bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission
Authors: Guo Ya-wen , Zhu Lei , Duan Yan-ting , Hu Yi-qun , Li Le-bao , Fan Wei-jiao , Song Fa-huan , Cai Ye-feng , Liu Yun-ye , Zheng Guo-wan , Ge Ming-hua 
Published: February 2024

AbstractAnaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.
Protein thermal sensing regulates physiological amyloid aggregation
Authors: Marijan Dane , Momchilova Evgenia A. , Burns Daniel , Chandhok Sahil , Zapf Richard , Wille Holger , Potoyan Davit A. , Audas Timothy E. 
Published: February 2024

AbstractTo survive, cells must respond to changing environmental conditions. One way that eukaryotic cells react to harsh stimuli is by forming physiological, RNA-seeded subnuclear condensates, termed amyloid bodies (A-bodies). The molecular constituents of A-bodies induced by different stressors vary significantly, suggesting this pathway can tailor the cellular response by selectively aggregating a subset of proteins under a given condition. Here, we identify critical structural elements that regulate heat shock-specific amyloid aggregation. Our data demonstrates that manipulating structural pockets in constituent proteins can either induce or restrict their A-body targeting at elevated temperatures. We propose a model where selective aggregation within A-bodies is mediated by the thermal stability of a protein, with temperature-sensitive structural regions acting as an intrinsic form of post-translational regulation. This system would provide cells with a rapid and stress-specific response mechanism, to tightly control physiological amyloid aggregation or other cellular stress response pathways.
Structural basis for excitatory neuropeptide signaling
Authors: Kalienkova Valeria , Dandamudi Mowgli , Paulino Cristina , Lynagh Timothy 
Published: February 2024

AbstractRapid signaling between neurons is mediated by ligand-gated ion channels, cell-surface proteins with an extracellular ligand-binding domain and a membrane-spanning ion channel domain. The degenerin/epithelial sodium channel (DEG/ENaC) superfamily is diverse in terms of its gating stimuli, with some DEG/ENaCs gated by neuropeptides, and others gated by pH, mechanical force or enzymatic activity. The mechanism by which ligands bind to and activate DEG/ENaCs is poorly understood. Here we dissected the structural basis for neuropeptide-gated activity of a neuropeptide-gated DEG/ENaC, FMRFamide-gated sodium channel 1 (FaNaC1) from the annelid worm Malacoceros fuliginosus, using cryo-electron microscopy. Structures of FaNaC1 in the ligand-free resting state and in several ligand-bound states reveal the ligand-binding site and capture the ligand-induced conformational changes of channel gating, which we verified with complementary mutagenesis experiments. Our results illuminate channel gating in DEG/ENaCs and offer a structural template for experimental dissection of channel pharmacology and ion conduction.
Research on hydrogen leakage and diffusion mechanism in hydrogenation station
Authors: Zhang Zenggang , Shang Mingheng 
Published: February 2024

AbstractAs a clean, efficient and sustainable energy carrier, hydrogen energy has been accepted as one of the main directions of future energy development. In this paper, a hydrogenation station providing compressed hydrogen outside was adopted as the research object. Based on finite element method and virtual nozzle model, the influence of leakage of main equipment in hydrogenation station on the distribution of combustible hydrogen was investigated, including hydrogen storage tank group, tube trailer, compressor chamber and hydrogenator. The results showed that the shape and volume of the combustible hydrogen cloud generated by the leak were influenced by obstacles, hydrogen storage pressure, and wind velocity. The disturbance of external wind and the decrease in hydrogen storage pressure will have a positive impact on the reduction of leaked volume. The diffusion of combustible hydrogen clouds can be exacerbated by complex structure of obstacles, while partition wall in the adopted hydrogenation station model can limit the combustible hydrogen cloud in the process area. These conclusions can provide guidance and reference for the risk prevention measures of hydrogenation station.
Comparative mitochondrial genome brings insights to slight variation in gene proportion and large intergenic spacer and phylogenetic relationship of mudskipper species
Authors: Muhala Valdemiro , Guimarães-Costa Aurycéia , Bessa-Silva Adam Rick , Rabelo Luan Pinto , Carneiro Jeferson , Macate Isadola Eusébio , Watanabe Luciana , Balcázar Oscar David , Gomes Grazielle Evangelista , Vallinoto Marcelo , Sampaio Iracilda 
Published: February 2024

