bluuebunny/crossref_metadata_2025 huggingface dataset:
Derivation and Clinical Validation of a Redox-Driven Prognostic Signature for Colorectal Cancer
Authors: Dang Qin , Liu Zaoqu , Hu Shengyun , Chen Zhuang , Meng Lingfang , Hu Junhong , Wang Guixian , Yuan Weitang , Han Xinwei , Li Lifeng , Sun Zhenqiang
Published: October 2021

Colorectal cancer (CRC), a seriously threat that endangers public health, has a striking tendency to relapse and metastasize. Redox-related signaling pathways have recently been extensively studied in cancers. However, the study and potential role of redox in CRC remain unelucidated. We developed and validated a risk model for prognosis and recurrence prediction in CRC patients via identifying gene signatures driven by redox-related signaling pathways. The redox-driven prognostic signature (RDPS) was demonstrated to be an independent risk factor for patient survival (including OS and RFS) in four public cohorts and one clinical in-house cohort. Additionally, there was an intimate association between the risk score and tumor immune infiltration, with higher risk score accompanied with less immune cell infiltration. In this study, we used redox-related factors as an entry point, which may provide a broader perspective for prognosis prediction in CRC and have the potential to provide more promising evidence for immunotherapy.
Inhibition of Poly ADP-Ribose Glycohydrolase Sensitizes Ovarian Cancer Cells to Poly ADP-Ribose Polymerase Inhibitors and Platinum Agents
Authors: Matanes Emad , López-Ozuna Vanessa M. , Octeau David , Baloch Tahira , Racovitan Florentin , Dhillon Amandeep Kaur , Kessous Roy , Raban Oded , Kogan Liron , Salvador Shannon , Lau Susie , Gotlieb Walter H. , Yasmeen Amber
Published: October 2021

Background

Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin.

Methods

PARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle.

Results

PARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction.

Conclusions

PARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects.
Preoperative Magnetic Resonance Imaging Radiomics for Predicting Early Recurrence of Glioblastoma
Authors: Wang Jing , Yi Xiaoping , Fu Yan , Pang Peipei , Deng Huihuang , Tang Haiyun , Han Zaide , Li Haiping , Nie Jilin , Gong Guanghui , Hu Zhongliang , Tan Zeming , Chen Bihong T.
Published: October 2021

Purpose

Early recurrence of glioblastoma after standard treatment makes patient care challenging. This study aimed to assess preoperative magnetic resonance imaging (MRI) radiomics for predicting early recurrence of glioblastoma.

Patients and Methods

A total of 122 patients (training cohort: n = 86; validation cohort: n = 36) with pathologically confirmed glioblastoma were included in this retrospective study. Preoperative brain MRI images were analyzed for both radiomics and the Visually Accessible Rembrandt Image (VASARI) features of glioblastoma. Models incorporating MRI radiomics, the VASARI parameters, and clinical variables were developed and presented in a nomogram. Performance was assessed based on calibration, discrimination, and clinical usefulness.

Results

The nomogram consisting of the radiomic signatures, the VASARI parameters, and blood urea nitrogen (BUN) values showed good discrimination between the patients with early recurrence and those with later recurrence, with an area under the curve of 0.85 (95% CI, 0.77-0.94) in the training cohort and 0.84 [95% CI, 0.71-0.97] in the validation cohort. Decision curve analysis demonstrated favorable clinical application of the nomogram.

Conclusion

This study showed the potential usefulness of preoperative brain MRI radiomics in predicting the early recurrence of glioblastoma, which should be helpful in personalized management of glioblastoma.
A Review on the Application and Limitations of Administrative Health Care Data for the Study of Acute Kidney Injury Epidemiology and Outcomes in Children
Authors: Ulrich Emma H. , So Gina , Zappitelli Michael , Chanchlani Rahul
Published: October 2021

