bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Differentially Private Federated Learning Application in Privacy-Preserving Medical Imaging
Authors: FARES Mohamad HAJ , SERTBAŞ Ahmet 
Published: February 2024

Abstract
This research addresses the escalating concerns surrounding privacy, particularly in the context of safeguarding sensitive medical data within the increasingly demanding healthcare landscape. We undertake an experimental exploration of differentially private federated learning systems, employing three benchmark datasets—PathMNIST, BloodMNIST, and OrganAMNIST—for medical image classification. This study pioneers the application of federated learning with differential privacy in healthcare, closely simulating real-world data distribution across twelve hospitals. Additionally, we introduce a novel deep-learning architecture tailored for differentially private models. Our findings demonstrate the superior performance of federated learning models compared to traditional approaches, with accuracy levels approaching those of non-private settings. By leveraging resilient deep learning models, we aim to enhance privacy, efficiency, and effectiveness in healthcare solutions, benefiting patients, healthcare practitioners, and the overall healthcare system through privacy-protected healthcare.
Baseline Serum Cholinesterase Levels Predict the Outcome of HIV-Related Diffuse Large B-Cell Lymphoma
Authors: Zhou Minghan , Qin Jiaying , Tong Yong , Wang Lingyun , Ye Shasha , Xu Lijun 
Published: February 2024

Abstract
Background
Serum cholinesterase (CHE) has been utilized as a surrogate marker in the context of solid cancers. Nevertheless, its potential association with the prognosis of hematologic malignancies remains unclear.
Methods
Sixty-five patients with new-onset HIV-related diffuse large B-cell lymphoma (DLBCL) were enrolled in this retrospective study. The patients were categorized into a high CHE group (> 5500 U/L) and a low CHE group (≤ 5500 U/L). The demographic details, laboratory test results and clinical outcomes were compared between the high CHE group and the low CHE group. The overall response rate (ORR) at the end of chemotherapy was assessed by logistic regression analysis, and the 1-year overall survival rate (OS) was assessed by a multivariate Cox proportional hazards model.
Results
Compared with patients with high CHE, HIV-related DLBCL patients with low CHE exhibited lower levels of hemoglobin [g/L; 101.0 (81.0-115.0) vs. 123.5 (108.2–141.0), P < 0.001] and serum albumin [g/L; 31.2 ± 5.6 vs. 40.4 ± 4.5, P < 0.001] but higher levels of lactate dehydrogenase (LDH) [U/L; 404.0 (253.0-849.0) vs. 248.0 (178.3–372.0), P = 0.014] and C-reactive protein (CRP) [mg/L; 36.1 (5.8–66.6) vs. 5.1 (0.8–5.1), P < 0.001]. Moreover, HIV-related DLBCL patients with low CHE demonstrated a higher prevalence of Ann Arbor stage III/IV (92.6% vs. 56.8%, P < 0.001) and International Prognostic Index (IPI) ≥ 3 (85.2% vs. 35.1%, P = 0.002) at the time of diagnosis of DLBCL. The 1-year OS of patients was 84.2% in the high CHE group and 40.7% in the low CHE group (log-rank P < 0.001). At the end of chemotherapy, the ORR was 80.0% in the high CHE group and 31.8% in the low CHE group (P < 0.001). In multivariate analysis, CHE > 5500 U/L was independently associated with a higher ORR [adjusted odds ratio (AOR): 4.74 (1.02–22.06), P = 0.047] and lower 1-year mortality [hazard ratio (HR): 0.11 (0.03–0.52), P = 0.005].
Conclusion
Based on our robust data, baseline serum CHE levels show great potential as a surrogate marker for risk stratification and for guiding treatment decisions in HIV-related DLBCL patients.
Use of immune-modulating agents to regulate hyperinflammation in severe COVID-19; the assessment of tocilizumab use in combination with steroids
Authors: Sadeghi Somayeh , Naderi Zohre , Saghaei Mozhdeh , Tavakoli Fereshteh , Abdeyazdan Neda 
Published: February 2024

