bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of KIT and FLT3‐ITD mutation status with minimal residual disease levels guides treatment strategy for adult patients with inv(16) acute myeloid leukemia in first complete remission
Authors: Wang Jun , Dao Feng‐Ting , Wang Yu , Jiang Hao , Xu Lan‐Ping , Zhao Xiao‐Su , Zhang Xiao‐Hui , Liu Kai‐Yan , Huang Xiao‐Jun , Jiang Qian , Qin Ya‐Zhen 
Published: May 2022

AbstractAlthough several studies have investigated the benefits of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for patients with inv (16) acute myeloid leukemia (AML) in first complete remission (CR1) individually stratified by KIT or FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) mutation status or minimal residual disease (MRD) levels, evaluation based on the combination of mutation status and MRD levels remains absent. This study included 157 adult patients with inv (16) AML who were consecutively diagnosed and receiving treatment at our center. A total of 50 (31.6%) patients had KIT mutations (KITMU), and the risk of relapse was significantly higher in patients with KITMU than in patients with KITWT (p < 0.001). A total of 12 patients (7.6%) had FLT3‐ITD, and FLT3‐ITD+ tended to be related to a higher risk of relapse (p = 0.14). KITMU, FLT3‐ITD and MRD3‐H (beta subunit of core binding factor–myosin heavy chain 11 levels >0.2% after course 2 of consolidation therapy) were independent adverse prognostic factors for relapse with patients who received allo‐HSCT at CR1 were censored at the time of transplantation. After combination, patients were categorized into molecularly defined high‐risk (M‐HR; KITMU or FLT3‐ITD+ with MRD3‐H; n = 30), low‐risk (M‐LR; KITWT and FLT3‐ITD‐ with MRD3‐L; n = 45) and intermediate‐risk (M‐IR; others; n = 70) groups. For the M‐HR group, allo‐HSCT significantly improved both cumulative incidence of relapse cumulative incidence of relapse (CIR) and overall survival (OS) (11.1% vs. 92.6%, p < 0.001; 90.0% vs. 34.1%, p = 0.019). For the M‐IR group, allo‐HSCT significantly improved CIR but did not affect OS (14.1% vs. 62.2%, p = 0.0004; 73.3% vs. 68.3%, p = 0.43). For the M‐LR group, allo‐HSCT had no significant effect on both CIR and OS (0% vs. 35.1%, p = 0.31; 100% vs. 78.8%, p = 0.22). Therefore, the combination of KIT and FLT3‐ITD mutation status with MRD levels may identify inv (16) AML patients with high‐risk who can benefit from allo‐HSCT in CR1.
Dynamic modeling of a water tube boiler
Authors: Jha R. S. , Lele Mandar M. 
Published: May 2022

AbstractThe present work aims to develop an integrated heat transfer and hydrodynamic model for the study of boiler dynamics in fluctuating load conditions. A transient heat transfer model has been developed to estimate water side heat transfer and it is directly integrated with the hydrodynamic model. Two independent natural circulation circuits for furnace water wall and convection tube bank have been considered due to differences in heat transfer, dryness fraction, and void fraction. The transient heat transfer model calculates the heat transfer and water wall temperature of the various sections to calculate total gas side heat transfer, gas temperature profile, and waterside heat transfer in the furnace water wall and convection tube bank. Mass momentum and energy conservation equations are generated for both natural circulation circuits using the estimated value of waterside heat transfer of the transient heat transfer model. These equations are integrated with mass and energy conservation equations for the drum below water level and drum above water level to generate a system of equations to estimate drum pressure and water level fluctuation. This model has been extended for boiler feedback control systems, including the load management and the water level control system.
Event scale hydrograph responses highlight impacts of widespread stream burial and urban infrastructure failures
Authors: Forgrave Rebecca , Elliott Emily M. , Bain Daniel J. 
Published: May 2022