Administrative health care databases contain valuable patient information generated by health care encounters. These “big data” repositories have been increasingly used in epidemiological health research internationally in recent years as they are easily accessible and cost-efficient and cover large populations for long periods. Despite these beneficial characteristics, it is also important to consider the limitations that administrative health research presents, such as issues related to data incompleteness and the limited sensitivity of the variables. These barriers potentially lead to unwanted biases and pose threats to the validity of the research being conducted. In this review, we discuss the effectiveness of health administrative data in understanding the epidemiology of and outcomes after acute kidney injury (AKI) among adults and children. In addition, we describe various validation studies of AKI diagnostic or procedural codes among adults and children. These studies reveal challenges of AKI research using administrative data and the lack of this type of research in children and other subpopulations. Additional pediatric-specific validation studies of administrative health data are needed to promote higher volume and increased validity of this type of research in pediatric AKI, to elucidate the large-scale epidemiology and patient and health systems impacts of AKI in children, and to devise and monitor programs to improve clinical outcomes and process of care.
The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD
Authors: Li Jiansheng , Zhao Peng , Tian Yange , Li Kangchen , Zhang Lanxi , Guan Qingzhou , Mei Xiaofeng , Qin Yanqin
Published: October 2021

Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine–cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response–activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process.
Role of Ursodeoxycholic Acid in Treating and Preventing Idiosyncratic Drug-Induced Liver Injury. A Systematic Review
Authors: Robles-Díaz Mercedes , Nezic Lana , Vujic-Aleksic Vesna , Björnsson Einar S.
Published: October 2021

Introduction: Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI.

Methods: A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines.

Results: A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention.

Conclusion: According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed.
Angiogenesis is Inhibited by Arsenic Trioxide Through Downregulation of the CircHIPK3/miR-149-5p/FOXO1/VEGF Functional Module in Rheumatoid Arthritis
Authors: Zhang Juan , Ma Yeye , Zhang Yue , Niu Sijia , Chu Maolin , Zhang Zhiyi
Published: October 2021

Angiogenesis is a crucial event in the pathogenesis of rheumatoid arthritis (RA). Arsenic trioxide (ATO, As2O3) has been reported to inhibit synovial angiogenesis via the vascular endothelial growth factor (VEGF)-centered functional module. However, the exact mechanisms of ATO on VEGF modulation remain unclear. Circular RNAs (circRNAs) are emerging as important regulators in RA, and the detailed mechanisms remain largely unknown. Here, we reported a circRNA (circHIPK3), the expression of which was significantly increased in RA fibroblast-like synoviocytes (RA-FLS) after TNF-α induction. Moreover, VEGF content in the supernatants of a RA-FLS and human dermal microvascular endothelial cell (HDMEC) co-culture as well as in RA-FLS co-cultured was significantly elevated in accordance with circHIPK3 levels. This increased VEGF expression may significantly upregulate endothelial tube formation and transwell migration, as well as microvessel sprouting in the ex vivo aortic ring assay. CircHIPK3 was further illustrated to be a sponge for the forkhead box transcription factor O1 (FOXO1)-targeting miR-149-5p, leading to the changing expression of the downstream VEGF. These networked factors mainly form a functional module regulating angiogenesis in RA-FLS, and the expression of this functional module could be significantly downregulated by ATO with a consistently reduced vascularity in vitro. In the collagen-induced arthritis (CIA) mice model, an intra-articular injection of the adeno-associated virus-si-circHIPK3 or ATO was demonstrated to alleviate the synovial VEGF expression and arthritis severity respectively. Thus, we elucidate a previously unknown mechanism between circRNAs and RA, and ATO has a significant protective effect on RA-FLS and CIA synovium via its inhibition of the angiogenic functional module of circHIPK3/miR-149-5p/FOXO1/VEGF, suggesting great potential for the combination therapy of ATO with circHIPK3 silencing.
Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation
Authors: Hu Haibo , Hu Changling , Peng Jinnian , Ghosh Alokesh Kumar , Khan Ajmal , Sun Dan , Luyten Walter
Published: October 2021

The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.
Structure and Evolution of the International Pesticide Trade Networks
Authors: Li Jian-An , Xie Wen-Jie , Zhou Wei-Xing
Published: October 2021