Abstract
Introduction
COVID-19 infection might lead to hyperinflammatory state in severe cases leading to devastating outcomes. Immune modulation using steroids or other immune modulators can regulate the intensity of inflammatory response; however, this theory has not been adequately assessed in practice. The current study aims to investigate the use of corticosteroids alone or in combination with tocilizumab for the treatment of patients with severe COVID-19.
Methods
The current retrospective cross-sectional study has been conducted on 168 patients with severe COVID-19 infection who were categorized into three treatment groups of A: primary treatment with high-dose methylprednisolone (> 1 mg/kg) continued with tocilizumab; B: primary treatment with low-dose methylprednisolone (< 1 mg/kg) continued with tocilizumab and C: treatment with high-dose methylprednisolone (> 1 mg/kg) only. The parameters including clinical outcome, laboratory parameters, length of hospitalization, intensive care unit (ICU) admission requirement and drug-related adverse events were compared between the groups.
Results
The outcomes were significantly better in group B considering the shorter length of ICU stay, lower CRP, LDH, and higher oxygen saturation and platelet count in group B than the other groups (P-value < 0.05). Logistic regression assessment in crude and adjusted models revealed increased risks of mortality, the incidence of nosocomial infection and the incidence of adverse effects, including hepatic dysfunction, renal dysfunction and GIB in both groups A and C compared with group B (P-value < 0.05).
Conclusion
Based on the findings of this study, low-dose steroid continued with tocilizumab was superior over high-dose steroid alone or in combination with tocilizumab in terms of all evaluated parameters.
Quantum Biochemical Analysis of the TtgR Regulator and Effectors
Authors: Matias Érika G. C. , Bezerra Katyanna. S. , Costa Aranthya H. Lima , Clemente Washington S. , Oliveira Jonas I. N. , Junior Luiz A. Ribeiro , Galvão Douglas S. , Fulco Umberto L. 
Published: February 2024

Abstract
The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs through numerous mechanisms, including enzymatic inactivation of drugs, lack of pro-drug activation, and drug target alteration, increased active efflux of the drugs is a major concern, especially because a single species of efflux pump can produce simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC, a tripartite RND efflux pump implicated in the intrinsic antibiotic resistance in \textit{Pseudomonas putida} DOT-T1E. Expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. The association of effectors with the TtgR-DNA complex leads to the dissociation of TtgR from the operator region, allowing transcription. Therefore, studies that evaluate the action of these regulators are important for understanding the peculiarities of the resistance mechanisms promoted by the efflux pumps. In this context, by employing quantum chemistry methods based on density functional theory (DFT) within the MFCC approach, we investigated the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical, computational results show the [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most important amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve our understanding of the mechanism of binding of effectors and facilitate the development of new chemicals targeting TtgR, helping in the fight against the rise of resistance to antimicrobial drugs.
Naphthoquinone Derivative ZSW-4B Induces Apoptosis in Triple-negative Breast Cancer via AMPK signal Activation
Authors: Hu Xiyuan , Liu Hongdou , Luo Tiao , Chen Lin , Wen Min , Luo Wensong , Peng Ting , Xie Yuanzhu , Li Mo , Liu Mingquan , Liu Xiaohe , Liu Suyou , Zhu Shuaiwen , Zou Zizheng , Luo Zhiyong 
Published: February 2024

Abstract

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer characterized by its strong aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintain cellular energy balance, and its inactivation is associated with the malignancy breast cancer. Here, we identified the pharmacological mechanism of the 1, 4-naphthoquinone derivative ZSW-4B. The MTT assay, colony formation as-say, and nude mouse xenograft tumor model demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells in both vitro and vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomics analysis unveiled the activation of the AMPK signaling pathway by ZSW-4B, and the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines markedly reversed the anti-tumor effects elicited by ZSW-4B, both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cell apoptosis through the activation of the AMPK.
Hippo pathway in cancer cells modulates tumor microenvironment by inducing immunosuppressive NCAM1+αSMA+ fibroblasts
Authors: Moroishi Toshiro , Thinyakul Chanida , Sakamoto Yasuhisa , Shimoda Mayuko , Liu Yanliang , Thongchot Suyanee , Reda Omnia , Nita Akihiro , Sakamula Romgase , Sampattavanich Somponnat , Maeda Ayato , Niimura Mayumi , Kanamori Yohei , Thuwajit Peti , Nakayama Keiichi , Guan Kun-Liang , Satou Yorifumi , Thuwajit Chanitra 
Published: February 2024

