bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness and Knowledge of the Adult Population in Saudi Arabia on Teeth Discoloration and Treatment Options: A Cross-Sectional Study
Authors: Alamassi Basil Y. , Alahmari Hatem S. , Alhabashy Mohammed S. , Talha Abdulrahman A. , Alfehaid Khalil W. , Alhuwaymil Abdulaziz A.
Published: January 2022

Background: Tooth discoloration is a common condition. Discoloration can be a major aesthetic concern for some people and it can indicate pathology, so it needs to be addressed. The success of treatment of tooth discoloration is largely dependent on the knowledge and attitude of people towards it. Hence the aim of this cross-sectional questionnaire-based study was to evaluate knowledge and awareness of the adult Saudi population about the causes of tooth discoloration and its treatment options.

Materials and Methods: An online close-ended questionnaire consisting of 21 questions about tooth discoloration causes and treatment options were uploaded in Google Forms and was sent to 2000 adults in Saudi Arabia via email and social media websites. The questions were designed to evaluate patients’ knowledge about the various causes of tooth discoloration.

Results: A total of 1041 participants responded to our questionnaire. The study included 560 females (53.79%), and 448 participants aged between 18 and 24 years (43.04%), 192 (18.44%) between 25 and 35 years, 246 (23.63%) between 36 and 51 years, and 155 (14.89%) above 51 years. Most of the participants (n= 649; 62.34%) had a bachelor's degree. The most common answer to the type of teeth discoloration was internal and surface discoloration (n= 511; 49%). There was a positive response to the effect of diet, smoking, aging, and bacteria on tooth discoloration. 79% of the participants did not know what dental fluorosis is. The response to the effect of drugs on teeth discoloration split between "Yes" and "I don't know," and 688 of the participants (66.09%) did not know which drugs cause teeth discoloration. The personal effort was the most common way to obtain information about teeth discoloration (n= 678; 65.13%).

Conclusion: Within the limitations of this study, the level of knowledge about tooth discoloration was more concentrated on extrinsic factors, and the majority of the participants demonstrated poor knowledge about the intrinsic causes of tooth discoloration. The preferred treatment option of teeth discoloration was in office bleaching.
Desmoglein‐3 induces YAP phosphorylation and inactivation during collective migration of oral carcinoma cells
Authors: Ahmad Usama Sharif , Parkinson Eric Kenneth , Wan Hong
Published: January 2022

Alterations of the Hippo–YAP pathway are potential targets for oral squamous cell carcinoma (OSCC) therapy, but heterogeneity in this pathway could be responsible for therapeutic resistance. We analysed the Hippo–YAP signatures in a cohort of characterised keratinocyte cell lines derived from the mouth floor and buccal mucosa from different stages of OSCC tumour progression and focused on the specific role of YAP on invasive and metastatic potential. We confirmed heterogeneity in the Hippo–YAP pathway in OSCC lines, including overexpression ofYAP1,WWTR1(often referred to as TAZ) and the major Hippo signalling components, as well as the variations in the genes encoding the intercellular anchoring junctional proteins, which could potentially regulate the Hippo pathway. Specifically, desmoglein‐3 (DSG3) exhibited a unique and mutually exclusive regulation of YAP via YAP phosphorylation during the collective migration of OSCC cells. Mechanistically, such regulation was associated with inhibition of phosphorylation of epidermal growth factor receptor (EGFR) (S695/Y1086) and its downstream effectors heat shock protein beta‐1 (Hsp27) (S78/S82) and transcription factor AP‐1 (c‐Jun) (S63), leading to YAP phosphorylation coupled with its cytoplasmic translocation and inactivation. Additionally, OSCC lines displayed distinct phenotypes of YAP dependency or a mixed YAP and TAZ dependency for cell migration and present distinct patterns in YAP abundance and activity, with the latter being associated with YAP nuclear localisation. In conclusion, this study provides evidence for a newly identified paradigm in the Hippo–YAP pathway and suggests a new regulation mechanism involved in the control of collective migration in OSCC cells.
In vivo genome‐editing screen identifies tumor suppressor genes that cooperate with Trp53 loss during mammary tumorigenesis
Authors: Heitink Luuk , Whittle James R. , Vaillant François , Capaldo Bianca D. , Dekkers Johanna F. , Dawson Caleb A. , Milevskiy Michael J. G. , Surgenor Elliot , Tsai Minhsuang , Chen Huei‐Rong , Christie Michael , Chen Yunshun , Smyth Gordon K. , Herold Marco J. , Strasser Andreas , Lindeman Geoffrey J. , Visvader Jane E.
Published: January 2022

Breast cancer is a heterogeneous disease that comprises multiple histological and molecular subtypes. To gain insight into mutations that drive breast tumorigenesis, we describe a pipeline for the identification and validation of tumor suppressor genes. Based on an in vivo genome‐wide CRISPR/Cas9 screen in Trp53+/– heterozygous mice, we identified tumor suppressor genes that included the scaffold protein Axin1, the protein kinase A regulatory subunit gene Prkar1a, as well as the proof‐of‐concept genes Pten, Nf1, and Trp53 itself. Ex vivo editing of primary mammary epithelial organoids was performed to further interrogate the roles of Axin1 and Prkar1a. Increased proliferation and profound changes in mammary organoid morphology were observed for Axin1/Trp53 and Prkar1a/Trp53 double mutants compared to Pten/Trp53 double mutants. Furthermore, direct in vivo genome editing via intraductal injection of lentiviruses engineered to express dual short‐guide RNAs revealed that mutagenesis of Trp53 and either Prkar1a, Axin1, or Pten markedly accelerated tumor development compared to Trp53‐only mutants. This proof‐of‐principle study highlights the application of in vivo CRISPR/Cas9 editing for uncovering cooperativity between defects in tumor suppressor genes that elicit mammary tumorigenesis.
Feline XRCC4 undergoes rapid Ku‐dependent recruitment to DNA damage sites
Authors: Koike Manabu , Yutoku Yasutomo , Koike Aki
Published: January 2022

