bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoleamine 2,3‐dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival
Authors: Souissi Sameh , Ghedira Randa , Macherki Yosra , Ben‐Haj‐Ayed Ahlem , Gabbouj Sallouha , Remadi Yasmine , Sfar Imen , Chadli Zohra , Aouam Karim , Hassine Mohsen , Bouaouina Noureddine , Zakhama Abdelfattah , Hassen Elham 
Published: August 2022

AbstractIntroductionIndoleamine 2,3‐dioxygenase (IDO) is an immunosuppressive tryptophan‐depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.MethodsWe evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real‐time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls.ResultsCompared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease‐specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn/Trp ratio in patients with earlier stages (I–II–III) but negatively correlated in patients with the late‐stage cancer (IV). Tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐10 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn/Trp ratio and high plasma IL‐6 and IL‐10 levels at diagnosis died approximately 1 year after first diagnosis.ConclusionMeasuring blood IDO mRNA expression and Kyn/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.
Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in patients with previously untreated non‐germinal centre B‐cell‐like diffuse large B‐cell lymphoma: A Chinese subgroup analysis of the phase III PHOENIX trial
Authors: Zhu Jun , Hong Xiaonan , Song Yu Qin , Hodkinson Brendan , Balasubramanian Sriram , Wang Songbai , Zhang Qingyuan , Shi Yuankai , Huang Huiqiang , Zhang Huilai , Zhu Yan , Shreeve Stephen Martin , Sun Steven , Wang Ze , Wang Xiaocan , Fan Yue , Wilson Wyndham , Vermeulen Jessica 
Published: August 2022

AbstractIn this post hoc subgroup analysis of 200 patients enrolled in China from the phase III PHOENIX trial (N = 838, NCT01855750), addition of ibrutinib to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) did not improve event‐free survival (EFS) versus placebo+R‐CHOP in the intent‐to‐treat (ITT; n = 200, hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0·509–1.349; p = 0.4495) or activated B‐cell‐like (ABC; n = 141 [based on available gene‐expression profiling data], HR = 0.86, 95% CI: 0.467–1.570; p = 0.6160) subpopulations. However, ibrutinib+R‐CHOP improved EFS (HR = 0·50, 95% CI: 0.251–1.003) and progression‐free survival (PFS; HR = 0.48, 95% CI: 0.228–1.009) versus placebo+R‐CHOP in patients aged <60 but not ≥60 years. Grade ≥3 serious treatment‐emergent adverse events occurred more with ibrutinib+R‐CHOP (45·6% vs. 31·3%). The percentage of patients receiving ≥6 cycles of R‐CHOP was similar across treatment arms in those <60 years. A numerical trend was seen towards improved EFS and PFS with ibrutinib+R‐CHOP versus placebo+R‐CHOP in patients with MYC‐high/BCL2‐high co‐expression. In this slightly younger Chinese subgroup, ibrutinib+R‐CHOP did not improve EFS in the ITT and ABC subpopulations but improved outcomes with manageable safety in patients <60 years, consistent with overall PHOENIX study outcomes.
Broadly neutralizing antibodies recognizing different antigenic epitopes act synergistically against the influenza B virus
Authors: Zhai Linlin , Zhang Limin , Jiang Yushan , Li Baisheng , Yang Minghui , Victorovich Khrustalev Vladislav , Aleksandrovna Khrustaleva Tatyana , Li Mengjun , Wang Yuelin , Huang Dong , Zeng Zhujun , Ren Zuning , Cao Hua , Zhu Li , Wu Qinghua , Xiao Weiwei , Zhang Bao , Wan Chengsong , Wang Fuxiang , Xia Ningshao , Zhao Wei , Chen Yixin , Shen Chenguang 
Published: August 2022

