bluuebunny/crossref_metadata_2025_split huggingface dataset:
A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells
Authors: Matsufuji Shohei , Kitajima Yoshihiko , Higure Kazuki , Kimura Naoya , Maeda Sachiko , Yamada Kohei , Ito Kotaro , Tanaka Tomokazu , Kai Keita , Noshiro Hirokazu 
Published: December 2023

Abstract
Background
A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid β-oxidation (FAO) in hypoxic cancer cells.

Methods
We aimed to investigate potential new drug therapy options for targeting hypoxic cancer cells within HCC tumors, specifically through combining HIF-1α inhibition with palmitic acid (PA) + L-carnitine (LC) treatment to effectively induce apoptosis in hypoxic HCC cells. To test this hypothesis, in vitro and in vivo studies were performed.

Results
We first demonstrated that hypoxia-dependent apoptosis was induced by an overload of PA in two HCC cell lines (HepG2 and Hep3B) via excessive production of reactive oxygen species (ROS). Moreover, this observed PA-induced apoptosis was enhanced by HIF-1α knockdown (KD) in these cells under hypoxia. In addition, the combination of PA with FAO activator LC increased FAO activity and led to stronger cell death than PA alone in hypoxic HIF-1α KD cells, specifically through further ROS generation. To clarify the mechanism of hypoxia-induced FA metabolism reprogramming, expression levels of the genes encoding FAO enzymes CPT1A, ACSL1, MCAD, and LCAD, FA transporter CD36, and FA esterification enzymes DGAT and APGAT were analyzed using HIF-1α KD and scramble control (SC) cells. The results suggested that HIF-1α could repress mRNA expression of the FAO-related enzymes and CD36, while it upregulated FA esterification gene expression. This suggested a central role for HIF-1α in hypoxia-induced reprogramming of FA metabolism in HCC cells. Using a nude mouse model, PA administration was found to induce apoptosis from ROS overproduction in HIF-1α KD tumors compared with SC tumors. Additional LC treatment synergistically enhanced the PA-induced apoptosis in HIF-1α KD tumors. Finally, in vivo therapy composed of HIF-1α inhibitor YC-1 with PA + LC could induce ROS-mediated apoptosis in HepG2 tumors without significant toxicity.

Conclusions
A combination therapy of YC-1 with PA + LC may be a unique anti-tumor therapy for targeting hypoxic HCC cells, specifically by ROS overproduction leading to forced FAO activation.
The effects of intermittent fasting diet in comparison with low-calorie diet on lipid profile, glycemic status, and liver fibrosis in patients with non-alcoholic fatty liver (NAFLD): a study protocol for a randomized controlled clinical trial
Authors: Karimi Mehdi , Nejad Maryam Mofidi , Akhgarjand Camellia , Sohrabpour Amir Ali , Poustchi Hossein , Imani Hossein , Mohammadi Hamed 
Published: December 2023

Abstract
Introduction
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by an increase in fat in liver cells. The outbreak of NAFLD is estimated to be 32.4% worldwide, with higher rates in Asia and Iran. Nutritional factors such as excessive calorie intake, high fructose intake, copper deficiency, and increased iron intake play an important role in NAFLD. Since there is no specific treatment for NAFLD, intermittent fasting (IF) diet has been suggested as an alternative treatment for obesity and related complications. Previous studies showed the potential positive effects of IF on metabolic health and the reduction of oxidative stress in NAFLD. This randomized controlled trial (RCT) will be aimed to examine the effect of the IF diet in comparison with a low-calorie diet (LCD) on lipid profile, glycemic status, and liver fibrosis in patients with NAFLD.

Methods and analysis
This is a parallel randomized clinical trial conducted on 52 overweight and obese patients with NAFLD. Participants will be randomly assigned to receive either 16:8 IF (fasting from 8 P.M. to 12 P.M. the next day) or a low-calorie (55% carbohydrate- 30% fat, 15% protein) diet for 12 weeks. Anthropometric measurements, liver assessments, and metabolic evaluations will be assessed before and after the intervention. Primary outcomes include liver steatosis and fibrosis, while secondary outcomes include liver function enzymes, insulin resistance, lipid profile, and anthropometric measurements.