To meet the increasing demand for food around the world, pesticides are widely used and will continue to be widely used in agricultural production to reduce yield losses and maintain product quality. International pesticide trade serves to reallocate the distribution of pesticides around the world. We investigate the statistical properties of the international trade networks of five categories of pesticides from the view angle of temporal directed and weighted networks. We observed an overall increasing trend in network size, network density, average in- and out-degrees, average in- and out-strengths, temporal similarity, and link reciprocity, indicating that the rising globalization of pesticides trade is driving the networks denser. However, the distributions of link weights remain unchanged along time for the five categories of pesticides. In addition, all the networks are disassortatively mixed because large importers or exporters are more likely to trade with small exporters or importers. We also observed positive correlations between in-degree and out-degree, in-strength and out-strength, link reciprocity and in-degree, out-degree, in-strength, and out-strength, while node’s local clustering coefficient is negatively related to in-degree, out-degree, in-strength, and out-strength. We show that some structural and dynamic properties of the international pesticide trade networks are different from those of the international trade networks, highlighting the presence of idiosyncratic features of different goods and products in the international trade.
Variance-Reduction Methods for Monte Carlo Simulation of Radiation Transport
Authors: García-Pareja Salvador , Lallena Antonio M. , Salvat Francesc
Published: October 2021

After a brief description of the essentials of Monte Carlo simulation methods and the definition of simulation efficiency, the rationale for variance-reduction techniques is presented. Popular variance-reduction techniques applicable to Monte Carlo simulations of radiation transport are described and motivated. The focus is on those techniques that can be used with any transport code, irrespective of the strategies used to track charged particles; they operate by manipulating either the number and weights of the transported particles or the mean free paths of the various interaction mechanisms. The considered techniques are 1) splitting and Russian roulette, with the ant colony method as builder of importance maps, 2) exponential transform and interaction-forcing biasing, 3) Woodcock or delta-scattering method, 4) interaction forcing, and 5) proper use of symmetries and combinations of different techniques. Illustrative results from analog simulations (without recourse to variance-reduction) and from variance-reduced simulations of various transport problems are presented.
Ultrafast Terahertz Complex Conductivity Dynamics of Layered MoS2 Crystal Probed by Time-Resolved Terahertz Spectroscopy
Authors: Yang Yong , He Chuan , Huang Yuanyuan , Zhu Lipeng , Zhou Yixuan , Xu Xinlong
Published: October 2021

Ultrafast carrier dynamics, including the carrier photoexcitation and relaxation processes, plays an essential role in improving the performance of molybdenum disulfide (MoS2)-based optoelectronic devices. Herein, we investigate the photo-generated carrier dynamics in layered MoS2 crystal using a time-resolved terahertz (THz) spectroscopy. We have analyzed the ultrafast changes of the THz complex photoconductivity deduced from the peak and zero-crossing of THz waveforms. The decay time of the real part of the THz photoconductivity in layered MoS2 crystal is independent with the pump power, while the imaginary part increases with the pump power. We attribute the decay time of the real part to the carrier recombination process via phonon-assistance and the decay time of the imaginary part to the defect-assisted exciton recombination. The peak values of the complex photoconductivity show a trend of saturation with the increase of the pump power because of the many-body effect at high carrier concentration. This work deepens the understanding of the basic ultrafast physical process in MoS2 crystal, which is enlightening for the design of novel optoelectronic devices.
Harnessing Conductive Oxide Interfaces for Resistive Random-Access Memories
Authors: Li Yang , Kvatinsky Shahar , Kornblum Lior
Published: October 2021

Two-dimensional electron gases (2DEGs) can be formed at some oxide interfaces, providing a fertile ground for creating extraordinary physical properties. These properties can be exploited in various novel electronic devices such as transistors, gas sensors, and spintronic devices. Recently several works have demonstrated the application of 2DEGs for resistive random-access memories (RRAMs). We briefly review the basics of oxide 2DEGs, emphasizing scalability and maturity and describing a recent trend of progression from epitaxial oxide interfaces (such as LaAlO3/SrTiO3) to simple and highly scalable amorphous-polycrystalline systems (e.g., Al2O3/TiO2). We critically describe and compare recent RRAM devices based on these systems and highlight the possible advantages and potential of 2DEGs systems for RRAM applications. We consider the immediate challenges to revolve around scaling from one device to large arrays, where further progress with series resistance reduction and fabrication techniques needs to be made. We conclude by laying out some of the opportunities presented by 2DEGs based RRAM, including increased tunability and design flexibility, which could, in turn, provide advantages for multi-level capabilities.
Periodontal Inflammation and Systemic Diseases: An Overview
Authors: Martínez-García Mireya , Hernández-Lemus Enrique
Published: October 2021

Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.
Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes
Authors: Xu Linxin , Xu Chaofei , Liu Xiangyang , Li Xiaoyu , Li Ting , Yu Xiaochen , Xue Mei , Yang Jing , Kosmas Constantine E. , Moris Dimitrios , Sanchis-Gomar Fabian , Yoshida Naofumi , Berger Nathan A. , Aronow Wilbert S. , Sun Bei , Chen Liming
Published: October 2021

Background: White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and in vivo studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects.

Methods: Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, and function were evaluated by gene expression analyses, fluorescence microscopy, and enzymatic assays. The roles of adenosine monophosphate–activated protein kinase (AMPK) and peroxisome proliferator–activated receptor-γ coactivator-1-alpha (PGC-1α) were determined through AICAR (5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside)/Compound C and RNA interference, respectively.

Results: Empagliflozin substantially reduced the bodyweight of KKAy mice. Mice treated with empagliflozin exhibited elevated cold-induced thermogenesis and higher expression levels of uncoupling protein 1 (UCP1) and other brown adipose tissue signature proteins in epididymal and perirenal WAT, which was an indication of browning in these WAT depots. At the same time, empagliflozin enhanced fusion protein mitofusin 2 (MFN2) expression, while decreasing the levels of the fission marker phosphorylated dynamin-related protein 1 (Ser616) [p-DRP1 (Ser616)] in epididymal and perirenal WAT. Empagliflozin also increased mitochondrial biogenesis and fusion, improved mitochondrial integrity and function, and promoted browning of 3T3-L1 adipocytes. Further, we found that AMPK signaling activity played an indispensable role in empagliflozin-induced browning and mitochondrial biogenesis, and that PGC-1α was required for empagliflozin-induced fusion. Whether empagliflozin activates AMPK by inhibition of SGLT2 or by independent mechanisms remains to be tested.

Conclusion: Our results suggest that empagliflozin is a promising anti-obesity treatment, which can immediately induce WAT browning mitochondrial biogenesis, and regulate mitochondrial dynamics.
Different Cis-Regulatory Elements Control the Tissue-Specific Contribution of Plastid ω-3 Desaturases to Wounding and Hormone Responses
Authors: Luján María A. , Soria-García Ángel , Claver Ana , Lorente Patricia , Rubio María C. , Picorel Rafael , Alfonso Miguel
Published: October 2021

Trienoic fatty acids are essential constituents of biomembranes and precursors of jasmonates involved in plant defense responses. Two ω-3 desaturases, AtFAD7 and AtFAD8, synthetize trienoic fatty acids in the plastid. Promoter:GUS and mutagenesis analysis was used to identify cis-elements controlling AtFAD7 and AtFAD8 basal expression and their response to hormones or wounding. AtFAD7 promoter GUS activity was much higher than that of AtFAD8 in leaves, with specific AtFAD7 expression in the flower stamen and pistil and root meristem and vasculature. This specific tissue and organ expression of AtFAD7 was controlled by different cis-elements. Thus, promoter deletion and mutagenesis analysis indicated that WRKY proteins might be essential for basal expression of AtFAD7 in leaves. Two MYB target sequences present in the AtFAD7 promoter might be responsible for its expression in the flower stamen and stigma of the pistil and in the root meristem, and for the AtFAD7 wound-specific response. Two MYB target sequences detected in the distal region of the AtFAD8 gene promoter seemed to negatively control AtFAD8 expression, particularly in true leaves and flowers, suggesting that MYB transcription factors act as repressors of AtFAD8 gene basal expression, modulating the different relative abundance of both plastid ω-3 desaturases at the transcriptional level. Our data showed that the two ABA repression sequences detected in the AtFAD7 promoter were functional, suggesting an ABA-dependent mechanism involved in the different regulation of both ω-3 plastid desaturases. These results reveal the implication of different signaling pathways for the concerted regulation of trienoic fatty acid content in Arabidopsis.
Green Leaf Volatile-Burst in Selaginella moellendorffii
Authors: Tanaka Moena , Koeduka Takao , Matsui Kenji
Published: October 2021

