bluuebunny/crossref_metadata_2025_split huggingface dataset:
interFLOW: maximum flow framework for the identification of factors mediating the signaling convergence of multiple receptors
Authors: Sheinin Ron , Salomon Koren , Yeini Eilam , Dulberg Shai , Kaminitz Ayelet , Satchi-Fainaro Ronit , Sharan Roded , Madi Asaf 
Published: June 2024

AbstractCell-cell crosstalk involves simultaneous interactions of multiple receptors and ligands, followed by downstream signaling cascades working through receptors converging at dominant transcription factors, which then integrate and propagate multiple signals into a cellular response. Single-cell RNAseq of multiple cell subsets isolated from a defined microenvironment provides us with a unique opportunity to learn about such interactions reflected in their gene expression levels. We developed the interFLOW framework to map the potential ligand-receptor interactions between different cell subsets based on a maximum flow computation in a network of protein-protein interactions (PPIs). The maximum flow approach further allows characterization of the intracellular downstream signal transduction from differentially expressed receptors towards dominant transcription factors, therefore, enabling the association between a set of receptors and their downstream activated pathways. Importantly, we were able to identify key transcription factors toward which the convergence of multiple receptor signaling pathways occurs. These identified factors have a unique role in the integration and propagation of signaling following specific cell-cell interactions.
Safety and efficacy of C. muridarum vaccines adjuvanted with CpG-1826 and four concentrations of Montanide-ISA-720-VG
Authors: Slepenkin Anatoli , Pal Sukumar , Rasley Amy , Coleman Matthew A. , de la Maza Luis M. 
Published: June 2024

AbstractIt is recommended that the adjuvant Montanide ISA 720 VG be used at a concentration of 70% v/v. At this concentration, Montanide causes at the site of immunization a local granuloma that can last for several weeks. To determine the safety and protective efficacy of a Chlamydia muridarum MOMP vaccine, formulated with CpG-1826 and four different concentrations of Montanide (70%, 50%, 30% and 10%), BALB/c (H-2d) female mice were immunized twice intramuscularly. Local reactogenicity was significant for vaccines formulated with 70% or 50% Montanide but not for those inoculated with 30% or 10% Montanide. Robust humoral and cell mediated memory immune responses were elicited by the 70%, 50% and 30% Montanide formulations. Mice were challenged intranasally with 104 C. muridarum inclusion forming units (IFU). Based on changes in body weight, lungs’s weight and number of IFU recovered, mice vaccinated with the 70%, 50% and 30% Montanide formulations were significantly protected, but not mice receiving 10% Montanide. To conclude, we recommend the 30% Montanide concentration to be tested in humans and animal models to determine its safety and efficacy, in comparison to the 70% Montanide concentration currently used. The 30% Montanide formulation could significantly facilitate licensing of this adjuvant for human use.
T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector
Authors: Fert Ingrid , Douguet Laëtitia , Vesin Benjamin , Moncoq Fanny , Noirat Amandine , Authié Pierre , Ciret Sylvain , Le Chevalier Fabien , Blanc Catherine , Vitrenko Yakov , Charneau Pierre , Majlessi Laleh , Anna François 
Published: June 2024

AbstractWe recently developed an immuno-oncotherapy against human papillomavirus (HPV)-induced tumors based on a lentiviral vector encoding the Early E6 and E7 oncoproteins of HPV16 and HPV18 genotypes, namely “Lenti-HPV-07”. The robust and long-lasting anti-tumor efficacy of Lenti-HPV-07 is dependent on CD8+ T-cell induction and remodeling of the tumor microenvironment. Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. To longitudinally monitor the evolution of the T-cell repertoire generated after the prime, homologous or heterologous boost with Lenti-HPV-07, we tracked T-cell clonotypes by deep sequencing of T-Cell Receptor (TCR) variable β and α chain mRNA, applied to whole peripheral blood cells (PBL) and a T cell population specific of an immunodominant E7HPV16 epitope. We observed a hyper-expansion of clonotypes post prime, accompanied by increased frequencies of HPV-07-specific T cells. Additionally, there was a notable diversification of clonotypes post boost in whole PBL, but not in the E7HPV16-specific T cells. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.
Artificially regulated humification in creating humic-like biostimulators
Authors: Sun Kai , Niu Ziyan , Xiao Shenghua , Qi Xuemin , Li Shunyao , Chen Meihua , Dai Lingzhi , Si Youbin 
Published: June 2024