Discussion
Since obesity and insulin resistance are the most important risk factors of NAFLD, and there is no treatment for it, it seems that lifestyle changes such as low caloric diet like IF and exercise can improve lipid metabolism and liver enzymes.

Trial registration
Iranian registry of clinical trials (IRCT20170202032367N5).
Improved postprocessing of dynamic glucose-enhanced CEST MRI for imaging brain metastases at 3 T
Authors: Wu Yulun , Derks Sophie H. A. E. , Wood Tobias C. , de Blois Erik , van der Veldt Astrid A. M. , Smits Marion , Warnert Esther A. H. 
Published: December 2023

Abstract
Background
Dynamic glucose-enhanced (DGE) chemical exchange saturation transfer (CEST) has the potential to characterize glucose metabolism in brain metastases. Since the effect size of DGE CEST is small at 3 T (< 1%), measurements of signal-to-noise ratios are challenging. To improve DGE detection, we developed an acquisition pipeline and extended image analysis for DGE CEST on a hybrid 3-T positron emission tomography/magnetic resonance imaging system.

Methods
This cross-sectional study was conducted after local ethical approval. Static Z-spectra (from -100 to 100 ppm) were acquired to compare the use of 1.2 versus 2 ppm to calculate static glucose-enhanced (glucoCEST) maps in 10 healthy volunteers before and after glucose infusion. Dynamic CEST images were acquired during glucose infusion. Image analysis was optimized using motion correction, dynamic B0 correction, and principal component analysis (PCA) to improve the detection of DGE CEST in the sagittal sinus, cerebrospinal fluid, and grey and white matter. The developed DGE CEST pipeline was applied to four patients diagnosed with brain metastases.

Results
GlucoCEST was strongest in healthy tissues at 2 ppm. Correcting for motion, B0, and use of PCA locally improved DGE maps. A larger contrast between healthy tissues and enhancing regions in brain metastases was found when dynamic B0 correction and PCA denoising were applied.

Conclusion
We demonstrated the feasibility of DGE CEST with our developed acquisition and analysis pipeline at 3 T in patients with brain metastases. This work enables a direct comparison of DGE CEST to 18F-fluoro-deoxy-D-glucose positron emission tomography of glucose metabolism in patients with brain metastases.

Relevance statement
Contrast between brain metastasis and healthy brain tissue in DGE CEST MR images is improved by including principle component analysis and dynamic magnetic field correction during postprocessing. This approach enables the detection of increased DGE CEST signal in brain metastasis, if present.

Key points
• Despite the low signal-to-noise ratio, dynamic glucose-enhanced CEST MRI is feasible at 3 T.
• Principal component analyses and dynamic magnetic field correction improve DGE CEST MRI.
• DGE CEST MRI does not consequently show changes in brain metastases compared to healthy brain tissue.
• Increased DGE CEST MRI in brain metastases, if present, shows overlap with contrast enhancement on T1-weighted images.

Graphical Abstract
WAS: improved white-box cryptographic algorithm over AS iteration
Authors: Yang Yatao , Zhai Yuying , Dong Hui , Zhang Yanshuo 
Published: December 2023

