bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Estimators of Model Performance Efficiency for Skewed Hydrologic Data
Authors: Lamontagne Jonathan R. , Barber Caitline A. , Vogel Richard M. 
Published: September 2020

AbstractThe Nash‐Sutcliffe efficiency (NSE) and the Kling‐Gupta efficiency (KGE) are now the most widely used indices in hydrology for evaluation of the goodness of fit between model simulations S and observations O. We introduce two theoretical (probabilistic) definitions of efficiency, E and E′, based on the estimators NSE and KGE, respectively, which enable controlled Monte Carlo experiments at 447 watersheds to evaluate their performance. Although NSE is generally unbiased, it exhibits enormous variability from one sample to another, due to the remarkable skewness and periodicity of daily streamflow data. However, use of NSE with logarithms of daily streamflow leads to estimates of E with almost no variability from one sample to the next, though with high upward bias. We introduce improved estimators of E and E′ based on a bivariate lognormal monthly mixture model that are shown to yield considerable improvements over NSE and slight improvements over KGE in controlled Monte Carlo experiments. Our new estimators of E should avoid most previous criticisms of NSE implied by the literature. Improved estimators of E that account for skewness and periodicity are needed for daily and subdaily streamflow series because NSE is not suited to such applications.
FGF/FGFR signaling in health and disease
Authors: Xie Yangli , Su Nan , Yang Jing , Tan Qiaoyan , Huang Shuo , Jin Min , Ni Zhenhong , Zhang Bin , Zhang Dali , Luo Fengtao , Chen Hangang , Sun Xianding , Feng Jian Q. , Qi Huabing , Chen Lin 
Published: September 2020

AbstractGrowing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.
BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts
Authors: Yahiro Yuhei , Maeda Shingo , Morikawa Masato , Koinuma Daizo , Jokoji Go , Ijuin Toshiro , Komiya Setsuro , Kageyama Ryoichiro , Miyazono Kohei , Taniguchi Noboru 
Published: September 2020

AbstractAdult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone formation. Osteocytes or osteoblasts express receptor activator of nuclear factor κ-B ligand (Rankl) or osteoprotegerin (Opg) to promote or inhibit osteoclastogenesis, respectively. Bone morphogenetic protein (BMP) is a potent bone inducer, but its major role in adult bone is to induce osteocytes to upregulate sclerostin (Sost) and increase the Rankl/Opg expression ratio, resulting in promotion of osteoclastogenesis. However, the precise effect of BMP-target gene(s) in osteoblasts on the Rankl/Opg expression ratio remains unclear. In the present study, we identified atonal homolog 8 (Atoh8), which is directly upregulated by the BMP-Smad1 axis in osteoblasts. In vivo, Atoh8 was detected in osteoblasts but not osteocytes in adult mice. Although global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton, the bone volume was decreased and osteoclasts were increased in the adult phase. Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow cells. Atoh8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio, while Runx2 knockdown normalized the Rankl/Opg expression ratio. Moreover, Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression ratio. These results suggest that bone remodeling is regulated elaborately by BMP signaling; while BMP primarily promotes bone resorption, it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts, suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.
Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations
Authors: Todd William D. , Venner Anne , Anaclet Christelle , Broadhurst Rebecca Y. , De Luca Roberto , Bandaru Sathyajit S. , Issokson Lindsay , Hablitz Lauren M. , Cravetchi Olga , Arrigoni Elda , Campbell John N. , Allen Charles N. , Olson David P. , Fuller Patrick M. 
Published: September 2020

AbstractThe hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIPneurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIPneurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIPneurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIPneurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIPneurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIPcells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIPsubtypes.
Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output
Authors: Udakis Matt , Pedrosa Victor , Chamberlain Sophie E. L. , Clopath Claudia , Mellor Jack R. 
Published: September 2020

AbstractThe formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.
Circadian control of brain glymphatic and lymphatic fluid flow
Authors: Hablitz Lauren M. , Plá Virginia , Giannetto Michael , Vinitsky Hanna S. , Stæger Frederik Filip , Metcalfe Tanner , Nguyen Rebecca , Benrais Abdellatif , Nedergaard Maiken 
Published: September 2020