Abstract

Tumor cells adeptly manipulate the tumor microenvironment (TME) to evade host antitumor immunity. However, the role of tumor cell-intrinsic signaling in shaping the immunosuppressive TME remains unclear. Here, we found that the Hippo pathway in tumor cells orchestrated the immunosuppressive TME by influencing the composition of cancer-associated fibroblasts (CAFs). In a 4T1 mouse breast cancer model, Hippo pathway kinases, large tumor suppressor 1 and 2 (LATS1/2), promoted the formation of immunosuppressive neural cell adhesion molecule 1 (NCAM1)+alpha-smooth muscle actin (αSMA)+ CAFs expressing the transforming growth factor-β, thereby contributing to T cell dysfunction. Depletion of LATS1/2 in tumor cells resulted in a less immunosuppressive TME, indicated by the reduced proportions of NCAM1+αSMA+ CAFs and dysfunctional T cells. Notably, similar Hippo pathway-induced NCAM1+αSMA+ CAFs were observed in human breast cancer cells, highlighting the potential of TME-manipulating strategies to reduce immunosuppression in cancer immunotherapy.
Acceleration of bone repairation by BMSCs overexpressing NGF combined with NSA and allograft bone scaffolds
Authors: Ji Ying , Mao Yongkang , Lin Honghu , Wang Ye , Zhao Peishuai , Guo Yong , Gu L.T. , Fu Can , Chen Ximiao , Lv Zheng , Wang Ning , Li Qiang , Bei Chaoyong 
Published: February 2024

Abstract

Background Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis.
Methods The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair.
Results The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects.
Conclusion NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.
Precise anti-inflammatory nano-contrast agents to treat Hashimoto thyroiditis by sustainably targeting HLA-DR
Authors: Zhou Xiaoying , Guo Lu , Shi Dandan , Shang Mengmeng , Sun Xiao , Zhao Yading , Wang Xiaoxuan , Meng Dong , Xiao Shan , Li Jie 
Published: February 2024

Abstract
According to previous reports, in vivo precision treatment using nanocarrier systems has proven effective in a variety of diseases. This work aimed to synthesize controlled nano-ultrasound contrast agents loaded with small interfering ribonucleic acid (siRNA) and drugs to target thyroid tissue and to evaluate this non-invasive method’s therapeutic effect on Hashimoto thyroiditis (HT) and the underlying mechanism thereof. In this study, we used high-biocompatibility anti-inflammatory nano-contrast agents (AINAs) with an erythrocyte membrane as the shell; the surface of this membrane was grafted with rapamycin. Its core included mesoporous-silica nanoparticles loaded with class II transactivator (CIITA)–siRNA and Trans-Activator of Transcription (TAT) transduction peptide. As seen under light and electron microscopes, each AINA was a approximately 255nm elliptical nanodroplet. AINAs could achieve long-lasting circulation in the bloodstream and targeted release of CIITA-siRNA and rapamycin into thyroid cells and the thyroid tissue microenvironment, respectively, with the assistance of the ultrasound-targeted microbubble destruction effect and TAT transduction peptide. AINAs could also be clearly visualized on contrast-enhanced ultrasound. They worked against multiple mechanisms to alleviate inflammatory trauma, including downregulation of HLA-DR expression, inhibition of antigen presentation and T-cell activation, reactive oxygen species levels, and anti-apoptosis of thyroid cells. In summary, our results showed that AINAs are a safe, effective treatment for HT.
Near Infrared-spectroscopy in resin transfer molding – determination of the degree of cure
Authors: Salzmann Moritz , Märzinger Wolfgang , Teuchtmann Michael , Ravindran Bharath , Kirschnick Ulrike , Fauster Ewald 
Published: February 2024

Abstract

Near infrared (NIR) spectroscopy is employed to monitor the degree of cure of a composite material directly during the curing phase in the resin-transfer-molding (RTM) process. The composite material used consists of natural fibers and an epoxy/amine resin. The quantitative determination of the degree of cure, α, from the NIR spectra is realized by partial least square (PLS) regression in conjunction with various pre-treatments of the spectral data. As a reference, the degree of cure is also determined by isothermal DSC experiments. The best PLS model that could be obtained for α is characterized by a determination coefficient of prediction (R²P) of 0.980 and root-mean-square error of prediction (RMSEP) of 4.4 %. While for every RTM trial the spectra during curing change corresponding to literature, major differences can be observed between the spectra of different RTM trials. The reasons for this are discussed in detail. The findings show the potential of inline NIR spectroscopy for monitoring α in the RTM process.
Synthesis and radiolabeling of a nitrofuran derivate with 18F for identification of areas of hypoxia in the tumor microenvironment
Authors: Araujo Yasniel Babi , Carneiro Maria Ângela Pepe , Silva Fabio Fernando Alves da , Lapolli André Luis , Bernardes Emerson Soares 
Published: February 2024

