bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palmitoyltransferase ZDHHC6 promotes colon tumorigenesis by targeting PPARγ-driven lipid biosynthesis via regulating lipidome metabolic reprogramming
Authors: Shan Junqi , Li Xinyu , Sun Runqi , Yao Yao , Sun Yan , Kuang Qin , Dai Xianling , Sun Yanlai 
Published: August 2024

Abstract
Background
The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients.

Methods
Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc.

Results
To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis.

Conclusions
We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.
Spatial distribution characteristics of relationship network of Beijing-Hangzhou Grand Canal water engineering facilities based on Gephi
Authors: Cheng Wang , Lifeng Tan , Xin Qiu , Yiwen Zhang , Guanhua Wang , Zhichao Sun 
Published: August 2024

Abstract
The Beijing-Hangzhou Grand Canal, China’s oldest and most crucial water transportation project, ensures smooth operation and efficient water transportation through interconnected water engineering facilities. Studying the connections among the water engineering facilities of the Beijing-Hangzhou Grand Canal is theoretically and practically significant for preserving and innovating canal heritage. Therefore, this study utilizes social network analysis to comprehensively examine the spatial connections and network status of water engineering facilities along the Beijing-Hangzhou Grand Canal across different channel structure. Gephi 0.10.1 was utilized in this study to construct a relational network of water engineering facilities along the Beijing-Hangzhou Grand Canal, with each facility considered as a network node. By applying network analysis indices such as degree, closeness centrality, and betweenness centrality, the correlation between water engineering facilities was thoroughly investigated. The study’s findings reveal that: (1) the Beijing-Hangzhou Grand Canal possesses numerous overall network nodes with extensive coverage; however, its overall network density is relatively low, and the inter-node connection is weak. (2) Across the entire network, the spatial distribution of degree and betweenness centrality exhibits a clustered pattern. Their distribution patterns are centered on the Lake region section where Hongze Lake is located and the segment from Liucheng to Zhenjiang in the Lake region, the River transport confluence section, and the Nature river section, respectively. The spatial distribution characteristics of closeness centrality show a dispersed shape, with stronger areas mainly concentrated in the canal’s tributaries, especially the Nature river section, which shows more prominence. (3) Analyzed from a channel structure perspective, water engineering facilities in different sections assume distinct linking roles within the network. Facilities in the Lake region section play the strongest overall linkage role, partly due to its highest node proportion. Conversely, in the Nature river section, facilities primarily serve transshipment and direct connection functions, whereas in the River transport confluence section, they act mainly as intermediaries or “bridges”. Notably, water control facilities in the Nature river section and river engineering facilities in the River transport confluence section play pivotal driving roles in their respective sections, warranting special attention and protection as critical canal nodes.
Combining stress inoculation with virtual reality simulation training of malignant hyperthermia
Authors: Blanchard Erin E , Trost Zina , Brown Michelle R , Shum Corey , Meese Merrick 
Published: August 2024

Abstract
Background
Limited research has been conducted on how healthcare simulation can mitigate clinician stress. Stress exposure training (SET) has been shown to decrease stress’s impact on performance. Combining SET with virtual reality (VR) simulation training has not yet been explored in the context of stress inoculation. The primary purpose of this pilot study was to determine if a VR module could induce stress. The secondary purpose was to determine if repeated exposure to stressors could decrease stress response in a simulated environment.

Methods
Medical students were recruited to partake in VR simulation modules aimed at treatment of malignant hyperthermia (MH). Those in the SET group were exposed to stressful stimuli during training modules, while those in the Control group were not. Both groups then completed a Test Module with the presence of stressful stimuli. Objective and subjective indicators of stress were measured after each module.

Results
Both groups indicated increases in perceived stress and module stressfulness after Training Module 1 and decreases after Training Module 2. After the Test Module, the Control group experienced significant elevation in perceived stress (p = .05), and the SET group had a significant decrease in perceived module stressfulness (p < .05). Both groups had a decrease in perceived competence after Training Module 1 (p < .001) and an increase after Training Module 2 (p < .001), with the SET group having significant elevation after the Test Module (p < .01). Both groups found the VR module to be feasible as a teaching tool. Objectively, the SET group showed an upward trend in electrodermal activity (EDA) from the Tutorial to Test Modules (p < .05), with the Control group showing a decrease after Training Module 2 (p = .05) and an increase after the Test Module (p < .01).