Radiation and chemotherapy resistance remain some of the greatest challenges in human and veterinary cancer therapies. XRCC4, an essential molecule for nonhomologous end joining repair, is a promising target for radiosensitizers. Genetic variants and mutations of XRCC4 contribute to cancer susceptibility, and XRCC4 is also the causative gene of microcephalic primordial dwarfism (MPD) in humans. The development of clinically effective molecular‐targeted drugs requires accurate understanding of the functions and regulatory mechanisms of XRCC4. In this study, we cloned and sequenced the cDNA of feline XRCC4. Comparative analysis indicated that sequences and post‐translational modification sites that are predicted to be involved in regulating the localization of human XRCC4, including the nuclear localization signal, are mostly conserved in feline XRCC4. All examined target amino acids responsible for human MPD are completely conserved in feline XRCC4. Furthermore, we found that the localization of feline XRCC4 dynamically changes during the cell cycle. Soon after irradiation, feline XRCC4 accumulated at laser‐induced DNA double‐strand break (DSB) sites in both the interphase and mitotic phase, and this accumulation was dependent on the presence of Ku. Additionally, XRCC4 superfamily proteins XLF and PAXX accumulated at the DSB sites. Collectively, these findings suggest that mechanisms regulating the spatiotemporal localization of XRCC4 are crucial for XRCC4 function in humans and cats. Our findings contribute to elucidating the functions of XRCC4 and the role of abnormal XRCC4 in diseases, including cancers and MPD, and may help in developing XRCC4‐targeted drugs, such as radiosensitizers, for humans and cats.
Quantitatively evaluating activity and number of catalytic sites on metal oxide for ammonium perchlorate decomposition
Authors: Zhou Lin‐Yu , Cao Shao‐Bo , Zhang Liang‐Liang , Xiang Guolei , Zeng Xiao‐Fei , Chu Guang‐Wen , Chen Jian‐Feng
Published: January 2022

Ammonium perchlorate (AP) catalytic thermal decomposition by metal oxides is complex and there is still no suitable quantitative evaluation method to characterize intrinsic catalytic activity. Here, a new method to quantitatively evaluate the catalytic capability of metal oxides for AP decomposition has been proposed. We introduce two indicators, intrinsic peak temperature () and catalytic density () in high‐temperature decomposition process, to uncouple activity and number of catalyst sites. Hematite (α‐Fe2O3) nanostructures with different shapes have been used as model catalysts to verify the feasibility of this method. Rod‐like α‐Fe2O3shows the best catalytic performance in AP decomposition with the lowest of 345.1°C and highest of 0.544, which indicate the largest number and highest activity of catalytic sites. Moreover, these new indicators are theoretically proven to be reasonable by density functional theory calculations.
One‐pot microwave‐assisted synthesis of dialkytin 2‐[(4‐methylbenzoyl) hydrazono]‐3‐phenylpropanoic acid complexes and their anticarcinoma activities and DNA‐binding properties
Authors: Jiang Wu‐Jiu , Tan Yu‐Xing , Peng Yi‐Yuan
Published: January 2022

Under microwave irradiation, five organotin complexes were produced through the reaction of 4‐methylbenzhydrazide, sodium phenylpyruvate and corresponding dialkyltin. Fourier transform infrared spectroscopy; 1H, 13C and 119Sn nuclear magnetic resonance spectroscopy; high‐resolution mass spectrometry; X‐ray crystallography and thermogravimetric analysis (TGA) were performed to characterise the synthesised complexes. The in vitro antitumour activity for the complexes involved was assessed using the MTT assay on the human carcinoma cells of HepG2, NCI‐H460 and MCF7. 2‐Oxo‐3‐pheny propionic acid p‐methyl benzoylhydrazone dibutyltin, C5, exhibited an intensive anticarcinoma activity. Cell apoptosis revealed that C5 mediated the cell apoptosis of HepG2 cells. DNA binding in C5 was investigated through UV‐visible absorption spectrometry and viscosity measurement. Molecular docking was performed for predicting C5‐DNA binding, which revealed C5 could be implanted into the DNA double helix.
Perspectives of online anatomy teachers: A neglected study population struggles with the invisible student
Authors: Attardi Stefanie M. , Mintz Noah M. , Rogers Kem A.
Published: January 2022

