bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Quantifying Streamflow Variability Across Continental Scales: 1. Identifying Natural and Anthropogenic Controlling Factors in the USA Using a Spatially Explicit Modeling Method
Authors: Alexander Richard B. , Schwarz Gregory E. , Boyer Elizabeth W. 
Published: November 2019

AbstractDespite considerable progress in hydrological modeling, challenges remain in the interpretation and accurate transfer of hydrological information across watersheds and scales. In the conterminous United States (CONUS), these limitations are related to spatial inconsistencies and constraints in hydrological model structures, including a lack of spatially explicit process components (streams, reservoirs, and watershed development) and restricted estimation of model parameters across watersheds. Collectively, such limitations can impede identification of the causes of streamflow variations across the diversity of watershed sizes and land uses in the CONUS and contribute to model imprecision and spatial inconsistencies in prediction uncertainties. We addressed these concerns with a new approach, the first hybrid (statistical‐mechanistic) SPARROW (SPAtially Referenced Regression On Watershed attributes) model of long‐term mean annual streamflow, applied across diverse environmental settings of the CONUS. The hybrid model coupled previous catchment‐scale (1 km) water balance predictions of “natural” unit area runoff, which are inclusive of major water cycling processes, with additional explanatory variables (e.g., soils, vegetation, land use, topography, water losses in streams, and reservoirs) that account for the effects of natural and cultural water supply and demand processes that operate over large spatial scales and explain streamflow variability across CONUS river basins. Accounting for these statistically unique effects, including a nonlinear surface area‐dependent scaling of water loss in river networks, significantly improved the accuracy of mean streamflow predictions in CONUS basins. Our hybrid modeling approach provides new methods for transferring hydrological information to ungauged locations in river networks, especially those in larger and more culturally diverse CONUS watersheds.
BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration
Authors: Loveridge Carolyn J. , Slater Sarah , Campbell Kirsteen J. , Nam Noor A. , Knight John , Ahmad Imran , Hedley Ann , Lilla Sergio , Repiscak Peter , Patel Rachana , Salji Mark , Fleming Janis , Mitchell Louise , Nixon Colin , Strathdee Douglas , Neilson Matthew , Ntala Chara , Bryson Sheila , Zanivan Sara , Edwards Joanne , Robson Craig N. , Goodyear Carl S. , Blyth Karen , Leung Hing Y. 
Published: November 2019

AbstractBRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (PtenΔ/ΔBRF1Tg) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In PtenΔ/ΔBRF1Tg tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis.
TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p
Authors: Dong Ke-shuai , Chen Yan , Yang Guang , Liao Zhi-bin , Zhang Hong-wei , Liang Hui-fang , Chen Xiao-ping , Dong Han-hua 
Published: November 2019

AbstractIncreasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial–mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.
Water vapor thermal therapy to alleviate catheter-dependent urinary retention secondary to benign prostatic hyperplasia
Authors: McVary Kevin T. , Holland Bradley , Beahrs J. Randolf 
Published: November 2019

Abstract
Background
Water vapor thermal therapy utilizes convectively delivered thermal energy to target ablation of obstructive prostatic tissue. We report results of this thermal therapy for relief of nonneurogenic complete urinary retention associated with BPH.

Patients and methods
We conducted a retrospective analysis of 38 catheter-dependent men with complete urinary retention consecutively enrolled in a registry in two centers: median age 75.5 years and multiple comorbidities, median prostate volume 58.5 cc (23–153), median 2 failed trials without catheter (TWOCs), and median catheter dependency 3 months (0.3–35). The Rezūm™ System thermal therapy procedure was performed in an ambulatory surgery center with conscious sedation or an office procedure room with a modified periprostatic block. Water vapor injections were customized to the configuration of the hyperplastic gland, including median lobe and/or enlarged central zone.

Results
Of the 38 treated patients, one was lost to follow-up and 26 of 37 (70.3%) voided spontaneously (mean of 1.6 ± 0.8 TWOCs) and were catheter free a median of 26 days (range 4–65) after the procedure; 18 of these 26 (69%) patients discontinued BPH medications. No significant differences in age, prostate volume, number of water vapor injections, or presence of the median lobe were associated with predicting a successful treatment outcome. Duration of follow-up for 20 catheter-free patients was a median of 475 days or 15.8 months (140–804 days); six patients were followed a median of 31.5 days (0–60). Adverse events were infrequent, mild, and resolved quickly including dysuria in five patients (13%), gross hematuria in four (10.5%), and UTIs in two (2.6%) with indwelling catheters.

