authors: Wickenhagen Arthur , Flagg Meaghan , Port Julia R. , Yinda Claude Kwe , Goldin Kerry , Gallogly Shane , Schulz Jonathan E. , Lutterman Tessa , Williamson Brandi N. , Kaiser Franziska , Mukesh Reshma K. , van Tol Sarah , Smith Brian , van Doremalen Neeltje , Russell Colin A. , de Wit Emmie , Munster Vincent J. 
Published: January 2025

AbstractThe emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.
Magnetic anisotropy of 4f atoms on a WSe2 monolayer: a DFT + U study
Authors: Carbone Johanna P. , Bihlmayer Gustav , Blügel Stefan 
Published: January 2025

AbstractInspired by recent advancements in the field of single-atom magnets, particularly those involving rare-earth (RE) elements, we present a theoretical exploration employing DFT+U calculations to investigate the magnetic properties of selected 4f atoms, specifically Eu, Gd, and Ho, on a monolayer of the transition-metal dichalcogenide WSe2 in the 1H-phase. This study comparatively examines RE with diverse 4f orbital fillings and valence chemistry, aiming to understand how different coverage densities atop WSe2 affect magnetocrystalline anisotropy. We observe that RE lacking 5d occupation exhibit larger magnetic anisotropy energies at high densities, while those with outer 5d electrons show larger anisotropies in dilute configurations. Additionally, even half-filled 4f shell atoms with small orbital magnetic moments can generate substantial energy barriers for magnetization rotation due to prominent orbital hybridizations with WSe2. Open 4f shell atoms further enhance anisotropy barriers through spin-orbit coupling effects. These aspects are crucial for realizing stable magnetic information units experimentally.
Unconventional broadening of Rashba spin splitting in a Au2Sb surface alloy with periodic structural defects
Authors: Hu Jinbang , Wang Xiansi , Åsland Anna Cecilie , Wells Justin W. 
Published: January 2025

AbstractMost Rashba spin splitting experimentally studied so far has ideal lattice with inversion symmetry broken, which limits the possibility to minimize the presence of spin-degenerate carriers near the Fermi level. Here, we report a novel 2D Au2Sb surface alloy decorated with periodic structural defects that exhibits modulation on the Rashba spin-orbit coupling band. Spin- and angle-resolved photoemission spectroscopy reveals a Rashba spin-split band with antiparallel spin polarization, significantly broadened compared to the Au₂Sn surface alloy. From the good agreement between the experimental results and DFT calculations, we identify that the broadening of the Rashba bands comes from variations in Sb atom corrugation induced by the periodic three-pointed star-shaped defects. These periodic defects can shift the energy position of the Rashba bands without breaking the in-plane rotational and mirror symmetries. Our findings highlight the potential to tune spin-dependent properties in 2D materials for spintronic applications.
Deterministic patterns in single-cell transcriptomic data
Authors: Cao Zhixing , Wang Yiling , Grima Ramon 
Published: January 2025

AbstractWe report the existence of deterministic patterns in statistical plots of single-cell transcriptomic data. We develop a theory showing that the patterns are neither artifacts introduced by the measurement process nor due to underlying biological mechanisms. Rather they naturally emerge from finite sample size effects. The theory precisely predicts the patterns in data from multiplexed error-robust fluorescence in situ hybridization and five different types of single-cell sequencing platforms.
Effective removal of heavy metal ions (Pb, Cu, and Cd) from contaminated water by limestone mine wastes
Authors: Fathy Aya T. , Moneim Mohamed A. , Ahmed Ezzat A. , El-Ayaat Abdalla M. , Dardir Fatma M. 
Published: January 2025