Green leaf volatiles (GLVs) consist of six-carbon volatile aldehydes, alcohols, and their esters. They are formed from polyunsaturated fatty acids and are involved in the defense of plants against herbivores and pathogens. GLVs generally have low concentrations in intact healthy plant tissues, but the biosynthetic pathway to form GLVs is quickly activated by mechanical damage to tissues, an event called the GLV-burst. Most seed plants have the ability to implement GLV-burst; however, this potential in non-seed plants has not been extensively researched. In this study, we examined the GLV-burst capacity of monilophytes, lycophytes, and bryophytes, and confirmed that monilophytes and lycophytes showed substantial GLV-burst ability, while bryophytes did not, with a few exceptions. When the genome sequence of a model lycophyte, Selaginella moellendorffii was reviewed, 10 genes were found that showed high similarity with the non-canonical cytochrome P450 enzymes, CYP74s, specialized in oxylipin formation. Recombinant proteins expressed with Escherichia coli showed that one of them had the ability to encode allene oxide synthase, and another encoded hydroperoxide lyase (HPL), preferring linolenic acid 13-hydroperoxide, and it was inferred that this gene was responsible for GLV-burst in S. moellendorffii. Based on the phylogenetic tree constructed with CYP74s of non-seed and seed plants, we hypothesized that HPL was acquired independently in the lycophyte and seed plants through diversification of CYP74 genes.
Detecting Plant Stress Using Thermal and Optical Imagery From an Unoccupied Aerial Vehicle
Authors: Stutsel Bonny , Johansen Kasper , Malbéteau Yoann M. , McCabe Matthew F.
Published: October 2021

Soil and water salinization has global impact on the sustainability of agricultural production, affecting the health and condition of staple crops and reducing potential yields. Identifying or developing salt-tolerant varieties of commercial crops is a potential pathway to enhance food and water security and deliver on the global demand for an increase in food supplies. Our study focuses on a phenotyping experiment that was designed to establish the influence of salinity stress on a diversity panel of the wild tomato species, Solanum pimpinellifolium. Here, we explore how unoccupied aerial vehicles (UAVs) equipped with both an optical and thermal infrared camera can be used to map and monitor plant temperature (Tp) changes in response to applied salinity stress. An object-based image analysis approach was developed to delineate individual tomato plants, while a green–red vegetation index derived from calibrated red, green, and blue (RGB) optical data allowed the discrimination of vegetation from the soil background. Tp was retrieved simultaneously from the co-mounted thermal camera, with Tp deviation from the ambient temperature and its change across time used as a potential indication of stress. Results showed that Tp differences between salt-treated and control plants were detectable across the five separate UAV campaigns undertaken during the field experiment. Using a simple statistical approach, we show that crop water stress index values greater than 0.36 indicated conditions of plant stress. The optimum period to collect UAV-based Tp for identifying plant stress was found between fruit formation and ripening. Preliminary results also indicate that UAV-based Tp may be used to detect plant stress before it is visually apparent, although further research with more frequent image collections and field observations is required. Our findings provide a tool to accelerate field phenotyping to identify salt-resistant germplasm and may allow farmers to alleviate yield losses through early detection of plant stress via management interventions.
Stomatal Responses to Light, CO2, and Mesophyll Tissue in Vicia faba and Kalanchoë fedtschenkoi
Authors: Santos Mauro G. , Davey Phillip A. , Hofmann Tanja A. , Borland Anne , Hartwell James , Lawson Tracy
Published: October 2021