Online teachers are an under‐researched population, but their perspectives are crucial to the successful implementation of online education. A fully online section of an established face‐to‐face (F2F) two‐semester undergraduate anatomy course with a prosection laboratory commenced in 2012 at The University of Western Ontario, Canada. Professors' lectures for F2F students were broadcast in live and archived format to online students using Blackboard Collaborate (BBC) video conferencing software. Teaching assistants (TAs) delivered online laboratories using BBC and three‐dimensional (3D) anatomical computer models. This study explored the common experiences and issues faced by the course teachers from 2012 to 2014. Transcripts from open‐ended, individual interviews with professors (n = 4) and TAs (n = 5) were coded and analyzed thematically. The teachers' concern for their inability to see the students during sessions to assess class engagement and their teaching effectiveness, and to develop social relationships, was the main finding. However, video conferencing software and email were sufficient communication methods for the students' questions and the teachers' answers. The TAs noted usability challenges and anatomical inaccuracies in the 3D models compared to cadavers. Due to limitations of BBC's screen sharing function, live manipulation for the 3D computer models was not possible; however, the TAs found pedagogical value in using screen captures of the models for drawing activities with the students. Overall, preparation time for teaching online was longer than for F2F. The study's findings provide science educators with issues to consider when preparing for online teaching and recommendations to optimize the teaching experience.
Attention mechanisms underlying dual‐color digital visual search based on Schulte grid: An event‐related potential study
Authors: Lu Aiqiang , Wang Dongmei , He Shengxi , Zhongcheng Qiuyi , Zhang Wei , Li Zezhi
Published: January 2022

Background

Attention selection is considered to be determined by the perceptual load of cognitive tasks and attention resources that are assigned to processing‐independent stimuli.

Methods

Using visual search paradigm and Schulte grid, the behavioral responses and event‐related potential (ERP) of 27 pupils aged 8–11 (12 girls and 15 boys) were recorded. The subjects were asked to search for the numbers 1, 2, and 3 sequentially and locate the number 5 in the case of monochromatic (black) and bicolor (black‐red) numbers.

Results

We found that the sequential search task took longer than the location search task (p < .05). Furthermore, both search tasks took longer in two‐color conditions than in monochromatic conditions. However, as for sequential search and location search tasks, no significant intra‐group difference was found. ERP data showed that there was significant difference between monochromatic and bichromatic conditions in locating search tasks (P2–P4: p < .05; T7: p < .05, T8: p < .05), but there was no significant difference in sequential search tasks.

Conclusions

Our results indicates that red will be interfered when searching for one number, but will not be interfered when searching for three numbers, which is related to the higher perceptual load of sequential search tasks and less attention resources than those used to interfere with stimulus processing.
Engineering a switchable single‐chain TEV protease to control protein maturation in living neurons
Authors: Renna Pietro , Ripoli Cristian , Dagliyan Onur , Pastore Francesco , Rinaudo Marco , Re Agnese , Paciello Fabiola , Grassi Claudio
Published: January 2022

Engineered proteases are promising tools to address physiological and pathophysiological questions as well as to develop new therapeutic approaches. Here we introduce a new genetically encoded engineered single‐chain tobacco etch virus protease, allowing to control proprotein cleavage in different compartments of living mammalian cells. We demonstrated a set of controllable proteolytic effects, including cytosolic protein cleavage, inducible gene expression, and maturation of brain‐derived neurotrophic factor (BDNF) in the secretory pathway thus showing the versatility of this technique. Of note, the secretory pathway exhibits different characteristics from the cytosol and it is difficult to target because inaccessible to some small molecules. We were able to induce ligand‐mediated BDNF maturation and monitor its effects on dendritic spines in hippocampal pyramidal cells and in the mouse brain. This strategy paves the way to dissect proteolytic cleavage product signaling in various processes as well as for future therapeutic applications.
Offline identification and output prediction for a class of SISO Wiener process
Authors: Wang Zhu , Chen Haichao , Zhao Likai , Luo Xionglin
Published: January 2022

In this paper, a simplified Wiener structure (SWS) for single‐input‐single‐output (SISO) Wiener processes and an identification method based on Gaussian mixture model (GMM) and expectation maximization (EM) algorithm are proposed. The vast majority of industrial processes can be regarded as approximately monotonic non‐linear processes. Approximately, a monotonic characteristic is introduced into the non‐linear module and a rich dynamic characteristic is added into the linear module of the Wiener model. Thus, SWS is exploited and has strong generalization ability. Because GMM can describe the arbitrary distribution of sample data in theory, it is used to accurately describe the output data, including the system error term of SWS. Hence, a statistical model (Equation (17)) is obtained. Then, the EM algorithm is introduced to identify the parameters of the statistical model that contains the parameters of SWS. In the end, two numerical examples demonstrate the effectiveness of both the SWS and the GMM‐EM‐based iterative offline identification algorithm.
Polymorph Structures, Rich Physical Properties and Potential Applications of Two‐Dimensional MoTe2, WTe2 and Their Alloys†
Authors: Zhou Rui , Wu Juanxia , Chen Yuansha , Xie Liming
Published: January 2022

Comprehensive Summary

2D MoTe2, WTe2 and their alloys have received intensive research interest because of their unique properties arising from the polymorph structures, chiral anomaly, strong spin‐orbit coupling, and so on. In this review, we have summarized recent advances of 2D MoTe2, WTe2 and their alloys from the materials perspective with special focus on the synthesis, electrical and magnetic properties. The polymorph structures of MoTe2, WTe2 and their alloys are presented first and then the preparation methods have been discussed, including mechanical exfoliation, metal‐organic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), chemical vapor deposition (CVD) and solution‐phase method. After that, fascinating physical properties arising from the large spin–orbit coupling and non‐trivial band structures have been summarized, including phase transition, optoelectrical properties, Weyl semimetal state, superconducting and ferromagnetism. At last, potential device applications of MoTe2, WTe2 and their alloys are reviewed, including field‐effect transistors (FETs), memory devices, spin‐to‐charge conversion, solar cells, and so on.
Endoscopic resection of a duodenal duplication cyst: A case report
Authors: Kurita Sayumi , Kitagawa Kazuo , Toya Naoki , Kawamura Masahiko , Kawamura Muneo , Eto Ken
Published: January 2022

