bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma
Authors: Job Sylvie , Rapoud Delphine , Dos Santos Alexandre , Gonzalez Patrick , Desterke Christophe , Pascal Gérard , Elarouci Nabila , Ayadi Mira , Adam René , Azoulay Daniel , Castaing Denis , Vibert Eric , Cherqui Daniel , Samuel Didier , Sa Cuhna Antonio , Marchio Agnès , Pineau Pascal , Guettier Catherine , de Reyniès Aurélien , Faivre Jamila 
Published: December 2019

Background and Aims
Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME‐based classification of ICC tumors that detects potentially targetable ICC subtypes.

Approach and Results
We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population‐counter package and compared with immunohistochemistry. We performed an unsupervised TME‐based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME‐based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor‐infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival.

Conclusion
We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.
Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches
Authors: Kim Borahm , Kim Esl , Lee Seung‐Tae , Cheong June‐Won , Lyu Chuhl Joo , Min Yoo Hong , Choi Jong Rak 
Published: December 2019

AbstractIdentification of gene fusion is an essential part in the management of patients with acute leukemia, not only for diagnosis but also in predicting the treatment outcome and selecting appropriate treatment. Adopting next‐generation sequencing (NGS) technology for identification of gene fusion in patients with acute leukemia can be a good alternative to conventional tests. In the present study, the NGS RNA fusion gene panel test was applied to diagnostic samples of patients with acute leukemia to identify fusion genes more efficiently. Among 134 patients with acute leukemia, 53 gene fusions were detected in 52 patients. In addition to the recurrent gene fusions specified in the WHO diagnostic criteria, 11 rare or novel gene fusions were identified. Of those, two were gene fusions associated with Philadelphia‐like acute lymphoblastic leukemia (Ph‐like ALL), two were novel gene fusions, three were gene fusions with novel partner genes, and six were rare gene fusions from previous reports. We confirmed the clinical utility of the NGS test in identifying clinically significant gene fusions such as gene fusions involving KMT2A that has a large number of partners. Notably, Ph‐like ALL‐associated gene fusions could be easily identified despite the wide variety of genes involved. The results from the present study may contribute toward a better understanding of the genomic landscape of acute leukemia as well as patient management.
The isotope hydrology of the Muskoka River Watershed, Ontario, Canada
Authors: James April L. , Dusome Emily , Field Tim , Yao Huaxia , McConnell Chris , Beaton Andy , Tafvizi Arghavan 
Published: December 2019

AbstractStable isotope tracers of δ18O and δ2H are increasingly being applied in the study of water cycling in regional‐scale watersheds in which human activities, like river regulation, are important influences. In 2015, δ18O and δ2H were integrated into a water quality survey in the Muskoka River Watershed with the aim to provide new regional‐scale characterization of isotope hydrology in the 5,100‐km2 watershed located on the Canadian Shield in central Ontario, Canada. The forest dominated region includes ~78,000 ha of lakes, 42 water control structures, and 11 generating stations, categorized as “run of river.” Within the watershed, stable isotope tracers have long been integrated into hydrologic process studies of both headwater catchments and lakes. Here, monthly surveys of δ18O and δ2H in river flow were conducted in the watershed between April 2015 and November 2016 (173 surface water samples from 10 river stations). Temporal patterns of stable isotopes in river water reflect seasonal influences of snowmelt and summer‐time evaporative fractionation. Spatial patterns, including differences observed during extreme flood levels experienced in the spring of 2016, reflect variation in source contributions to river flow (e.g., snowmelt or groundwater versus evaporatively enriched lake storage), suggesting more local influences (e.g., glacial outwash deposits). Evidence of combined influences of source mixing and evaporative fractionation could, in future, support application of tracer‐enabled hydrological modelling, estimation of mean transit times and, as such, contribute to studies of water quality and water resources in the region.
Dysmorphic concern and behavioural impairment related to body image in adolescents
Authors: Senín‐Calderón Cristina , Gálvez‐González Jenifer , Perona‐Garcelán Salvador , Camacho Carlos , Rodríguez‐Testal Juan F. 
Published: December 2019