The responses of stomatal aperture to light intensity and CO2 concentration were studied in both Vicia faba (C3) and Kalanchoë fedtschenkoi (Crassulacean acid metabolism; CAM), in material sampled from both light and dark periods. Direct comparison was made between intact leaf segments, epidermises grafted onto exposed mesophyll, and isolated epidermal peels, including transplantations between species and between diel periods. We reported the stomatal opening in response to darkness in isolated CAM peels from the light period, but not from the dark. Furthermore, we showed that C3 mesophyll has stimulated CAM stomata in transplanted peels to behave as C3 in response to light and CO2. By using peels and mesophyll from plants sampled in the dark and the light period, we provided clear evidence that CAM stomata behaved differently from C3. This might be linked to stored metabolites/ions and signalling pathway components within the guard cells, and/or a mesophyll-derived signal. Overall, our results provided evidence for both the involvement of guard cell metabolism and mesophyll signals in stomatal responses in both C3 and CAM species.
Plant Secondary Metabolite Transporters: Diversity, Functionality, and Their Modulation
Authors: Nogia Panchsheela , Pati Pratap Kumar
Published: October 2021

Secondary metabolites (SMs) play crucial roles in the vital functioning of plants such as growth, development, defense, and survival via their transportation and accumulation at the required site. However, unlike primary metabolites, the transport mechanisms of SMs are not yet well explored. There exists a huge gap between the abundant presence of SM transporters, their identification, and functional characterization. A better understanding of plant SM transporters will surely be a step forward to fulfill the steeply increasing demand for bioactive compounds for the formulation of herbal medicines. Thus, the engineering of transporters by modulating their expression is emerging as the most viable option to achieve the long-term goal of systemic metabolic engineering for enhanced metabolite production at minimum cost. In this review article, we are updating the understanding of recent advancements in the field of plant SM transporters, particularly those discovered in the past two decades. Herein, we provide notable insights about various types of fully or partially characterized transporters from the ABC, MATE, PUP, and NPF families including their diverse functionalities, structural information, potential approaches for their identification and characterization, several regulatory parameters, and their modulation. A novel perspective to the concept of “Transporter Engineering” has also been unveiled by highlighting its potential applications particularly in plant stress (biotic and abiotic) tolerance, SM accumulation, and removal of anti-nutritional compounds, which will be of great value for the crop improvement program. The present study creates a roadmap for easy identification and a better understanding of various transporters, which can be utilized as suitable targets for transporter engineering in future research.
The Research Trend of Big Data in Education and the Impact of Teacher Psychology on Educational Development During COVID-19: A Systematic Review and Future Perspective
Authors: Li Jia , Jiang Yuhong
Published: October 2021

The COVID-19 outbreak, along with post-pandemic impact has prompted Internet Plus education to re-examine numerous facets of technology-oriented academic research, particularly Educational Big Data (EBD). However, the unexpected transition from face-to-face offline education to online lessons has urged teachers to introduce educational technology into teaching practice, which has had an overwhelming impact on teachers' professional and personal lives. The aim of this present work is to fathom which research foci construct EBD in a comprehensive manner and how positive psychological indicators function in the technostress suffered by less agentic teachers. To this end, CiteSpace 5.7 and VOSviewer were applied to examine a longitudinal study of the literature from Web of Science Core Collection with the objective of uncovering the explicit patterns and knowledge structures in scientific network knowledge maps. Thousand seven hundred and eight articles concerned with educational data that met the criteria were extracted and analyzed. Research spanning 15 years was conducted to reveal that the knowledge base has accumulated dramatically after many governments' initiatives since 2012 with an accelerating annual growth and decreasing geographic imbalance. The review also identified some influential authors and journals whose effects will continue to have future implications. The authors identified several topical foci such as data mining, student performance, learning environment and psychology, learning analytics, and application. More specifically, the authors identified the scientific shift from data mining application to data privacy and educational psychology, from general scan to specific investigation. Among the conclusions, the results highlighted the important integration of educational psychology and technology during critical periods of educational development.
Prevalence and Risk Factors of Dance Injury During COVID-19: A Cross-Sectional Study From University Students in China
Authors: Dang Yanan , Koutedakis Yiannis , Chen Rouling , Wyon Matthew A.
Published: October 2021

Objectives:Although coronavirus disease 2019 (COVID-19) has transformed the training environment of dancers worldwide, little is known on how this has affected injury prevalence, causes, and risk factors.