AbstractThe glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.
Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques
Authors: Deng Wei , Bao Linlin , Gao Hong , Xiang Zhiguang , Qu Yajin , Song Zhiqi , Gong Shuran , Liu Jiayi , Liu Jiangning , Yu Pin , Qi Feifei , Xu Yanfeng , Li Fengli , Xiao Chong , Lv Qi , Xue Jing , Wei Qiang , Liu Mingya , Wang Guanpeng , Wang Shunyi , Yu Haisheng , Chen Ting , Liu Xing , Zhao Wenjie , Han Yunlin , Qin Chuan 
Published: September 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1–7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1–7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.
Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis
Authors: Yang Jing , McGovern Amanda , Martin Paul , Duffus Kate , Ge Xiangyu , Zarrineh Peyman , Morris Andrew P. , Adamson Antony , Fraser Peter , Rattray Magnus , Eyre Stephen 
Published: September 2020

AbstractGenome-wide association studies have identified genetic variation contributing to complex disease risk. However, assigning causal genes and mechanisms has been more challenging because disease-associated variants are often found in distal regulatory regions with cell-type specific behaviours. Here, we collect ATAC-seq, Hi-C, Capture Hi-C and nuclear RNA-seq data in stimulated CD4+ T cells over 24 h, to identify functional enhancers regulating gene expression. We characterise changes in DNA interaction and activity dynamics that correlate with changes in gene expression, and find that the strongest correlations are observed within 200 kb of promoters. Using rheumatoid arthritis as an example of T cell mediated disease, we demonstrate interactions of expression quantitative trait loci with target genes, and confirm assigned genes or show complex interactions for 20% of disease associated loci, including FOXO1, which we confirm using CRISPR/Cas9.
Reconfigurable emergent patterns in active chiral fluids
Authors: Zhang Bo , Sokolov Andrey , Snezhko Alexey 
Published: September 2020

AbstractActive fluids comprised of autonomous spinning units injecting energy and angular momentum at the microscopic level represent a promising platform for active materials design. The complexity of the accessible dynamic states is expected to dramatically increase in the case of chiral active units. Here, we use shape anisotropy of colloidal particles to introduce chiral rollers with activity-controlled curvatures of their trajectories and spontaneous handedness of their motion. By controlling activity through variations of the energizing electric field, we reveal emergent dynamic phases, ranging from a gas of spinners to aster-like vortices and rotating flocks, with either polar or nematic alignment of the particles. We demonstrate control and reversibility of these dynamic states by activity. Our findings provide insights into the onset of spatial and temporal coherence in a broad class of active chiral systems, both living and synthetic, and hint at design pathways for active materials based on self-organization and reconfigurability.
Taking electrodecarboxylative etherification beyond Hofer–Moest using a radical C–O coupling strategy
Authors: Martínez Ángel Manu , Hayrapetyan Davit , van Lingen Tim , Dyga Marco , Gooßen Lukas J. 
Published: September 2020

AbstractEstablished electrodecarboxylative etherification protocols are based on Hofer-Moest-type reaction pathways. An oxidative decarboxylation gives rise to radicals, which are further oxidised to carbocations. This is possible only for benzylic or otherwise stabilised substrates. Here, we report the electrodecarboxylative radical-radical coupling of lithium alkylcarboxylates with 1-hydroxybenzotriazole at platinum electrodes in methanol/pyridine to afford alkyl benzotriazole ethers. The substrate scope of this electrochemical radical coupling extends to primary and secondary alkylcarboxylates. The benzotriazole products easily undergo reductive cleavage to the alcohols. They can also serve as synthetic hubs to access a wide variety of functional groups. This reaction prototype demonstrates that electrodecarboxylative C–O bond formation can be taken beyond the intrinsic substrate limitations of Hofer-Moest mechanisms.
Synthesis, characterization, and regeneration of an inorganic–organic nanocomposite (ZnO@biomass) and its application in the capture of cationic dye
Authors: Akpomie Kovo G. , Conradie Jeanet 
Published: September 2020