AbstractHumic substances (HSs), as the “black gold” of global agriculture, have a crucial environmental significance in cleaning harmful compounds, maintaining carbon mass balance, and increasing crop productivity. Unfortunately, the resources of HSs extracted from nature are insufficient, causing the supply, demand, and budget of the humus market to gradually increase. Given the analogous architectures of lignin and HSs, artificially regulated humification (ARH) has a great potential for directionally controlling the oxidative cleavage of lignin and/or the radical copolymerization of lignin precursors, to produce reassembled oligomers and/or polymers that can compare favorably with the function and efficacy of HSs. Herein, different ARH strategies are innovatively proposed to tackle hazardous chemicals and create humic-like biostimulators (H-LBs). We briefly describe the characteristics and functionalities of natural HSs, and summarize the latest approaches and mechanisms of lignin and its precursor-based ARH. In particular, the ARH routes of bio-composting, laccase catalysis, white-rot fungal degradation, Fenton-based advanced oxidation, and hydrothermal humification are comparatively highlighted to govern harmful substrates, enhance carbon sequestration, generate H-LBs, and practice sustainable agriculture. Furthermore, the mechanisms for promoting crop growth of H-LBs are also illustrated. Advances in modulating humification pathways may solve the technological bottlenecks of ARH in-situ and ex-situ by well-stocked lignin and its small derivatives, which are important for decontaminating contaminants, reducing CO2 emissions, and enriching H-LBs in agroecosystems.
A folding motif formed with an expanded genetic alphabet
Authors: Wang Bang , Rocca James R. , Hoshika Shuichi , Chen Cen , Yang Zunyi , Esmaeeli Reza , Wang Jianguo , Pan Xiaoshu , Lu Jianrong , Wang Kevin K. , Cao Y. Charles , Tan Weihong , Benner Steven A. 
Published: June 2024

AbstractAdding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ−:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ−:dZ pairs join parallel strands in a four-stranded compact down–up–down–up fold. These have two possible structures: one with intercalated dZ−:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.
Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis
Authors: Li Ling , Wang Tao , Chen Zhi , Liang Jianqin , Ding Hong 
Published: June 2024

AbstractTuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.
Investigating the impact of the quantity of wet and dry cycles on the mechanical characteristics and fracture variations of sandstones
Authors: He Ruiyu , Tang Xin , Yin Hong , Qin Yujia , Guo Zhengchao , Fang Li , Zhou Xiaoyi , Zhou Yuerong 
Published: June 2024

AbstractThe sandstone is in a state of dry–wet cycle under the repeated action of rainfall, and its mechanical properties are deteriorated to varying degrees, which causes cracks in the sandstone. Therefore, it is of great significance to study the mechanical properties and fracture propagation of sandstone under the action of dry–wet cycles. Currently, there are limited studies using numerical simulation methods to study the fracture extension of rocks under various dry and wet cycling conditions.Therefore, in this paper, the effects of different amounts of dry and wet cycling on the mechanical properties and fracture behavior of sandstone are investigated through uniaxial compression tests and numerical simulations of fracture extension. The findings indicate that the deformation stage of sandstone remains unchanged by the dry–wet cycle. The uniaxial compressive potency and coefficient of restitution gradually diminish as the quantity of cycles rises, while the Poisson's ratio exhibits the opposite trend, and the impact on the mechanical performance of sandstone wanes with cycle increments, and the correlation coefficient surpasses 0.93, signifying a substantial influence of the dry–wet cycle on sandstone's mechanical performances. The discrepancy between the numerical simulation and experimental results is minimal, with a maximum error of only 3.1%, demonstrating the congruence of the simulation and experimental outcomes.The mesoscopic examination of the simulations indicates that the quantity of fractures in the sandstone specimens rises with the escalation of dry–wet cycles, and the steps of analysis linked to crack inception and fracture propagation are accelerated, and the analysis steps from fracture initiation to penetration are also reduced.
Quality of life and associated factors for community health workers in the context of the COVID-19 pandemic in northeastern Brazil
Authors: Forte Franklin Delano Soares , Vieira Neiva Francenely Cunha , Farias Sidney Feitoza , Campelo Isabella Lima Barbosa , Castro Marcia , Yousafzai Aisha Khizar , Vieira-Meyer Anya Pimentel Gomes Fernandes 
Published: June 2024