Methods:An online investigation involving Chinese full-time dance students was conducted (September–November 2020), which covered two 6-month periods just before and during the first COVID-19 lockdown.

Results:2086 students (19 ± 2.4 years) responded to the investigation. Injury prevalence dropped from 39.6% (before the lockdown) to 16.5% (during the lockdown) (p< 0.01). It was noted that a significant increase in injury severity during the lockdown was caused due to a 4.1% increase in moderate-to-severe injuries (p< 0.05). During the lockdown, the injuries on the lower back, feet, and shoulders decreased significantly (p< 0.01), but the knee, ankle, and groin/hip joint injuries remained the same. Fatigue and the recurrence of an old injury remained as the top two perceived causes of an injury between the two periods with the increase in an unsuitable floor (p< 0.01), a cold environment (p< 0.05), and set/props (p< 0.05). The fatigue degree of students decreased (p< 0.01) and their hours of sleep increased (p< 0.01) during the lockdown. Binary Logistic Regression analysis indicated that dance injury is associated with fatigue, the hours of sleep, and the actions taken if they suspect an injury during the lockdown (p< 0.05), but is only related to the time set aside for a cooldown and age before the lockdown period (p< 0.05).

Conclusion:Although injury prevalence dropped significantly during the first COVID-19 lockdown in Chinese dance students, the main dance injury characteristics remained the same. Decreased fatigue and longer hours of sleep could explain the aforementioned drop in injury prevalence during the lockdown.
Mental Health in Residential Healthcare Workers During the COVID-19 Pandemic: The Moderating Role of Selfobject Needs
Authors: Arble Eamonn P. , Shankar Sneha , Steinert Steven W. , Daugherty Ana M.
Published: October 2021

The COVID-19 outbreak has affected healthcare across all levels. Older adults and those with chronic illness are at greatest risk for infection complications and mortality, which presents significant psychological distress for residential healthcare workers. The concept of selfobject needs, consisting of Mirroring, Idealizing, and Twinship, may be relevant in explaining psychological distress. This study seeks to enhance our understanding of the needs of healthcare workers responsible for elderly patients and evaluate the role of psychosocial support through selfobject needs to mitigate the effects of trauma during the pandemic. Participants (N= 103) employed in residential healthcare facilities in the metropolitan Detroit, MI (USA) region completed an online survey during the peak initial infection. Assessments included standardized measures of trauma-related symptoms, depression, anxiety, and general distress symptoms, as well as a validated measure of selfobject needs. Residential healthcare workers reported mental health symptoms across domains, including clinical elevations in symptoms of trauma, depression, and anxiety. Selfobject needs and mental health outcomes were positively correlated, indicating that greater unmet relational need was associated with greater severity of symptoms. Greater trauma symptom severity as a proxy index of current experience during the pandemic predicted high depressive symptoms, and greater Mirroring need worsened the effect. These results suggest that interventions targeting selfobject needs, specifically Mirroring, may be effective at mitigating acute mental health symptoms among healthcare workers during a distressing event.
Does Participation in Local Non-agricultural Employment Improve the Mental Health of Elderly Adults in Rural Areas? Evidence From China
Authors: Jia Peng , Zhuang Jincai , Vaca Lucero Andrea Maria , Osei Charles Dwumfour , Li Juan
Published: October 2021

