bluuebunny/crossref_metadata_2025_split huggingface dataset:
RGS6 inhibits the proliferation, migration, and invasion of breast cancer through the SMAD6-HMGA1 signaling pathway
Authors: Sun Qiang , Kang Ye , Liu Yushi , Zhang Yang , Wang Yitong , Tan Xiaodong , Zhang Miss Qi 
Published: January 2024

Abstract
The regulator of G protein signal 6 (RGS6) is a newly discovered tumor inhibitor that protects against the development of various types of cancer such as lung and bladder cancer. However, the mechanisms underlying these tumor-inhibition effects of RGS6 are not fully understood. In this study, we described the role of RGS6 in inhibiting the proliferation, migration, and invasion of breast cancer (BC) in vivo. Using bioinformatics and experimental tools, we found that RGS6 was generally downregulated in breast cancer tissues while a low expression of RGS6 was associated with poorer survival and prognosis of patients with breast cancer compared to those with normal breast tissues. The overexpression of RGS6 inhibited the migration and invasion of tumor cells by HMGA1. The results of rescue experiments showed that SMAD6 in the TGF-β signaling pathway plays a key role in this inhibitory effect of RGS6. Additionally, the ability of RGS6 to inhibit the expression of the HMGA1 gene depends on its ability to inhibit SMAD6. Based on these results, we identified a new function of RGS6 in regulating HMGA1-induced EMT and the proliferation, migration, and invasion of BC. The results suggested that RGS6 can act as an indicator of prognosis and might be a new target for treating breast cancer. This strategy can improve the outcomes of patients and transform therapeutic approaches.
Cell restriction factors, and not receptor compatibility, block Jamaican fruit bat (Artibeus jamaicensis) susceptibility to mucosal inoculation with SARS-CoV-2 Delta variant
Authors: Port Julia R. , Riopelle Jade C. , Tol Sarah van , Wickenhagen Arthur , Bohrnsen Eric , Sturdevant Daniel E. , Rosenke Rebecca , Lovaglio Jamie , Lack Justin , Anzick Sarah L. , Cordova Kathleen , Yinda Kwe Claude , Hanley Patrick W. , Schountz Tony , Kendall Lon V. , Shaia Carl I. , Saturday Greg , Martens Craig , Schwarz Benjamin , Munster Vincent J. 
Published: January 2024

Abstract
The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited to have originated in bats. While SARS-CoV-2 causes asymptomatic to severe respiratory disease in humans, little is known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses in bats. SARS-CoV-2 has been shown to infect multiple mammalian species, including various rodent species, non-human primates, and Egyptian fruit bats. Here, we investigate the Jamaican fruit bat (Artibeus jamaicensis) as a possible model species to study reservoir responses. SARS-CoV-2 can utilize Jamaican fruit bat ACE2 spike for entry in vitro. However, we find that SARS-CoV-2 Delta does not efficiently replicate in Jamaican fruit bats in vivo. We observe infectious virus in the lungs of only one animal on day 1 post inoculation and find no evidence for shedding or seroconversion. This is possibly due to host factors restricting virus egress after aborted replication. Furthermore, we observe no significant immune gene expression changes in the respiratory tract but do observe changes in the intestinal metabolome after inoculation. This suggests that, despite its broad host-range, SARS-CoV-2 is unable to infect all bat species and Jamaican fruit bats are not an appropriate model to study SARS-CoV-2 reservoir infection.
Ginsenoside Rh2-induced inhibition of HDAC6 promotes autophagy and apoptosis in human leukemia cells
Authors: Liu Xiao-Xia , Shi Shi , Shi Xue-Ping , Hou Ji-Ying , Hou Yan-Hua , Li Jing , Liu Ze-Hong 
Published: January 2024

