bluuebunny/crossref_metadata_2025 huggingface dataset:
SARM1 Suppresses Axon Branching Through Attenuation of Axonal Cytoskeletal Dynamics
Authors: Ketschek Andrea , Holland Sabrina M. , Gallo Gianluca
Published: February 2022

Axon branching is a fundamental aspect of neuronal morphogenesis, neuronal circuit formation, and response of the nervous system to injury. Sterile alpha and TIR motif containing 1 (SARM1) was initially identified as promoting Wallerian degeneration of axons. We now report a novel function of SARM1 in postnatal sensory neurons; the suppression of axon branching. Axon collateral branches develop from axonal filopodia precursors through the coordination of the actin and microtubule cytoskeleton. In vitro analysis revealed that cultured P0-2 dorsal root ganglion sensory neurons from a SARM1 knockout (KO) mouse exhibit increased numbers of collateral branches and axonal filopodia relative to wild-type neurons. In SARM1 KO mice, cutaneous sensory endings exhibit increased branching in the skin in vivo with normal density of innervation. Transient axonal actin patches serve as cytoskeletal platforms from which axonal filopodia emerge. Live imaging analysis of axonal actin dynamics showed that SARM1 KO neurons exhibit increased rates of axonal actin patch formation and increased probability that individual patches will give rise to a filopodium before dissipating. SARM1 KO axons contain elevated levels of drebrin and cortactin, two actin regulatory proteins that are positive regulators of actin patches, filopodia formation, and branching. Live imaging of microtubule plus tip dynamics revealed an increase in the rate of formation and velocity of polymerizing tips along the axons of SARM1 KO neurons. Stationary mitochondria define sites along the axon where branches may arise, and the axons of SARM1 KO sensory neurons exhibit an increase in stationary mitochondria. These data reveal SARM1 to be a negative regulator of axonal cytoskeletal dynamics and collateral branching.
A Novel U-Shaped Association Between Serum Magnesium on Admission and 28-Day In-hospital All-Cause Mortality in the Pediatric Intensive Care Unit
Authors: Yue Chao Yan , Zhang Chun Yi , Huang Zhen Ling , Ying Chun Mei
Published: February 2022

Objective

Our purpose is to evaluate whether serum magnesium when entering the ICU is related to 28-day in-hospital all-cause mortality in the pediatric ICU.

Methods

We used the PIC database to conduct a retrospective analysis to investigate the first-time serum magnesium levels of 10,033 critically ill children admitted to the pediatric ICU, and analyzed association between serum magnesium and all-cause mortality. Smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between serum magnesium and all-cause mortality. The shape of the curve was used to describe the relationship between magnesium and 28-day in-hospital mortality.

Results

There is a non-linear relationship between serum magnesium and 28-day in-hospital all-cause mortality. The U-type relationship between serum magnesium and all-cause mortality was observed. The optimal range of serum magnesium with the lowest risk of mortality was 0.74–0.93 mmol/L. As the serum magnesium level reaches the turning point (0.74 mmol/L), the risk of death decreases by 60% for every 0.1 mmol/L increase in serum magnesium; when the serum magnesium level exceeds 0.93, an increase of 0.1 mmol/L increases the risk of death by 38 %.

Conclusion

Serum magnesium has a U-shaped relationship with 28-day in-hospital all-cause mortality. Both low and high serum magnesium can increase the risk of death. The best serum magnesium range when the risk of death is the lowest is 0.74–0.93 mmol/L.
Immunotherapeutic Strategies in Chronic Lymphocytic Leukemia: Advances and Challenges
Authors: Perutelli Francesca , Jones Rebecca , Griggio Valentina , Vitale Candida , Coscia Marta
Published: February 2022

