bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton beam radiotherapy versus transarterial chemoembolization for hepatocellular carcinoma: Results of a randomized clinical trial
Authors: Bush David A. , Volk Michael , Smith Jason C. , Reeves Mark E. , Sanghvi Samrat , Slater Jerry D. , deVera Michael 
Published: July 2023

AbstractBackgroundThis study compares survival rates, recurrence patterns, toxicity, and treatment cost in patients with hepatocellular carcinoma (HCC) treated with either transarterial chemoembolization (TACE) or proton beam radiotherapy (PBT).MethodsSubjects with untreated HCC meeting Milan or San Francisco transplant criteria were recruited. Subjects were randomized to receive PBT (n = 36) or TACE (n = 40). Proton therapy was administered in 15 fractions over 3 weeks to a total dose of 70.2 Gy. TACE was repeated until complete or maximal response. The primary outcome measure was overall survival (OS). Secondary end points were progression‐free survival (PFS), local control (LC), toxicity, and cost.ResultsOf the 76 randomized patients, 74 were assessed for outcome measures. The 2‐year OS for PBT versus TACE was similar at 68%, 95% confidence interval (CI), 0.54–0.86, and 65%, 95% CI, 0.52–0.83 (p = .80), however, median PFS was improved for PBT versus TACE (not reached vs. 12 months, p = .002). LC was improved with PBT versus TACE (hazard ratio, 5.64; 95% CI, 1.78–17.9, p = .003). Days of posttreatment hospitalization were 24 for PBT and 166 for TACE (p < .001). Total mean cost per patient for treatment and posttreatment care revealed a 28% cost savings for PBT.ConclusionsPBT and TACE yielded similar OS for treatment of HCC, but PFS and LC were improved with PBT compared to TACE. Patients treated with PBT required fewer courses of treatment, fewer posttreatment hospitalization days, and reduced cost of treatment compared to TACE. These data support the use of PBT as a viable treatment alternative to TACE for patients with HCC within transplant criteria.
Integrated bidirectional converter with voltage equalizer for energy storage system
Authors: Yang Xiaoguang , Zhao Xiaobing , Liu Jietao 
Published: July 2023

SummaryIn energy storage systems, a voltage equalizer is always needed. The voltage equalizers often include a DC‐DC converter. In this paper, the DC‐DC converter in the voltage equalizer is saved by integrating the voltage equalization circuit into the bidirectional converter of the battery system, thus simplifying the system. The voltage equalization circuit in the integrated system is composed of a LC resonant circuit and a voltage multiplier, which has the advantages of simplicity and low complexity. This paper presents the design process based on the analysis model, which enables the equalizer to obtain the optimal parameter configuration. Test results show the proposed LC‐SVM can automatically realize voltage balance between energy storage cells without additional control.
From bench to bedside: The role of cough hypersensitivity in chronic cough
Authors: Drake Matthew G. , McGarvey Lorcan P. , Morice Alyn H. 
Published: July 2023

AbstractBackgroundChronic cough is a burdensome condition characterized by persistent cough lasting longer than 8 weeks. Chronic cough can significantly affect quality of life, physical function and productivity, with many people troubled with a cough that lasts for months or even years. People with chronic cough commonly report a persistent urge to cough with frequent bouts of coughing triggered by innocuous stimuli, which has led to the concept of cough hypersensitivity.Main bodyBoth central and peripheral neural pathways regulate cough, and although mechanisms driving development of cough hypersensitivity are not fully known, sensitization of these neural pathways contributes to excessive cough triggering in cough hypersensitivity. Effective therapies that control chronic cough are currently lacking. Recent therapeutic development has focused on several ion channels and receptors involved in peripheral activation of cough (e.g., transient receptor potential channels, P2 × 3 receptors and voltage‐gated sodium channels) or central cough processing (e.g., neurokinin‐1 [NK‐1] receptors and nicotinic acetylcholine receptors).ConclusionThese targeted therapies provide novel insights into mechanisms underlying cough hypersensitivity and may offer new treatment options for people with chronic cough. In this review, we explore preclinical and clinical studies that have improved our understanding of the mechanisms responsible for chronic cough and discuss the most promising targeted approaches to date, including trials of P2 × 3‐receptor antagonists and NK‐1–receptor antagonists.
Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology
Authors: Singh Brijdeep , Srinivasan Radhika , Bansal Deepak , Rohilla Manish , Dey Pranab , Saikia Uma Nahar , Nada Ritambhra 
Published: July 2023