Abstract
Background
Positron Emission Tomography (PET) is a non-invasive molecular imaging technique widely known for studying hypoxia mostly employing 2-nitroimidazole-based radiotracers. These probes are based on the oxygen-mimetic chemical sensitizers of hypoxic cells developed for cancer therapy during the 1970s. 5-nitrofuran derivates are more electron affinic than nitroimidazoles, therefore, higher specificity for hypoxic regions is expected for the formers, and new radiotracer probes bearing a 5-nitrofuran ring could be used for imaging hypoxia.
Results
A nitrofuran-based radiotracer for detection of hypoxic areas in the tumor microenvironment, (E)-1-(4-[18F]-fluorophenyl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one, baptized as [18F]FNFP, was obtained. Two copper-mediated nucleophilic radiofluorination procedures were tested and compared using the same pinacol-derived aryl boronic ester precursor: method 1, using K222/K2CO3 and [Cu(OTf)2(py)4] afforded the product in 56 ± 8% (n = 5) RCY after HPLC analysis of the crude reaction mixture; method 2: an azeotropic drying-free [18F]-labelling procedure, using Cu(OTf)2 as [18F]-elution agent and copper source, yielded [18F]FNFP in 88 ± 4% (n = 5) RCY. Method 2 was chosen as the standard for the synthesis of the radiotracer, obtaining the product with an overall radiochemical yield of 38,4 ± 3% (n = 5), high radiochemical purity (> 99%), total synthesis time of 85 minutes and a molar activity of 41.56 GBq/µmol. [18F]FNFP was found to be stable in serum and Phosphate-buffered saline for up to 6h, and lipophilicity measurements concluded that it is more hydrophilic than [18F]FMISO (log10𝑃=2.6), with log10𝑃=1.05.
Conclusion:
The first nitrofuran-based radiotracer to be used as a PET hypoxia imaging agent was efficiently radiolabeled with 18F. In vitro and in vivo studies are being lined up to compare [18F]FNFP with [18F]FMISO and [18F]FAZA.
Research on optimization of Pricing and Replenishment Decision Making Problem Based on LightGBM and Dynamic Programming
Authors: Tao Wenyue , Wu Chaoran , Wu Ting , Chen Fuyuan 
Published: February 2024

Abstract
The fresh-keeping period of vegetable commodities was relatively short, and its sales problem had always been of great concern under the vegetable production and distribution pattern of ”small production and big market” in China. Therefore, it was necessary to establish a systematic and comprehensive mathematical model, and rationally formulate the replenishment plans and pricing strategies for each category and individual product of vegetables. In this paper, we mainly solved the following three questions:
Question One: What was the distribution law and relationship between the sales volume of vegetable categories and single products?
Question Two: What was the relationship between total sales volume and costplus pricing of vegetable categories? Could you give the daily total replenishment and pricing strategy of each vegetable category in the next week, so that the supermarket would have the greatest profit?
Question Three: On the premise of meeting the market demand for various categories of vegetable products, how to further formulate the replenishment plan requirements of single products to maximize the revenue of supermarkets?
For the first question, we used the Pearson correlation coefficient and the Mfuzz package based on fuzzy c-means clustering to analyze the distribution law and correlation between vegetable categories and single products.We found that mosaic leaves, peppers and edible mushrooms accounted for a larger proportion, while cauliflower, aquatic rhizomes and eggplants accounted for a small proportion. And for single items, lettuce, cabbage, green pepper, screw pepper, enoki mushroom and shiitake mushroom accounted for a large proportion of their respective categories. We also found that there was a strong correlation between vegetable categories. And the sales of vegetable items belonging to the same category showed the same change pattern over time. For the second question, we established the LightGBM sales forecasting model to solve it. Combined with previous sales data, we forecasted the daily replenishment volume of each vegetable category in the coming week. And we developed a pricing strategy for vegetable categories to maximize the benefits of the supermarket. For the third question, we built a dynamic programming model to solve it. We developed an optimal replenishment volume and pricing strategy for single items, which let the supermarket maximize its income on the premise of meeting the constraints.
Mathematics Subject Classification (2020) 68M07 · 91B03 · 91B24
Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs.
Authors: Verdoodt Fien , Bhatti Sofie F.M. , Kragic Karla , Ham Luc , Vanhaecke Lynn , Hesta Myriam , Hemeryck Lieselot Y. 
Published: February 2024

Abstract
Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, D-pantothenol, and 2-phenylethylamine (P-values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P-value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.