Conclusions
A VR module targeting treatment of MH successfully induced stress and was regarded favorably by participants. Those in the SET group perceived less stress and more competence after the Test Module than those in the Control. Findings suggest that repeated exposure to stressors through VR may desensitize participants from future stress in a simulated environment.
Host plant-derived benzoic acid interferes with 4-hydroxybenzoic acid degradation in the phytopathogen Xanthomonas campestris by competitively binding to PobR
Authors: Chen Bo , Zhou Lian , Song Kai , Thawai Chitti , He Ya-Wen 
Published: August 2024

AbstractXanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in Brassica vegetables, which can induce the host plant to produce salicylic acid and 4-hydroxybenzoic acid (4-HBA) during infection. Xcc was previously shown to sense and degrade host plant-derived 4-HBA via the sensor PobR and a PobA-dependent pathway. The degradation of 4-HBA is associated with Xcc virulence in cabbage. The present study generated a reporter strain XC1::PpobA-gusA to monitor pobA transcription. 4-HBA-like compounds were screened for their ability to interfere with pobA transcription. Benzoic acid (BA) was found to efficiently decrease pobA transcription in a dose-dependent manner. Xcc neither produced nor degraded BA; however, the exogenous addition of BA to the 4-HBA-containing Xcc culture significantly decreased the 4-HBA degradation rate. Furthermore, addition of BA into the Xcc culture did not significantly affect the transcription of pobA or pobR; however, addition of BA into the 4-HBA-containing culture significantly decreased the transcription of both genes. Isothermal titration calorimetry and an electrophoretic mobility shift assay revealed that BA binds to PobR with a moderate affinity, which interfered with the binding of 4-HBA/PobR complex to the pobA promoter and thereby inhibiting pobA transcription and 4-HBA degradation. The endogenous BA level of the infected cabbage leaves increased in response to Xcc infection. In the presence of BA, the virulence of Xcc on cabbage decreased significantly. Taken together, these results suggest that cabbage utilizes BA to interfere with 4-HBA degradation, thereby reducing Xcc virulence. Thus, BA has the potential to be developed as a bactericide against Xcc infection.
Urachal and Nonurachal Adenocarcinomas of the Urinary Bladder: A Comprehensive Genomic Profiling Study
Authors: Cigliola Antonio , Basnet Alina , Jacob Joseph M. , Mercinelli Chiara , Tateo Valentina , Patanè Damiano Alfio , Bratslavsky Gennady , Cheng Liang , Grivas Petros , Kamat Ashish M. , Spiess Philippe E. , Pavlick Dean C. , Lin Douglas I. , Ross Jeffrey S. , Necchi Andrea 
Published: August 2024

PURPOSE Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials. MATERIALS AND METHODS Overall, 133 U and 328 NU adenoCas were analyzed. Hybrid capture–based comprehensive genomic profiling (CGP) was performed to evaluate all classes of GA. Germline status of GA was predicted using a validated somatic-germline computational method. CGP was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc). RESULTS The most frequent GA in both U and NU cohorts included TP53 (86.5% v 81.1%) and KRAS (34.6% v 27.7%). GAs characteristic of colorectal adenoCa, such as SMAD4 ( P = .069) and GNAS ( P = .071), were more common in U versus NU. Conversely, TERT ( P < .01) and RB1 ( P = .071) were more prevalent in NU adenoCa. Notably, both U and NU adenoCas exhibited possibly targetable GA in PIK3CA (7.5% v 7.9%) and ERBB2 (6.8% v 7.6%). Biomarkers associated with potential benefit from anti–PD-1/L1 were infrequent. Median tumor mutational burden was 2.6 and 3.5 mutations per megabase for U and NU, respectively, and PD-L1 expression >1% was rare. Genomic ancestry and genomic signature distribution were similar in both tumor types. GAs were most commonly of somatic nature. Limitations include lack of clinical data, tumor heterogeneity, and retrospective nature. CONCLUSION U and NU adenoCAs revealed differences in GA, with PIK3CA and ERBB2 being identified as putative therapeutic targets. Biomarkers of response to anti–PD-(L)1 were uncommon. Results highlight the potential of CGP to personalize treatment options of bladder adenoCa and inform clinical trial designs.
Estudo de direito administrativo: uma metodologia e um relatório sobre novas pesquisas empíricas
Authors: Schuck Peter H. , Elliott E. Donald 
Published: August 2024