AbstractFast hydrologic responses to storms in urban areas are often attributed to high percentages of impervious surfaces; however, another factor affecting urban storm response is channel burial. No previous studies have documented storm event responses in buried streams despite how common stream burial is in urban areas, with some US cities having over 75% of all headwater channels buried. Understanding event dynamics is particularly important as climate change predictions suggest an increase in frequency of high intensity storms and urban flooding. This study used 15‐min precipitation and discharge data over a period of 6.5 years to categorize storm event responses in Nine Mile Run, an urban watershed in Pittsburgh, Pennsylvania where 98% of all channels are buried. Extensive stream burial led to lower watershed retention capacity and resulted in faster storm event responses relative to other urban streams with comparable imperviousness. Additionally, urban water subsidies in the form of sewer overflows, hydrant flushing, or water line breaks can have measurable contributions to flow event responses and result in seemingly unfeasible runoff ratios. This study demonstrates novel watershed runoff responses in systems dominated by subsurface infrastructure, which play a key role in urban water balance. Additionally, this study highlights the fact that stream restoration is not a universal solution to urban stream flashiness because downstream restoration cannot resolve the impacts of upstream burial.
Blends of gelatin and hyaluronic acid stratified by stereolithographic bioprinting approximate cartilaginous matrix gradients
Authors: Shopperly Lennard K. , Spinnen Jacob , Krüger Jan‐Philipp , Endres Michaela , Sittinger Michael , Lam Tobias , Kloke Lutz , Dehne Tilo 
Published: May 2022

AbstractStereolithographic bioprinting holds great promise in the quest for creating artificial, biomimetic cartilage‐like tissue. To introduce a more biomimetic approach, we examined blending and stratifying methacrylated hyaluronic acid (HAMA) and methacrylated gelatin (GelMA) bioinks to mimic the zonal structure of articular cartilage. Bioinks were suspended with porcine chondrocytes before being printed in a digital light processing approach. Homogenous constructs made from hybrid bioinks of varying polymer ratios as well as stratified constructs combining different bioink blends were cultivated over 14 days and analyzed by histochemical staining for proteoglycans/collagen type II, cartilage marker expression analysis, and for cellular viability. The stiffness of blended bioinks increased gradually with HAMA content, from 2.41 ± 0.58 kPa (5% GelMA, 0% HAMA) to 8.84 ± 0.11 kPa (0% GelMA, 2% HAMA). Cell‐laden constructs maintained vital chondrocytes and supported the formation of proteoglycans and collagen type II. Higher concentrations of GelMA resulted in increased formation of cartilaginous matrix proteins and a more premature phenotype. However, decreased matrix production in central areas of constructs was observed in higher GelMA content constructs. Biomimetically stratified constructs retained their gradient‐like structure even after ECM formation, and exclusively exhibited a significant increase in COL2A1 gene expression (+178%). Concluding, we showed the feasibility of blending and stratifying photopolymerizable, natural biopolymers by SLA bioprinting to modulate chondrocyte attributes and to create zonally segmented ECM structures, contributing to improved modeling of cartilaginous tissue for regenerative therapies or in vitro models.
Identification of a novel lncRNA‐miRNA‐mRNA competing endogenous RNA network associated with prognosis of breast cancer
Authors: Wan Xiaohui , Hao Shuhong , Hu Chunmei , Qu Rongfeng 
Published: May 2022

AbstractRecently, the effects of competing endogenous RNA (ceRNA) on molecular biological mechanism of cancer have aroused great interest. In this study, long noncoding RNA‐microRNA‐messenger RNA (lncRNA‐miRNA‐mRNA) ceRNA network was screened and constructed based on the Cancer Genome Atlas (TCGA) database, and its efficacy in predicting the prognosis of breast cancer patients was evaluated. The RNA‐sequencing, miRNA‐sequencing, and corresponding clinical information were downloaded from the TCGA database, and differentially expressed genes were screened after data searching. The similarity between two groups of genes was analyzed by weighted correlation network analysis (WGCNA). Next, the interaction among lncRNA, miRNA, and mRNA was predicted followed construction of the lncRNA‐miRNA‐mRNA ceRNA network. Finally, univariate and multivariate Cox regression analysis was used to screen prognostic factors to construct prognostic risk model. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of this model in predicting the prognosis of breast cancer patients. In total 5056 differentially expressed lncRNAs, 712 differentially expressed miRNAs, and 9878 differentially expressed mRNAs were identified in breast cancer tissues. WGCNA predicted that 823 lncRNAs and 1813 mRNAs were closely related to breast cancer. The lncRNA‐miRNA‐mRNA ceRNA network involved in breast cancer was constructed based on 27 lncRNA, 14 miRNAs, and 4 mRNAs. ZC3H12B, HRH1, TMEM132C, and PAG were the possible independent risk factors for the prognosis of breast cancer patients with the area under the signal characteristic curve under ROC curve of 0.609. This study suggested that the prognosis risk model based on ZC3H12B, HRH1, TMEM132C, and PAG1 accurately predicted the prognosis of breast cancer patients.
Gliadin induced oxidative stress and altered cellular responses in human intestinal cells: An in‐vitro study to understand the cross‐talk between the transcription factor Nrf‐2 and multifunctional APE1 enzyme
Authors: Gupta Kunj Bihari , Dhiman Monisha , Mantha Anil Kumar 
Published: May 2022