AbstractPilomatrixoma is a relatively rare benign skin appendageal tumor, often presenting in the pediatric age group as a nodular lesion and most commonly involving the head and neck, making it amenable to primary fine needle aspiration (FNA) diagnosis. We report the clinical and histopathological findings of two cases of pilomatrixoma in children, both of which were initially misdiagnosed as small round blue cell tumors due to high cellularity and misinterpretation of the proliferating basaloid cells. Histopathology revealed basal cell proliferation and mitoses indicating that they were progressive, early lesions. The first case showed membranous positivity for CD99 which prompted a diagnosis of Ewing sarcoma. Awareness of the morphological spectrum including positivity for CD99 and careful evaluation of cell block histology could have averted the misdiagnosis. Pilomatrixoma should be included as an important differential diagnosis when faced with primitive‐appearing cells on FNA, especially in children with mass lesions in the head and neck region.
A temporally‐restricted pattern of endothelial cell collagen 4 alpha 1 expression during embryonic development determined with a novel knockin Col4a1‐P2A‐eGFP mouse line
Authors: Lartey Nathaniel L. , van der Ent Martijn , Alonzo Roxann , Chen Di , King Philip D. 
Published: July 2023

SummaryClassical collagen type IV comprising of a heterotrimer of two collagen IV alpha 1 chains and one collagen IV alpha 2 chain is the principal type of collagen synthesized by endothelial cells (EC) and is a major constituent of vascular basement membranes. In mouse and man, mutations in genes that encode collagen IV alpha 1 and alpha 2 result in vascular dysfunction. In addition, mutations in genes that encode the Ephrin receptor B4 (EPHB4) and the p120 Ras GTPase‐activating protein (RASA1) that cause increased activation of the Ras mitogen‐activated protein kinase (MAPK) signaling pathway in EC result in vascular dysfunction as a consequence of impaired export of collagen IV. To understand the pathogenesis of collagen IV‐related vascular diseases and phenotypes it is necessary to identify at which times collagen IV is actively synthesized by EC. For this purpose, we used CRISPR/Cas9 targeting in mice to include immediately after the terminal Col4a1 codon a sequence that specifies a P2A peptide followed by enhanced green fluorescent protein (eGFP). Analysis of eGFP expression in Col4a1‐P2A‐eGFP mice revealed active embryonic EC synthesis of collagen IV alpha 1 through mid to late gestation followed by a sharp decline before birth. These results provide a contextual framework for understanding the basis for the varied vascular abnormalities resulting from perturbation of EC expression and export of functional collagen IV.
The complex genomic diversity of Yersinia pestis on the long‐term plague foci in Qinghai–Tibet plateau
Authors: Liang Junrong , Duan Ran , Qin Shuai , Lv Dongyue , He Zhaokai , Zhang Haoran , Duan Qun , Xi Jinxiao , Chun Hua , Fu Guoming , Zheng Xiaojin , Tang Deming , Wu Weiwei , Han Haonan , Jing Huaiqi , Wang Xin 
Published: July 2023

AbstractPlague is a typical natural focus disease that circulates in different ecology of vectors and reservoir hosts. We conducted genomic population and phylogenetic analyses of the Yersinia pestis collected from the 12 natural plague foci in China with more than 20 kinds of hosts and vectors. Different ecological landscapes with specific hosts, vectors, and habitat which shape various niches for Y. pestis. The phylogeographic diversity of Y. pestis in different kinds plague foci in China showed host niches adaptation. Most natural plague foci strains are region‐and focus‐specific, with one predominant subpopulation; but the isolates from the Qinghai–Tibet plateau harbor a higher genetic diversity than other foci. The Y. pestis from Marmota himalayana plague foci are defined as the ancestors of different populations at the root of the evolutionary tree, suggesting several different evolutionary paths to other foci. It has the largest pan‐genome and widest SNP distances with most accessory genes enriched in mobilome functions (prophages, transposons). Geological barriers play an important role in the maintenance of local Y. pestis species and block the introduction of non‐native strains. This study provides new insights into the control of plague outbreaks and epidemics, deepened the understanding of the evolutionary history of MHPF (M. himalayana plague focus) in China. The population structure and identify clades among different natural foci of China renewed the space cognition of the plague.
A size‐based perspective on the decoupling between compositional and functional changes in planktonic communities
Authors: Zhu Konghao , Zhang Huan , Li Hailu , Zhang Peiyu , Zhang Min , Urrutia‐Cordero Pablo , Xu Jun 
Published: July 2023