AbstractThe attacker in white-box model has full access to software implementation of a cryptographic algorithm and full control over its execution environment. In order to solve the issues of high storage cost and inadequate security about most current white-box cryptographic schemes, WAS, an improved white-box cryptographic algorithm over AS iteration is proposed. This scheme utilizes the AS iterative structure to construct a lookup table with a five-layer ASASA structure, and the maximum distance separable matrix is used as a linear layer to achieve complete diffusion in a small number of rounds. Attackers can be prevented from recovering the key under black-box model. The length of nonlinear layer S and affine layer A in lookup table is 16 bits, which effectively avoids decomposition attack against the ASASA structure and makes the algorithm possess anti-key extraction security under the white-box model, while WAS possesses weak white-box (32 KB, 112)-space hardness to satisfy anti-code lifting security. WAS has provable security and better storage cost than existing schemes, with the same anti-key extraction security and anti-code lifting security, only 128 KB of memory space is required in WAS, which is only 14% of SPACE-16 algorithm and 33% of Yoroi-16 algorithm.
The impact of controlling diseases of significant global importance on greenhouse gas emissions from livestock production
Authors: Capper Judith L. 
Published: December 2023

Abstract
Background
A considerable body of evidence has reported the beneficial effects of improving productivity on reducing environmental impacts from livestock production. However, despite the negative impacts of animal diseases on reproduction, growth and milk production, there is little information available upon the impacts of animal disease on greenhouse gas emissions (GHGe). This study aimed to partially address this knowledge gap by investigating the effects of globally important vaccine-preventable diseases on GHGe from various livestock systems, namely: intensive dairy, extensive beef, commercial swine and backyard poultry production.

Methods
Simple deterministic models were developed within Microsoft Excel to quantify the impacts of livestock disease on productivity (defined as total milk and/or meat yield, MMY) adjusted for disease prevalence both at the population level (high or low), and at the herd or flock level. Disease-induced changes in MMY were applied to the GHGe per kg of milk or meat according to the consequent changes in livestock populations required to maintain milk or meat production. Diseases investigated comprised foot and mouth, brucellosis, anthrax, lumpy skin disease, classical swine fever, porcine reproductive and respiratory syndrome (PRRS), low and high pathogenicity avian influenza (LPAI and HPAI), avian infectious bronchitis and Newcastle disease.

Results
All diseases investigated had multifactorial impacts on total MMY, yet diseases that increased mortality in breeding or growing livestock (e.g. anthrax, classical swine fever and HPAI) showed greater impacts on GHGe per unit of milk or meat produced than those that primarily affecting yields or reproduction (e.g. brucellosis or LPAI). Prevalence also had considerable effects on potential GHGe. For example, maintaining backyard poultry meat production from a 100,000 hen population with 70% prevalence of HPAI increased GHGe by 11,255 MT CO2eq compared to a 30% prevalence at 3475 MT CO2eq above the baseline (0% prevalence). Effective reduction of the prevalence of PRRS in swine from 60 to 10%, FMD in beef cattle from 45 to 5% prevalence, or AIB in poultry from 75 to 20% prevalence would reduce GHGe intensities (CO2eq/kg CW) by 22.5%, 9.11% and 11.3% respectively.

Conclusions
Controlling livestock disease can reduce MMY losses at the farm level, which improves food security, reduces GHGe and enhances livestock system sustainability.
Reduced graphene oxide/TiO2/NiFe2O4 nanocomposite as a stable photocatalyst and strong antibacterial agent
Authors: Jihad Kamal Mohammed , Roknabadi Mahmood Rezaee , Mohammadi Mojtaba , Goharshadi Elaheh K. 
Published: December 2023