AbstractThe present study examined the wheat protein gliadin‐induced oxidative and nitrosative stress and its downstream responses in human intestinal HCT‐116 and HT‐29 cells. The beneficial role of dietary phytochemical curcumin and role of multifunctional enzyme Apurinic/aprymidinic endonuclease 1 (APE1) a major player involved in the base excision repair (BER)‐pathway in gliadin intolerant intestinal HCT‐116 and HT‐29 cell lines were evaluated as an in vitro model study. The cultured cells were exposed to gliadin protein, H2O2, and curcumin followed by the assessment of oxidative stress and the consequences were measured using spectrophotometric, PCR, flow cytometer, Western blotting, confocal microscopy, and other methods. Results demonstrate that a 3 h pretreatment of curcumin, followed by the treatment of gliadin protein for 24 h time period protected both the HCT‐116 and HT‐29 cells via: (i) decreasing the ROS/RNS, restoring the mitochondrial transmembrane potential; (ii) re‐establishing the cellular antioxidant defense system (superoxide dismutase, catalase, and GSH); (iii) enhancing the functions of APE1 viz. endonuclease activity and redox activation of transcription factor Nrf‐2, the later binds with the antioxidant response elements (ARE) and activates downstream targets involved in cell survival. The cross‐talk between APE1 and Nrf‐2 was also established using immunofluorescence imaging and co‐immunoprecipitation assays. In conclusion, gliadin protein induces oxidative/nitrosative stress, mitochondrial dysfunction and it damages cellular biomolecules in the intestinal cells. Hence it can be attributed to the tissue damage and disease pathogenesis in wheat intolerance‐associated intestinal diseases. The gliadin‐induced stress and its consequences are significantly reduced by the pretreatment of curcumin via BER‐pathway and ARE‐pathway; which is evident through the interaction between these two essential proteins. Hence suggesting for the intervention of curcumin and other natural dietary phytochemicals‐based disease management and treatment of gliadin intolerance associated intestinal diseases like celiac disease.
Nucleocapsid protein of SARS‐CoV‐2 is a potential target for developing new generation of vaccine
Authors: Feng Weixu , Xiang Yunru , Wu Lianpeng , Chen Zhuo , Li Qingfeng , Chen Jun , Guo Yanru , Xia Dandan , Chen Na , Zhang Lifang , Zhu Shanli , Zhao Kong‐Nan 
Published: May 2022

AbstractBackgroundSARS‐CoV‐2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS‐CoV‐2 are facing great challenge from the infection of SARS‐CoV‐2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS‐CoV‐2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS‐CoV‐2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines.MethodsThe N protein of SARS‐CoV‐2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID‐19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA.ResultsThe N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID‐19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine‐IFN‐γ were produced in the N protein‐immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice.ConclusionSARS‐CoV‐2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS‐CoV‐2 and its variants.
Novel combined UGT1A1 mutations in Crigler Najjar Syndrome type I
Authors: Abdellaoui Nawel , Abdelmoula Balkiss , Abdelhedi Rania , Kharrat Najla , Tabebi Mouna , Rebai Ahmed , Bouayed Abdelmoula Nouha 
Published: May 2022