A rising rate of suicide among the elderly in rural China has been recognized to be triggered by mental health-associated factors. This study uses 3,397 sampled rural elderly adults from China Labor-force Dynamic Survey in 2016 to explore the response mechanism through which non-agricultural employment participation by the elderly adults in rural China can influence their mental health. Utilizing the Multivariate Regression, Instrumental Variable and Propensity Score Matching methods, we find that, the rural elderly adults who participate in local non-agricultural employment significantly improve their mental health. Self-employment tends to have a greater positive contribution to the mental health of the elderly population than waged employment. Further, work income, need for belongingness and respect, and human capital development significantly mediates the influence of participation in local non-agricultural employment on the mental health of the elderly adults. Finally, we put forward relevant policy suggestions to improving the mental health of the elderly in the countryside.
An Intervention by and for Transgender Women Living With HIV: Study Protocol for a Two-Arm Randomized Controlled Trial Testing the Efficacy of “Healthy Divas” to Improve HIV Care Outcomes
Authors: Sevelius Jae M. , Neilands Torsten B. , Reback Cathy J. , Castro Danielle , Dilworth Samantha E. , Kaplan Rachel L. , Johnson Mallory O.
Published: October 2021

Introduction:Transgender women (assigned “male” at birth but who do not identify as male) are disproportionately impacted by HIV and experience unique barriers and facilitators to HIV care engagement. In formative work, we identified culturally specific and modifiable barriers to HIV treatment engagement among transgender women living with HIV (TWH), including prioritizing transition-related healthcare over HIV treatment, avoiding HIV care settings due to gender-related and HIV stigma, concerns about potential drug interactions with hormones, and inadequate social support. Grounded in the investigators' Models of Gender Affirmation and Health Care Empowerment, we developed theHealthy Divasintervention to optimize engagement in HIV care among TWH at risk for treatment failure and consequential morbidity, mortality, and onward transmission of HIV.

Methods and Analysis:We conducted a 2-arm randomized controlled trial (RCT) of the intervention's efficacy in Los Angeles and San Francisco to improve engagement in care among TWH (N= 278). The primary outcome was virologic control indicated by undetectable HIV-1 level (undetectability = < 20 copies/mL), at baseline and follow-up assessment for 12 months at 3-month intervals.

Ethics and Dissemination:This study was approved by University of California, San Francisco Institutional Review Board (15-17910) and Western Institutional Review Board (20181370). Participants provided informed consent before enrolment in the study. We are committed to collaboration with National Institutes of Health officials, other researchers, and health and social services communities for rapid dissemination of data and sharing of materials. The results will be published in peer-reviewed academic journals and scientific presentations. We will make our results available to researchers interested in transgender health to avoid unintentional duplication of research, as well as to others in health and social services communities, including HIV clinics, LGBT community-based organizations, and AIDS service organizations.

Clinical Trial Registration:Clinicaltrials.gov, identifier NCT03081559.
On the Use and Interpretation of Areola/Nipple Retention as a Biomarker for Anti-androgenic Effects in Rat Toxicity Studies
Authors: Schwartz Camilla Lindgren , Christiansen Sofie , Hass Ulla , Ramhøj Louise , Axelstad Marta , Löbl Nathalie Michelle , Svingen Terje
Published: October 2021

Areola/nipple retention (NR) is an established biomarker for an anti-androgenic mode of action in rat toxicity studies. It is a mandatory measurement under several OECD test guidelines and is typically assessed in combination with anogenital distance (AGD). Both NR and AGD are considered retrospective biomarkers of insufficient androgen signaling during the masculinization programming window in male fetuses. However, there are still aspects concerning NR as a biomarker for endocrine disruption that remains to be clarified. For instance, can NR be regarded a permanent adverse effect? Is it a redundant measurement if AGD is assessed in the same study? Is NR equally sensitive and specific to anti-androgenic chemical substances as a shortening of male AGD? In this review we discuss these and other aspects concerning the use of NR as a biomarker in toxicity studies. We have collected available literature from rat toxicity studies that have reported on NR and synthesized the data in order to draw a clearer picture about the sensitivity and specificity of NR as an effect biomarker for an anti-androgenic mode of action, including comparisons to AGD measurements. We carefully conclude that NR and AGD in rats for the most part display similar sensitivity and specificity, but that there are clear exceptions which support the continued assessment of both endpoints in relevant reproductive toxicity studies. Available literature also support the view that NR in infant male rats signifies a high risk for permanent nipples in adulthood. Finally, the literature suggests that the mechanisms of action leading from a chemical stressor event to either NR or short AGD in male offspring are overlapping with respect to canonical androgen signaling, yet differ with respect to other mechanisms of action.