AbstractIn this study, we prepared reduced graphene oxide (rGO)/titanium dioxide (TiO2)/nickel ferrite (NiFe2O4) nanocomposites with different mass ratios of rGO, TiO2, and NiFe2O4 by a simple hydrothermal method. These nanocomposites were found to exhibit enhanced visible light harvesting, reduced electron–hole recombination, and improved magnetic properties compared to rGO, TiO2, and NiFe2O4. The study evaluated the photocatalytic and antibacterial activity of the nanocomposites, with particular emphasis on the GTN211 (with a mass ratio of 2:1:1 for rGO:TiO2:NiFe2O4) nanocomposite. The results showed that the GTN211 nanocomposite exhibited the best photocatalytic performance under both UV and visible light irradiation, achieving 95 and 89% degradation of Methylene Blue dye in 15 min, respectively. The study also investigated the photodegradation mechanism using various scavengers and found that holes were the main active species in the process. In addition to photocatalytic activity, the GTN211 nanocomposite also showed good antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria, with the minimum inhibitory concentration of 1 mg mL−1 for both bacteria and a minimum bactericidal concentration of 0.8 and 1 mg mL−1, respectively. Hence, the GTN211 nanocomposite has potential as a material for environmental remediation and biomedical applications. The combination of photocatalytic and antibacterial activity makes this material a promising candidate for a wide range of applications.
Diagnostic accuracy of the different pulse sequences of multi-parametric prostate MRI in the diagnosis of prostate cancer in the peripheral and transitional zones
Authors: Gadalla Amr A. Elfattah Hassan , Sabet Marianne Abdallah , Edesa Wael Abdelgawwad , Wahba Manal Halim , Abolyazid Sherif M. 
Published: December 2023

Abstract
Background
One of the most prevalent malignancies among males is prostate carcinoma (PCa). For the diagnosis of PCa, multiparametric magnetic resonance imaging (mpMRI) constitutes by far the most accurate imaging technique. The PI-RADS v2.1 indications for dynamic contrast enhanced (DCE) sequence include identifying PI-RADS score 3 lesions, as clinically significant prostate carcinoma, aiding evaluation of examinations having poor quality of T2 as well as diffusion weighted imaging (DWI), and helping readers having relatively reduced expertise. Most articles don't provide outcomes pertaining to these indications, which weakens their conclusions. All MRI scans, even those with low quality T2 or DWI, were included in our study. Additionally, special emphasis on assessing peripheral zone lesions was made. Our objective was to assess the diagnostic accuracy of the various mpMRI pulse sequences, including the T2 sequence, diffusion and apparent diffusion coefficient (ADC) sequences, both T2 and diffusion sequences (biparametric (bp) MRI), DCE sequence, and the entire examination (mpMRI), in the diagnosis of PCa in the peripheral as well as the transitional zone using PI-RADS version 2.1 scoring system, once when malignant lesions are considered as those having PI-RADS scores 4 and 5 and once when PI-RADS categories 3, 4 and 5 were regarded as malignant.

Results
In the assessment of peripheral zone lesions, when PI-RADS categories 3, 4, and 5 were considered malignant, both bpMRI and mpMRI showed similar sensitivity (94.29%) and diagnostic accuracy (77.78%) while when considering scores 4 and 5 malignant, mpMRI demonstrated increased diagnostic accuracy and sensitivity but lower specificity (sensitivity was 82.86%/60%, specificity was 80%/100%, and diagnostic accuracy was 82.22%/68.89% for mpMRI/bpMRI test comparaison). Both bpMRI and mpMRI had similar sensitivity (95.83%) and diagnostic accuracy (71.05%) when PI-RADS categories 3, 4, and 5 were regarded as malignant; however, mpMRI demonstrated better diagnostic accuracy and sensitivity considering scores 4 and 5 malignant (sensitivity was 77.08% for mpMRI compared to 60.42% for bpMRI and diagnostic accuracy was 82.89% for mpMRI compared to 75% for bpMRI).

Conclusions
Both bpMRI and mpMRI demonstrated similar diagnostic accuracy when PI-RADS categories 3, 4, and 5 were taken into account as malignant while mpMRI had higher diagnostic accuracy considering categories 4 and 5 malignant.
Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
Authors: Zhang Yulin , Cheng Ziwei , Hong Liyu , Liu Jia , Ma Xinyue , Wang Wenjing , Pan Ran , Lu Wenjie , Luo Qichao , Gao Shan , Kong Qin 
Published: December 2023

AbstractObesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.
Image-domain seismic inversion by deblurring with invertible recurrent inference machines
Authors: Peng Haorui , Vasconcelos Ivan , Ravasi Matteo 
Published: December 2023