AbstractFish mitochondrial genome have been largely studied worldwide for evolutionary and other genetic purposes and the structure and gene organization are commonly conservative. However, several studies have demonstrated that this scenario may present variations in some taxa, showing differentiation on the gene rearrangement. In this study, the complete mitogenome of terrestrial fish Boleophthalmus dussumieri was generated and compared with other species of the Exudercidae fishes. The newly complete mitogenome generated is circular and 16,685 bp of length, and it contained 13 protein-coding genes (PCGs), two ribosomal RNA (rRNAs), 22 transfer RNA genes (tRNAs), and one control region (CR), with high conservative structure, like other Mudskippers. Most of the PCG showed similar codon usage bias. The gene length was found to be different specially for the CR, 12S rRNA gene and ND5 gene in some taxon. All the Boleophthalmus species showed a gene duplication in the CR, except for B. dussumieri, and they presented a long intergenic spacer specially on the tRNA-Pro/ OH Tandem duplication/random loss (TDRL) and dimer-mitogenome and nonrandom loss (DMNL) are suitable to explain the mitogenome rearrangement observed in this study. The phylogenetic analysis well supported the monophyly of all mudskipper species and the analysis positioned the Periophthalmus clade as the most basal of the terrestrial fishes. This finding provides basis and brings insights for gene variation, gene rearrangements and replications showing evidence for variety of mitochondrial structure diversity within mudskippers.
Barbary macaques show sex-related differences in body weight based on anthropogenic food exposure despite comparable female–male stable isotope ratios
Authors: Saiyed Sana T. , Fuentes Agustin , Shaw Eric , Schurr Mark R. , Gettler Lee T. 
Published: February 2024

AbstractAs the human–primate interface expands, many nonhuman primate (NHP) populations exploit anthropogenic foods to survive, while some populations opportunistically target them. Though anthropogenic food consumption is sometimes associated with greater reproductive output and survival in these populations, there is a dearth of research on possible health effects. We explore how differential exposure to anthropogenic foods is linked to variation in isotopic compositions (δ13C and δ15N) and body weights in Barbary macaques (Macaca sylvanus) in the Upper Rock Nature Reserve, Gibraltar. We placed monkeys into three categories based on anthropogenic food exposure. We then analyzed individuals for isotopic signatures (N = 147) and body weight measurements (N = 80). Using the lowest exposure category as the comparison, we found body weights and δ15N values, but not δ13C values, significantly differed across key categories. Within categories, we found no significant associations between sex and δ13C or δ15N values, suggesting that individuals within categories consumed similar foods regardless of sex. We found a significant interaction effect between category and sex for predicting body weights. These results suggest that sex plays a role in how anthropogenic foods are accessed and consumed regardless of exposure, which may result in differential health profiles for female and male macaques.
Impact of prescribed opioid use on development of dementia among patients with chronic non-cancer pain
Authors: Oh Tak Kyu , Song In-Ae 
Published: February 2024

AbstractWe aimed to examine the association between opioid use and the development of dementia in patients with chronic non-cancer pain in South Korea. Data were extracted from the National Health Insurance Service database in South Korea. Adult patients diagnosed with musculoskeletal diseases with chronic non-cancer pain between 2010 and 2015 were included in the analysis. Patients who were prescribed opioids regularly and continuously for ≥ 90 days were classified as opioid users. In total, 1,261,682 patients with chronic non-cancer pain were included in the final analysis, of whom 21,800 (1.7%) were opioid users. From January 1, 2016 to December 31, 2020, 35,239 (2.8%) patients with chronic non-cancer pain were newly diagnosed with dementia. In the multivariable model, opioid users showed a 15% higher risk of developing dementia than the control group. Additionally, opioid users showed a 15% and 16% higher risk of developing Alzheimer’s disease and unspecified dementia, respectively, than the control group, but did not show any significant differences for vascular dementia. Among adult patients with chronic non-cancer pain, opioid users were at a higher risk of developing dementia than the control group; the risk was significantly higher for Alzheimer’s disease but not for vascular dementia in this study. Our results suggest that in patients with CNCP, public health strategies should target opioid users for early dementia detection and intervention.
Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure
Authors: Gil Laborda Raquel , de Frías Edgard Rodríguez , Subhi-Issa Nabil , de Albornoz Elena Carrillo , Meliá Elena , Órdenes Marcos , Verdú Victoria , Vidal Juan , Suárez Esther , Santillán Isabel , Ordóñez Daniel , Pintado-Vera David , González Villafáñez Victoria , Lorenzo Ángel , Fariñas Manuel , Rodríguez-Paíno Mario , Núñez Beltrán María , García Segovia Áurea , del Olmo Ainhoa , Martín Cañadas Fernando , Daurelio Rosa , de la Fuente Alfonso , González Casbas José Manuel , Cabezuelo Vega , Ros Berruezo Francisco , Moreno Hidalgo Miguel Ángel , Iniesta Silvia , Bueno Beatriz , Martínez Acera Álvaro , Izquierdo Alexandra , Vicario José Luis , Fernández-Arquero Miguel , Sánchez-Ramón Silvia 
Published: February 2024

AbstractThroughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case–control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal–fetal KIR-HLA-C mismatch in patients.
Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma
Authors: Huang Ketuan , He Yongfei , Liang Tianyi , Mo Shutian , Liao Yuan , Gao Qiang , Liao Xiwen , Han Chuangye , Zhu Guangzhi , Peng Tao 
Published: February 2024

AbstractDual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.
Breast cancer detection using enhanced IRI-numerical engine and inverse heat transfer modeling: model description and clinical validation
Authors: Gutierrez Carlos , Owens Alyssa , Medeiros Lori , Dabydeen Donnette , Sritharan Nithya , Phatak Pradyumna , Kandlikar Satish G. 
Published: February 2024

AbstractEffective treatment of breast cancer relies heavily on early detection. Routine annual mammography is a widely accepted screening technique that has resulted in significantly improving the survival rate. However, it suffers from low sensitivity resulting in high false positives from screening. To overcome this problem, adjunctive technologies such as ultrasound are employed on about 10% of women recalled for additional screening following mammography. These adjunctive techniques still result in a significant number of women, about 1.6%, who undergo biopsy while only 0.4% of women screened have cancers. The main reason for missing cancers during mammography screening arises from the masking effect of dense breast tissue. The presence of a tumor results in the alteration of temperature field in the breast, which is not influenced by the tissue density. In the present paper, the IRI-Numerical Engine is presented as an adjunct for detecting cancer from the surface temperature data. It uses a computerized inverse heat transfer approach based on Pennes’s bioheat transfer equations. Validation of this enhanced algorithm is conducted on twenty-three biopsy-proven breast cancer patients after obtaining informed consent under IRB protocol. The algorithm correctly predicted the size and location of cancerous tumors in twenty-four breasts, while twenty-two contralateral breasts were also correctly predicted to have no cancer (one woman had bilateral breast cancer). The tumors are seen as highly perfused and metabolically active heat sources that alter the surface temperatures that are used in heat transfer modeling. Furthermore, the results from this study with twenty-four biopsy-proven cancer cases indicate that the detection of breast cancer is not affected by breast density. This study indicates the potential of the IRI-Numerical Engine as an effective adjunct to mammography. A large scale clinical study in a statistically significant sample size is needed before integrating this approach in the current protocol.
Knowledge‐based deep learning system for classifying Alzheimer's disease for multi‐task learning
Authors: Dhaygude Amol Dattatray , Ameta Gaurav Kumar , Khan Ihtiram Raza , Singh Pavitar Parkash , Maaliw Renato R. , Lakshmaiya Natrayan , Shabaz Mohammad , Khan Muhammad Attique , Hussein Hany S. , Alshazly Hammam 
Published: February 2024