AbstractBackgroundUridine diphosphate‐glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5–8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. The A (TA) 7TAA allele has been identified as the most frequent allele in the Caucasian populations while A (TA) 8TAA allele remains the rarest allele worldwide in North Africa, including the Arab populations.MethodsThe spectrum of UGT1A1 genetic mutations in seventeen Tunisian children affected by persistent unconjugated hyperbilirubinemias is represented in addition to their relatives, notably parents, sisters, and brothers. Tunisian children, from 16 unrelated families as well as a 17th family without CN1 affected child, were originated from the West Center of Tunisia. The promoter region and coding exons of the UGT1A1 were PCR amplified, subsequently subjected to Sanger sequencing.ResultsThe frequencies of genotypes in CN1 patients were as follows (TA) (7/7) (12/17: 70.6%) and (TA) (8/8) (5/17: 29.4%). All patients harbored the c.1070A>G mutation of exon 3 (UGT1A1*16) in the homozygous state. Among relatives of our patients (n = 16), who were all heterozygotes for UGT1A1*16, 13/16 (81.25%) had a heterozygous state for UGT1A1∗1/UGT1A1∗28 or (TA) (6/7) and, 18.75% (3/16) were heterozygous for UGT1A1∗28/UGT1A1∗37 or (TA) (7/8) of the promoter polymorphisms.ConclusionUGT1A1*16 accompanied with UGT1A1*28 or UGT1A1*37 had a specific geographic and ethnic distribution for CN pathogenesis in this Tunisian cohort.
The socio‐ecological psychology of residential mobility
Authors: Oishi Shigehiro , Tsang Shelly 
Published: May 2022

AbstractFrom ancient time, Homo sapiens moved around in search of a better life. Although the development of agriculture and industrialization no longer necessitates frequently moving to find new food sources, people today still change their residences for a variety of reasons. This article highlights key findings from residential mobility, focusing on its implications for the self, social relationships, societies, and well‐being. Generally, residential mobility shifts individual attention away from collective attributes toward personal attributes. It also changes people's relationship styles and preferences, leading individuals to favor wider social networks, more open communication, low‐commitment groups, and egalitarian helpers. In addition, it increases tolerance for norm violations and moral deviations. Lastly, residential mobility can explain some cross‐national and within‐nation variations. This article reviews recent psychological research on residential mobility and then discusses limitations, paradoxical findings, and future directions.
Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer
Authors: Almeida Anna , Gabriel Marc , Firlej Virginie , Martin‐Jaular Lorena , Lejars Matthieu , Cipolla Rocco , Petit Floriane , Vogt Nicolas , San‐Roman Mabel , Dingli Florent , Loew Damarys , Destouches Damien , Vacherot Francis , de la Taille Alexandre , Théry Clotilde , Morillon Antonin 
Published: May 2022

AbstractLong noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and antitumourigenic functions by controlling the immune response. In contrast to extracellular nonvesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and have compared them with their tissue of origin. Here, we performed Total RNA‐Sequencing on six Formalin‐Fixed‐Paraffin‐Embedded (FFPE) prostate cancer (PCa) tumour tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron‐free cytoplasmic transcripts and enriched lnc/circular (circ)RNAs, strikingly common to an independent 20 patients’ urinary cohort. Our full cellular and EVs transcriptome comparison within three PCa cell lines identified a set of overlapping 14 uEV‐circRNAs characterized as essential for prostate cell proliferation in vitro and 28 uEV‐lncRNAs belonging to the cancer‐related lncRNA census (CLC2). In addition, we found 15 uEV‐lncRNAs, predicted to encode 768 high‐affinity neoantigens, and for which three of the encoded‐ORF produced detectable unmodified peptides by mass spectrometry. Our dual analysis of EVs‐lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV‐lnc/circRNAs phenotypic characterization involved in PCa.
Liver cancer cells with nuclear MET overexpression release translation regulatory protein‐enriched extracellular vesicles exhibit metastasis promoting activity
Authors: Tey Sze Keong , Wong Samuel Wan Ki , Yeung Cherlie Lot Sum , Li Jason Ying Ki , Mao Xiaowen , Chung Clive Yik Sham , Yam Judy Wai Ping 
Published: May 2022