AbstractThe discovery of broadly neutralizing monoclonal antibodies against influenza viruses has raised hope for the successful development of new antiviral drugs. However, due to the speed and variety of mutations in influenza viruses, single‐component antibodies that recognize specific epitopes are susceptible to viral escape and have limited efficacy when administration is delayed. Hence, it is necessary to develop alternative strategies with better antiviral activity. Influenza B virus infection can cause severe illness in children and the elderly. Commonly used anti‐influenza drugs have low clinical efficacy against influenza B virus. In this study, we investigated the antiviral efficacy of combinations of representative monoclonal antibodies targeting different antigenic epitopes against the influenza B virus. We found that combinations of antibodies recognizing the hemagglutinin (HA) head and stem regions showed a stronger neutralizing activity than single antibodies and other antibody combinations in vitro. In addition, we found that pair‐wise combinations of antibodies recognizing the HA head region, HA stem region, and neuraminidase enzyme‐activated region showed superior antiviral activity than single antibodies in both mouse and ferret in vivo protection assays. Notably, these antibody combinations still displayed good antiviral efficacy when treatment was delayed. Mechanistic studies further revealed that combining antibodies recognizing different epitope regions resulted in extremely strong antibody‐dependent cell‐mediated cytotoxicity, which may partly explain their superior antiviral effects. Together, the findings of this study provide new avenues for the development of better antiviral drugs and vaccines against influenza viruses.
An ERA5 global climatology of tropical cyclone size asymmetry
Authors: Zhang Kailin , Chan Kelvin T. F. 
Published: August 2022

AbstractThe size of tropical cyclone (TC), defined as the radius of gale‐force (34‐kt) 10‐m winds (R34) from a TC centre, is often asymmetric but received limited attention. Understanding the asymmetry of TC size is particularly essential to enhance the applicability, predictability, and preparedness for the parties in the coastal regions. In this study, the ERA5 reanalysis data are first validated by the QuikSCAT satellite data. Results demonstrate that the radius of ERA5 32‐kt 10‐m winds estimates best R34 in the QuikSCAT satellite data with a promising linear relationship (r = .75). A 41‐year (1979–2019) homogeneous ERA5 global climatology of TC size asymmetry is hence established based on this linear regression model. Both the temporal and spatial characteristics of the TC size asymmetry are investigated and discussed. This study lays the important groundwork for future sophisticated research on TC size.
More frequent consecutive extreme precipitation in the dry regions of China
Authors: Huang Lirong , Du Haibo , Dang Yongcai , He Hong S. , Na Risu , Wu Zhengfang 
Published: August 2022

AbstractPrecipitation extremes occurring on consecutive days may be of crucial importance for the formation of extensive and long‐lasting flooding. Changes in such consecutive extreme precipitation (CEP) events between different regions (i.e., dry and wet regions) still remain unclear in China, which may result in different impacts on human livelihoods and ecosystems. Here, the changes in CEP frequency between dry and wet regions of China were studied by utilizing an observation‐based gridded precipitation dataset. We further determined the driving factors of the changes in CEP frequency by separating the effects of precipitation intensification and temporal clustering of daily extreme precipitation. Our results showed that the CEP frequency in dry regions increased faster (9.73%·decade−1) compared with wet regions (1.14%·decade−1) during the last ~60 years. The increasing precipitation intensity primarily (over 90%) resulted in the increases of CEP events. However, changes in the temporal clustering of daily extreme precipitation can benefit the effects of the changes in precipitation intensity in dry regions but can reverse these effects in wet regions. In dry regions, the regression relationship of precipitation intensity and temperature (7.38%·°C−1) was stronger than that in wet regions (3.44%·°C−1), suggesting that the same magnitude of warming would cause greater precipitation intensity and consequently cause more frequent CEP events in dry regions. Therefore, as the intensification of precipitation and the increasing temporal clustering of daily extreme precipitation, more CEP events may increase the flooding risk in dry regions over China with a stronger warming signal.
Two‐ and three‐dimensional in vitro nucleus pulposus cultures: An in silico analysis of local nutrient microenvironments
Authors: McDonnell Emily E. , Buckley Conor T. 
Published: August 2022