Conclusions
Water vapor thermal therapy may provide an effective and safe alternative to surgical treatment in this group of catheter-dependent patients in complete urinary retention.
Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem
Authors: Lawson Melissa A E , O’Neill Ian J , Kujawska Magdalena , Gowrinadh Javvadi Sree , Wijeyesekera Anisha , Flegg Zak , Chalklen Lisa , Hall Lindsay J 
Published: November 2019

Abstract
Diet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2′FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or ‘conditioned’ media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as ‘foundation’ species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.
Integrative proteomics and pharmacogenomics analysis of methylphenidate treatment response
Authors: da Silva Bruna S. , Leffa Douglas T. , Beys-da-Silva Walter O. , Torres Iraci L. S. , Rovaris Diego L. , Victor Marcelo M. , Rohde Luis A. , Mota Nina R. , Oliveira Carla de , Berger Markus , Yates John R. , Sabnis Renuka , Peña Ramón Díaz , Campos Alexandre Rosa , Grevet Eugenio H. , Santi Lucelia , Bau Claiton H. D. , Contini Verônica 
Published: November 2019

AbstractTranscriptomics and candidate gene/protein expression studies have indicated several biological processes modulated by methylphenidate (MPH), widely used in attention-deficit/hyperactivity disorder (ADHD) treatment. However, the lack of a differential proteomic profiling of MPH treatment limits the understanding of the most relevant mechanisms by which MPH exerts its pharmacological effects at the molecular level. Therefore, our aim is to investigate the MPH-induced proteomic alterations using an experimental design integrated with a pharmacogenomic analysis in a translational perspective. Proteomic analysis was performed using the cortices of Wistar-Kyoto rats, which were treated by gavage with MPH (2 mg/kg) or saline for two weeks (n = 6/group). After functional enrichment analysis of the differentially expressed proteins (DEP) in rats, the significant biological pathways were tested for association with MPH response in adults with ADHD (n = 189) using genome-wide data. Following MPH treatment in rats, 98 DEPs were found (P < 0.05 and FC < −1.0 or > 1.0). The functional enrichment analysis of the DEPs revealed 18 significant biological pathways (gene-sets) modulated by MPH, including some with recognized biological plausibility, such as those related to synaptic transmission. The pharmacogenomic analysis in the clinical sample evaluating these pathways revealed nominal associations for gene-sets related to neurotransmitter release and GABA transmission. Our results, which integrate proteomics and pharmacogenomics, revealed putative molecular effects of MPH on several biological processes, including oxidative stress, cellular respiration, and metabolism, and extended the results involving synaptic transmission pathways to a clinical sample. These findings shed light on the molecular signatures of MPH effects and possible biological sources of treatment response variability.
Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma
Authors: Maes Anke , Maes Ken , Vlummens Philip , De Raeve Hendrik , Devin Julie , Szablewski Vanessa , De Veirman Kim , Menu Eline , Moreaux Jerome , Vanderkerken Karin , De Bruyne Elke 
Published: November 2019

AbstractDiffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor prognosis in several cancer cell types. In this study, the role of MELK in DLBCL and MCL and the therapeutic potential of MELK targeting is evaluated. MELK is highly expressed in DLBCL and MCL patient samples, correlating with a worse clinical outcome in DLBCL. Targeting MELK, using the small molecule OTSSP167, impaired cell growth and survival and induced caspase-mediated apoptosis in the lymphoma cells. Western blot analysis revealed that MELK targeting decreased the phosphorylation of FOXM1 and the protein levels of EZH2 and several mitotic regulators, such as Cdc25B, cyclin B1, Plk-1, and Aurora kinases. In addition, OTSSP167 also sensitized the lymphoma cells to the clinically relevant Bcl-2 inhibitor venetoclax by strongly reducing Mcl1 levels. Finally, OTSSP167 treatment of A20-inoculated mice resulted in a significant prolonged survival. In conclusion, targeting MELK with OTSSP167 induced strong anti-lymphoma activity both in vitro and in vivo. These findings suggest that MELK could be a potential new target in these aggressive B cell malignancies.
Tumor suppressor ZHX2 inhibits NAFLD–HCC progression via blocking LPL-mediated lipid uptake
Authors: Wu Zhuanchang , Ma Hongxin , Wang Liyuan , Song Xiaojia , Zhang Jie , Liu Wen , Ge Yutong , Sun Yang , Yu Xiangguo , Wang Zehua , Wang Jianping , Zhang Yankun , Li Chunyang , Li Nailin , Gao Lifen , Liang Xiaohong , Yue Xuetian , Ma Chunhong 
Published: November 2019

