bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐type‐specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B
Authors: Wang Jun , Li Qian , Qiu Yuanwang , Kitanovski Simo , Wang Chen , Zhang Chenxia , Li Fahong , Li Xiaoguang , Zhang Zhenfeng , Huang Lihua , Zhang Jiming , Hoffmann Daniel , Lu Mengji , Lu Hongzhou 
Published: July 2024

AbstractFunctional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.
Comparative proteomics uncovers low asparagine content in Plasmodium tRip‐KO proteins
Authors: Pitolli Martina , Cela Marta , Kapps Delphine , Chicher Johana , Despons Laurence , Frugier Magali 
Published: July 2024

AbstracttRNAs are not only essential for decoding the genetic code, but their abundance also has a strong impact on the rate of protein production, folding, and on the stability of the translated messenger RNAs. Plasmodium expresses a unique surface protein called tRip, involved in the import of exogenous tRNAs into the parasite. Comparative proteomic analysis of the blood stage of wild‐type and tRip‐KO variant of P. berghei parasites revealed that downregulated proteins in the mutant parasite are distinguished by a bias in their asparagine content. Furthermore, the demonstration of the possibility of charging host tRNAs with Plasmodium aminoacyl‐tRNA synthetases led us to propose that imported host tRNAs participate in parasite protein synthesis. These results also suggest a novel mechanism of translational control in which import of host tRNAs emerge as regulators of gene expression in the Plasmodium developmental cycle and pathogenesis, by enabling the synthesis of asparagine‐rich regulatory proteins that efficiently and selectively control the parasite infectivity.
Unpaired fundus image enhancement based on constrained generative adversarial networks
Authors: Yang Luyao , Yao Shenglan , Chen Pengyu , Shen Mei , Fu Suzhong , Xing Jiwei , Xue Yuxin , Chen Xin , Wen Xiaofei , Zhao Yang , Li Wei , Ma Heng , Li Shiying , Tuchin Valery V. , Zhao Qingliang 
Published: July 2024

AbstractFundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence‐assisted ophthalmic examination.
T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells
Authors: Murayama Masatoshi , Shinohara Issei , Toya Masakazu , Susuki Yosuke , Lee Max L. , Young Bill , Gao Qi , Chow Simon Kwoon‐Ho , Goodman Stuart B. 
Published: July 2024

AbstractApproximately 5%–10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA‐approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti‐inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC‐based therapies.
Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy‐related apoptosis
Authors: Xin Zhen , Holgersson Kristian , Zhu Pengcheng , Tan Hongtu , Shi Guangyan , Szekely Laszlo , Wu Tao 
Published: July 2024

AbstractGlioma is a central nervous system (CNS) malignant tumor with high heterogeneity and mortality, which severely threatens the health of patients. The overall survival of glioma patients is relatively short and it is critical to identify new molecular targets for developing effective treatment strategies. UBE2K is a ubiquitin conjugating enzyme with oncogenic function in several malignant tumors. However, whether UBE2K participates in gliomas remains unknown. Herein, in glioma cells, UBE2K was found highly expressed in U87 and U251 cells. Subsequently, U87 and U251 cells were transfected with si‐UBE2K to silence UBE2K, with the si‐NC transfection as the negative control. In both U87 and U251 cells, the cell viability was sharply reduced by transfecting si‐UBE2K for 48 and 72 h. Markedly decreased colony number, reduced number of migrated cells and invaded cells, and declined relative wound healing rate were observed in si‐UBE2K transfected U87 and U251 cells. Moreover, the Bcl‐2 level was markedly reduced, while the Bax and cleaved‐caspase‐3 levels were sharply increased in U87 and U251 cells after the si‐UBE2K transfection. Furthermore, the p62 level was signally declined, while the Beclin‐1 and LC‐3 II/I levels were greatly increased in U87 and U251 cells by the si‐UBE2K transfection. Furthermore, the facilitating effect of si‐UBE2K on the apoptosis and autophagy in U87 and U251 cells was abolished by the coculture of 3‐MA, an inhibitor of autophagy. Collectively, UBE2K facilitated the in vitro growth of glioma cells, possibly by inhibiting the autophagy‐related apoptosis, which might be a promising target for treating glioma.
Effects of substituted chalcogen atoms on excited state proton transfer reaction for 2,5‐bis(benzoxazole‐2‐yl)‐thiophene‐3,4‐diol derivatives: A theoretical study
Authors: Chen Jiahe , Zhao Jinfeng 
Published: July 2024