AbstractBackgroundIt is well established that the unique biochemical microenvironment of the intervertebral disc plays a predominant role in cell viability and biosynthesis. However, unless the effect of microenvironmental conditions is primary to a study objective, in vitro culture parameters that are critical for reproducibility are both varied and not routinely reported.AimsThis work aims to investigate the local microenvironments of commonly used culture configurations, highlighting physiological relevance, potential discrepancies, and elucidating possible heterogeneity across the research field.Materials and MethodsThis work uses nutrient‐transport in silico models to reflect on the effect of often underappreciated parameters, such as culture geometry and diffusional distance (vessel, media volume, construct size), seeding density, and external boundary conditions on the local microenvironment of two‐dimensional (2D) and three‐dimensional (3D) in vitro culture systems.ResultsWe elucidate important discrepancies between the external boundary conditions such as the incubator level or media concentrations and the actual local cellular concentrations. Oxygen concentration and cell seeding density were found to be highly influential parameters and require utmost consideration when utilizing 3D culture systems.DiscussionThis work highlights that large variations in the local nutrient microenvironment can easily be established without consideration of several key parameters. Without careful deliberation of the microenvironment within each specific and unique system, there is the potential to confound in vitro results leading to heterogeneous results across the research field in terms of biosynthesis and matrix composition.ConclusionOverall, this calls for a greater appreciation of key parameters when designing in vitro experiments. Better harmony and standardization of physiologically relevant local microenvironments are needed to push toward reproducibility and successful translation of findings across the research field.
Electromembrane extraction of clenbuterol from swine urine for monitoring illegal use in livestock
Authors: Wan Libin , Gao Haidong , Liu Xiao , Gao Shucai , Zhou Li , Wang Fayun , Chen Mantang 
Published: August 2022

The illegal use of clenbuterol seriously endangers food safety and human health. Accurate monitoring of the illegal use of clenbuterol in livestock can efficiently prevent the clenbuterol residue pork products from entering the consumer market. Thus, in this study, a simple, rapid, and sensitive method for the determination of clenbuterol in swine urine was developed using electromembrane extraction combined with liquid chromatography‐tandem mass spectrometry. It should be noted that the electromembrane extraction method presented many advantages of simple operation, fast mass transfer rate, good sample clean‐up capability, and less organic solvent consumption. The effect of important factors on the extraction efficiency of clenbuterol was investigated. Under the optimal conditions, good linearity was achieved for clenbuterol over the range of 1–1000 ng/ml (linear correlation [R2] = 0.9996). The recoveries of clenbuterol in swine urine at three spiked levels ranged from 83.7% to 110.0% with relative standard deviation values lower than 9.7% (n = 4). The limits of detection and quantification for clenbuterol were 0.07 and 0.25 ng/ml, respectively. These results suggested that the proposed method has great potential for the extraction and determination of trace analyte in a complex sample matrix for monitoring illegal use in livestock.
LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR‐126‐5p/GAB1 axis
Authors: Sun Kan‐Da , Ni Yi‐Jiang , Qin Hui , Xu Qing‐Feng 
Published: August 2022

AbstractOral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC‐25 and CAL‐27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT‐qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR‐126‐5p, as well as miR‐126‐5p and GAB1, which were further validated using a dual‐luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR‐126‐5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR‐126‐5p, which directly targeted GAB1. miR‐126‐5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR‐126‐5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR‐126‐5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.
Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients
Authors: Archibald Hunter , Kalland Krystina , Kuehne Alexander , Ondrey Frank , Roby Brianne , Jakubowski Luke 
Published: August 2022

