bluuebunny/crossref_metadata_2025_split huggingface dataset:
Milestones toward cochlear gene therapy for patients with hereditary hearing loss
Authors: Yoshimura Hidekane , Nishio Shin‐Ya , Usami Shin‐Ichi 
Published: August 2021

AbstractA number of genes are reportedly responsible for hereditary hearing loss, which accounts for over 50% of all congenital hearing loss cases. Recent advances in genetic testing have enabled the identification of pathogenic variants in many cases, and systems have been developed to provide personalized treatment based on etiology. Gene therapy is expected to become an unprecedented curative treatment. Several reports have demonstrated the successful use of cochlear gene therapy to restore auditory function in mouse models of genetic deafness; however, many hurdles remain to its clinical application in humans. Herein, we focus on the frequency of deafness genes in patients with congenital and late‐onset progressive hearing loss and discuss the following points regarding which genes need to be targeted to efficiently proceed with clinical application: (a) which cells' genes are expressed within the cochlea, (b) whether gene transfer to the targeted cells is possible using vectors such as adeno‐associated virus, (c) what phenotype of hearing loss in patients is exhibited, and (d) whether mouse models exist to verify the effectiveness of treatment. Moreover, at the start of clinical application, gene therapy in combination with cochlear implantation may be useful for cases of progressive hearing loss.
Clinical translation of hyperpolarized13C pyruvate and urea MRI for simultaneous metabolic and perfusion imaging
Authors: Qin Hecong , Tang Shuyu , Riselli Andrew M. , Bok Robert A. , Delos Santos Romelyn , van Criekinge Mark , Gordon Jeremy W. , Aggarwal Rahul , Chen Rui , Goddard Gregory , Zhang Chunxin Tracy , Chen Albert , Reed Galen , Ruscitto Daniel M. , Slater James , Sriram Renuka , Larson Peder E. Z. , Vigneron Daniel B. , Kurhanewicz John 
Published: August 2021

PurposeThe combined hyperpolarized (HP)13C pyruvate and urea MRI has provided a simultaneous assessment of glycolytic metabolism and tissue perfusion for improved cancer diagnosis and therapeutic evaluation in preclinical studies. This work aims to translate this dual‐probe HP imaging technique to clinical research.MethodsA co‐polarization system was developed where [1‐13C]pyruvic acid (PA) and [13C,15N2]urea in water solution were homogeneously mixed and polarized on a 5T SPINlab system. Physical and chemical characterizations and toxicology studies of the combined probe were performed. Simultaneous metabolic and perfusion imaging was performed on a 3T clinical MR scanner by alternatively applying a multi‐slice 2D spiral sequence for [1‐13C]pyruvate and its downstream metabolites and a 3D balanced steady‐state free precession (bSSFP) sequence for [13C,15N2]urea.ResultsThe combined PA/urea probe has a glass‐formation ability similar to neat PA and can generate nearly 40% liquid‐state13C polarization for both pyruvate and urea in 3‐4 h. A standard operating procedure for routine on‐site production was developed and validated to produce 40 mL injection product of approximately 150 mM pyruvate and 35 mM urea. The toxicology study demonstrated the safety profile of the combined probe. Dynamic metabolite‐specific imaging of [1‐13C]pyruvate, [1‐13C]lactate, [1‐13C]alanine, and [13C,15N2]urea was achieved with adequate spatial (2.6 mm × 2.6 mm) and temporal resolution (4.2 s), and urea images showed reduced off‐resonance artifacts due to theJCNcoupling.ConclusionThe reported technical development and translational studies will lead to the first‐in‐human dual‐agent HP MRI study and mark the clinical translation of the first HP13C MRI probe after pyruvate.
An Assessment of Fish Herding Techniques: Management Implications for Mass Removal and Control of Silver Carp
Authors: Ridgway Josey L. , Lawson Katelyn M. , Shier Stephen A. , Calfee Robin D. , Chapman Duane C. 
Published: August 2021