Este artigo relata um estudo empírico concluído recentemente sobre algumas tendências gerais do direito administrativo federal. Apesar de o estudo completo ter sido publicado em outro lugar, também relatamos nossas conclusões aqui por dois motivos. Primeiro, esperamos ampliar o público desta pesquisa, especialmente entre os advogados administrativos em exercício. Acreditamos que o estudo oferece algumas perspectivas novas, importantes e intrigantes sobre várias questões: a mudança de estilo das decisões de apelação no direito administrativo; a evolução do direito administrativo desde meados da década de 1960; os padrões de remessas para órgãos administrativos; e os efeitos da decisão Chevron da Suprema Corte. Em segundo lugar, gostaríamos de chamar atenção especial para a metodologia de nosso estudo, na esperança de que outros pesquisadores a utilizem para investigar outras questões de interesse de advogados e acadêmicos da área administrativa. Este artigo, que consiste essencialmente em trechos do longo estudo publicado, está dividido em três partes. Na Parte I, apresentamos nosso estudo, situando-o em um contexto intelectual mais amplo. A Parte II descreve nossa metodologia de pesquisa. A Parte III resume as principais conclusões do estudo.
Calibration of V-Notch and Compound Weirs for Subsurface Drainage Water Level Control Structures
Authors: Katuwal Sheela , Johnson Gabriel M. , Craig Andrew J. , Rogovska Natalia P. , Isenhart Thomas M. , Malone Rob W. 
Published: August 2024

Highlights

Accurate discharge estimation is important when evaluating edge-of-field conservation practices.

V-notch weir equations were developed for three sizes of subsurface drainage water level control structures.

Compound weir equations were developed for subsurface drainage water level control structures.

The compound weir equation accurately estimates discharge for flows within and overtopping the V-notch.

Abstract. Numerous edge-of-field conservation practices use subsurface drainage water level control structures to monitor water levels and estimate discharge. In a control structure, procedures for calculating discharge when flow depth (head) exceeds the V-notch depth and overflows in the rectangular portion of the compound weir (CW) are ambiguous. In this study, we developed calibration equations for V-notch weirs in Agri Drain inline water level control structures of different sizes for flows within the V-notch and overtopping flow events. The discharge equation for overtopping events (QCW, L s-1) was determined as: QCW = a1(hb1-h1
b1)+a2(We-Wv)h1
b2, where h and h1 are heads above vertex/bottom and top of V-notch (cm), respectively, W is the effective crest width of rectangular weir (cm), Wv is the top width of V-notch (cm), a1 and b1 are parameters for V-notch weir obtained by calibration, and a2 and b2 are calibration parameters for rectangular weir obtained from literature. Results were compared with a weir equation available in the literature (QV+R), which combines a V-notch equation with a head equal to V-depth and a rectangular weir equation for flow above V-depth. Discharge at overflow was estimated with high accuracy with QCW, whereas QV+R underestimated discharge (e.g., PBIAS of 0.67% vs. 17.82% for a 15.2 cm structure). An example using QV+R resulted in a 14% lower annual estimation of nitrate-N load diverted to a saturated buffer than QCW due to underestimation of drainage discharge during overflow events. Results suggest that the developed equation (QCW) accurately estimates discharge and will thus improve the estimated N load compared to QV+R. Keywords: Compound weir, Flow monitoring, Subsurface drainage, V-notch weir, Water level control structure, Weir calibration.
Clinical validation of enhanced CT imaging for distal radius fractures through conditional Generative Adversarial Networks (cGAN)
Authors: Kim Hyojune , Ryu Seung Min , Keum Ji-Soo , Oh Sang-Il , Kim Kyung-Nam , Shin Young Ho , Jeon In-Ho , Koh Kyoung Hwan 
Published: August 2024

Background/purpose
Distal radius fractures (DRFs) account for approximately 18% of fractures in patients 65 years and older. While plain radiographs are standard, the value of high-resolution computed tomography (CT) for detailed imaging crucial for diagnosis, prognosis, and intervention planning, and increasingly recognized. High-definition 3D reconstructions from CT scans are vital for applications like 3D printing in orthopedics and for the utility of mobile C-arm CT in orthopedic diagnostics. However, concerns over radiation exposure and suboptimal image resolution from some devices necessitate the exploration of advanced computational techniques for refining CT imaging without compromising safety. Therefore, this study aims to utilize conditional Generative Adversarial Networks (cGAN) to improve the resolution of 3 mm CT images (CT enhancement).