AbstractMotivated by the captivating allure of exquisitely regulated characteristics exhibited by 2‐(2‐hydroxyphenyl)‐benzoxazole and its derivatives in the domains of photochemistry and photophysics, our current endeavor primarily focuses on delving into the intricacies of photo‐induced excited state reactions for derivatives of 2,5‐bis(benzoxazol‐2‐yl)‐thiophene‐3,4‐diol (BTD). Given the profound impact of chalcogen element doping, our primary focus lies in investigating the excited state behaviors of BTD‐O, BTD‐S, and BTD‐Se fluorophores. Through simulations encompassing variations in geometry and vertical excitation charge reorganization, we unveil atomic‐electronegativity‐dependent hydrogen bonding interactions and photoexcitation‐induced charge recombination that can significantly augment the intramolecular double proton transfer (ESDPT) reaction in the excited state for BTD‐O, BTD‐S, and BTD‐Se fluorophores. By constructing potential energy surfaces and identifying transition state forms, we elucidate the ultrafast stepwise ESDPT mechanism facilitated by the low potential barriers. Moreover, we rigorously validate the chalcogen atomic electronegativity‐driven regulation of the stepwise ESDPT mechanism. We sincerely anticipate that manipulating solvent polarity will pave the way for groundbreaking advancements in luminescent materials.
Clinical outcomes in patients switching from agalsidase beta to migalastat: A Fabry Registry analysis
Authors: Pisani Antonio , Wilson Kathryn M. , Batista Julie L. , Kantola Ilkka , Ortiz Alberto , Politei Juan , Al‐Shaar Laila , Maski Manish , Crespo Ana , Ponce Elvira , Linhart Aleš 
Published: July 2024

AbstractFabry Registry data were analyzed among 83 agalsidase beta‐treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein‐creatinine ratio [UPCR], plasma globotriaosylceramide [GL‐3], plasma globotriaosylsphingosine [lyso‐GL‐3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre‐ and postswitch periods. eGFR decreased throughout both periods (preswitch: −0.85 mL/min/1.73 m2/year; postswitch: −1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late‐onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late‐onset patients. GL‐3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late‐onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (−0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late‐onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late‐onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL‐3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late‐onset patients. These findings indicate variability in long‐term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.
Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adult climbing deficit in a GALT‐null D. Melanogaster model of classic galactosemia
Authors: Daenzer Jennifer M. I. , Druss Jared J. , Fridovich‐Keil Judith L. 
Published: July 2024

AbstractClassic galactosemia (CG) is an autosomal recessive disorder that results from profound deficiency of galactose‐1‐phosphate uridylyltransferase (GALT), the middle enzyme in the highly conserved Leloir pathway of galactose metabolism. That galactose metabolism is disrupted in patients with CG, and in GALT‐null microbial, cell culture, and animal models of CG, has been known for many years. However, whether the long‐term developmental complications of CG result from disrupted galactose metabolism alone, or from loss of some independent moonlighting function of GALT, in addition to disrupted galactose metabolism, has been posed but never resolved. Here, we addressed this question using a GALT‐null Drosophila melanogaster model of CG engineered to express uridine diphosphate (UDP)‐glucose/galactose pyrophosphorylase (UGGP), a plant enzyme that effectively bypasses GALT in the Leloir pathway by converting substrates uridine triphosphate (UTP) plus galactose‐1‐phosphate (gal‐1P) into products UDP‐galactose plus pyrophosphate (PPi). While GALT and UGGP share one substrate (gal‐1P) and one product (UDP‐galactose), they are structurally and evolutionarily unrelated enzymes. It is therefore extremely unlikely that they would also share a moonlighting function. We found that GALT‐null flies expressing UGGP showed not only partial rescue of metabolic abnormalities and acute larval sensitivity to dietary galactose, as expected, but also full rescue of an adult motor deficit otherwise seen in this model. By extension, these results may offer insights to the underlying bases of at least some acute and long‐term complications experienced by patients with CG.
Successful endoscopic submucosal dissection of an esophageal granular cell tumor in a pediatric patient: A case report and a therapeutic insight
Authors: Dogom Sara Al , Thongpiya Jerapas , Elmassry Marawan , Feist Mark , Sharma Meenu , Rateb George 
Published: July 2024