AbstractDespite the efficiency of ZnO nanoparticle (NPs) composite adsorbents in the adsorption of various pollutants, there is presently no report on the combo of ZnONPs with biomass for adsorption. Besides, there is a dearth of information on the biosorption of celestine blue (CEB), a dye used in the nuclear and textile industry. In this study, biogenic-chemically mediated synthesis of a composite (ZnO@ACP) was prepared by the impregnation of ZnONPs onto Ananas comosus waste (ACP) for the adsorption of CEB. The SEM, EDX, FTIR, XRD, BET, and TGA characterizations showed the successful presence of ZnONPs on the biomass to form a nanocomposite. The uptake of CEB was enhanced by the incorporation of ZnONPs on ACP. A faster CEB adsorption onto ZnO@ACP (120 min) compared to ACP (160 min) was observed. The Langmuir (R2 > 0.9898) and pseudo-second-order (R2 > 0.9518) models were most appropriate in the description of the adsorption process. The impregnation of ZnONPs onto the biomass enhanced the spontaneity of the process and displayed endothermic characteristics. High CEB desorption of 81.3% from the dye loaded ZnO@ACP as well as efficient reusability showed the efficacy of the prepared nanocomposite for CEB adsorption.
Prediction of cardiopulmonary events using the STOP-Bang questionnaire in patients undergoing bronchoscopy with moderate sedation
Authors: Cho Jaeyoung , Choi Sun Mi , Park Young Sik , Lee Chang-Hoon , Lee Sang-Min , Yoo Chul-Gyu , Kim Young Whan , Lee Jinwoo 
Published: September 2020

AbstractThe objective was to evaluate the prevalence of patients at a high risk of having OSA by using a screening questionnaire and to investigate whether the questionnaire can predict patients who are at risk of cardiopulmonary events occurring during a bronchoscopy under sedation. We prospectively enrolled consecutive adult patients who underwent flexible bronchoscopies under moderate sedation. The snoring, tiredness, observed apnea, high blood pressure-body mass index, age, neck circumference and gender (STOP-Bang) questionnaire was used to identify patients at a high (score ≥ 3 of 8) or low risk (score < 3 of 8) of having OSA. The cardiopulmonary events included hypoxemia and hypotension. Multivariable logistic regression was performed with variables selected by the least absolute shrinkage and selection operator. The prevalence of a STOP-Bang score of ≥ 3 was 67.2% (195/290), and 36.9% (107/290) experienced cardiopulmonary events. The multivariable analysis adjusting for chronic obstructive pulmonary disease, chronic kidney disease, baseline SpO2, and procedure time revealed that a STOP-Bang score of ≥ 3 was significantly associated with cardiopulmonary events in a subgroup of patients without a history of cerebrovascular disease (adjusted odds ratio, 1.94; 95% confidence interval, 1.06–3.54). The STOP-Bang questionnaire can predict cardiopulmonary events occurring during this procedure.Trial registration: NCT03325153.
Serum Midkine, estimated glomerular filtration rate and chronic kidney disease-related events in elderly women: Perth Longitudinal Study of Aging Women
Authors: Wang Jeffrey , Lewis Joshua R. , Byrnes Elizabeth , Wong Germaine , Raymond Warren D. , Zhu Kun , Robertson Graham R. , Lim Wai H. , Cao Qi , Prince Richard L. , Lee Vincent W. 
Published: September 2020

AbstractMidkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.5 years, respectively, was examined. Baseline serum MDK was not associated with 5-year change in estimated glomerular filtration rate using the CKD Epidemiology Collaboration creatinine and cystatin C equation (Standardised β = − 0.09, 95% confidence interval − 3.76–0.48, p = 0.129), 5-year rapid decline in renal function (odds ratio = 0.97, 95% confidence interval 0.46–2.02, p = 0.927) or the risk of 14.5-year CKD-related hospitalisations and deaths (hazard ratio = 1.27, 95% confidence interval .66–2.46, p = 0.470) before or after adjusting for major risk factors. In conclusion, in this cohort of elderly women with normal or mildly impaired renal function, serum MDK was not associated with renal function change or future CKD-related hospitalisations and deaths, suggesting that MDK may not be an early biomarker for progression of CKD.
A deep learning approach in diagnosing fungal keratitis based on corneal photographs
Authors: Kuo Ming-Tse , Hsu Benny Wei-Yun , Yin Yu-Kai , Fang Po-Chiung , Lai Hung-Yin , Chen Alexander , Yu Meng-Shan , Tseng Vincent S. 
Published: September 2020