AbstractLimestone mining waste and its derived CaO were checked as an adsorbents of pb2+, Cu2+, and Cd2+ ions from water solution. The characterization of Limestone and calcined limestone was studied by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Scanning Electron Microscope (SEM), and Surface area measurements (BET). The optimum conditions of sorbent dosage, pH, initial concentration, and contact time factors were investigated for pristine limestone and calcined limestone absorbents. The results indicate that the optimum initial concentrations of (Ci) were 1200, 500, and 300 ppm for Pb, Cu, and Cd, respectively, using calcined limestone adsorbent, while using the pristine limestone adsorbent, the corresponding optimum initial concentrations were 700, 110, and 50 ppm. In the ternary system sorption, the results indicated that the selectivity sequence of the studied metals by limestone can be expressed as Pb2+ > Cd2+ > Cu2+, while calcined limestone exhibits a higher selectivity for Pb2+ compared to Cu2+ and Cd2+. Hence, various adsorption isotherm and kinetic models were examined to explore different patterns and behaviors of adsorption. So, the results indicate that calcined limestone has great potential for eliminating cationic heavy metal species from industrial water solutions.
Intelligent skin disease prediction system using transfer learning and explainable artificial intelligence
Authors: Abbas Sagheer , Ahmed Fahad , Khan Wasim Ahmad , Ahmad Munir , Khan Muhammad Adnan , Ghazal Taher M. 
Published: January 2025

AbstractSkin diseases impact millions of people around the world and pose a severe risk to public health. These diseases have a wide range of effects on the skin’s structure, functionality, and appearance. Identifying and predicting skin diseases are laborious processes that require a complete physical examination, a review of the patient’s medical history, and proper laboratory diagnostic testing. Additionally, it necessitates a significant number of histological and clinical characteristics for examination and subsequent treatment. As a disease’s complexity and quantity of features grow, identifying and predicting it becomes more challenging. This research proposes a deep learning (DL) model utilizing transfer learning (TL) to quickly identify skin diseases like chickenpox, measles, and monkeypox. A pre-trained VGG16 is used for transfer learning. The VGG16 can identify and predict diseases more quickly by learning symptom patterns. Images of the skin from the four classes of chickenpox, measles, monkeypox, and normal are included in the dataset. The dataset is separated into training and testing. The experimental results performed on the dataset demonstrate that the VGG16 model can identify and predict skin diseases with 93.29% testing accuracy. However, the VGG16 model does not explain why and how the system operates because deep learning models are black boxes. Deep learning models’ opacity stands in the way of their widespread application in the healthcare sector. In order to make this a valuable system for the health sector, this article employs layer-wise relevance propagation (LRP) to determine the relevance scores of each input. The identified symptoms provide valuable insights that could support timely diagnosis and treatment decisions for skin diseases.
Evaluating climate-related financial policies’ impact on decarbonization with machine learning methods
Authors: D’Orazio Paola , Pham Anh-Duy 
Published: January 2025

AbstractThis study examines how Climate-Related Financial Policies (CRFPs) support decarbonization and renewable energy transitions across 87 countries from 2000 to 2023. Using the Policy Sequencing Score (PSS) and a bindingness-weighted adoption indicator, it explores the relationships between CRFPs, CO2 emissions, and Renewable Energy Production (REP) across diverse economic and institutional contexts. Findings reveal significant variation in outcomes. Advanced economies and OECD countries leverage structured policies and robust institutions to achieve steady emissions reductions and REP growth, with diminishing returns at higher policy intensities. Emerging Markets and Developing Economies (EMDEs) face institutional and structural constraints but show strong responsiveness to targeted policies, particularly in Sub-Saharan Africa and South Asia, where renewable energy growth potential is notable. Regions such as Latin America and East Asia display mixed trends, reflecting unique challenges and opportunities. Binding policies prove essential for environmental outcomes, particularly in institutionalized settings, while EMDEs require capacity building and international cooperation to address barriers. This study highlights the importance of tailoring CRFPs to specific contexts, emphasizing policy sequencing, enforcement, and capacity building. By identifying global and regional variations, the findings provide actionable insights for aligning financial systems with climate goals, fostering a sustainable low-carbon transition, and addressing equity challenges.
No evidence for active viral infection in unicentric and idiopathic multicentric Castleman disease by Viral-Track analysis
Authors: Miller Ira , Mumau Melanie D. , Shyamsundar Saishravan , Sarmiento Bustamante Mateo , Horna Pedro , Gonzalez Michael V. , Fajgenbaum David C. 
Published: January 2025