This study examined a moderated mediation model testing whether dysmorphic concern is related to behaviour altered to change appearance. This relationship is potentially mediated by depressive symptomatology (dysphoria and self‐esteem) and ideas of reference about “laughing, commenting” and “attention, appearance,” and each mediated relationship moderated by sex. The sample was made up of 3377 adolescents from 12 to 18 years old (Mage = 14.52; SD = 1.65, 56.5% girls). The results showed that dysphoria and ideas of reference about “laughing, commenting” and “attention, appearance” partially mediated the relationship between dysmorphic concern and behavioural impairment related to body image. The relationship with dysphoria was moderated by sex, such that the mediation effect was stronger in girls than in boys. This result implies that girls who are worried about some characteristic of their appearance and show dysphoria are at greater risk of altered behaviour involving avoidance or controlling their appearance than boys. In addition, a possible risk of body dysmorphic disorder (3.45% of the sample) was found, with very prominent hiding behaviour using clothing or control behaviours, such as frequent weighing and looking at oneself in the mirror too much. Implications of these findings are discussed.
Medical image fusion based on laws of texture energy measures in stationary wavelet transform domain
Authors: Ganasala Padma , Prasad Achanta Durga 
Published: December 2019

AbstractMedical image fusion is widely used in various clinical procedures for the precise diagnosis of a disease. Image fusion procedures are used to assist real‐time image‐guided surgery. These procedures demand more accuracy and less computational complexity in modern diagnostics. Through the present work, we proposed a novel image fusion method based on stationary wavelet transform (SWT) and texture energy measures (TEMs) to address poor contrast and high‐computational complexity issues of fusion outcomes. SWT extracts approximate and detail information of source images. TEMs have the capability to capture various features of the image. These are considered for fusion of approximate information. In addition, the morphological operations are used to refine the fusion process. Datasets consisting of images of seven patients suffering from neurological disorders are used in this study. Quantitative comparison of fusion results with visual information fidelity‐based image fusion quality metric, ratio of spatial frequency error, edge information‐based image fusion quality metric, and structural similarity index‐based image fusion quality metrics proved the superiority. Also, the proposed method is superior in terms of average execution time to state‐of‐the‐art image fusion methods. The proposed work can be extended for fusion of other imaging modalities like fusion of functional image with an anatomical image. Suitability of the fused images by the proposed method for image analysis tasks needs to be studied.
The effect of burnout on postgraduate year‐one pharmacy residents' pursuit of additional training
Authors: Hammond Drayton A. , Swanson Joseph M. , Rech Megan A. 
Published: December 2019

AbstractBackgroundThe decision for postgraduate year one (PGY1) pharmacy residents to pursue additional postgraduate training (PGT) is impacted by a variety of internal and external factors. The purpose of this research was to evaluate burnout in PGY1 residents and its impact on the decision to pursue additional PGT, most commonly postgraduate year two (PGY2) training.MethodsPharmacy residents were surveyed in February and March 2018 regarding burnout, demographics, and intention to pursue additional PGT. Two respondent groups were developed: additional PGT and no additional PGT. Burnout domains (emotional exhaustion, depersonalization, and personal fulfillment) and profiles (engaged, ineffective, overextended, disengaged, and burnout) were compared between groups. A multivariable logistic regression was conducted to determine variables associated with additional PGT pursuit.ResultsOf 539 PGY1 residents who participated, 313 (58.1%) were in the additional PGT group. Those in the no additional PGT group scored higher in emotional exhaustion (median 24, interquartile range [IQR] 19‐29 vs median 21, IQR 17‐26) and depersonalization (median 11, IQR 9‐13 vs median 11, IQR 9‐13) and lower in personal fulfillment (median 14, IQR 11‐17 vs median 16, IQR 12‐19). Following multivariable logistic regression analysis, not having the burnout profile (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.29‐0.98) and opportunity to complete PGY2 training at the PGY1 institution (OR 0.30, 95% CI 0.23‐0.40) were associated with additional PGT pursuit. PGY1 residents in the no additional PGT group were categorized as more frequently having a burnout profile (36.3% vs 23.0%).ConclusionPGY1 residents pursuing or planning to pursue additional PGT felt less burned out than those not pursuing additional PGT. Opportunity to complete PGY2 training at the resident's PGY1 institution and not having a burnout profile were associated with pursuit of additional PGT.
Retinoid X receptor α (RXRα)‐mediated erythroid‐2‐related factor‐2 (NRF2) inactivation contributes to N,N‐dimethylformamide (DMF)‐induced oxidative stress in HL‐7702 and HuH6 cells
Authors: Jiang Hongmei , Li Ruobi , Zhang Zhen , Chang Chong , Liu Ye , Liu Ziqi , He Qianmei , Wang Qing 
Published: December 2019

AbstractN,N‐dimethylformamide (DMF) is a colorless industrial solvent that is frequently used for chemical reactions. Epidemiologic studies and clinical case reports have consistently indicated that the main toxic effect after exposure to DMF is hepatotoxicity. Previous studies have suggested that oxidative stress is the pivotal molecular event of DMF‐mediated hepatotoxicity; however, its underlying mechanism remains unclear. In this study, we found that DMF (0–150 mM) exposure induced an increase in reactive oxygen species (ROS) levels and inhibited the transcriptional activity of nuclear factor erythroid‐2‐related factor‐2 (NRF2) in a dose‐dependent manner. Subsequently, our research revealed that the elevated ROS levels and the decline in NRF2‐mediated anti‐oxidative response in HL‐7702 and HuH6 cells might be due to the DMF‐induced accumulation of retinoid X receptor α (RXRα) protein. Further investigation demonstrated that phosphorylation of the RXRα protein, which is mediated by the activation of extracellular signal‐regulated kinase (ERK), leads to the inhibition of RXRα protein degradation and in turn the accumulation of RXRα after DMF exposure. These findings provide information that improves our understanding of the role of RXRα in DMF‐induced hepatotoxicity.
A rapid and non‐invasive fluorescence method for quantifying coenzyme Q10 in blood and urine in clinical analysis
Authors: Fei Xuechao , Yu Yan , Di Yalan , Ai Li , Yao Dandan , Bai Shangying , Zhao Shengjie , Lyu Jihui , Cai Xiang , He Rongqiao , Tong Zhiqian 
Published: December 2019

AbstractBackgroundCoenzyme Q10 (CoQ10) supplementation can improve cognition in patients with Alzheimer's disease (AD) and AD transgenic model mice. To ameliorate the discomfort that patients with AD suffer after several blood extractions, a non‐invasive method for detecting urine CoQ10 levels needs to be established.MethodsHere, we developed a new technique of fluorescence spectrophotometry with ethyl cyanoacetate (FS‐ECA), on the basis of the principle that the chemical derivative obtained from the interaction between CoQ10 and ECA was detected by a fluorescence detector at λex/em = 450/515 nm. As a standard reference method, the same batches of the clinical samples were analyzed by high‐performance liquid chromatography with an ultraviolet detector (HPLC‐UV) at 275 nm.ResultsThe limits of detection (LOD) and limits of quantization (LOQ) (serum: 0.021 and 0.043 mg/L; urine: 0.012 and 0.025 mg/L) determined by the FS‐ECA method were similar to that obtained through HPLC‐UV (serum: 0.017 and 0.035 mg/L; urine: 0.012 and 0.025 mg/L). More importantly, this new FS‐ECA technique as well as the conventional HPLC‐UV method could detect a marked difference in urine CoQ10 levels between AD and controls.ConclusionOur findings suggest that this non‐invasive method for quantifying urine CoQ10 potentially replaces HPLC to detect blood CoQ10.
Association between serum homocysteine level and unexplained infertility in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): A retrospective, hospital‐based, case‐control study
Authors: Liu Linli , Lin Zhou , Lin Peihong , Jiang Zhongqing 
Published: December 2019