ObjectiveThere is a lack of data supporting cancer surveillance in pediatric Fanconi Anemia patients. We sought to describe the rates of upper aerodigestive lesions and malignancy in this population to augment current management guidelines.MethodsA retrospective cohort study of patients with Fanconi Anemia from a quaternary referral center between 2007–2021 was completed for head and neck cancer risk.ResultsOne hundred and five FA patients were reviewed. Average age at presentation was 11.3 years old and 90.5% of patients underwent hematopoietic stem cell transplant (HSCT). A total of 8.6% of patients had leukoplakia or erythroplakia and 3.8% developed malignancy. The standardized incidence ratio of head and neck malignancy was 483.8. Patients presented with leukoplakia and malignancy at an average age of 14.6 and 25.1 years old, respectively. Malignancies were aggressive and marked by recurrence. There were no premalignant or malignant lesions found on flexible laryngoscopy. This series represents the largest longitudinal series of pediatric FA head and neck lesions.ConclusionsFanconi Anemia patients should begin screening for head and neck cancer at age 10 or after HSCT.Level of EvidenceLevel 4 Laryngoscope, 133:1745–1748, 2023
Assessment of the influence of benzalkonium chloride addition on radiocarbon analysis of dissolved inorganic carbon
Authors: Takahashi Hiroshi A. , Minami Masayo 
Published: August 2022

AbstractThis study aimed to assess whether benzalkonium chloride (BAC) addition to water samples could be used as a disinfectant in the radiocarbon (14C) analysis of dissolved inorganic carbon (DIC). We investigated the effectiveness of BAC addition in inhibiting 14C changes in DIC due to microbial activity during water preservation. The DIC and 14C concentration of natural waters (groundwater, seawater, river water, and lake water) without BAC increased by 1.4–3.3 mg L−1 and 1.8–4.2 percent modern carbon (pMC) for 2 weeks, and 2.2–7.9 mg L−1 and 3.0–11.9 pMC for 4 weeks, respectively, while none of the BAC‐treated water samples, excluding seawater, exhibited changes in DIC or 14C concentration. Although slight increases in DIC and 14C concentrations in seawater with BAC treatment were observed, 0.4 mg L−1 and 0.4 pMC for 2 weeks, and 1.6 mg L−1 and 1.5 pMC for 4 weeks, respectively, these changes were 20–40% lower than that in seawater without BAC treatment. Furthermore, carbon contamination into the sample water due to BAC decomposition and BAC‐induced microorganism decomposition was negligible in 14C analysis, albeit using BAC solution without atmospheric CO2 contamination could be a significant issue. Our results demonstrate that BAC is an effective inhibitor of biological DIC changes for 14C analysis of freshwater samples, although slightly less effective in seawater
Topological Chiral Edge States in Deep‐Subwavelength Valley Photonic Metamaterials
Authors: Xi Rui , Chen Qiaolu , Yan Qinghui , Zhang Li , Chen Fujia , Li Ying , Chen Hongsheng , Yang Yihao 
Published: August 2022

AbstractTopological valley photonics has emerged as a new frontier in photonics with many promising applications. Previous valley boundary transport relies on kink states at internal boundaries between two topologically distinct domains. However, recent studies have revealed a novel class of topological chiral edge states (CESs) at external boundaries of valley materials, which have remained elusive in photonics. Here, topological CESs are proposed and experimentally demonstrated in valley photonic metamaterials (VPMMs) by accurately tuning on‐site edge potentials. Moreover, the VPMMs work at deep‐subwavelength scales. Thus, the supported CESs are highly confined and self‐guiding without relying on a cladding layer to prevent leakage radiation. Via direct near‐field measurements, the bulk bandgap, the edge dispersions, and the robust edge transport passing through sharp corners, which are hallmark signatures of the CESs, are observed. This work paves a way to explore novel topological edge states in valley photonics and sheds light on robust and miniaturized photonic devices.
Ultra‐High Modulus Hydrogels Mimicking Cartilage of the Human Body
Authors: Demott Connor J. , Jones McKenzie R. , Chesney Caleb D. , Yeisley Daniel J. , Culibrk Robert A. , Hahn Mariah S. , Grunlan Melissa A. 
Published: August 2022