A duodenal duplication cyst (DDC) is a rare congenital anomaly. Gastrointestinal duplication cysts are traditionally treated by complete surgical resection due to the potential precancerous conditions. Here, we describe an asymptomatic DDC that was successfully treated using endoscopic resection. A submucosal tumor in the descending portion of the duodenum was detected in a 71‐year‐old female during a regular checkup at our hospital. Upper gastrointestinal endoscopy showed a 10‐mm pedunculated submucosal tumor. Endoscopic ultrasonography revealed a 10‐mm cystic tumor of low echogenicity that included nodules and debris. Endoscopic resection with hot snare polypectomy was performed for diagnosis and treatment. The postoperative course was uneventful. Histologic examination revealed that the cystic tumor was a DDC. Endoscopic resection is a safe, effective, and minimally invasive alternative to surgical resection for small DDCs with malignant potential.
Measuring fetal heart rate and variability: Fetal cardiotocography versus electrocardiography
Authors: DiPietro Janet A. , Watson Heather , Raghunathan Radhika S.
Published: January 2022

Fetal heart rate variability is a key indicator of fetal neurodevelopment and well‐being. Most studies have relied on Doppler‐based fetal cardiotocography (fCTG) but recent technologies have made fetal electrocardiography (fECG) more widely available. We compared simultaneous recordings of fCTG and fECG in 131 fetuses twice during gestation (28 and 36 weeks) using a commercially available device (Monica AN24). Within‐individual correlations for fetal heart rate values, based on averaged data during 50‐min recordings, neared 1.0. Continuous and episodic measures of variability were also correlated, particularly at 36 weeks. Data collected during maternal polysomnography at 36 weeks were used to evaluate reliability of variability measures collected during the 50‐min recording. Both fCTG‐ and fECG‐derived measures of variability exhibited correspondence with variability during maternal presleep wakefulness and most sleep states. Results did not appreciably differ by data source or method used to calculate variability. fECG monitoring presented challenges, particularly at 28 weeks, when recordings with signal loss of ≤30% were available from only 27% of participants. Success rates improved to 84% at 36 weeks. fCTG was successful in over 90% of participants at each gestational age. Considerations in the selection of fECG versus fCTG in developmental research are discussed.
Mixed‐severity wildfire and salvage logging affect the populations of a forest‐dependent carnivoran and a competitor
Authors: Green David S. , Martin Marie E. , Powell Roger A. , McGregor Eric L. , Gabriel Mourad W. , Pilgrim Kristine L. , Schwartz Michael K. , Matthews Sean M.
Published: January 2022

Effects of historical fire suppression in forested ecosystems, combined with increasingly frequent and prolonged periods of drought due to a changing climate, are predicted to drive increases in the extent and intensity of wildfires in western North America and elsewhere. Understanding the effects of wildfires on forest‐dependent species and interactions among species is important for conservation and management decisions. We used data collected from a long‐term carnivore monitoring program in northern California and southern Oregon, USA to investigate the effects of three mixed‐severity wildfires and salvage logging on a population of fishers (Pekania pennanti), forest‐dependent carnivoran of conservation concern, and a co‐occurring population of gray foxes (Urocyon cinereoargenteus), a competitor of similar body size. We developed a spatial capture‐recapture population model to estimate the short‐term effects of the wildfires and salvage logging on fisher and gray fox abundances, distributions, apparent survival and recruitment, and species interactions using non‐invasive genetic data collected three years prior to and three years following wildfires. Fisher abundance decreased significantly in areas of low‐, medium‐, and high‐severity wildfire. Gray fox abundance decreased in the years before the wildfires, but rebounded in subsequent years. Medium‐severity wildfire had a negative effect on gray fox density, but high‐severity wildfire and fisher density had positive effects on gray fox density. Salvage logging had negative effects on both fisher and gray fox density. Our results suggest that increased severity, extent, and frequency of wildfires in the western USA will affect fisher populations negatively and alter the composition of mesocarnivoran communities.
Woody perennial polycultures in the U.S. Midwest enhance biodiversity and ecosystem functions
Authors: Kreitzman Maayan , Eyster Harold , Mitchell Matthew , Czajewska Aldona , Keeley Keefe , Smukler Sean , Sullivan Noah , Verster Adrian , Chan Kai M. A.
Published: January 2022

Given the massive and growing environmental impacts of conventional agriculture, humanity needs new methods for growing food that not only meet dietary needs but also provide for multiple ecosystem functions with potential benefits to people and biodiversity. Concepts from ecology and complex adaptive systems suggest that persistent structural heterogeneity and functional diversity are key for supporting biodiversity, ecosystem services, and resilience, but these concepts have not been extensively applied in agriculture, which is still dominated by annual monocropping systems. Perennial agriculture seems to embody these ecological concepts—particularly perennial polycultures that combine a variety of long‐lived woody perennial food crops with continuous ground cover. However, our understanding of the benefits and trade‐offs of such systems compared to conventional agriculture is limited, especially in temperate climates. Here, we provide a systematic and comprehensive study of the ecological attributes of 14 woody perennial polyculture farm fields to conventional annual and hay fields in the U.S. Midwest, one of the most industrialized food‐producing regions in the world. We found that perennial fields had (1) more diverse soil fungal, invertebrate, plant, and bird communities but found no difference in soil bacterial communities; (2) less compacted soil; (3) denser ground cover; (4) more active carbon, organic carbon, and nitrogen and the same available phosphorus in the top layer of soil; and (5) more species of predatory, detritivorous, and herbivorous insects, and approximately fourfold higher abundance of herbivorous insects. Food production from the oldest half of perennial fields was only 14.7% of a regional corn/soy rotation by weight, but increased with the age of the perennial field and had high nutritional diversity. Together, these findings indicate that woody perennial polyculture fields in the U.S. Midwest are characterized by higher biodiversity and ecosystem functions than adjacent conventional fields. Woody perennial polycultures in the temperate north might play a role in the transition of agricultural landscapes toward sustaining both people and nature over the long term.
Angler Choices That Help Catch Lots of Big Fish
Authors: Bade Andrew P , Dippold David A , Schmidt Brian A , DuFour Mark R , Hartman Travis J , Ludsin Stuart A
Published: January 2022

A primary goal of fisheries management is to maximize angler satisfaction (e.g., by catching more and bigger fish), while maintaining sustainable populations. In addition to environmental and ecological factors, angler choices may influence recreational catches. Using interviews (92,838) from Walleye Sander vitreus anglers in Lake Erie during 1989–2017, we identified how angler behavior influences catch outcomes. Angler behaviors were associated with changes in catch rate and the length of harvested fish. For example, trolling resulted in a 50% increase in median catch and a 24-mm increase in length, relative to casting. Other behaviors led to tradeoffs between catch rate and size, such as the time of year anglers fished. We identified behaviors that maximize fishing success with respect to anglers’ desired catch outcomes. Our results can help increase angler satisfaction by providing realistic catch expectations, given the environmental and fishery conditions, while improving recreational catch outcomes through more informed angler decision making.
Top Ten Resolutions for Utility Executives in 2022: Addressing Major Issues Impacting Utilities for the Coming Year and Decade Ahead
Authors: Price Jason , Shah Niki
Published: January 2022

When the clock strikes midnight on December 31st we embrace the new year with a fresh start. However, utilities do not have the luxury of starting the new year from a clean slate. As each year passes, the utility's role grows more complicated; arrearages are increasing year‐over‐year, the planet is getting warmer and weather events are more severe, calls for decarbonization are getting louder, and the world is demanding the energy industry take action. While utilities are not in the business of solving the world's problems, regulators, policy makers and the general public expects results.
Engaging Technologies Evolve
Authors: de Ramos Kevin Monte
Published: January 2022

Recently, colleagues on LinkedIn have been asking why I am reposting articles regarding blockchain, emergent crypto coins, non‐fungible tokens, and the metaverse. Readers will learn in this column that these trending platforms are not just ancillary trends, but rather key transformative technologies that will influence today's utility industry towards a climate conscious future.
Diverse facets of MDSC in different phases of chronic HBV infection: Impact on HBV‐specific T‐cell response and homing
Authors: Pal Sourina , Dey Debangana , Chakraborty Bidhan Chandra , Nandi Madhuparna , Khatun Mousumi , Banerjee Soma , Santra Amal , Ghosh Ranajoy , Ahammed SK Mahiuddin , Chowdhury Abhijit , Datta Simanti
Published: January 2022

Background and Aims

Chronic HBV infection (CHI) is associated with a diverse natural history that includes immune‐tolerant (IT), HBeAg‐positive chronic hepatitis B (CHB) (EP‐CHB), inactive carrier, and HBeAg‐negative CHB (EN‐CHB) phases. A hallmark of CHI is impairment of HBV‐specific T‐cell response. Recently, myeloid‐derived suppressor cells (MDSCs) have emerged as key regulator of T cells, and their properties are sculpted by their microenvironment. Here, we investigated the distinctive features of MDSCs during CHI, identified factors responsible for their functional discrepancies, and studied their impact on HBV‐specific T‐cell response and homing. Influence of antiviral therapy on MDSC profile and T‐cell response was also assessed.

Approach and Results

Flow cytometric analysis indicated that MDSCs in EP‐CHB/EN‐CHB patients had profound suppressive ability, expressing arginase 1 (Arg1)/inducible nitric oxide synthase (iNOS)/programmed death ligand 1 (PD‐L1)/cytotoxic T lymphocyte–associated protein 4 (CTLA‐4)/CD40 at significantly greater levels relative to healthy controls (HC). However, in IT, only Arg1+ MDSCs and in inactive carrier, iNOS+ and PD‐L1+ MDSCs were higher than HC. In vitro assays demonstrated that high HBsAg titer in IT/CHB induced Arg1+ MDSC. Furthermore, elevated serum TNF‐α and IL‐4 in CHB potentiated Arg1/PD‐L1/CD40/CTLA‐4 expression, whereas increased IL‐1β in CHB/IC triggered the expansion of PD‐L1+ MDSCs and iNOS+ MDSCs. MDSCs, sorted from CHB/IC, greatly attenuated IL‐2/interferon gamma (IFN‐γ) production by HBV‐specific CD8+/CD4+ T cells, the effect being more pronounced in CHB. However, MDSCs of IT minimally affected the cytokine production by T cells. Adding Arg1‐/iNOS‐inhibitor restored only IFN‐γ production, while neutralizing PD‐L1 recovered both IL‐2 and IFN‐γ secretion by T cells. Moreover, MDSCs from IT/CHB disrupted virus‐specific T‐cell trafficking by down‐regulating chemokine receptor type 5 on them via TGF‐β signaling. One year of tenofovir therapy failed to normalize MDSC phenotype and HBV‐specific T‐cell response.