AbstractEsophageal granular cell tumors (GCTs) are rare mesenchymal neoplasms that originate from the Schwann cells of the neural sheath in the esophageal wall. Esophageal GCTs represent approximately 2% of all GCTs. Most cases of esophageal GCT occur in adults with few cases reported in pediatric patients. Although typically benign, these tumors can occasionally exhibit malignant behavior, necessitating timely and appropriate intervention. Traditionally, surgical resection was considered for treatment, nonetheless, considering the invasive nature of such interventions, endoscopic approaches have been developed for diagnosis and treatment. Endoscopic approaches have been shown to lead to serious complications at times, such as incomplete resection or perforation. Here, we present a successful application of endoscopic submucosal dissection in the treatment of an adolescent female patient with esophageal GCT which was discovered during her prior esophagogastroduodenoscopy for vomiting.
Identification of water transitions using a combination of moisture sorption characteristics and dielectric properties of different parts of jasmine rice (Oryza sativa)
Authors: Changbandit Pitiwat , Santalunai Samran , Thongsopa Chanchai , Phahom Traiphop 
Published: July 2024

AbstractBACKGROUNDIn this work, water transition points (first transition: monolayer–multilayer water; and second transition: multilayer–free and solvent water) of different parts of jasmine rice including white rice, brown rice and bran were identified through the integration of sorption isotherm and dielectric properties data. Desorption isotherm data were fitted to four established models to select the optimal model for describing the sorption behaviors. Then, dielectric properties such as dielectric constant (ε′) and dielectric loss factor (ε″) were measured across various moisture content levels within the frequency range of 200–20 000 MHz.RESULTSA type III isotherm was observed for all samples and the Peleg model was the best fit with the experimental data. Monolayer moisture content of the samples, estimated using the GAB model, ranged from 3.25% to 4.17% dry basis. For dielectric properties, frequency and moisture dependencies were evident for all sample types. Moreover, the sorption isotherm models effectively described the relationship between water activity (aw) and dielectric properties as reflected by their goodness of fit, and their strong correlation through principal component analysis and Pearson's correlation results.CONCLUSIONThe first water transition occurs at aw values of 0.11, 0.12, and 0.22, while the second transition appears at aw values of 0.9, 0.9 and 0.75–0.85 for white rice, brown rice and bran, respectively. This knowledge will be useful for food processors, providing insights into the optimization of food processing and storage conditions to extend food products' shelf life. © 2024 Society of Chemical Industry.
Brown seaweed as a food ingredient contributing to an adequate but not excessive amount of iodine in the European diet. A case study with bread
Authors: Ballance Simon , Rieder Anne , Arlov Øystein , Knutsen Svein Halvor 
Published: July 2024

AbstractBACKGROUNDThe large amounts of iodine in brown seaweeds may contribute towards an adequate iodine intake, but also pose a food safety risk. In the current work we estimate the maximum amount of the cultivated brown seaweeds Saccharina latissima and Alaria esculenta (blanched and non‐blanched) that can be added to white loaf‐type wheat‐bread so European consumers are protected against excessive chronic intakes. We use data for high‐level consumers of bread with special ingredients added from the EFSA comprehensive European food consumption database to construct a conservative risk management model. We bake prototype seaweed bread and use the output from the model to assess exposure to iodine and trace metals. We also assess some bread quality parameters such as sensory characteristics, crumb firmness and specific volume.RESULTSThe maximum level of iodine in bread that would mitigate the European consumer from excess intakes was 857 μg I kg−1 bread. Assuming a typical 60% wheat flour per kilogram of bread, a maximum amount of 11.3 g of dried blanched A. esculenta (115 mg I kg−1 dry weight) could be incorporated per kilogram of wheat flour into the bread recipe whilst for non‐blanched S. latissima, which contained 3500 mg I kg−1 dry weight, only a minuscule 350 mg of seaweed was the limit. For prototype breads, seaweed addition had no significant impact on the specific volume and crumb firmness. Levels of cadmium and arsenic in the bread were also of low toxicological concern.CONCLUSIONA maximum 1–2% brown seaweed of total flour weight could be added to bread to contribute towards European consumers’ adequate iodine intake without overexposure. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A case of miliaria profunda after excessive sweating during a summer vacation
Authors: Palacio Ariana , Medrano Cebrian Karla , Koch Lin‐Kristin , Bierhoff Erhard , Bonness Sonja , Reinhold Uwe 
Published: July 2024

AbstractWe present the case of an otherwise healthy 34‐year‐old man of Asian descent diagnosed with miliaria profunda after a 6‐week history of generalised anhidrosis after a trip to Mallorca in the summer.
Gut microbiota‐derived metabolite trimethylamine N‐oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice
Authors: Xiong Ying , Pu Ya‐Nan , Li Li‐Ya , Su Yang , Niu Jia‐Yuan , Xiao Zhao‐Yang 
Published: July 2024

AbstractAn increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients.