bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid Neoplasms with Elevated Plasmacytoid Dendritic Cell Differentiation Reflect the Maturation Process of Dendritic Cells
Authors: Huang Yumei , Wang Yazhe , Chang Yan , Yuan Xiaoying , Hao Le , Shi Hongxia , Lai Yueyun , Huang Xiaojun , Liu Yanrong
Published: December 2019

To date, the research on dendritic cells (DCs) and their correlated neoplasms has not been clear. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature plasmacytoid dendritic cell proliferation (MPDCP) are two types of malignancies originating from plasmacytoid dendritic cells (pDCs). Some evidence has indicated the existence of other pDC neoplasms. In addition, cases of myeloid neoplasms (MNs), acute myeloblastic leukemia (AML), and myelodysplastic syndrome (MDS) with increased pDCs (AML/MDS‐pDCs) seem to have immature DCs according to the vaguely consistent expression of markers among MNs and pDCs, which appear to fit the developmental pattern of normal DCs. We analyzed 14 AML/MDS‐pDC cases mainly for their immunophenotype by flow cytometry and inferred their CD expression pattern. The patients' clinical information and other laboratory data were collected and reviewed. AML/MDS‐pDCs show a different pattern of markers from BPDCN and MPDCP. Three maturation‐involved stages were found in these AML/MDS‐pDCs patients. Stage I was the most immature stage and displayed an expression profile of CD34+/st+ CD117+/st+ BDCA2− BDCA4− CD123+ HLA‐DR+/st+ CD4− CD45dim+; Stage II was the more immature stage displayed a phenotype of CD34dim+ CD117dim+ BDCA2−/dim+ BDCA4−/dim+ CD123st+ HLA‐DR+/st+ CD4− CD45+; and Stage III was the mature stage showed CD34− CD117− BDCA2+/BDCA4+ CD123st+ HLA‐DR+/st+ CD4+ CD45+/st+. Three maturation‐involved stages overlapped well with the phenotypes of normal DC progenitors in a continuously developmental process: granulocyte, monocyte, and DC progenitors (GMDPs) and/or monocyte and DC progenitors (MDPs), common DC progenitors (CDPs), pDCs, and/or pre‐DCs. In this study, we considered AML/MDS‐pDCs as entities that were distinct from BPDCN and MPDCP and correlated the components of this tumor with the normal DC differentiation pathway, which provides new evidence for understanding DC neoplasms. © 2019 International Society for Advancement of Cytometry
Age‐ and performance‐related differences in source memory retrieval during early childhood: Insights from event‐related potentials
Authors: Canada Kelsey L. , Geng Fengji , Riggins Tracy
Published: December 2019

Across early childhood, children's ability to remember individual items and the details that accompany these items (i.e., episodic memory) improves greatly. Given that these behavioral improvements coincide with increases in age, effects of age and performance are often confounded. This study used event‐related potentials (ERPs) to investigate age‐ and performance‐related differences in the neural processes underlying the development of memory for details during early childhood. Using a source memory paradigm, ERP components related to episodic memory, the negative component (Nc), and late slow wave (LSW) were examined in 4‐ to 8‐year‐old children. Analyses focused on trials for which children correctly remembered the source related to an item versus trials where the item was remembered but the source was forgotten. Results revealed LSW, but not Nc, differed as a function of age and performance. Specifically, LSW effects were similar across source correct and source incorrect trials in all high‐performing children and in low‐performing older children; however, LSW effects differed across conditions in low‐performing younger children. Results show developmental differences in retrieval processes across early childhood and highlight the importance of considering age and performance when examining electrophysiological correlates of episodic memory during development.
Spatial sampling bias and model complexity in stream‐based species distribution models: A case study of Paddlefish (Polyodon spathula) in the Arkansas River basin, USA
Authors: Taylor Andrew T. , Hafen Thomas , Holley Colt T. , González Alin , Long James M.
Published: December 2019

Leveraging existing presence records and geospatial datasets, species distribution modeling has been widely applied to informing species conservation and restoration efforts. Maxent is one of the most popular modeling algorithms, yet recent research has demonstrated Maxent models are vulnerable to prediction errors related to spatial sampling bias and model complexity. Despite elevated rates of biodiversity imperilment in stream ecosystems, the application of Maxent models to stream networks has lagged, as has the availability of tools to address potential sources of error and calculate model evaluation metrics when modeling in nonraster environments (such as stream networks). Herein, we use Maxent and customized R code to estimate the potential distribution of paddlefish (Polyodon spathula) at a stream‐segment level within the Arkansas River basin, USA, while accounting for potential spatial sampling bias and model complexity. Filtering the presence data appeared to adequately remove an eastward, large‐river sampling bias that was evident within the unfiltered presence dataset. In particular, our novel riverscape filter provided a repeatable means of obtaining a relatively even coverage of presence data among watersheds and streams of varying sizes. The greatest differences in estimated distributions were observed among models constructed with default versus AICC‐selected parameterization. Although all models had similarly high performance and evaluation metrics, the AICC‐selected models were more inclusive of westward‐situated and smaller, headwater streams. Overall, our results solidified the importance of accounting for model complexity and spatial sampling bias in SDMs constructed within stream networks and provided a roadmap for future paddlefish restoration efforts in the study area.
Spatial variability in the amount of forest litter at the local scale in northeastern China: Kriging and cokriging approaches to interpolation
Authors: Qin Qianqian , Wang Haiyan , Lei Xiangdong , Li Xiang , Xie Yalin , Zheng Yonglin
Published: December 2019

Litter is essential to promote nutrient cycling and maintain the sustainability of forest resources. However, its variability has not been sufficiently studied at the local scale. The prediction of litter amount using ordinary cokriging with Pearson correlation analysis (COKP) and ordinary cokriging with principal component analysis (COKPCA) was compared with that using ordinary kriging (OK) based on cross‐validation at the local scale of a 1‐ha plot over natural spruce–fir mixed forest in Jilin Province, China. Litter samples in semidecomposed (F) and complete decomposed (H) horizons were collected using an equidistant grid point sampling of 10 m × 10 m. Pearson correlation analysis and principal component analysis (PCA) were used to confirm auxiliary variables. The results showed that the amount of litter was 19.65 t/ha in the F horizon and 10.37 t/ha in the H horizon. The spatial structure variance ratio in the H horizon was smaller than that in the F horizon, indicative of its stronger spatial autocorrelation. Spatial distributions of litter amount in both horizons exhibited a patchy and heterogeneous pattern. Of the selected stand characteristics and litter properties, litter moisture content indicated the strongest relationship with litter amount. Cross‐validation revealed that COKPCAusing the comprehensive score as an auxiliary variable produced the most accurate map. The average standard error and root‐mean‐square error between the predicted and measured values were always smaller, the mean error and mean standardized error were much closer to 0, and the root‐mean‐square standardized error was closer to 1 than COKPusing litter moisture and OK. Therefore, a clear advantage of cokriging based on principal component analysis was observed and COKPCAwas found to be a very useful approach for further interpolation prediction.
Temporal aspects of endogenous pain modulation during a noxious stimulus prolonged for 1 day
Authors: Hoeger Bement Marie , Petersen Kristian K. , Sørensen Line B. , Andersen Hjalte H. , Graven‐Nielsen Thomas
Published: December 2019

Background

This study investigated (a) if a prolonged noxious stimulus (24‐hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and (b) if acute pain relief or exacerbation (cooling and heating the capsaicin patch) during the prolonged noxious stimulus would affect central pain modulation.

Methods

Twenty‐eight participants (26.2 ± 1.0 years; 12 women) wore a transdermal 8% capsaicin patch on the forearm for 24 hr. Data were collected at baseline (Day 0), 1 hr, 3 hr, Day 1 (post‐capsaicin application) and Day 3/4 (post‐capsaicin removal) that included capsaicin‐evoked pain intensity, heat pain thresholds (HPTs), TSP (10 painful cuff pressure stimuli on leg) and CPM (cuff pressure pain threshold on the leg prior vs. during painful cuff pressure conditioning on contralateral leg). After 3 hr, cold (12°C) and heat (42°C) stimuli were applied to the capsaicin patch to transiently increase and decrease pain intensity.

Results

Participants reported moderate pain scores at 1 hr (2.5 ± 2.0), 3 hr (3.7 ± 2.4), and Day 1 (2.4 ± 1.8). CPM decreased 3‐hr post‐capsaicin (p = .001) compared to Day 0 and remained diminished while the capsaicin pain score was reduced (0.4 ± 0.7, p < .001) and increased (6.6 ± 2.2, p < .001) by patch cooling and heating. No significant differences occurred for CPM during patch cooling or heating compared to initial 3HR; however, CPM during patch heating was reduced compared with patch cooling (p = .01). TSP and HPT did not change.

Conclusions

This prolonged experimental pain model is useful to provide insight into subacute pain conditions and may provide insight into the transition from acute to chronic pain.

Significance

During the early hours of a prolonged noxious stimulus in healthy adults, CPM efficacy was reduced and did not recover by temporarily removing the ongoing pain indicating a less dynamic neuroplastic process.
In Situ Reproductive Bioassay with Caged Gammarus fossarum (Crustacea): Part 1—Gauging the Confounding Influence of Temperature and Water Hardness
Authors: Chaumot Arnaud , Coulaud Romain , Adam Olivier , Quéau Hervé , Lopes Christelle , Geffard Olivier
Published: December 2019

Monitoring the adverse effects of environmental contaminants on the reproduction of invertebrate species in the field remains a challenge in aquatic ecotoxicology. To meet the need for reliable tools for in situ toxicity assessment, we present the first part of a methodological study of the in situ implementation of a reproductive bioassay in Gammarus previously developed for screening the toxicity of chemical compounds during laboratory exposure. To ensure the correct interpretation of the modulation of reproductive markers (molting, fecundity, follicle growth, and embryonic development) in uncontrolled environmental conditions, we experimentally assessed and statistically modeled the variability in the female reproductive cycle during laboratory exposure under several temperature and water hardness conditions. Whereas water hardness did not influence the reproductive cycle, the significant accelerating effect of temperature on the dynamics of molting and marsupial development was finely modeled, by detailing the influence of temperature on the probability of transition between all molt and embryonic stages along the female cycle. In addition, no effect of temperature or water hardness was detected on the number of oocytes and embryos carried by females. Furthermore, the finding that the relative durations of the first 4 molt and embryonic stages are constant whatever the temperature makes it possible to predict the molting dynamics in fluctuating temperature conditions. Because this could allow us to take into account the confounding influence of temperature on the measurement of reproductive markers, the implications of these findings for an optimal in situ implementation of the reproductive bioassay with G. fossarum are discussed. The relevance of this modeling approach during in situ implementation is tested in a companion study. Environ Toxicol Chem 2020;39:667–677. © 2019 SETAC
Development and Application of a Microplate Assay for Toxicity Testing on Aquatic Cyanobacteria
Authors: Le Page Gareth , Gunnarsson Lina , Snape Jason , Tyler Charles R.
Published: December 2019

Regulatory environmental risk assessment, applied to establish a protection limit for all bacterial diversity in surface waters, relies on a growth inhibition test performed on a single species of cyanobacteria and the activated sludge respiration inhibition test. Recently, the ability of this approach to protect adequately for bacteria that provide important ecosystem services has been questioned, and empirical data on additional species to further investigate the effectiveness of the environmental risk assessment are urgently required. We present the development and validation of a cost-effective and time-efficient microplate assay that is comparable to the traditional shake flask test for measurement of cyanobacteria growth rate after chemical exposure. The assay has been optimized to ensure that comparisons of cyanobacteria sensitivity under exponential growth are assessed across equivalent experimental conditions using phycocyanin fluorescence as a surrogate for cell density. The test system is validated using potassium dichromate, and the results are compared with those obtained in an Organisation for Economic Co-operation and Development (2011) test guideline 201 shake flask test system. This assay is suitable for the screening of new and legacy chemicals (including antibiotics) for which ecotoxicology data are lacking across a wide range of cyanobacteria, with the aim of developing more comprehensive environmental risk assessment. Environ Toxicol Chem 2020;39:705–720. © 2019 SETAC
Prediction of hospital length of stay to achieve flexible healthcare in the field of Internet of Vehicles
Authors: Wang Tao , Zhang Haiqing , Duclos Antoine , Payet Cécile , Li Daiwei
Published: December 2019

The patient transfer from hospitals to followup care and rehabilitation facilities is an important aspect for maintaining the continuity of medical care. In order to achieve flexible healthcare within the field of Internet of Vehicles (IoVs) in terms of secure patient transfer and ambulance transport, the whole organization of patients' discharge and transfer should be anticipated, based mostly on a length of stay (LOS) given at the time of inpatient admission. Therefore, the prediction of LOS has serious impact on influx coordination, bed management, ambulance scheduling, and furthermore, on the financial balance of hospitals. Based on studying medical data, the prediction with good accuracy can help hospital managers get an efficient and robust resource management. The challenge is then how to extract valuable information from medical data, which contains considerable hesitation and uncertainty elements. In this article, a hesitant fuzzy‐rough nearest‐neighbor algorithm has been proposed and experimented with real medical data. Hesitation interpretation has been reflected in the process of determining class labels in our algorithm via hesitant fuzzy relation determination and hesitant fuzzy‐rough similarity measure. The experimental analysis has shown that the proposed algorithm has better performance and extensibility.
Variation of floral volatiles and fragrance reveals the phylogenetic relationship among nine wild tree peony species
Authors: Luo Xiaoning , Yuan Meng , Li Bingjie , Li Chenyao , Zhang Yanlong , Shi Qianqian
Published: December 2019

In recent years, more and more attention has been paid to the natural floral volatiles in tree peony and the fragrance components have been widely used in the fields of health care, perfumes, and cosmetics. However, there is little research on the identification of fragrance components of wild tree peony species. In present study, volatile components in petals of nine wild tree peony species were analyzed using a headspace solid‐phase microextraction (SPME) technique coupled with gas chromatography–mass spectrometry (GC‐MS). A total of 124 volatile components were identified and clustered into five major chemical classes: terpenoids, alkanes, alcohols, aldehydes, and ketones. Overall, combined with the sensory evaluation of nine wild tree peony species, Paeonia. ostii (P2) performed herbal and waxy attributes, mainly dominated by hexanal and pentadecane, respectively. P rockii (P1), P qiui (P3), P jishanensis (P4), and P decomposita (P5) all possessed sweet attribute, which was positively correlated with geraniol and citronellol. P delavayi (P9), P lutea (P7), P ludlowii (P8), and P potanini (P6) performed intense floral attribute dominated by linalool and trans‐linalool oxide. Moreover, the results of principal component analysis (PCA) and hierarchical clustering analysis (HCA) showed P decomposita (P5), P qiui (P3), P rockii (P1), P jishanensis (P4), and P ostii (P2) in the Subsect. Vagiatae were mixed to form one cluster while P lutea (P7), P delavayi (P9), P ludlowii (P8), and P potanini (P6) in the Subsect. Delavayanae formed the other cluster. In terms of geographical distribution, the two clusters are consistent with the distribution of wild tree peony species. The present study clarified the relationship between fragrance and components and further revealed the phylogenetic relationship of nine wild tree peony species, thus providing a theoretical basis for their development and utilization.
Microbial load and antibiotic resistance in raw beef preparations from northwest Spain
Authors: González‐Gutiérrez María , García‐Fernández Camino , Alonso‐Calleja Carlos , Capita Rosa
Published: December 2019

Beef preparations (meatballs, minced meat, hamburgers, white sausages, and red sausages) from northwest Spain were tested. Microbial counts ranged from 0.70 ± 0.00 log10 cfu/g (enterococci) to 9.57 ± 0.37 log10 cfu/g (psychrotrophs). In 73.3% of cases, total aerobic counts were higher than the microbiological limits set for the end of the manufacturing process in the European Union (EU Regulation 2073/2005). Forty Escherichia coli isolates were tested against thirteen clinically important antibiotics (disk diffusion method; CLSI). Three of the strains (7.5%) were susceptible to all the antibiotics, four (10.0%) showed resistance or reduced susceptibility to one antibiotic, and 33 (82.5%) were multiresistant (with resistance or reduced susceptibility to between two and eight antibiotics), with an average of 1.85 resistances per strain. The highest rates of resistance were observed for two antimicrobials widely used on cattle farms (cefalotin and tetracycline). The findings in this research emphasize the need to correctly handle beef preparations with the aim of reducing risks to consumers.
A feasibility study of CO2‐based solar‐assisted Rankine cycle: a comparative case study for Isparta, Turkey
Authors: Kizilkan Onder , Yamaguchi Hiroshi
Published: December 2019

In this study, a feasibility analysis of a solar‐assisted transcritical Rankine cycle working with carbon dioxide (CO2) is performed for Isparta, Turkey, in comparison with Kyoto, Japan, conditions. For the analyses, the characteristics of the system are adapted from the actual experimental research conducted at Doshisha University, Kyoto, Japan. In order to evaluate the performance of the CO2‐based integrated system, a mathematical model is established for the evacuated solar collectors. Energy and exergy analyses are carried out using the solar energy data of both cities. According to the simulation results, the average turbine power capacities are determined as 0.415 and 0.396 kW, while the average heat recovery capacities are calculated as 2.10 and 1.89 kW for Isparta and Kyoto, respectively. The yearly electricity generation for Isparta conditions is found to be about 40% higher than the Kyoto conditions with 1138.09 kWh. The results of second law analyses are showed that the highest exergy destruction rate occurs in August for Isparta conditions with 8.18 kW due to the higher solar radiation rates. From the results, it appears that the CO2‐based next‐generation solar‐assisted power and heat generation system can be established and utilized in Isparta more effectively. The future research should, therefore, concentrate on moving the actual experimental setup to Isparta for field test experiments. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Architecture and evolution of a modern braided fluvial system: The Weihe River in northern China
Authors: Zhao Junfeng , Liu Rui , Xue Rui , Wang Ke , Li Xuan , Wang Zhiyou , Zhang Xiangyu
Published: December 2019

Modern sedimentation plays a crucial role for understanding ancient sedimentation in the stratigraphic record. This study reveals 3D architecture and evolution of a modern braided fluvial system. The Weihe River is the largest tributary of the Yellow River in northern China. Recent archaeological excavations revealed sets of ancient bridges in the Xi'an segment over this waterway, which provided an opportunity to understand the inner architecture and evolution of this river. Excavated pits and adjacent natural gullies were analysed using the architectural elements methods, revealing nine lithofacies types, and seven distinct architectural elements. Architectural elements typical of braided fluvial deposits including downstream accretion, lateral accretion, and channel fill elements can be identified in the studied sections. The results suggest that the Xi'an segment of the Weihe River was deposited as a braided fluvial system during the Western Han Dynasty (ca. 2,000 years ago). The sandy sediments which filled in the abandoned riverbed were mainly transported by the main stream from the west, whereas the gravel lithofacies packages were supplied by near‐source tributaries that originated from the southern Qinling Mountains. Calculations based on empirical equations suggest that at the time of the Western Han Dynasty, the width of the river course was between 400 m and 500 m, and the river depth was between 2.7 and 3.4 m, similar to the dimensions recorded in historic documents. The Weihe River has migrated approximately 4.3 km to the north since the time of the Western Han Dynasty. Considering the regional geological setting, the data suggest that this northward migration was controlled by the continuous uplift of the Qinling Mountains as well as movement of syn‐sedimentary normal faults to the south of the Weihe Basin. These tectonic movements controlled the evolution of the basin and maintained the geomorphologic characteristics of such higher topography in the south and lower in the north over a long period of time.
Neuronal lactate levels depend on glia‐derived lactate during high brain activity in Drosophila
Authors: González‐Gutiérrez Andrés , Ibacache Andrés , Esparza Andrés , Barros Luis Felipe , Sierralta Jimena
Published: December 2019

Lactate/pyruvate transport between glial cells and neurons is thought to play an important role in how brain cells sustain the high‐energy demand that neuronal activity requires. However, the in vivo mechanisms and characteristics that underlie the transport of monocarboxylates are poorly described. Here, we use Drosophila expressing genetically encoded FRET sensors to provide an ex vivo characterization of the transport of monocarboxylates in motor neurons and glial cells from the larval ventral nerve cord. We show that lactate/pyruvate transport in glial cells is coupled to protons and is more efficient than in neurons. Glial cells maintain higher levels of intracellular lactate generating a positive gradient toward neurons. Interestingly, during high neuronal activity, raised lactate in motor neurons is dependent on transfer from glial cells mediated in part by the previously described monocarboxylate transporter Chaski, providing support for in vivo glia‐to‐neuron lactate shuttling during neuronal activity.
Age‐related structural and functional variations in 5,967 individuals across the adult lifespan
Authors: Luo Na , Sui Jing , Abrol Anees , Lin Dongdong , Chen Jiayu , Vergara Victor M. , Fu Zening , Du Yuhui , Damaraju Eswar , Xu Yong , Turner Jessica A. , Calhoun Vince D.
Published: December 2019

Exploring brain changes across the human lifespan is becoming an important topic in neuroscience. Though there are multiple studies which investigated the relationship between age and brain imaging, the results are heterogeneous due to small sample sizes and relatively narrow age ranges. Here, based on year‐wise estimation of 5,967 subjects from 13 to 72 years old, we aimed to provide a more precise description of adult lifespan variation trajectories of gray matter volume (GMV), structural network correlation (SNC), and functional network connectivity (FNC) using independent component analysis and multivariate linear regression model. Our results revealed the following relationships: (a) GMV linearly declined with age in most regions, while parahippocampus showed an inverted U‐shape quadratic relationship with age; SNC presented a U‐shape quadratic relationship with age within cerebellum, and inverted U‐shape relationship primarily in the default mode network (DMN) and frontoparietal (FP) related correlation. (b) FNC tended to linearly decrease within resting‐state networks (RSNs), especially in the visual network and DMN. Early increase was revealed between RSNs, primarily in FP and DMN, which experienced a decrease at older ages. U‐shape relationship was also revealed to compensate for the cognition deficit in attention and subcortical related connectivity at late years. (c) The link between middle occipital gyrus and insula, as well as precuneus and cerebellum, exhibited similar changing trends between SNC and FNC across the adult lifespan. Collectively, these results highlight the benefit of lifespan study and provide a precise description of age‐related regional variation and SNC/FNC changes based on a large dataset.
Pilot study for a novel and personalized voice restoration device for patients with laryngectomy
Authors: Rameau Anaïs
Published: December 2019

Background

The main modalities for voice restoration after laryngectomy are the electrolarynx, and the tracheoesophageal puncture [Correction added on 30 January 2020 after first online publication: The preceding sentence has been revised. It originally read “The main modalities for voice restoration after laryngectomy are the electrolarynx and the tracheoesophageal puncture.”]. All have limitations and new technologies may offer innovative alternatives via silent speech.

Objective

To describe a novel and personalized method of voice restoration using machine learning applied to electromyographic signal from articulatory muscles for the recognition of silent speech in a patient with total laryngectomy.

Methods

Surface electromyographic (sEMG) signals of articulatory muscles were recorded from the face and neck of a patient with total laryngectomy who was articulating words silently. These sEMG signals were then used for automatic speech recognition via machine learning. Sensor placement was tailored to the patient's unique anatomy, following radiation and surgery. A personalized wearable mask covering the sensors was designed using 3D scanning and 3D printing.

Results

Using seven sEMG sensors on the patient's face and neck and two grounding electrodes, we recorded EMG data while he was mouthing “Tedd” and “Ed.” With data from 75 utterances for each of these words, we discriminated the sEMG signal with 86.4% accuracy using an XGBoost machine‐learning model.

Conclusions

This pilot study demonstrates the feasibility of sEMG‐based alaryngeal speech recognition, using tailored sensor placement and a personalized wearable device. Further refinement of this approach could allow translation of silently articulated speech into a synthesized voiced speech via portable devices.
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

Identification 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

Stable 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.
School and individual factors on game addiction: A multilevel analysis
Authors: Chang Eunbi , Kim Boyoung
Published: December 2019

This study investigated the protective or risk factors of game addiction at individual and school‐level using multilevel modelling. Data from Korea Children and Youth Panel Survey was used for the analyses. The findings revealed that individual‐level variables, including gender, delinquency, family intimacy, stress, self‐esteem and self‐control, were significant predictors of game addiction. Furthermore, protective school climate contributed to decreasing the level of game addiction and risky school climates positively predicted game addiction. The effect of individual‐level variables on game addiction was different depending on the type or level of school‐level variables. Based on the findings, implications and suggestions for future studies were discussed.
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

Medical 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

Background

The 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.

Methods

Pharmacy 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.

Results

Of 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%).

Conclusion

PGY1 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

N,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

Background

Coenzyme 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.

Methods

Here, 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.

Results

The 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.

Conclusion

Our 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

Background

Lower 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.

Methods

A 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.

Results

A 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.

Conclusion

Serum 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

The 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

Pancreatic 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.