Conclusions

Diversity of MDSCs during CHI affects HBV‐specific T‐cell response and homing. Hence, therapeutic targeting of MDSCs could boost anti‐HBV immunity.
A comparison of National Water Model retrospective analysis snow outputs at snow telemetry sites across the Western United States
Authors: Garousi‐Nejad Irene , Tarboton David G.
Published: January 2022

This study compares the US National Water Model (NWM) reanalysis snow outputs to observed snow water equivalent (SWE) and snow‐covered area fraction (SCAF) at snow telemetry (SNOTEL) sites across the Western United States. SWE was obtained from SNOTEL sites, while SCAF was obtained from moderate resolution imaging spectroradiometer (MODIS) observations at a nominal 500 m grid scale. Retrospective NWM results were at a 1000 m grid scale. We compared results for SNOTEL sites to gridded NWM and MODIS outputs for the grid cells encompassing each SNOTEL site. Differences between modelled and observed SWE were attributed to both model errors, as well as errors in inputs, notably precipitation and temperature. The NWM generally under‐predicted SWE, partly due to precipitation input differences. There was also a slight general bias for model input temperature to be cooler than observed, counter to the direction expected to lead to under‐modelling of SWE. There was also under‐modelling of SWE for a subset of sites where precipitation inputs were good. Furthermore, the NWM generally tends to melt snow early. There was considerable variability between modelled and observed SCAF as well as the binary comparison of snow cover presence that hampered useful interpretation of SCAF comparisons. This is in part due to the shortcomings associated with both model SCAF parameterization and MODIS observations, particularly in vegetated regions. However, when SCAF was aggregated across all sites and years, modelled SCAF tended to be more than observed using MODIS. These differences are regional with generally better SWE and SCAF results in the Central Basin and Range and differences tending to become larger the further away regions are from this region. These findings identify areas where predictions from the NWM involving snow may be better or worse, and suggest opportunities for research directed towards model improvements.
New insights into particle transport in karst conduits using comparative tracer tests with natural sediments and solutes during low‐flow and high‐flow conditions
Authors: Richter Dominik , Goeppert Nadine , Goldscheider Nico
Published: January 2022

Colloidal particles are an important vector for the transport of contaminants in karst aquifers, characterized by a high degree of hydrologic variability. Understanding this heterogeneity and hydrogeological functioning is of particular importance for water management strategies. Until now, transport parameters for particles were mostly determined by injection of solutes or surrogates for natural sediments. But suspended particles are easier to analyse, less expensive and better represent natural conditions. Therefore, tracer tests with sediments represent natural transport and a conservative solute dye were conducted simultaneously in an active and partly accessible cave system in Vietnam during constant high‐flow and low‐flow conditions. Breakthrough curves (BTCs) for 10 different particle sizes classes ranging from 1 to 15 μm and the solute were recorded in situ at the two main resurgences of the cave stream at high temporal resolution. This study gives new insights into the transport processes of suspended particles and the highly dynamic exchange between mobile and immobile regions. Major findings include: (1) at low‐flow conditions, inflow from the surrounding aquifer matrix and the velocity distribution inside the karst conduits themselves lead to hydrodynamic focusing, mainly affecting particles; (2) this highly advective, preferential transport of particles in the centre of the karst conduits results in narrow BTC. The more dispersive transport of solutes results in a longer tailing; (3) at high‐flow conditions a more homogeneous distribution of the particles indicates a reversal of the conduit‐matrix interaction; (4) by comparing the results at different hydraulic conditions, the activation of additional flow paths with increasing discharge could be identified. This study also presents the first tracer test in the field resulting in pronounced double peaks for the particulate tracer but only a single, right‐skewed BTC for the simultaneously injected solute, including a conceptual model for particle transport.
Three‐year clinical interventions from an outpatient multidisciplinary direct oral anticoagulant monitoring service
Authors: Dietrich Eric , Davis Kyle , Talana Amy , Holland Neal , Akhavan Neeka , Panna Danielle , Wright Ashleigh , Huber Katherine
Published: January 2022

Introduction

Direct oral anticoagulants (DOAC) are increasingly utilized for the prevention of thrombotic events. Unlike warfarin they do not require drug‐level monitoring making dedicated DOAC monitoring uncommon. The purpose of this study is to describe the interventions made by a DOAC monitoring service over 3 years.

Materials and Methods

This was a single‐center prospective observational study of patients seen at an outpatient clinic between February 14, 2017 and February 13, 2020. Following referral patients met a pharmacist for a DOAC‐specific visit. Patient demographics and clinical interventions were collected for all patients. Continuous quality improvement status was received from the local Institutional Review Board.

Results

A total of 153 patients completing 336 visits were included. The median age was 75 years (interquartile range [IQR] 69‐81) and 41.2% were male. Apixaban was the most common DOAC (82.4% of visits) and atrial fibrillation (AF) was the most common indication (69.7% of visits). A total of 299 interventions were made over 336 visits with an average of 0.9 interventions per visit; the first visit had an average of 1.1 interventions per visit made. Need for updated laboratory monitoring (101 visits, 30.1% of visits) was the most common intervention. There were 94 interventions related to nonadherence and 24 interventions for incorrect dosing due to renal function, drug‐drug interaction, or indication.