Abstract
Background and Objective: Previous research has demonstrated that the total saponins of Panax ginseng (TSPG) and other ginsenoside monomers can inhibit the proliferation of leukemia cells. However, the underlying mechanism remains unclear. Autophagy is a response mechanism utilized by cancer cells in response to various anticancer therapies. Therefore, we aimed to investigate the role of autophagy in the anti-leukemia effects of ginsenosides.
Methods: The proliferation and apoptosis of cultured K562 and KG1α cells were evaluated using CCK-8 and FCM assays. The cytotoxicity of bone marrow stromal cell line HS-5 was determined using the CCK-8 method to assess the individual components. Cells were transfected with a small interfering RNA (siRNA) to silence HDAC6 expression, and the effects of Rh2 on HDAC6 were investigated using CCK-8 and FCM assays. The relationships between HDAC6 and Rh2 in terms of autophagy and apoptosis were further characterized using western blot analysis and RT-PCR. In vivo experiments were conducted using K562 xenograft tumors to assess autophagy and apoptosis.
Results: TSPG and other monomers demonstrated cytotoxic effects against leukemia cells, with Rh2 exhibiting greater cytotoxicity compared to other monomers. Furthermore, Rh2 effectively killed leukemia cells while exhibiting reduced toxicity towards normal bone marrow stromal cells. Rh2 induced both apoptosis and autophagy in leukemia cells. The autophagy inhibitor 3-MA reduced the cytotoxicity of Rh2, indicating that autophagy plays a role in its mechanism of action. Silencing HDAC6 expression increased the sensitivity of leukemia cells to Rh2, suppressing HSP90 expression. Additionally, Rh2 enhanced apoptosis and autophagy in vivo, providing further evidence for its therapeutic potential in leukemia treatment.
Conclusion: Conclusion: These findings suggest that Rh2-induced autophagy serves as a cytotoxic mechanism, indicating its potential therapeutic application in leukemia treatment. Additionally, downregulation of HDAC6
The Effect of Inhaled Nitric Oxide on the Exercise Capacity of Patients with Advanced Interstitial Lung Disease: A Randomized Controlled Trial
Authors: Freidkin Lev , Kramer Mordechai R , Rosengarten Dror , Izhakian Shimon , Taieb Shani , Pertzov Barak 
Published: January 2024

Abstract
Purpose
To assess the impact of inhaled nitric oxide (iNO) on the six-minute walk distance in patients with advanced interstitial lung disease
Methods
In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests: one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension.
Results
Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265–409) vs 371 m (IQR 250–407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWTD with iNO and placebo, median 339 (256–402) vs 332 (238–403) for the iNO and placebo tests respectively (P = 0.50).
Conclusion
In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. (NCT03873298, MOH_2018-04-24_002331)
Defending the Integrity of Machine Learning Models in the Face of Adversarial Threats
Authors: Roy Hrittick , Anand Sourabh 
Published: January 2024

Abstract
The primary objective of the research is to examine the resilience of models based on machine learning when confronted with adversarial threats. The focus will be on developing effective strategies to safeguard the integrity of these models. This study employs a carefully designed framework to undertake the task of simulating adversarial attacks on machine learning models. The central objective of the research centres on the intentional manipulation of numerical variables in order to accurately simulate real-world threats. The investigation of statistical analyses, such as t-tests and comprehensive data visualisations, enables the evaluation of the impact exerted by adversarial attacks on both data distributions and model outputs. The primary objective of the current investigation is to assess the effectiveness of a mimicked defence mechanism in the domain of machine learning model restoration, with the ultimate goal of preserving model integrity. The results gathered by our study emphasise the significant significance of adversarial threats, thereby underscoring the need for a comprehensive analysis of robust defence strategies. The analysis of correlation matrices, both before and after adversarial attacks, provides valuable insights into the changes in the fundamental structure induced by these interventions. The current investigation offers valuable insights into the preservation of the integrity of machine learning models and suggests possible ways to enhance their resilience against ever-changing adversarial tactics.
A novel lab-on-chip cartridge overcoming centrifugation and slide preparation for automated urinalysis
Authors: Sahu Avinash , Kandaswamy Srinivasan , Singh Dhanu Vardhan , Thyagarajan Eshwarmurthy , Parthasarathy Arun Koushik , Naganna Sharitha , Dastidar Tathagato Rai 
Published: January 2024