Abstract
We assessed the effectiveness of herding techniques on adult Silver Carp Hypophthalmichthys molitrix in a tributary to the Missouri River. Sites (600 m) were contained using block nets and treated with one of five herding techniques: (1) a method commonly used by commercial fishers in the United States (commercial technique), (2) pulsed-DC electrofishing (electric technique), (3) broadband sound administered with underwater speakers (sound technique), (4) both sound and electric in combination (combination technique), and (5) solely the boat, with no added stimulus (control). Treatments were administered at sites with repeated 20-min runs (3×) in a slow, bank-to-bank pattern downstream through a 4.5-m opening between the block net and shoreline. Herding effectiveness was quantified by run category (cumulative for the second and third runs) using adaptive resolution imaging sonar. Mean herding effectiveness of the combination technique was three to four times greater than that of the other techniques regardless of the number of runs included. The effectiveness of the combination technique was significantly greater than the sound technique and control with inclusion of the second run and the commercial technique with inclusion of the third run. All herding techniques, excluding the combination technique, were statistically similar to the control. Inclusion of the second run was advantageous for all techniques, as herding effectiveness increased 54–103%, whereas inclusion of the third run was less beneficial (9–17% increase). Repeated runs allowed fish additional time to vacate the sample reach, but behavioral responses (i.e., acclimation or sensitization) were likely technique dependent. This study describes which techniques are most effective for herding Silver Carp and provides insight for improving mass removal efforts.
Multi‐innovation gradient parameter estimation for multivariable systems based on the maximum likelihood principle
Authors: Xia Huafeng , Xu Sheng , Zhou Cheng , Chen Feiyan 
Published: August 2021

AbstractThis article considers the parameter estimation problems of linear multivariable systems with unknown disturbances. For the parameter matrices in the multivariable systems, the model decomposition technique is used to reduce the computational complexity by decomposing the multivariable system into several subsystems with only the parameter vectors. By means of the negative gradient search, a decomposition‐based maximum likelihood recursive extended stochastic gradient algorithm is derived. In order to improve the parameter estimation accuracy, by introducing the multi‐innovation identification theory, a decomposition‐based maximum likelihood multi‐innovation extended stochastic gradient algorithm is proposed. The simulation results illustrate the effectiveness of the proposed algorithms.
Control charts in financial applications: An overview
Authors: Bisiotis Konstantinos , Psarakis Stelios , Yannacopoulos Athanasios N. 
Published: August 2021

AbstractStatistical process control (SPC) methods have been widely popular not only in industrial applications but also in recent years in several nonindustrial scientific areas. The basic tools of SPC are control charts. SPC methods have been applied to various financial applications such as portfolio surveillance, stock trading, and interest rates. The purpose of this paper is to present the main applications of statistical monitoring process methods, specifically control charts, to the financial area. We focus on applications in stock markets such as technical trading rules, portfolio monitoring problems providing some directions for future research.
Modeling the thermic soil temperature regime boundary of the eastern United States
Authors: D'Avello Tom , Bathgate Jon , Thompson James Alan 
Published: August 2021

AbstractWithin U.S. soil taxonomy,soil temperature regimes (STRs) are recognized and incorporated in the classification and mapping of soils. Although knowledge of STR can inform crop selection, yield estimates, and nutrient management decisions, detailed and current maps of STRs derived from measured data are not available for most of the United States. Soil temperature measurements at the prescribed depth of 50 cm were summarized for 69 Soil Climate Analysis Network (SCAN) stations in the eastern United States. Mean annual soil temperature (MAST) was calculated for the 2005–2015 period from monthly averages calculated from daily soil temperature observations. A prediction equation for MAST was developed using mean annual air temperature (MAAT) from the PRISM (Parameter‐elevation Regressions on Independent Slopes Model) group as a predictor: MAST = 2.49 + (0.91 × MAAT). The adjusted r2 was .96 with a RMSE of 0.74 °C and mean absolute error of 0.59 °C based on 10‐fold cross‐validation. Orographic influence is incorporated in PRISM MAAT, yielding a simple model. The MAST surfaces were calculated by applying the prediction equation to MAAT grids for the 1895–2015 period. The yearly MAST surfaces allow estimation of STR over time and for various summary periods including the 1895–2015 record, 30‐yr normal, and probabilities based on individual years for the 1895–2015 period. Based on this investigation, the mesic–thermic STR boundary occurs north of the presently recognized location, is dynamic, and is supported by existing native plant communities associated with thermic STR.
Spatial thinking in science, technology, engineering, and mathematics: Elementary teachers' beliefs, perceptions, and self‐efficacy
Authors: Gagnier Kristin Michod , Holochwost Steven J. , Fisher Kelly R. 
Published: August 2021