AbstractCastleman disease (CD) is a rare hematologic disorder characterized by pathologic lymph node changes and a range of symptoms due to excessive cytokine production. While uncontrolled infection with human herpesvirus-8 (HHV-8) is responsible for the cytokine storm in a portion of multicentric CD (HHV-8-associated MCD) cases, the etiology of unicentric CD (UCD) and HHV-8-negative/idiopathic MCD (iMCD) is unknown. Several hypotheses have been proposed regarding the pathogenesis of UCD and iMCD, including occult infection given the precedent established by HHV-8 infection. To investigate potential active infections in UCD and iMCD, we implemented Viral-Track, a computational method that identifies viral mRNA sequences from next-generation sequencing data. We applied Viral-Track to short sequencing reads from a cohort of UCD (n = 22), iMCD (n = 19), and controls (n = 86). While viral sequences for several unusual viruses were identified in individual CD patients, sequences for the same virus were not found across multiple CD patients or they were not specific to CD samples and were also found in non-CD samples. These results suggest that active viral infection is unlikely to be a pathological driver of UCD or iMCD.
Influence of heat-assisted vat photopolymerization on the physical and mechanical characteristics of dental 3D printing resins
Authors: Lim Jung-Hwa , Shin Seung-Ho , Jung Young-Eun , An Hongseok , Kim Jong-Eun 
Published: January 2025

AbstractThe effects of heat-assisted vat photopolymerization (HVPP) on the physical and mechanical properties of 3D-printed dental resins, including the morphometric stability of 3D-printed crowns, were investigated. A resin tank was designed to maintain the resin at 30, 40, and 50 ℃ during the 3D printing process. Test specimens were fabricated using a commercial dental resin, with untreated resin serving as the control group. Key properties such as viscosity, curing kinetics, surface microhardness, flexural properties, and dimensional accuracy were evaluated. The viscosity of the resin decreased significantly (P < 0.05) with increasing temperature, thereby enhancing its flow properties. Photo-DSC analysis revealed a 17.58% increase in peak heat flow at 50 ℃, indicating accelerated polymerization. Surface microhardness improved significantly (P < 0.05) with HVPP, though a slight reduction was observed at 50 ℃ compared to that at 30 and 40 ℃. The flexural strength, modulus, and resilience were significantly enhanced (P < 0.05) at higher temperatures, with 50 ℃ yielding the best mechanical properties. However, 3D morphometric analysis showed increased root mean square deviation from the CAD design at elevated temperatures. Our results suggest that HVPP enhances the durability of dental prostheses, although careful optimization of the printing temperature is essential to balance their strength and accuracy.
A sensory neuroprosthesis enhances recovery from treadmill-induced stumbles for individuals with lower limb loss
Authors: Li Suzhou , Triolo Ronald J. , Charkhkar Hamid 
Published: January 2025

AbstractOver 50% of individuals with lower limb loss report a fear of falling and avoiding daily activities partly due to a lack of plantar sensation. Providing direct somatosensory feedback via neural stimulation holds promise for addressing this issue. In this study, three individuals with lower limb loss received a sensory neuroprosthesis (SNP) that provided plantar somatosensory feedback corresponding to prosthesis-floor interactions perceived as arising from the missing foot generated by electrically activating the peripheral nerves in the residuum. Participants walked on a treadmill while receiving perturbations involving brief increases in the belt speed. Perturbations were initiated during early stance and randomly delivered to intact and prosthetic sides with the SNP active or inactive. With the SNP active, participants exhibited decreased trunk angular sway and peak trunk flexion angular velocity during recovery from both prosthetic and intact side perturbations. For prosthetic side perturbations, peak ground reaction force magnitudes decreased when the SNP was active. For intact side perturbations, peak ground reaction force magnitudes increased on the prosthetic side’s first recovery step after the perturbation, which resulted in a more symmetric recovery because the force approached the response on the intact side’s first recovery step following a prosthetic side perturbation. These results suggest participants integrated the feedback from the SNP into their sensorimotor control for maintaining stability and gained confidence in relying on their prosthetic limb during recovery. Restoring plantar sensation with a SNP for individuals with lower limb loss could lead to reduced risk of falling by improving recovery from trips.