AbstractRecent studies have shown a decoupling in the way community composition and functions respond to environmental changes. A common pattern observed is that aggregated functions at the community level are more stable than community composition, which is likely the result of functional compensatory dynamics driven by interspecific differences in response to environmental change. However, the mechanisms by which these patterns emerge remain largely unexplored. Here we investigated in a mesocosm experiment for four weeks the compositional and functional responses of edible phytoplankton (<64 μm) and cladoceran zooplankton communities to climate warming (a constant increase of +3.5°C plus heat wave) and eutrophication (nutrient additions) from a size‐based perspective. Our results show that warming increases small‐sized taxa and decreases large‐sized taxa within both phytoplankton and zooplankton community composition. We found that such opposite responses of different‐sized taxa contributed to the stability of planktonic community functions and thereby resulted in a decoupling between compositional and functional changes. We also found that nutrient additions increased the abundance of all‐sized algal taxa, while phytoplankton community function remained stable. Nutrient additions did not alter the zooplankton community, neither compositionally nor functionally. Under the combined stress of warming and nutrient additions, the compositional and functional responses of planktonic communities were mainly driven by warming. In a broader perspective, our findings reveal a size‐dependent compensation mechanism and suggest that functional stability relies on compensatory effects among different‐sized taxa, and it is therefore important that communities host a large range of taxa differing in size to withstand an increasingly more variable environment in the future.
LC‐MS based metabolite profiling, in‐vitro antioxidant and in‐vivo antihyperlipidemic activity ofNigella sativaextract
Authors: Shrivastava Amit Kumar , Shrestha Laxmi , Pokhrel Buddhi Raj , Joshi Bishal , Lamichhane Gopal , Vidović Bojana , Koirala Niranjan 
Published: July 2023

AbstractThe aim of this study was to identify the bioactive phytoconstituents present in the aqueous extract ofNigella sativaand also, to evaluate the antioxidant and antihyperlipidemic activity in Wistar rats. The LC‐MS/MS analysis was assessed for the determination of different bioactive compounds present inN. sativaextract. Total phenolic and flavonoid content were determined by using validated Folin‐Ciocalteu and Aluminum chloride colorimetric methods, respectively. The in‐vitro antioxidant and in‐vivo antihyperlipidemic activity in Wistar rats were also evaluated. Preliminary phytochemical screening of the extract showed the presence of alkaloids, flavonoids, phenols, glycosides, and amino acids in the aqueous extract. The bioactive compounds of the aqueous extract were identified through LC‐MS/MS analysis. The in‐vitro antioxidant activity ofN. sativashowed the highest free radical scavenging capacity in DPPH, H2O2, and OH radical scavenging assays with IC50values 11.916 ± 2.828, 30.294 ± 13.790, and 12.048 ± 2.828 µg/mL, respectively. Evaluation of antihyperlipidemic activity of extract in Wistar rats showed that a high dose (800 mg/kg) of extract significantly decreased total cholesterol (TC) 71.76 ± 6.91 mg/dL, TG 83.6 ± 8.09 mg/dL, low‐density lipoproteins (LDL‐c) 33.86 ± 6.05 mg/dL, very low‐density lipoproteins (VLDL‐c) 16.72 ± 1.61 mg/dL level in blood. However, the HDL‐C level was significantly improved (21.18 ± 1.80 mg/dL) as compared to HFD‐induced control rats (11.76 ± 1.14 mg/dL) after 28 days of treatment. Also, at the same dose, animal body weight was also decreased to 162.6 ± 16.40 g compared with control 184.4 ± 10.24 g. The aqueous extract ofN. sativawas found to be an effective natural source of antioxidant and hypolipidemic agents. This activity was attributed to the presence of diverse bioactive compounds in it.
Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses
Authors: Daud Muhammad , Dasari Prasad , Adelfinger Marion , Langenhorst Daniela , Lother Jasmin , Slavkovic‐Lukic Dragana , Berges Carsten , Kruhm Michaela , Galler Annette , Schleussner Cathrin , Luther Christian H. , Alberter Karl , Althammer Anton , Shaikh Haroon , Pallmann Niklas , Bodem Jochen , El‐Mowafy Mohammed , Beilhack Andreas , Dittrich Marcus , Topp Max S. , Zipfel Peter F. , Beyersdorf Niklas 
Published: July 2023