AbstractFostering students' spatial thinking skills holds great promise for improving Science, Technology, Engineering, and Mathematics (STEM) education. Recent efforts have focused on the development of classroom interventions to build students' spatial skills, yet these interventions will be implemented by teachers, and their beliefs and perceptions about spatial thinking influence the effectiveness of such interventions. However, our understanding of elementary school teachers' beliefs and perceptions around spatial thinking and STEM is in its infancy. Thus, we created novel measures to survey elementary teachers' anxiety in solving spatial problems, beliefs in the importance of spatial thinking skills for students' academic success, and self‐efficacy in cultivating students' spatial skills during science instruction. All measures exhibited high internal consistency and showed that elementary teachers experience low anxiety when solving spatial problems and feel strongly that their skills can improve with practice. Teachers were able to identify educational problems that rely on spatial problem‐solving and believed that spatial skills are more important for older compared to younger students. Despite reporting high efficacy in their general teaching and science teaching, teachers reported significantly lower efficacy in their capacities to cultivate students' spatial skills during science instruction. Results were fairly consistent across teacher characteristics (e.g., years of experience and teaching role as generalist or specialist) with the exception that only years of teaching science was related to teachers' efficacy in cultivating students' spatial thinking skills during science instruction. Results are discussed within the broader context of teacher beliefs, self‐efficacy, and implications for professional development research.
Unleashing the power of NK cells in anticancer immunotherapy
Authors: Vogler Meike , Shanmugalingam Senthan , Särchen Vinzenz , Reindl Lisa Marie , Grèze Victoria , Buchinger Leon , Kühn Michael , Ullrich Evelyn 
Published: August 2021

AbstractDue to their physiological role in removing damaged cells, natural killer (NK) cells represent ideal candidates for cellular immunotherapy in the treatment of cancer. Thereby, the cytotoxicity of NK cells is regulated by signals on both, the NK cells as well as the targeted tumor cells, and the interplay and balance of these signals determine the killing capacity of NK cells. One promising avenue in cancer treatment is therefore the combination of NK cell therapy with agents that either help to increase the killing capacity of NK cells or sensitize tumor cells to an NK cell-mediated attack. In this mini-review, we present different strategies that can be explored to unleash the potential of NK cell immunotherapy. In particular, we summarize how modulation of apoptosis signaling within tumor cells can be exploited to sensitize tumor cells to NK cell-mediated cytotoxicity.
The diarrhetic shellfish-poisoning toxin, okadaic acid, provokes gastropathy, dysbiosis and susceptibility to bacterial infection in a non-rodent bioassay, Galleria mellonella
Authors: Emery Helena , Traves William , Rowley Andrew F. , Coates Christopher J. 
Published: August 2021

AbstractDiarrhetic shellfish-poisoning (DSP) toxins such as okadaic acid and dinophysistoxins harm the human gastrointestinal tract, and therefore, their levels are regulated to an upper limit of 160 μg per kg tissue to protect consumers. Rodents are used routinely for risk assessment and studies concerning mechanisms of toxicity, but there is a general move toward reducing and replacing vertebrates for these bioassays. We have adopted insect larvae of the wax moth Galleria mellonella as a surrogate toxicology model. We treated larvae with environmentally relevant doses of okadaic acid (80–400 μg/kg) via intrahaemocoelic injection or gavage to determine marine toxin-related health decline: (1) whether pre-exposure to a sub-lethal dose of toxin (80 μg/kg) enhances susceptibility to bacterial infection, or (2) alters tissue pathology and bacterial community (microbiome) composition of the midgut. A sub-lethal dose of okadaic acid (80 μg/kg) followed 24 h later by bacterial inoculation (2 × 105Escherichia coli) reduced larval survival levels to 47%, when compared to toxin (90%) or microbial challenge (73%) alone. Histological analysis of the midgut depicted varying levels of tissue disruption, including nuclear aberrations associated with cell death (karyorrhexis, pyknosis), loss of organ architecture, and gross epithelial displacement into the lumen. Moreover, okadaic acid presence in the midgut coincided with a shift in the resident bacterial population over time in that substantial reductions in diversity (Shannon) and richness (Chao-1) indices were observed at 240 μg toxin per kg. Okadaic acid-induced deterioration of the insect alimentary canal resembles those changes reported for rodent bioassays.
Toward Inclusive Landscape Governance in Contested Landscapes: Exploring the Contribution of Participatory Tools in the Upper Suriname River Basin
Authors: Best Lisa , Fung-Loy Kimberley , Ilahibaks Nafiesa , Ramirez-Gomez Sara O. I. , Speelman Erika N. 
Published: August 2021