Conclusions

A DOAC monitoring service frequently made interventions. Routine DOAC monitoring should be considered for all patients. It remains unclear if routine DOAC monitoring reduces the rate of clinical outcomes.
A facile synthesis of pyrrolo[2,3‐j]phenanthridines via the cascade reaction of indoleanilines and aldehydes
Authors: Huang Wen‐Jun , Chen Zhi‐Peng , Liu Li‐Xia , Zhou Yong‐Gui , Wu Bo , Jiang Guo‐Fang
Published: January 2022

A facile method for the synthesis of pyrrolo[2,3‐j]phenanthridines from indoleanilines and aldehydes in the presence of Brønsted acid catalyst and benzoquinone oxidant has been established. This approach features excellent yields, high efficiency and a wide range of substrate scope. Mechanism studies exhibited that this reaction was a cascade process including acid‐catalyzed condensation of indoleanilines with aldehydes, cyclization and oxidative aromatization.
Effects of superfine grinding on the physicochemical properties, antioxidant capacity, and hygroscopicity of Rosa rugosa cv. Plena powders
Authors: Qiu Liqing , Zhang Min , Xu Baoguo , Wang Bin
Published: January 2022

BACKGROUND

Rosa rugosa cv. Plena (RP) is a commercially significant crop with edible flowers. Due to its high medicinal and nutritional value, it has recently attracted increasing attention in the food industry. In this study, the physicochemical properties, antioxidant capacity, and hygroscopicity of four RP powders produced by ball milling were compared.

RESULTS

The brightness, redness, and blueness of RP powders improved after superfine grinding. The water and oil holding capacity decreased with a reduction in the particle size but the water solubility index increased from 7.10% to 29.93%. The elements present in the powders were not significantly (P > 0.05) affected by particle size while phytochemicals were released and extracted more easily after superfine grinding, resulting in higher anthocyanin, polyphenol, and flavonoid content (3.06, 34.01, and 3.97 mg g−1, respectively), and stronger antioxidant capacity than was found with other powders (ABTS (2,2′‐azinobis‐3‐ethylbenzothiazoline‐6‐sulphonic acid) and DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging activities were 24.51 and 39.81 mM trolox equivalents (TE) g−1, respectively). Superfine grinding also improved the water‐absorption capacity of RP powders under a high‐RH environment.

CONCLUSION

Superfine grinding is a promising technique for the production of RP powders with stronger bioactive substances and bioactivity. © 2022 Society of Chemical Industry.
Identification ofPulsatilla chinensis(Bge.) Regel and look‐alike species by UHPLC‐TOF‐MS using multivariate statistical analysis
Authors: Zhang Lu , Li Ming‐Hua , Tian Jing , Yin Meng , Cheng Xian‐Long , Wei Feng , Ma Shuang‐Cheng
Published: January 2022

Pulsatillae Radix, the root ofPulsatilla chinensis(Bge.) Regel, is recorded in the Pharmacopoeia of the People's Republic of China and has been widely used for its pharmacological activities, such as anti‐inflammatory, antioxidant, antibacterial, antitumor, and cardiovascular benefits. However, there are several look‐alike species that can be marketed as Pulsatillae Radix. To distinguishP. chinensis(Bge.) Regel from its look‐alikes, viz.Pulsatilla cernua(Thunb.) Bercht et Opiz.,Pulsatilla dahurica(Fisch.) Spreng.,Anemone tomeutosa(Maxim.) Pei., andRhaponticum uniflorum(L.) DC, we used ultra high performance liquid chromatography with time‐of‐flight mass spectrometry combined with principal component analysis to compare their chemical compositions. Four ions, a (RT 8.98 min,m/z1381.6671), b (RT 10.64 min,m/z1219.6143), c (RT 11.52 min,m/z1217.5978), and d (RT 13.6 min,m/z749.4463), fromP. chinensis(Bge.) Regel were identified as potential chemical markers to distinguish it from look‐alike species using an unsupervised statistical model combined with orthogonal partial least‐squares discriminant analysis. The results of this study provide an effective method for identifying and distinguishingP. chinensis(Bge.) Regel from similar plants.
DETERMINANTS OF SMALL BUSINESS REOPENING DECISIONS AFTER COVID RESTRICTIONS WERE LIFTED
Authors: Balla‐Elliott Dylan , Cullen Zoë B. , Glaeser Edward L. , Luca Michael , Stanton Christopher
Published: January 2022

The COVID‐19 pandemic led to dramatic economic disruptions, including government‐imposed restrictions that temporarily shuttered millions of American businesses. We use a nationwide survey of thousands of small business owners to establish three main facts about business owners’ decisions to reopen at the end of the lockdowns. First, roughly 60 percent of firms planned to reopen within days of the end of legal restrictions, suggesting that the lockdowns were generally binding for businesses—although nearly 30 percent expected to delay their reopening by at least a month. Second, decisions to delay reopenings did not seem to be driven by concerns about employee or customer health; even businesses in high‐proximity sectors with the highest health risks generally reported intentions to reopen as soon as regulations allowed. Third, pessimistic demand projections primarily explain delays among firms that could legally reopen. Owners expected demand to be one‐third lower than before the crisis throughout the pandemic. Using experimentally induced shocks to perceived demand, we find that a 10 percent decline in expected demand results in a 1.5 percentage point (8 percent) increase in the likelihood that firms expected to remain closed for at least one month after being legally able to open. We use follow‐up surveys to cross‐validate expectations with realized outcomes. Overall, our results suggest that governments set more stringent guidelines for reopening than what many businesses would have selected, suggesting that governments may have internalized costs of contagion that businesses did not.
Empagliflozin protects glomerular endothelial cell architecture in experimental diabetes through the VEGF‐A/caveolin‐1/PV‐1 signaling pathway
Authors: Locatelli Monica , Zoja Carlamaria , Conti Sara , Cerullo Domenico , Corna Daniela , Rottoli Daniela , Zanchi Cristina , Tomasoni Susanna , Remuzzi Giuseppe , Benigni Ariela
Published: January 2022