AbstractDeep learning has recently become a viable approach for classifying Alzheimer's disease (AD) in medical imaging. However, existing models struggle to efficiently extract features from medical images and may squander additional information resources for illness classification. To address these issues, a deep three‐dimensional convolutional neural network incorporating multi‐task learning and attention mechanisms is proposed. An upgraded primary C3D network is utilised to create rougher low‐level feature maps. It introduces a new convolution block that focuses on the structural aspects of the magnetic resonance imaging image and another block that extracts attention weights unique to certain pixel positions in the feature map and multiplies them with the feature map output. Then, several fully connected layers are used to achieve multi‐task learning, generating three outputs, including the primary classification task. The other two outputs employ backpropagation during training to improve the primary classification job. Experimental findings show that the authors’ proposed method outperforms current approaches for classifying AD, achieving enhanced classification accuracy and other indicators on the Alzheimer's disease Neuroimaging Initiative dataset. The authors demonstrate promise for future disease classification studies.
Tranexamic Acid: An Evergreen Hemostatic Agent
Authors: Franchini Massimo , Focosi Daniele , Mannucci Pier Mannuccio 
Published: February 2024

AbstractTranexamic acid (TXA) is an important antifibrinolytic agent, which inhibits plasminogen activation and fibrinolysis. Several controlled randomized trials have investigated the role of TXA in preventing or decreasing blood loss across different surgical interventions or medical conditions characterized by excessive bleeding, consistently documenting its effectiveness and safety. Although the first clinical use of TXA dates back to more than 60 years ago, TXA remains the focus of intense research. This narrative review summarizes the more recent results and indications on the clinical use of TXA.
Adjust or crumble while studying abroad
Authors: Harrison J. Kline , Brower Holly , Brunsting Nelson C. 
Published: February 2024

Abstract
This study provides greater understanding of the student characteristics and practices that affect the success of a study abroad experience as evidenced by students’ adjustment. Two personal characteristics of students, grit and cultural intelligence (CQ), and one learning behavior, reflective thinking, were investigated. The study was conducted among undergraduate students from the United States participating in study abroad semester programs with 309 matched/completed surveys returned. Results show that grit, entailing consistency of interest and perseverance of effort, has a positive effect on student adjustment when abroad. Also, three of the four dimensions of CQ (metacognitive, cognitive, and motivational) positively influenced study abroad; however, behavioral CQ did not have a significant effect. Furthermore, this study demonstrates that reflection and critical reflection have a positive impact on students’ adjustment when abroad. These results can inform the design of study abroad orientation programs to better facilitate cultural adjustment.
Do students carry their home in their pocket?
Authors: Mroz Aurore 
Published: February 2024

Abstract
This longitudinal mixed methods study followed 16 U.S.-affiliated learners of French in Paris. After merging
monthly social network and weekly smartphone usage reports, K-means clusters analysis revealed significant differences between (1)
learners displaying attachment to versus detachment from their friends and family at home, and (2) smartphone usage profiles –
spectators versus communicators and explorers. Triangulation with pre-/during-/post-study abroad in-depth interviews allowed
identification of what was most instrumental for participants’ interactions in the target language and intercultural gains:
geolocation applications on their phones and living with host families. The electronic umbilical cord hypothesized to exist for
those displaying attachment was in fact not a detrimental force – quite the opposite. Instead, the way participants had
(detrimentally) taken their home with them to Paris was by being visited by friends and family, by often interacting with U.S.
students on site, and by frequently consuming English-speaking audiovisual content on their phones.