Abstract
After haematology, urinalysis is the most common biological test performed in clinical settings. Hence, simplified workflow and automated analysis of urine elements are of absolute necessities. In the present work, a novel lab-on-chip cartridge (Gravity Sedimentation Cartridge) for the auto analysis of urine elements is developed. The GSC consists of a capillary chamber that uptakes a raw urine sample by capillary force and performs particles and cells enrichment within 5 min through a gravity sedimentation process for the microscopic examination. Centrifugation, which is necessary for enrichment in the conventional method, was circumvented in this approach. The AI100 device (Image based autoanalyzer) captures microscopic images from the cartridge at 40x magnification and uploads them into the cloud. Further, these images were auto-analyzed using an AI-based object detection model, which delivers the reports. These reports were available for expert review on a web-based platform that enables evidence-based tele reporting. A comparative analysis was carried out for various analytical parameters of the data generated through GSC (manual microscopy, tele reporting, and AI model) with the gold standard method. The presented approach makes it a viable product for automated urinalysis in point-of-care and large-scale settings.
Large language models for generating medical examinations: systematic review
Authors: Artsi Yaara , Sorin Vera , Konen Eli , Glicksberg Benjamin S. , Nadkarni Girish , Klang Eyal 
Published: January 2024

Abstract
Background
Writing multiple choice questions (MCQs) for the purpose of medical exams is challenging. It requires extensive medical knowledge, time and effort from medical educators. This systematic review focuses on the application of large language models (LLMs) in generating medical MCQs.
Methods
The authors searched for studies published up to November 2023. Search terms focused on LLMs generated MCQs for medical examinations. MEDLINE was used as a search database.
Results
Overall, eight studies published between April 2023 and October 2023 were included. Six studies used Chat-GPT 3.5, while two employed GPT 4. Five studies showed that LLMs can produce competent questions valid for medical exams. Three studies used LLMs to write medical questions but did not evaluate the validity of the questions. One study conducted a comparative analysis of different models. One other study compared LLM-generated questions with those written by humans.
All studies presented faulty questions that were deemed inappropriate for medical exams. Some questions required additional modifications in order to qualify.
Conclusions
LLMs can be used to write MCQs for medical examinations. However, their limitations cannot be ignored. Further study in this field is essential and more conclusive evidence is needed. Until then, LLMs may serve as a supplementary tool for writing medical examinations.
Dynamical perspective of bifurcation analysis and soliton solutions to (1+1)-dimensional nonlinear perturbed Schrödinger model
Authors: Javed Sara , Ali Asghar , Muhammad Taseer 
Published: January 2024

Abstract

This work simulates the (1+1)-dimensional nonlinear perturbed Schrödinger model (NLPSM). This model has various applications in mathematical physics and engineering, including hydrodynamics, elastic media, nonlinear optical fiber communication, and plasma physics. There are two primary goals for the study. First, it seeks to find unique soliton solutions such as solitary, dark, periodic, and plane wave solutions that haven’t been found in the literature before using the modified Sardar sub-equation approach (MSSEA). Second, a novel approach to analysis called bifurcation analysis is used to investigate the dynamic behavior of the model. Physical compatibility findings are supported by density, 3-D, and 2-D illustrations made with parametric variables. The analysis shows that the approach used to quickly acquire complete and typical answers was successful. This approach works well for solving challenging problems in physics, engineering, mathematics and fiber optic phenomena.
Assessment of serum essential/non-essential elements, biochemical variables and its association with semen parameters and the risk of male infertility
Authors: Kaur Mandeep , Kaur Rajinder , Kapoor Harmanpreet Singh , Chhabra Kiran , Khetarpal Preeti 
Published: January 2024