In addition to having blood glucose‐lowering effects, inhibitors of sodium glucose cotransporter 2 (SGLT2) afford renoprotection in diabetes. We sought to investigate which components of the glomerular filtration barrier could be involved in the antiproteinuric and renoprotective effects of SGLT2 inhibition in diabetes. BTBR (black and tan, brachyuric) ob/ob mice that develop a type 2 diabetic nephropathy received a standard diet with or without empagliflozin for 10 weeks, starting at 8 weeks of age, when animals had developed albuminuria. Empagliflozin caused marked decreases in blood glucose levels and albuminuria but did not correct glomerular hyperfiltration. The protective effect of empagliflozin against albuminuria was not due to a reduction in podocyte damage as empagliflozin did not affect the larger podocyte filtration slit pore size nor the defective expression of nephrin and nestin. Empagliflozin did not reduce the thickening of the glomerular basement membrane. In BTBR ob/ob mice, the most profound abnormality seen using electron microscopy was in the endothelial aspect of the glomerular capillary, with significant loss of endothelial fenestrations. Remarkably, empagliflozin ameliorated the subverted microvascular endothelial ultrastructure. Caveolae and bridging diaphragms between adjacent endothelial fenestrae were seen in diabetic mice and associated with increased expression of caveolin‐1 and the appearance of PV‐1. These endothelial abnormalities were limited by the SGLT2 inhibitor. Although no expression of SGLT2 was found in glomerular endothelial cells, SGLT2 was expressed in the podocytes of diabetic mice. VEGF‐A, which is a known stimulus for endothelial caveolin‐1 and PV‐1, was increased in podocytes of BTBR ob/ob mice and normalized by SGLT2 inhibitor treatment. Thus, empagliflozin’s protective effect on the glomerular endothelium of diabetic mice could be due to a limitation of the paracrine signaling of podocyte‐derived VEGF‐A that resulted in a reduction of the abnormal endothelial caveolin‐1 and PV‐1, with the consequent preservation of glomerular endothelial function and permeability. © 2022 The Pathological Society of Great Britain and Ireland.
A Maximum Caliber analysis of the Foldon Hypothesis
Authors: Johnson Eric
Published: January 2022

Different models of protein folding favor different mechanisms. Some models rely on a defined pathway, while other models rely on a more heterogeneous set of pathways. The Foldon Hypothesis is based on the concept of a defined pathway. According to the Foldon Hypothesis, protein folding is characterized by the stepwise assembly of small, cooperative units called foldons. The Maximum Caliber (Max Cal) method provides an opportunity to test this model. The Max Cal method gives the probabilities for dynamical trajectories, in much the same way that the maximum entropy principle gives the probabilities for equilibrium states. In this study, the Max Cal method was applied to folding data for the protein cytochrome c (cyt c; Hu W, Kan ZY, Mayne L, Englander SW. Proc Natl Acad Sci U S A. 2016;113:3809–3814). The overall picture to emerge from this analysis is that the data do not require a dominant, defined pathway. The folding of cytochrome c is likely a heterogeneous process that includes multiple pathways.
Seedling growth and fall armyworm feeding preference influenced by dhurrin production in sorghum
Authors: Gruss Shelby M. , Ghaste Manoj , Widhalm Joshua R. , Tuinstra Mitchell R.
Published: January 2022

Cyanogenic glucosides (CGs) play a key role in host-plant defense to insect feeding; however, the metabolic tradeoffs between synthesis of CGs and plant growth are not well understood. In this study, genetic mutants coupled with nondestructive phenotyping techniques were used to study the impact of the CG dhurrin on fall armyworm [Spodoptera frugiperda (J.E. Smith)] (FAW) feeding and plant growth in sorghum [Sorghum bicolor (L.) Moench]. A genetic mutation in CYP79A1 gene that disrupts dhurrin biosynthesis was used to develop sets of near-isogenic lines (NILs) with contrasting dhurrin contents in the Tx623 bmr6 genetic background. The NILs were evaluated for differences in plant growth and FAW feeding damage in replicated greenhouse and field trials. Greenhouse studies showed that dhurrin-free Tx623 bmr6 cyp79a1 plants grew more quickly than wild-type plants but were more susceptible to insect feeding based on changes in green plant area (GPA), total leaf area, and total dry weight over time. The NILs exhibited similar patterns of growth in field trials with significant differences in leaf area and dry weight of dhurrin-free plants between the infested and non-infested treatments. Taken together, these studies reveal a significant metabolic tradeoff between CG biosynthesis and plant growth in sorghum seedlings. Disruption of dhurrin biosynthesis produces plants with higher growth rates than wild-type plants but these plants have greater susceptibility to FAW feeding.