AbstractNowadays, tropical forest landscapes are commonly characterized by a multitude of interacting institutions and actors with competing land-use interests. In these settings, indigenous and tribal communities are often marginalized in landscape-level decision making. Inclusive landscape governance inherently integrates diverse knowledge systems, including those of indigenous and tribal communities. Increasingly, geo-information tools are recognized as appropriate tools to integrate diverse interests and legitimize the voices, values, and knowledge of indigenous and tribal communities in landscape governance. In this paper, we present the contribution of the integrated application of three participatory geo-information tools to inclusive landscape governance in the Upper Suriname River Basin in Suriname: (i) Participatory 3-Dimensional Modelling, (ii) the Trade-off! game, and (iii) participatory scenario planning. The participatory 3-dimensional modelling enabled easy participation of community members, documentation of traditional, tacit knowledge and social learning. The Trade-off! game stimulated capacity building and understanding of land-use trade-offs. The participatory scenario planning exercise helped landscape actors to reflect on their own and others’ desired futures while building consensus. Our results emphasize the importance of systematically considering tool attributes and key factors, such as facilitation, for participatory geo-information tools to be optimally used and fit with local contexts. The results also show how combining the tools helped to build momentum and led to diverse yet complementary insights, thereby demonstrating the benefits of integrating multiple tools to address inclusive landscape governance issues.
Pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment
Authors: Akce Mehmet , El-Khoueiry Anthony , Piha-Paul Sarina A. , Bacque Emeline , Pan Peng , Zhang Zhi-Yi , Ewesuedo Reginald , Gupta Divya , Tang Yongqiang , Milton Ashley , Zajic Stefan , Judson Patricia L. , O’Bryant Cindy L. 
Published: August 2021

Abstract
Purpose
The purpose of this study is to characterize niraparib pharmacokinetics (PK) and safety in patients with normal hepatic function (NHF) versus moderate hepatic impairment (MHI).

Methods
Patients with advanced solid tumors were stratified by NHF or MHI (National Cancer Institute-Organ Dysfunction Working Group criteria [bilirubin > 1.5–3 × upper limit of normal and any aspartate aminotransferase elevation]). In the PK phase, all patients received one 300 mg dose of niraparib. In the extension phase, patients with MHI received niraparib 200 mg daily; patients with NHF received 200 or 300 mg based on weight (< 77 kg, ≥ 77 kg)/platelets (< 150,000/µL, ≥ 150,000/µL). PK parameters included maximum concentration (Cmax), area under the curve to last measured concentration (AUClast) and extrapolated to infinity (AUCinf). Safety was assessed in both phases. Exposure–response (E–R) modeling was used to predict MHI effects on exposure and safety of niraparib doses ≤ 200 mg or 300/200 mg or 200/100 mg weight/platelet regimens.

Results
In the PK phase (NHF, n = 9; MHI, n = 8), mean niraparib Cmax was 7% lower in patients with MHI versus NHF. Mean exposure (AUClast, AUCinf) was increased by 45% and 56%, respectively, in patients with MHI without impacting tolerability. In the extension phase (NHF, n = 8; MHI, n = 7), the overall safety profile was consistent with previous trials. In patients with MHI, E–R modeling predicted niraparib 200 mg reduced Grade ≥ 3 thrombocytopenia incidence, whereas a 200/100 mg regimen yielded exposures below efficacy-associated levels in 15% of patients.

Conclusion
These findings support adjusting the 300 mg niraparib starting dose to 200 mg QD in patients with MHI.

Trial registration
NCT03359850; registered December 2, 2017
The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males
Authors: Kuhn Leandra , Noack Hannes , Skoluda Nadine , Wagels Lisa , Röhr Ann-Kristin , Schulte Christina , Eisenkolb Sana , Nieratschker Vanessa , Derntl Birgit , Habel Ute 
Published: August 2021

AbstractThe experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.
Global drought monitoring with drought severity index (DSI) using Google Earth Engine
Authors: Khan Ramla , Gilani Hammad 
Published: August 2021

AbstractUnlike most disasters, drought does not appear abruptly. It slowly builds over time due to the changes in different environmental and climatological factors. It is one of the deadly disasters that has plagued almost every region of the globe since early civilization. Droughts are scientifically being studied with the help of either simple or composite indices. At 500-m spatial resolution, this study presents global scale drought severity index (DSI), a composite index using Moderate Resolution Imaging Spectroradiometer (MODIS), 8-day temporal resolution evapotranspiration (ET), potential evapotranspiration (PET), and normalized difference vegetation index (NDVI). This index is mainly used to identify meteorological droughts and also has proven reliable for studying agriculture droughts. In this study, Google Earth Engine (GEE), a cloud-based geospatial data computational platform, is used for drought mapping and monitoring from 2001 to 2019. For annual DSI spatial maps, the statistical median is computed ranging from − 1 to + 1, which means drought struck or dry regions have values closer to negative, and wet zones have values near to positive. For the validity of DSI results, the findings are compared with available records of droughts struck in previous years. This study declares that continent-wise, Australia, Africa, and Asia have the most extreme and frequent drought events while South America and North America come a close second. Europe is the least affected by this particular weather event when compared to other continents.