AbstractBackgroundLower serum homocysteine (Hcy) levels are found to correlate with a better chance of clinical pregnancy and better embryo grades in assisted reproductive technology (ART). However, there is little knowledge on the association between Hcy level and unexplained infertility until now.MethodsA total of 388 infertile women undergoing IVF/ICSI treatments were recruited, including 129 women with unexplained causes (case group) and 259 women with known causes (control group), and the case group was further divided into subgroups A (≤8 μmol/L), B (>8 and <15 μmol/L), and C (≥15 μmol/L) based on the serum Hcy level. The associations between serum Hcy level and IVF/ICSI pregnancy outcomes were examined in infertile women with unknown causes.ResultsA significantly higher serum Hcy level was measured in the case group than in the control group (P = .008). Subgroup analysis revealed a significant difference in the total number of oocytes retrieved among subgroups A, B, and C (P = .031), and no significant difference was seen among these three groups in terms of age, BMI, E2 level on the hCG day, number of M‐II oocytes, number of fertilized oocytes, or total number of high‐quality embryos (P > .05). Spearman correlation analysis revealed a negative correlation between serum Hcy level and total number of oocytes retrieved (r = −.406, P = .019). Univariate and multivariate linear regression analyses revealed that serum Hcy level had no correlations with any IVF/ICSI outcomes.ConclusionSerum Hcy level has no associations with IVF/ICSI pregnancy outcomes.
The impact of a brief RNR‐based training on Turkish juvenile probation officers' punitive and rehabilitative attitudes and recidivism risk perceptions
Authors: Tuncer Ayşe E. , Erdem Gizem , de Ruiter Corine 
Published: December 2019

AbstractThe present quasi‐experimental study examined the impact of a brief training program based on the risk–need–responsivity (RNR) model on Turkish juvenile probation officers' (JPOs) punitive and rehabilitative attitudes toward justice‐involved youth and recidivism risk perceptions. Fifty‐nine JPOs were recruited through three probation offices in Istanbul, Turkey. Thirty‐six JPOs, who received a 1‐day training in the RNR model of offending behavior, were compared to JPOs in a wait‐list control condition (n = 23). Participants in both conditions completed surveys at baseline and 1‐week posttraining. Mixed‐factorial analysis of variances revealed a significantly higher decrease in JPOs' punitive attitudes from pre‐ to posttest, in the training condition compared to the control group, with a medium effect size. Rehabilitative attitudes decreased in both conditions, while recidivism risk perceptions did not change from pre‐ to posttest in either condition. Future research could expand on these promising results using a more intensive training program and a randomized‐controlled design in a larger sample of JPOs.
KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8
Authors: Li Baoyu , Liu Bin , Zhang Xianglian , Liu Hui , He Lijie 
Published: December 2019

AbstractPancreatic cancer is one of the malignant tumors with the worst prognosis, and the 5‐year survival rate of this disease is less than 1%. About 90% of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and targeting therapy has become a promising treatment for PDAC in recent years. To improve the survival rate, novel therapeutic targets for PDAC are still urgently needed. KIF18B was initially identified as a member of the kinesin family and involved in multiple cellular processes, such as separation of chromosomes in mitosis. Recently, it was found that KIF18B was involved in the growth and development of multiple cancers. However, the potential link between KIF18B and PDAC is still unclear. In this study, we demonstrated that KIF18B was highly expressed in human PDAC tissues, and related with the poor prognosis and clinical features, such as tumor size (*p = .013) and pTNM stage (*p = .025), of patients with PDAC. We further found that KIF18B knockdown blocked the cell proliferation of PDAC in vitro and in vivo, and the cell cycle was arrested caused by KIF18B depletion. Additionally, we also found that KIF18B bound to the promoter region of the cell division cycle associated 8 and thus activated its transcription. Taken together, this study explored the molecular mechanism underlying KIF18B promoting PDAC and provided a novel therapeutic target of this disease.
Grip strength mediates the relationship between muscle mass and frailty
Authors: Choe Yu‐Ri , Jeong Ju‐Ri , Kim Yeon‐Pyo 
Published: December 2019