AbstractMET receptor tyrosine kinase is a cell surface receptor that plays important role in embryonic development and tissue regeneration. Aberrant MET activation has been widely reported in different human cancers, making MET an attractive therapeutic target. The presence of truncated MET within the nucleus (nMET) with potential novel functions poses a great challenge to the current therapeutic strategies against MET surface receptor. Previous work has demonstrated the promoting effect of nMET in aggressive properties of hepatocellular carcinoma (HCC) cells by activating TAK1/NF‐κB signalling pathway. Herein, we report the role of nMET in modulating tumour microenvironment and tumour metastasis mediated by extracellular vesicles (EVs). EVs released by nMET overexpressing cells enhanced cell motility and provoked metastasis. Proteomic profiling revealed the enrichment of translational regulatory proteins in EVs derived from nMET overexpressing cells. These proteins include eukaryotic initiation factor (EIF), ribosomal protein small subunit (RPS) and ribosomal protein larger subunit (RPL) gene families. Knockdown of EIF3I, RPS3A and RPL10 diminished the promoting effect of EVs in cell migration invasiveness and metastasis. In conclusion, the findings reveal an unrecognized capacity of nMET to augment HCC through the release of EVs with oncogenic effect. Targeting these translation‐related proteins may serve as an alternative treatment for patients with nMET overexpression.
Hamiltonian decompositions of 4‐regular Cayley graphs of infinite abelian groups
Authors: Erde Joshua , Lehner Florian 
Published: May 2022

AbstractA well‐known conjecture of Alspach says that every ‐regular Cayley graph of a finite abelian group can be decomposed into Hamiltonian cycles. We consider an analogous question for infinite abelian groups. In this setting one natural analogue of a Hamiltonian cycle is a spanning double‐ray. However, a naive generalisation of Alspach's conjecture fails to hold in this setting due to the existence of ‐regular Cayley graphs with finite cuts , where and differ in parity, which necessarily preclude the existence of a decomposition into spanning double‐rays. We show that every 4‐regular Cayley graph of an infinite abelian group all of whose finite cuts are even can be decomposed into spanning double‐rays, and so characterise when such decompositions exist. We also characterise when such graphs can be decomposed either into Hamiltonian circles, a more topological generalisation of a Hamiltonian cycle in infinite graphs, or into a Hamiltonian circle and a spanning double‐ray.
Advance directives completion and hospital out‐of‐pocket expenditures
Authors: Zhu Yujun , Enguidanos Susan 
Published: May 2022

AbstractIntroductionHealth care costs remain high at the end of life. It is not known if there is a relationship between advance directive (AD) completion and hospital out‐of‐pocket costs. This analysis investigated whether AD completion was associated with lower hospital out‐of‐pocket costs at end of life.MethodsWe used Health and Retirement Study participants who died between 2000 and 2014 (N = 9228) to examine the association between AD completion status and hospital out‐of‐pocket spending in the last 2 years of life through the use of a two‐part model controlling for socioeconomic status, death‐related characteristics and health insurance coverage.ResultsAbout 44% of decedents had completed ADs. Having an AD was significantly associated with $673 lower hospital out‐of‐pocket costs, with a higher magnitude of savings among younger decedents. Decedents who completed ADs 3 months or less before death had higher out‐of‐pocket costs ($1854 on average) than those who completed ADs more than 3 months before death ($1176 on average).ConclusionsAD completion was significantly associated with lower hospital out‐of‐pocket costs, with greater out‐of‐pocket savings among younger decedents. Early AD completers experienced lower costs than decedents who completed ADs closer to death.
「いわゆる日本型ER」のありかた提言 初版(Proposal for an ideal “Japanese–style ER”: First Edition)
Authors: (Emergency Department Review Committee, Japanese Association 日本救急医学会 救急外来部門検討委員会 
Published: May 2022

要旨【背景】初期・二次救急を含む幅広い救急診療を行う能力を持つ医師が求められている。そのようななか「『いわゆる日本型ERのありかた』につき検討する」という課題に取り組んだ。【方法】欧米における救急医のありかたおよび教育体制を参考に，日本の社会情勢に適した救急診療のありかたにつき議論を行った。【結果】「診療領域・重症度を問わない救急外来診療を専門に行う医師」の専門性確立のための枠組み整備が重要課題として抽出された。我々は，診療科を問わない初期・二次救急診療において，専門性を発揮できる医師を“Emergency Physician”と位置づけ，備えるべき技能・プロフェッショナリズムを，Milestoneの形式で提示することとした。また，救急外来という“場所”に備えるべき機能を，地域救急システムの中で担うべき役割を考慮し，提示した。【結論】我々は，Emergency Physicianが救急科専門医のsubspecialtyの一つとして位置づけられることが望ましいと考える。将来的には公的なライセンスとして確立されるべく，本提言をたたき台として今後議論が深まることを期待する。救急医の常駐化が必須とされるであろう将来を見据え，救急外来診療においてEmergency Physicianが有機的に機能することにより，救急患者診療の質向上につながると確信している。