In complex geologic settings and in the presence of sparse acquisition systems, seismic migration images manifest as nonstationary blurred versions of the unknown subsurface model. Thus, image-domain deblurring is an important step to produce interpretable and high-resolution models of the subsurface. Most deblurring methods focus on inverting seismic images for their underlying reflectivity by iterative least-squares inversion of a local Hessian approximation; this is obtained by either direct modeling of the so-called point-spread functions (PSFs) or by a migration-demigration process. In this work, we adopt a novel deep-learning (DL) framework, based on invertible recurrent inference machines (i-RIMs), which allows approaching any inverse problem as a supervised learning task informed by the known modeling operator (convolution with PSFs in our case): our algorithm can directly invert migrated images for impedance perturbation models, assisted with the prior information of a smooth velocity model and the modeling operator. Because i-RIMs are constrained by the forward operator, they implicitly learn to shape/regularize output models in a training-data-driven fashion. As such, the resulting deblurred images indicate great robustness to noise in the data and spectral deficiencies (e.g., due to limited acquisition). The key role played by the i-RIM network design and the inclusion of the forward operator in the training process is supported by several synthetic examples. Finally, using field data, we find that i-RIM-based deblurring has great potential in yielding robust, high-quality relative impedance estimates from migrated seismic images. Our approach could be of importance toward future DL-based quantitative reservoir characterization and monitoring.
Association Between a History of Breast Cancer and Decreased Thyroid Cancer-specific Mortality
Authors: Lin Shuhuang , Wang Zhuo , Xing Mingzhao 
Published: December 2023

Abstract

Context
The clinical relevance of the well-known association between thyroid cancer (TC) and breast cancer (BC) remains to be further defined.

Objective
This work aimed to investigate the effect of history of BC on the prognosis of TC.

Methods
This was a comparative cohort study of tumor behaviors and TC-specific mortality in 5598 patients with papillary thyroid cancer (PTC) and 604 patients with follicular thyroid cancer (FTC), all with a history of BC (TC-BC patients), and their propensity score–matched TC patients without a history of BC (TCnoBC patients) in Surveillance, Epidemiology and End Results (SEER) 18. The main outcome measure was TC-specific mortality.

Results
Lower TC distant metastasis rates of 2.4% vs 3.0% in PTC and 6.1% vs 9.1% in FTC and TC-specific mortality rates of 1.3% vs 2.6% in PTC and 5.8% vs 8.4% in FTC were found in TC-BC patients vs matched TCnoBC patients (all P &lt; .05). Comparing TC-BC patients with matched TCnoBC patients, hazard ratios (HRs) for mortality were 0.472 (95% CI, 0.370-0.601) in PTC and 0.656 (95% CI, 0.461-0.934) in FTC (all P &lt; .05). Such HRs for mortality in PTC were 0.397 (95% CI, 0.268-0.588; P &lt; .001) when TC occurred before BC vs 0.607 (95% CI, 0.445-0.827; P = .002) when BC occurred before TC.

Conclusion
This study demonstrates a robust protective effect of a history of BC on TC-specific patient survival, which has strong implications for more precise prognostication of TC in such patients.
TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway
Authors: Nguyen Timothy T. , Mitchell Jennyfer M. , Kiel Michaela D. , Kenny Colin P. , Li Hong , Jones Kenneth L. , Cornell Robert A. , Williams Trevor J. , Nichols James T. , Van Otterloo Eric 
Published: December 2023

ABSTRACT
Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underlies facial shape variation, yet how those networks in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both TFAP2 family members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning and differentiation. Notably, Alx1, Alx3 and Alx4 (ALX) transcript levels are reduced, whereas ChIP-seq analyses suggest TFAP2 family members directly and positively regulate ALX gene expression. Tfap2a, Tfap2b and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a zebrafish mutants present with abnormal alx3 expression patterns, Tfap2a binds ALX loci and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development in part by activating expression of ALX transcription factor genes.