AbstractIn this study, we evaluated the quality of life (QoL) and associated factors of community health workers (CHWs) in different urban settings as a contributor to the preparedness of Brazilian primary care for future sanitary emergencies. The sample included 1935 CHWs from 4 state capitals and 4 inland municipalities in northeastern Brazil. Information was collected on QoL (WHOQOL-BREF), work routines, sociodemographics, direct and indirect exposure to violence, general self-efficacy, social support (MSPSS), mental health (SRQ-20) and coronavirus anxiety. The data were subjected to multiple linear regression analysis (α = 5%). In the state capitals, the factors associated with loss of QoL were poor mental health, lack of training, uncertainty about occupational biosafety, and lack of adaptation of services to tend to patients diagnosed with COVID-19. Among the inland municipalities, the main factors were coronavirus anxiety, poor mental health, lack of adaptation of services, lack of training, and lack of personal protective equipment (PPE). A high MSPSS (family and friends) score and self-efficacy had positive impacts on QoL in both urban settings. Our results highlight the need for investment in permanent education, PPE, social support, and mental health care for CHWs.
Efficient deep learning-based approach for malaria detection using red blood cell smears
Authors: Mujahid Muhammad , Rustam Furqan , Shafique Rahman , Montero Elizabeth Caro , Alvarado Eduardo Silva , de la Torre Diez Isabel , Ashraf Imran 
Published: June 2024

AbstractMalaria is an extremely malignant disease and is caused by the bites of infected female mosquitoes. This disease is not only infectious among humans, but among animals as well. Malaria causes mild symptoms like fever, headache, sweating and vomiting, and muscle discomfort; severe symptoms include coma, seizures, and kidney failure. The timely identification of malaria parasites is a challenging and chaotic endeavor for health staff. An expert technician examines the schematic blood smears of infected red blood cells through a microscope. The conventional methods for identifying malaria are not efficient. Machine learning approaches are effective for simple classification challenges but not for complex tasks. Furthermore, machine learning involves rigorous feature engineering to train the model and detect patterns in the features. On the other hand, deep learning works well with complex tasks and automatically extracts low and high-level features from the images to detect disease. In this paper, EfficientNet, a deep learning-based approach for detecting Malaria, is proposed that uses red blood cell images. Experiments are carried out and performance comparison is made with pre-trained deep learning models. In addition, k-fold cross-validation is also used to substantiate the results of the proposed approach. Experiments show that the proposed approach is 97.57% accurate in detecting Malaria from red blood cell images and can be beneficial practically for medical healthcare staff.
Electrospray deposition of physical unclonable functions for drug anti-counterfeiting
Authors: Kingsley Bryce J. , Schaffer J. David , Chiarot Paul R. 
Published: June 2024

AbstractIn recent years, pharmaceutical counterfeiting has become an increasingly dangerous situation. A patient who unknowingly consumes a counterfeit drug is at a serious health risk. To address this problem, a low-cost and robust approach for authentication that can be administered at the point-of-care is required. Our proposed solution uses Optical Physical Unclonable Functions (PUFs); patterns formed by a stochastic process that can be used for authentication. We create edible PUFs (ePUFs) using electrospray deposition, which utilizes strong electric fields to atomize a liquid suspension into a plume of micro-scale droplets that are delivered to the target. The ePUFs are electrospray-deposited from an edible ink directly onto the surface of the drug tablets. The process parameters (flow rate, translation speed, and suspension concentration) govern the characteristics of the ePUF to provide highly stochastic patterns. To evaluate our approach, 200 ePUFs were deposited onto tablets at various conditions, followed by imaging and storage of the patterns in a database. For ePUF authentication, a machine vision approach was created using the open source SIFT pattern matching algorithm. Using optimized pattern-matching constraints, our algorithm was shown to be 100% successful in authenticating the cellphone images of the ePUFs to the database. Additionally, the algorithm was found to be robust against changes in illumination and orientation of the cellphone images.
Legal analysis of South Korean cosmetic filler litigations for safer medical practices
Authors: Kang Daihun , Hong Seung Eun 
Published: June 2024

AbstractCosmetic filler injections have gained popularity in recent years, but the rise in complications has led to an increase in legal disputes. This study analyzes civil court rulings related to cosmetic filler injection lawsuits in South Korea from 2007 to 2023. A retrospective case analysis was performed using a systematic database search, and a mixed-methods approach was employed for data analysis. The study examined 27 cases, revealing a high rate of liability findings against medical practitioners. Skin necrosis and blindness were the most common complications, and intravascular filler injection was recognized as negligence. Violation of informed consent was found in most cases, with mean compensation awards of ￦193,019,107 KRW ($142,831 USD) for first instance cases and ￦81,845,052 KRW ($60,564 USD) for second instance cases. The findings emphasize the importance of practitioner awareness, adherence to precautionary measures, and proactive prevention and management of complications. Collaboration among stakeholders is crucial for developing strategies that prioritize patient safety and minimize legal disputes in the aesthetic medicine industry. This study provides valuable insights for enhancing medical practices and safeguarding patient well-being in the field of cosmetic filler injections.
ProteinCoLoc streamlines Bayesian analysis of colocalization in microscopic images
Authors: Seefelder Manuel , Kochanek Stefan , Klein Fabrice A. C. 
Published: June 2024