AbstractNon-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD–HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD–HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival
Authors: Zhou Kailiang , Chen Huanwen , Lin Jinti , Xu Hui , Wu Hongqiang , Bao Guodong , Li Jiafeng , Deng Xiangyang , Shui Xiaolong , Gao Weiyang , Ding Jian , Xiao Jian , Xu Huazi 
Published: November 2019

AbstractRandom-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21’s therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.
Becker muscular dystrophy caused by exon 2-truncating mutation of DMD
Authors: Ikeda Tetsuhiko , Fujinaka Hidehiko , Goto Kiyoe , Nakajima Takashi , Ozawa Tetsuo 
Published: November 2019

AbstractNonsense and frameshift mutations of the dystrophin (DMD) gene usually cause severe Duchenne muscular dystrophy (DMD). Interestingly, however, premature stop codons in exons 1 and 2 result in relatively mild Becker muscular dystrophy (BMD). Herein, we report the clinical course of a patient with a very mild phenotype of BMD caused by a frameshift mutation, NM_004006.2: c.40_41del GA/p.(Glu14ArgfsX17), in exon 2 of the DMD gene.
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome
Authors: Aguado Julio , Sola-Carvajal Agustin , Cancila Valeria , Revêchon Gwladys , Ong Peh Fern , Jones-Weinert Corey Winston , Wallén Arzt Emelie , Lattanzi Giovanna , Dreesen Oliver , Tripodo Claudio , Rossiello Francesca , Eriksson Maria , d’Adda di Fagagna Fabrizio 
Published: November 2019

AbstractHutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo.
Microbial reduction of metal-organic frameworks enables synergistic chromium removal
Authors: Springthorpe Sarah K. , Dundas Christopher M. , Keitz Benjamin K. 
Published: November 2019

AbstractRedox interactions between electroactive bacteria and inorganic materials underpin many emerging technologies, but commonly used materials (e.g., metal oxides) suffer from limited tunability and can be challenging to characterize. In contrast, metal-organic frameworks exhibit well-defined structures, large surface areas, and extensive chemical tunability, but their utility as microbial substrates has not been examined. Here, we report that metal-organic frameworks can support the growth of the metal-respiring bacteriumShewanella oneidensis, specifically through the reduction of Fe(III). In a practical application, we show that cultures containingS. oneidensisand reduced metal-organic frameworks can remediate lethal concentrations of Cr(VI) over multiple cycles, and that pollutant removal exceeds the performance of either component in isolation or bio-reduced iron oxides. Our results demonstrate that frameworks can serve as growth substrates and suggest that they may offer an alternative to metal oxides in applications seeking to combine the advantages of bacterial metabolism and synthetic materials.
Fast, accurate, and transferable many-body interatomic potentials by symbolic regression
Authors: Hernandez Alberto , Balasubramanian Adarsh , Yuan Fenglin , Mason Simon A. M. , Mueller Tim 
Published: November 2019

AbstractThe length and time scales of atomistic simulations are limited by the computational cost of the methods used to predict material properties. In recent years there has been great progress in the use of machine-learning algorithms to develop fast and accurate interatomic potential models, but it remains a challenge to develop models that generalize well and are fast enough to be used at extreme time and length scales. To address this challenge, we have developed a machine-learning algorithm based on symbolic regression in the form of genetic programming that is capable of discovering accurate, computationally efficient many-body potential models. The key to our approach is to explore a hypothesis space of models based on fundamental physical principles and select models within this hypothesis space based on their accuracy, speed, and simplicity. The focus on simplicity reduces the risk of overfitting the training data and increases the chances of discovering a model that generalizes well. Our algorithm was validated by rediscovering an exact Lennard-Jones potential and a Sutton-Chen embedded-atom method potential from training data generated using these models. By using training data generated from density functional theory calculations, we found potential models for elemental copper that are simple, as fast as embedded-atom models, and capable of accurately predicting properties outside of their training set. Our approach requires relatively small sets of training data, making it possible to generate training data using highly accurate methods at a reasonable computational cost. We present our approach, the forms of the discovered models, and assessments of their transferability, accuracy and speed.