AbstractTo obtain a better understanding of the biology behind life‐threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti‐CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte‐specific protein tyrosine kinase (LCK), which was also the case for anti‐CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T‐cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1‐specific T‐cell receptor developed for adoptive T‐cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T‐cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T‐cell responses.
Efficiently Aerobic Dehydrogenation of N‐Heterocycles and Hydrocarbons over MnAl Oxides
Authors: Wang Anwei , Zhou Xue , Yan Jiaqi , Hou Tao , He Mingyang , Qian Junfeng , Zhou Weiyou , Sun Yunjuan 
Published: July 2023

AbstractDehydrogenation of saturated N‐heterocycles and hydrocarbons provides an important route to corresponding aromatic compounds. Herein, an efficient and selective MnAlO‐catalyzed aerobic oxidative dehydrogenation of five‐ and six‐membered N‐heterocycles, imines and hydrocarbons is presented. The reaction features excellent yields of the products, mild reaction conditions, readily available and reusable catalyst. Various N‐heterocycles and hydrocarbons can be tolerated by the reaction system and transformed to the corresponding aromatic counterparts. Mechanistic studies revealed that the reaction proceeds mainly through an electron transfer mechanism.
Socioeconomic risk factors for long‐term opioid use: A national registry‐linkage study
Authors: Nestvold H. H. , Skurtveit S. S. , Hamina A. , Hjellvik V. , Odsbu I. 
Published: July 2023

AbstractBackgroundOpioid use has increased substantially as a treatment for chronic pain, although harms from long‐term opioid therapy outweigh the benefits. More knowledge about factors associated with long‐term opioid use is needed. We aimed to investigate the association between socioeconomic status and long‐term opioid use in the period 2010–2019.MethodsThis was a nested case–control study in which the cases were all persons ≥18 years with long‐term opioid use, that is use of opioids for more than 3 months (N = 215,642). Cases were matched on gender, age and index year (first long‐term use period) with four controls who filled at least one opioid prescription, but never developed long‐term opioid use in the study period (N = 862,568). We performed a logistic regression analysis adjusted for relevant confounders, stratified on age groups (18–67 years and 68 years and above).ResultsIn the younger age group, long‐term opioid use was associated with low education (adjusted odds ratio, aOR = 1.54; 95% confidence interval, CI [1.51–1.57]), low income (1.33 [1.31–1.36]), being unemployed (1.40 [1.38–1.42]) and receiving disability pension (1.36 [1.33–1.38]). Weaker associations were found for living in a single‐person household or in a dense geographical area. Similar associations were found for the older age group.ConclusionWe found that low socioeconomic status was associated with long‐term opioid use both among people in working age and older people. These results indicate a need for social and financial support for non‐pharmacological treatment of chronic pain among people with lower socioeconomic status.SignificanceThis study shows that people with low socioeconomic status are at higher risk of developing long‐term opioid use. In the clinical setting, physicians should consider socioeconomic status when prescribing opioids for chronic pain. Non‐pharmacological treatment options funded by public health services should be prioritized to those with low socioeconomic status as long‐term opioid use in chronic pain patients is not recommended.
Experimental and mathematical model of the variable friction adaptive self‐centering energy dissipative brace
Authors: Liu Tong , Zhu Li‐Hua , Dong Yao‐Rong , Luo Jin‐Wu , Li Zi‐Jie 
Published: July 2023