Methods
Following institutional review board approval, 3 mm-1 mm paired CT data from 11 patients with DRFs were collected. cGAN was used to improve the resolution of 3 mm CT images to match that of 1 mm images (CT enhancement). Two distinct methods were employed for training and generating CT images. In Method 1, a 3 mm CT raw image was used as input with the aim of generating a 1 mm CT raw image. Method 2 was designed to emphasize the difference value between the 3 mm and 1 mm images; using a 3 mm CT raw image as input, it produced the difference in image values between the 3 mm and 1 mm CT scans. Both quantitative metrics, such as peak signal-to-noise ratio (PSNR), mean squared error (MSE), and structural similarity index (SSIM), and qualitative assessments by two orthopedic surgeons were used to evaluate image quality by assessing the grade (1~4, which low number means high quality of resolution).

Results
Quantitative evaluations showed that our proposed techniques, particularly emphasizing the difference value in Method 2, consistently outperformed traditional approaches in achieving higher image resolution. In qualitative evaluation by two clinicians, images from method 2 showed better quality of images (grade: method 1, 2.7; method 2, 2.2). And more choice was found in method 2 for similar image with 1 mm slice image (15 vs 7, p = 201).

Conclusion
In our study utilizing cGAN for enhancing CT imaging resolution, the authors found that the method, which focuses on the difference value between 3 mm and 1 mm images (Method 2), consistently outperformed.
The Hypercontemporary Novel in Portugal: Fictional Aesthetics and Memory after Postmodernism, Paulo de Medeiros and Ana Paula Arnaut (eds) (2024)
Authors: Glaze Olivia 
Published: August 2024

Review of: The Hypercontemporary Novel in Portugal: Fictional Aesthetics and Memory after Postmodernism, Paulo de Medeiros and Ana Paula Arnaut (eds) (2024)
London: Bloomsbury, 178 pp.,
ISBN 979-8-76510-031-8, h/bk, £75
ISBN 979-8-76510-032-5, e-book, e-pub and Mobi, £67.50
ISBN 979-8-76510-033-2, e-book and PDF, £67.50
Diagnostic utility of the average peak LH levels measured during GnRH stimulation test
Authors: Koca Serkan Bilge , Demirbilek Hüseyin 
Published: August 2024

Abstract

Objectives
Gonadotropin-releasing hormone (GnRH) test is the gold standard test to evaluate the hypothalamus–pituitary–gonadal (HPG) axis for the diagnosis of central precocious puberty (CPP). However, the diagnosis of cases with clinical features of CPP whilst have borderline peak luteinizing hormone (LH) remain challenges. We aimed to evaluate diagnostic performance of the average of LH levels measured during GnRH stimulation test.

Methods
Cases with diagnosis of CPP and premature thelarche (PT) who had a GnRH stimulation test results were retrospectively reviewed. Anthropometric measurements (weight, height, and body mass index), age and sex-specific standard deviation scores, growth velocity, puberty stages, bone ages, serum FSH, LH, and estradiol levels were measured by electrochemiluminescence immunological method (ECLIA), and the GnRH stimulation test results, which performed by obtaining venous blood samples at basal, 20th, and 40th minutes for FSH and LH measurement, were recorded.

Results
A total of 76 girls (38 CPP, 38 PT) were included. We detected an average peak LH cut-off value of 4.25 IU/L with 94.7 % sensitivity and 97.4 % specificity, a 97.3 % positive predictive value, and a 94.9 % negative predictive value in GnRH test to differentiate cases with CPP from PT.

Conclusions
This is the first study evaluating the diagnostic utility of the average of LH levels measured during GnRH stimulation test. We showed that the average of two LH measurements has a high diagnostic performance. Therefore, it can be used as a valid and reliable diagnostic tool for assessment of HPG axis activation, particularly for cases with a borderline peak LH level.
Non-Existence: The Nuclear Option
Authors: Priest Graham 
Published: August 2024

Abstract
This article concerns the work of the prime movers of the Neo-Meinongian “revival,” Terry Parsons and Richard Routley, and specifically their solution to the issue of how to formulate the Characterisation Principle (a thing that is so and so, is so and so). Both adopted variations of the nuclear/non-nuclear (characterising/non-characterising) strategy. This article discusses their implementations of the strategy and its problems.