Abstract
Essential metals are involved in various cellular processes of the body and non-essential metals are toxic even in small amounts and have no biological role. The deficiency or over-exposure of these elements perturbs the reproductive health of males. A cross-sectional study has been conducted to investigate the association of a) essential (Cr, Co, Ni, Fe, Mn, Cu, Zn, Se) and non-essential elements (Pb, Cd, As, Ba, Bi, U, V); b) biochemical variables (glucose, triglycerides, cholesterol, HDL, LDL, albumin, and total protein) with risk of male infertility. A total of 46 males from infertile couples have been selected for the study. Serum element concentrations were estimated using ICP-MS and biochemical parameters were estimated by colorimetric methods. Statistical analysis was performed with IBM SPSS and R package. A significant difference was observed for Cr and LDL at p < 0.10 among study groups. Significant difference was found for spermatozoa volume, count and motility between study groups. Serum albumin levels are positively associated with sperm motility. Cr is negatively correlated with triglyceride levels (p = 0.03). Fe and Co are also significantly but negatively correlated with cholesterol levels (p = 0.05). Mn, Cu, Pd, Cd, and Ba are significantly positively correlated with semen volume. Cr, Co, Ni, Mn, Cu, Zn, Pd, Cd, As, Ba, U, and V are significantly positively correlated with liquefaction time (p < 0.05). The investigation of metals may help in the screening of male infertility as some metals may have therapeutic potential or toxic nature that can be used in the management of condition.
Nano-Scaffold Containing a Functional Motif of Stromal Cell-Derived Factor 1 Enhances Neural Stem Cell Behavior and Promotes Synaptogenesis in a Traumatic Brain Injury Model
Authors: Tork Mohammad Amin Bayat , Saberifar Mohsen , Yekta Hamed Joneidi , Hajinejad Mehrdad , Ravandi Hassan Hosseini , Gorji Ali , Negah Sajad Sahab 
Published: January 2024

Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, presenting a significant challenge due to the lack of effective therapies. Neural stem cells (NSCs) have shown promising potential in preclinical studies as a therapy for TBI. However, their application is limited by challenges related to poor survival and integration within the injured brain. In this study, we investigated the effect of a novel nano-scaffold containing stromal cell-derived factor 1 (SDF-1) on NSC behavior and synaptogenesis after TBI. Using an innovative design, we successfully fabricated a nano-scaffold with Young's modulus of approximately 3.21 kPa, which aligns closely with the mechanical properties exhibited by neural tissue. This achievement marks the first time such a scaffold has been created and has promising implications for its potential use in neural tissue engineering applications. Our findings demonstrate that the nano-scaffold enhances NSC proliferation, migration, and differentiation capacity in vitro. Moreover, when transplanted into the injured brain, the nano-scaffold promotes the survival and integration of NSCs, leading to increased synaptogenesis and functional recovery. These findings suggest that the use of the novel nano-scaffold containing SDF-1 could provide a promising approach to the treatment of TBI by improving NSC behavior and promoting synaptogenesis.
Characteristic Burn Temperature Markers of Bones as Revealed by Electron Paramagnetic Resonance
Authors: Knaflič Tilen , Legan Lea , Cavalli Fabio , Ropret Polonca 
Published: January 2024

Abstract
This research paper presents a novel methodology for determining the burn temperature of archaeological bones using Electron Paramagnetic Resonance (EPR) supported by Fourier Transform Infrared (FTIR) spectroscopy. A selection of bone samples, burned at different temperatures, were examined with EPR. The EPR spectra displayed dependency on burn temperature, showing characteristic narrow spectra of carbon radicals, Mn2+ signals and signals from different carbonate ions. This methodology was applied to selected archaeological samples of burned bones, sucessfully determining the burn temperature these bones were exposed to in the past. The extracted burn temperatures showed good agreement with those determined from a complementary reflectance FTIR study.
KDM5B/H3K4me3-mediated METTL14 regulates the function of LINC02747 through N6-methyladenosine modification in non-small cell lung cancer
Authors: Wang Jiemin , Wang Shu , Shi Kesong , Yang Haopeng , Wang Ruixuan , Liu Yueshi , Dou Le , Yu Haiquan 
Published: January 2024