AbstractFungal keratitis (FK) is the most devastating and vision-threatening microbial keratitis, but clinical diagnosis a great challenge. This study aimed to develop and verify a deep learning (DL)-based corneal photograph model for diagnosing FK. Corneal photos of laboratory-confirmed microbial keratitis were consecutively collected from a single referral center. A DL framework with DenseNet architecture was used to automatically recognize FK from the photo. The diagnoses of FK via corneal photograph for comparing DL-based models were made in the Expert and NCS-Oph group through a majority decision of three non-corneal specialty ophthalmologist and three corneal specialists, respectively. The average percentage of sensitivity, specificity, positive predictive value, and negative predictive value was approximately 71, 68, 60, and 78. The sensitivity was higher than that of the NCS-Oph (52%, P < .01), whereas the specificity was lower than that of the NCS-Oph (83%, P < .01). The average accuracy of around 70% was comparable with that of the NCS-Oph. Therefore, the sensitive DL-based diagnostic model is a promising tool for improving first-line medical care at rural area in early identification of FK.
Advanced distributed feedback lasers based on composite fiber heavily doped with erbium ions
Authors: Skvortsov Mikhail I. , Wolf Alexey A. , Vlasov Alexander A. , Proskurina Kseniya V. , Dostovalov Alexander V. , Egorova Olga N. , Galagan Boris I. , Sverchkov Sergey E. , Denker Boris I. , Semjonov Sergey L. , Babin Sergey A. 
Published: September 2020

AbstractSpecially designed composite heavily Er3+-doped fiber in combination with unique point-by-point inscription technology by femtosecond pulses at 1,026 nm enables formation of distributed-feedback (DFB) laser with ultra-short cavity length of 5.3 mm whose parameters are comparable and even better than those for conventional Er3+-doped fiber DFB lasers having much longer cavity. The composite fiber was fabricated by melting rare-earth doped phosphate glass in silica tube. The ultra-short DFB laser generates single-polarization single-frequency radiation at 1,550 nm with narrow linewidth (3.5 kHz) and 0.5 mW output power at 600 mW 980-nm pumping. The same fiber with conventional CW UV (244 nm) inscription technology using phase mask enables fabrication of 40-mm long DFB laser with > 18 mW output power at 3.3% pump conversion, which is a record efficiency for Er3+-doped fiber DFB lasers. The developed technologies form an advanced platform for Er3+-doped fiber DFB lasers operating around 1.55 µm with excellent output characteristics and unique practical features, in particular, the ultra-short DFB lasers are attractive for sensing applications.
Direct formalin fixation induces widespread transcriptomic effects in archival tissue samples
Authors: Wehmas Leah C. , Hester Susan D. , Wood Charles E. 
Published: September 2020

AbstractSequencing technologies now provide unprecedented access to genomic information in archival formalin-fixed paraffin-embedded (FFPE) tissue samples. However, little is known about artifacts induced during formalin fixation, which could bias results. Here we evaluated global changes in RNA-sequencing profiles between matched frozen and FFPE samples. RNA-sequencing was performed on liver samples collected from mice treated with a reference chemical (phenobarbital) or vehicle control for 7 days. Each sample was divided into four parts: (1) fresh-frozen, (2) direct-fixed in formalin for 18 h, (3) frozen then formalin-fixed, and (4) frozen then ethanol-fixed and paraffin-embedded (n = 6/group/condition). Direct fixation resulted in 2,946 differentially expressed genes (DEGs) vs. fresh-frozen, 98% of which were down-regulated. Freezing prior to formalin fixation had ≥ 95% fewer DEGs vs. direct fixation, indicating that most formalin-derived transcriptional effects in the liver occurred during fixation. This finding was supported by retrospective studies of paired frozen and FFPE samples, which identified consistent enrichment in oxidative stress, mitochondrial dysfunction, and transcription initiation pathways with direct fixation. Notably, direct formalin fixation in the parent study did not significantly impact response profiles resulting from chemical exposure. These results advance our understanding of FFPE samples as a resource for genomic research.