AbstractThe human body is comprised of numerous types of cartilage with a range of high moduli, despite their high hydration. Owing to the limitations of cartilage tissue healing and biological grafting procedures, synthetic replacements have emerged but are limited by poorly matched moduli. While conventional hydrogels can achieve similar hydration to cartilage tissues, their moduli are substantially inferior. Herein, triple network (TN) hydrogels are prepared to synergistically leverage intra‐network electrostatic repulsive and hydrophobic interactions, as well as inter‐network electrostatic attractive interactions. They are comprised of an anionic 1st network, a neutral 2nd network (capable of hydrophobic associations), and a cationic 3rd network. Collectively, these interactions act synergistically as effective, yet dynamic crosslinks. By tuning the concentration of the cationic 3rd network, these TN hydrogels achieve high moduli of ≈1.5 to ≈3.5 MPa without diminishing cartilage‐like water contents (≈80%), strengths, or toughness values. This unprecedented combination of properties poises these TN hydrogels as cartilage substitutes in applications spanning articulating joints, intervertebral discs (IVDs), trachea, and temporomandibular joint disc (TMJ).
Yogurt Benefits Bone Mineralization in Ovariectomized Rats with Concomitant Modulation of the Gut Microbiome
Authors: He Weiwei , Xie Zhuqing , Wittig Nina Kølln , Zachariassen Line F. , Andersen Amanda , Andersen Henrik J. , Birkedal Henrik , Nielsen Dennis S. , Hansen Axel K. , Bertram Hanne Christine 
Published: August 2022

ScopeEvidence supports that gut‐modulating foods potentially can suppress bone loss in postmenopausal women. This study aims to investigate the effect of milk calcium‐enriched milk, yogurt, and yogurt‐inulin combination on the gut–bone association.Methods and resultsA 6‐week intervention study is conducted in ovariectomized rats. Four pastes containing milk calcium‐fortified milk (M‐Ca), milk calcium‐fortified yogurt (Y‐Ca), inulin‐fortified Y‐Ca (Y‐I‐Ca), or an isoconcentration of calcium carbonate (Ca‐N), and a calcium‐deficient paste are provided. M‐Ca does not influence bone mineral density and content (BMD and BMC), femur mechanical strength, or femoral microstructure compared to Ca‐N, but Y‐Ca increases spine BMD. The serum metabolome reveals that Y‐Ca modulated glycine‐related pathways with reduced glycine, serine, and threonine. No additive effects of yogurt and inulin are found on bone parameters. Correlation analysis shows that increased lactobacilli and reduced Clostridiaceae members in Y‐Ca is associated with an increased spine BMD. Increases in Bifidobacterium pseudolongum, Turicibacter, Blautia, and Allobaculum and gut short‐chain fatty acids in Y‐I‐Ca are not reflected in bone parameters.ConclusionYogurt as calcium vehicle contributes to increased spine BMD concomitant with changes in the gut microbiome and glycine‐related pathways, while adding inulin to yogurt does not affect bone mineralization in ovariectomized rats.
Maximizing reachability in a temporal graph obtained by assigning starting times to a collection of walks
Authors: Brunelli Filippo , Crescenzi Pierluigi , Viennot Laurent 
Published: August 2022

AbstractIn a temporal graph, each edge appears and can be traversed at specific points in time. In such a graph, temporal reachability of one node from another is naturally captured by the existence of a temporal path where edges appear in chronological order. Inspired by the optimization of bus/metro/tramway schedules in a public transport network, we consider the problem of turning a collection of walks (called trips) in a directed graph into a temporal graph by assigning a starting time to each trip in order to maximize the reachability among pairs of nodes. Each trip represents the trajectory of a vehicle and its edges must be scheduled one right after another. Setting a starting time to the trip thus forces the appearance time of all its edges. We call such a starting time assignment a trip temporalization. We obtain several results about the complexity of maximizing reachability via trip temporalization. Among them, we show that maximizing reachability via trip temporalization is hard to approximate within a factor in an ‐vertex digraph, even if we assume that for each pair of nodes, there exists a trip temporalization connecting them. On the positive side, we show that there must exist a trip temporalization connecting a constant fraction of all pairs if we additionally assume symmetry, that is, when the collection of trips to be scheduled is such that, for each trip, there is a symmetric trip visiting the same nodes in reverse order.