AbstractThe self‐centering energy dissipative (SCED) brace can limit the maximum story drift and eliminate residual drift during an earthquake. The inadequate reliability or excessive complexity of the energy dissipative system, the contradiction between the energy dissipative system and self‐centering system, the limited elongation capacity, and the difficulty in replacement and reuse are the main challenges faced by the existing developed SCED brace. To solve these problems, a variable friction adaptive self‐centering energy dissipative (VFA‐SCED) brace has been proposed. First, the details of the VFA‐SCED brace are introduced, and the force analysis of each component and the working mechanism of the brace are expounded. Then, the equations that govern the brace performance have been derived, key parameters and mathematical models have been identified. Finally, the feasibility of the new system was demonstrated with a set of experiments, in which five specimens with different key parameters were fabricated, tested, and analyzed. The test results show that the hysteretic curve of the VFA‐SCED brace is typically flag‐shaped, and there is almost no residual deformation after multiple cyclic loadings, which means that the brace has good energy dissipative capacity and self‐centering ability, replaceable and recyclable for each component, and stable working performance. The elongation capacity, friction, energy dissipative capacity, and self‐centering ability can be changed by adjusting the relevant key parameters of the spring and wedge block, and the proposed mathematical model can well predict the force‐deformation hysteresis of the brace with different parameters. The results show that the VFA‐SCED brace successfully avoids the main obstacles of previous SCED braces.
Effect of preserved eggs on the health of SD rats, and anti‐tumor action of HT‐29 cells
Authors: Wu Yan , Mao Changyi , Hu Gan , Ma Lulu , Li Shugang , Ma Meihu 
Published: July 2023

AbstractPreserved eggs are traditional alkali‐pickled food in China and have been enjoyed by consumers and extensively studied by researchers for their nutritional tastes and their anti‐tumor, anti‐inflammatory, antioxidant, lipid‐lowering, and blood pressure‐lowering properties. To study the anti‐tumor effects of preserved eggs, this project observed the health on rats, and anti‐tumor effects and separated anti‐tumor active components on HT‐29 cells. SD rats fed for 80 days showed that preserved eggs had no significant effect on weight, food intake, blood pH, liver tissues, or organ indices. Preserved eggs significantly increased blood levels of oxidative stress markers SOD and CAT, decreased MDA levels by 0.46, 0.23, and 0.25 times. Moreover, they also increased the level of IL‐2 from 1233 to 1340 pg/mL. Two water‐soluble bioactive peptide fractions, B1 and B2, with molecular weights ≥10 kDa were further obtained from preserved eggs by ultrafiltration and Superdex Peptide 10/300 GL. The potential mechanism of B1 and B2 is to activate the internal mitochondrial apoptotic pathway and induce apoptosis by up‐regulating the expression of the pro‐apoptotic factors cytochrome C, caspase‐3, and caspase‐9 mRNA in HT‐29 cells.
Reconstructing formation processes at the Canary Islands indigenous site of Belmaco Cave (La Palma, Spain) through a multiproxy geoarchaeological approach
Authors: Fernández‐Palacios Enrique , Jambrina‐Enríquez Margarita , Mentzer Susan M. , Rodríguez de Vera Caterina , Dinckal Ada , Égüez Natalia , Herrera‐Herrera Antonio V. , Navarro Mederos Juan Francisco , Marrero Salas Efraín , Miller Christopher E. , Mallol Carolina 
Published: July 2023

AbstractThe indigenous populations of La Palma (Canary Islands), who arrived on the island from Northwest Africa ca. 2000 years B.P., were predominantly pastoralists. Yet, many aspects of their subsistence economy such as the procurement, management, and use of wild plant resources remain largely unknown. To explore this, we studied the 600–1100‐year‐old archaeological site of Belmaco Cave, which comprises a stratified sedimentary deposit representative of a fumier. Here, we present a high‐resolution, multiproxy geoarchaeological study combining soil micromorphology, lipid biomarker analysis, X‐ray diffraction, μ‐X‐ray diffraction, μ‐X‐ray fluorescence, Fourier transform infrared spectroscopy, and μ‐Fourier transform infrared spectroscopy, to characterize formation processes and explore plant sources. Recurrent goat/sheep habitation and maintenance activities are represented by interstratified layers of unburned dung, charcoal‐rich sediment, and dung ash. Lipid biomarker data show a herd diet mainly composed of herbaceous plants, which is key to understanding the mobility of indigenous shepherds. Our results also revealed an unusual suite of authigenic minerals including hazenite, aragonite, and sylvite, possibly formed through diagenetic processes involving interaction between ash, dung, urine, volcanogenic components, and bacterial activity, coupled with arid and alkaline conditions. Our study shows the potential of a multiproxy approach to a fumier deposit in a volcanogenic sedimentary context.