AbstractColocalization, the spatial overlap of molecular entities, is often key to support their involvement in common functions. Existing colocalization tools, however, face limitations, particularly because of their basic statistical analysis and their low-throughput manual entry processes making them unsuitable for automation and potentially introducing bias. These shortcomings underscore the need for user-friendly tools streamlining colocalization assessments and enabling their robust and automated quantitative analyses. We have developed ProteinCoLoc, an innovative software designed for automated high-throughput colocalization analyses and incorporating advanced statistical features such as Bayesian modelling, automatic background detection and localised correlation analysis. ProteinCoLoc rationalises colocalization assessments without manual input, comes with a user-friendly graphical user interface and provides various analytics allowing to study and locally quantify colocalization. This easy-to-use application presents numerous advantages, including a direct comparison with controls employing a Bayesian model and the analysis of local correlation patterns, while reducing hands-on time through automatic background detection. The software was validated while studying the colocalization pattern of two proteins forming a stable complex: the huntingtin protein (HTT) and its partner huntingtin-associated protein 40 (HAP40). Our results showcase the software’s capacity to quantitatively assess colocalizations. ProteinCoLoc is available both as a Julia package and as a compiled software (https://github.com/ma-seefelder/ProteinCoLoc).
Influence of triangular obstacles on droplet breakup dynamics in microfluidic systems
Authors: Tazikeh Lemeski Azadeh , Seyyedi Seyyed Masoud , Hashemi-Tilehnoee Mehdi , Naeimi Azadeh Sadat 
Published: June 2024

AbstractMicrofluidic devices with complex geometries and obstacles have attracted considerable interest in biomedical engineering and chemical analysis. Understanding droplet breakup behavior within these systems is crucial for optimizing their design and performance. This study investigates the influence of triangular obstacles on droplet breakup processes in microchannels. Two distinct types of triangular obstructions, positioned at the bifurcation (case I) and aligned with the flow (case II), are analyzed to evaluate their impact on droplet behavior. The investigation considers various parameters, including the Capillary number (Ca), non-dimensional droplet length (L*), non-dimensional height (A*), and non-dimensional base length (B*) of the triangle. Utilizing numerical simulations with COMSOL software, the study reveals that the presence of triangular obstacles significantly alters droplet breakup dynamics. Importantly, the shape and location of the obstacle emerge as key factors governing breakup characteristics. Results indicate faster breakup of the initial droplet when the obstacle is positioned in the center of the microchannel for case I. For case II, the study aims to identify conditions under which droplets either break up into unequal-sized entities or remain intact, depending on various flow conditions. The findings identify five distinct regimes: no breakup, breakup without a tunnel, breakup with a tunnel, droplet fragmentation into unequal-sized parts, and sorting. These regimes depend on the presence or absence of triangular obstacles and the specific flow conditions. This investigation enhances our understanding of droplet behavior within intricate microfluidic systems and provides valuable insights for optimizing the design and functionality of droplet manipulation and separation devices. Notably, the results emphasize the significant role played by triangular obstacles in droplet breakup dynamics, with the obstacle’s shape and position being critical determinants of breakup characteristics.
RPS24 alternative splicing is a marker of cancer progression and epithelial-mesenchymal transition
Authors: Park Jiyeon , Nam Da Hae , Kim Dokyeong , Chung Yeun-Jun 
Published: June 2024

AbstractAlthough alternative splicing (AS) is a major mechanism that adds diversity to gene expression patterns, its precise role in generating variability in ribosomal proteins, known as ribosomal heterogeneity, remains unclear. The ribosomal protein S24 (RPS24) gene, encoding a ribosomal component, undergoes AS; however, in-depth studies have been challenging because of three microexons between exons 4 and 6. We conducted a detailed analysis of RPS24 AS isoforms using a direct approach to investigate the splicing junctions related to these microexons, focusing on four AS isoforms. Each of these isoforms showed tissue specificity and relative differences in expression among cancer types. Significant differences in the proportions of these RPS24 AS isoforms between cancerous and normal tissues across diverse cancer types were also observed. Our study highlighted a significant correlation between the expression levels of a specific RPS24 AS isoform and the epithelial–mesenchymal transition process in lung and breast cancers. Our research contributes to a better understanding of the intricate regulatory mechanisms governing AS of ribosomal protein genes and highlights the biological implications of RPS24 AS isoforms in tissue development and tumorigenesis.