Abstract
Background
Multiple epigenetic regulatory mechanisms exert critical roles in tumour development, understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. The main objective of this study was to elucidate the intricate crosstalk between N6-methyladenosine (m6A) modification and histone modification in the context of non-small cell lung cancer (NSCLC).
Results
Bioinformatics analyses and experiments confirmed that the m6A methyltransferase METTL14 was significantly downregulated in NSCLC tissues, with lower levels correlating with poorer overall survival. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. We confirmed using MeRIP-qPCR and dual-luciferase reporter assays that the long noncoding RNA LINC02747 was targeted and regulated by METTL14 via m6A modification, and inhibiting LINC02747 was observed to hinder the malignant progression of NSCLC by modulating the PI3K/Akt signaling pathway. Knockdown of METTL14 significantly decreased the m6A modification of LINC02747 and upregulated its expression. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the "GAACU" binding site by YTHDC2. Additionally, histone demethylase lysine-specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri-methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription, and KDM5B upregulated the expression of LINC02747 by suppressing the expression of METTL14.
Conclusions
In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a series of mechanisms that regulate the malignant phenotype of NSCLC cells, revealing the complex regulation involved in the occurrence and development of cancer.
Multiclass method for antimicrobial residue analysis in milk using liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-qTOF-MS): validation and application for real samples with ciprofloxacin
Authors: Crizel Rosane Lopes , Zandoná Giovana Paula , Barbosa Rosângela Silveira , Barreto Fabiano , Bonnet Marcelo 
Published: January 2024

Abstract
We developed and validated a novel method for screening and confirming 32 antimicrobial residues in raw, bovine milk using a single preparative step. Antimicrobials under the scope of the method belong to different classes, such as fluoroquinolones, tetracyclines, sulfonamides, macrolides and lincosamides. Sample preparation is simple, quick and requires just one extraction process to satisfactorily extract all analytes. Method performance requirements were found to be satisfactory according to the European (EU) Regulation 2021/808, thus confirming the applicability of LC-ESI-QTOF-MS/MS for reliable qualitative and quantitative purposes. Samples from animals undergoing ciprofloxacin treatment were also analyzed, further confirming the method´s fitness-for-purppose. This approach offers a quick and easy way to perform qualitative and quantitative assessment of 32 antimicrobial residues simultaneously, and therefore could be a valuable resource to optimize analytical routines as part of the efforts to help tackling the persistent, global public health silent pandemic of antimicrobial resistance.
A Novel Coil Array Compensation Structure Design with High-Misalignment Tolerance for UAV-Enable WPT system
Authors: Rong Cancan , Chang Jin , Liu Yachao , Ling Zhi , Xu Yunpeng , Lu Qibiao , Liu Yujie , Zhao Hailin , Wang Haoyang , Xia Chenyang 
Published: January 2024

Abstract

The problem of charging unmanned aerial vehicles (UAVs) is an important application area for wireless power transmission (WPT). However, the flight characteristics of UAVs make it difficult for the traditional single-coil coupling mechanism to ensure alignment between the transmitting and receiving ends. It also has poor anti-skewing performance and a cumbersome optimization process, which ultimately decreases the efficiency of charging UAVs. To address this problem, this paper takes the 2×2 square coil array as research object, analyzes the distribution characteristics of the axial magnetic field at a specific height, proposes a "cross" compensation structure, and adopts genetic algorithm to optimize the side length and turns of the compensation coil. The goal is to significantly improve the axial magnetic field uniformity in the charging area and reduce the degree of magnetic field leakage. Finally, the effectiveness and superiority of the proposed "crossover" compensation structure and its optimization method are demonstrated through the construction and testing of the system experimental platform, which significantly improves the anti-offset performance and transmission efficiency of the WPT system.