AbstractBackgroundAlthough sarcopenia and frailty are important diseases in geriatrics, few studies have investigated the association between the two diseases. Thus, this study aimed to examine the relationship between two components of sarcopenia (muscle mass and muscle function) and frailty.MethodsIn total, 997 Korean older adults (456 men and 541 women) were included in this cross‐sectional observational study. We used a polynomial linear regression analysis to obtain standardized sex, age, and height‐adjusted appendicular skeletal muscle mass (zASM), as well as to standardized sex, age, and height‐adjusted grip strength (zGS). We then performed a causal mediation analysis to confirm the relationship between zASM and frailty.ResultsIn both men and women, zGS mediated the relationship between zASM and frailty (average causal mediation effect in men: −0.096 {−0.159 to −0.050}; in women: −0.053 {−0.098 to −0.010}). For every one‐point increase in zGS score, the relative risk of a one‐point increase in frailty was reduced by 21% in men (e−0.238 = 0.788) and by 11% in women (e−0.113 = 0.893).ConclusionsIn this study on Korean older adults, muscle mass did not have a direct effect on frailty but had an indirect effect through altered muscle function.
Microwave‐assisted rapid and efficient synthesis of chromene‐fused pyrrole derivatives through multicomponent reaction and evaluation of antibacterial activity with molecular docking investigation
Authors: Baral Nilofar , Mishra Deepak Ranjan , Mishra Nilima Priyadarsini , Mohapatra Seetaram , Raiguru Bishnu Prasad , Panda Pravati , Nayak Sabita , Nayak Mukesh , Kumar P. Sudhir 
Published: December 2019

AbstractThe current study aimed to identify a new strategy of FeCl3 catalyzed multicomponent synthesis of substituted 2H‐chromene–fused pyrrole derivatives. A series of chromene‐based pyrrole prepared by employing an array of 3‐nitro‐2H‐chromenes, aniline, and acetylacetone in toluene under microwave irradiation. Using FeCl3 as a prompt catalyst and microwave irradiation to synthesize 2H‐chromene–fused pyrrole motifs significantly reduces the reaction time and facilitates to high yields (83%‐95%). Structure of all synthesized compounds analyzed by spectroscopic analysis. One‐pot reaction, short reaction period, and simple experimental procedure are the fascinating properties associated with this protocol. The in vitro antibacterial activity of the entire series was assessed against Staphylococcus aureus and Escherichia coli. Out of all the compounds, 15b and 15h revealed most excellent potency against both the bacterial strains relative to the reference gentamicin. Docking study was employed to determine the possible binding orientation of DNA gyrase with the active sites of chromene‐fused pyrrole analog. The docking results show that compounds 15b and 15h have higher binding affinity with energy −8.00 and −8.80 kcal/mol. These results illuminate the mode of binding progression and provide an esteemed pathway for the design and the structural modification of chromene‐fused pyrroles as a newly advanced class of antibacterial agent.
CsF promoted rapid synthesis of spirooxindole‐pyran annulated heterocycles at room temperature in ethanol
Authors: Wagh Yogesh B. , Padvi Swapnil A. , Mahulikar Pramod P. , Dalal Dipak S. 
Published: December 2019

AbstractA newer, versatile, and straightforward synthetic strategy for the construction of functionalized spirooxindole‐pyran annulated heterocycles is described. The procedure is based on CsF‐promoted rapid tandem Knoevenagel‐Michael‐Cyclocondensation reaction of isatin, malononitrile, and 4‐hydroxycoumarin/barbituric acids/pyrazolone at room temperature in ethanol. This methodology has various advantages like easy operational, excellent yields within short reaction time (3‐25 min), and simple isolation of products. The CsF has a dual role as a base and carbonyl activator.