Immune-based therapeutic strategies have drastically changed the landscape of hematological disorders, as they have introduced the concept of boosting immune responses against tumor cells. Anti-CD20 monoclonal antibodies have been the first form of immunotherapy successfully applied in the treatment of CLL, in the context of chemoimmunotherapy regimens. Since then, several immunotherapeutic approaches have been studied in CLL settings, with the aim of exploiting or eliciting anti-tumor immune responses against leukemia cells. Unfortunately, despite initial promising data, results from pilot clinical studies have not shown optimal results in terms of disease control - especially when immunotherapy was used individually - largely due to CLL-related immune dysfunctions hampering the achievement of effective anti-tumor responses. The growing understanding of the complex interactions between immune cells and the tumor cells has paved the way for the development of new combined approaches that rely on the synergism between novel agents and immunotherapy. In this review, we provide an overview of the most successful and promising immunotherapeutic modalities in CLL, including both antibody-based therapy (i.e. monoclonal antibodies, bispecific antibodies, bi- or tri- specific killer engagers) and adoptive cellular therapy (i.e. CAR T cells and NK cells). We also provide examples of successful new combination strategies and some insights on future perspectives.
Honokiol Ameliorates Post-Myocardial Infarction Heart Failure Through Ucp3-Mediated Reactive Oxygen Species Inhibition
Authors: Liu Jianyu , Tang Minghai , Li Tao , Su Zhengying , Zhu Zejiang , Dou Caixia , Liu Yan , Pei Heying , Yang Jianhong , Ye Haoyu , Chen Lijuan
Published: February 2022

Post-myocardial infarction heart failure (post-MI HF) is one of the leading global causes of death, and current prevention and treatment methods still cannot avoid the increasing incidence. Honokiol (HK) has previously been reported to improve myocardial ischemia/reperfusion injury and reverse myocardial hypertrophy by activating Sirt1 and Sirt3. We suspect that HK may also have a therapeutic effect on post-MI HF. In this study, we aimed to investigate the efficacy and mechanism of HK in the treatment of post-MI HF. We found that HK inhibited myocardial reactive oxygen species (ROS) production, reduced myocardial fibrosis, and improved cardiac function in mice after MI. HK also reduced the abnormality of mitochondrial membrane potential (MMP) and apoptosis of cardiomyocytes caused by peroxide in neonatal cardiomyocytes. RNAseq results revealed that HK restored the transcriptome changes to a certain extent and significantly enhanced the expression of mitochondrial inner membrane uncoupling protein isoform 3 (Ucp3), a protein that inhibits the production of mitochondrial ROS, protects cardiomyocytes, and relieves heart failure after myocardial infarction (MI). In cardiomyocytes with impaired Ucp3 expression, HK cannot protect against the damage caused by peroxide. More importantly, in Ucp3 knockout mice, HK did not change the increase in the ROS level and cardiac function damage after MI. Taken together, our results suggest that HK can increase the expression of the cardioprotective protein Ucp3 and maintain MMP, thereby inhibiting the production of ROS after MI and ameliorating heart failure.
Discovery of Novel and Highly Potent Inhibitors of SARS CoV-2 Papain-Like Protease Through Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, Molecular Dynamics Simulations, and Biological Evaluation
Authors: Tian Xiaoyan , Zhao Quanfeng , Chen Xiaohong , Peng Zhe , Tan Xiaodan , Wang Qin , Chen Lin , Yang Yang
Published: February 2022

Background and Objective: COVID-19 has struck our society as a great calamity, and the need for effective anti-viral drugs is more urgent than ever. Papain-like protease (PLpro) of SARS CoV-2 plays important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses, which is being regarded as a promising druggable target for the treatment of COVID-19. Here, we carried out a combined screening approach to identify novel and highly potent PLpro inhibitors for the treatment of COVID-19.

Methods: We used a combined screening approach of structure-based pharmacophore modeling and molecular docking to screen an in-house database containing 35,000 compounds. SARS CoV-2 PLpro inhibition assay was used to carry out the biological evaluation of hit compounds. Molecular dynamics (MD) simulations were conducted to check the stability of the PLpro-hit complexes predicted by molecular docking.

Results: We found that four hit compounds showed excellent inhibitory activities against PLpro with IC50 values ranging from 0.6 to 2.4 μM. Among them, the most promising compound, hit 2 is the best PLpro inhibitor and its inhibitory activity was about 4 times higher than that of the positive control (GRL0617). The study of MD simulations indicated that four hits could bind stably to the active site of PLpro. Further study of interaction analysis indicated that hit 2 could form hydrogen-bond interactions with the key amino acids such as Gln269 and Asp164 in the PLpro-active site.

Conclusion: Hit 2 is a novel and highly potent PLpro inhibitor, which will open the way for the development of clinical PLpro inhibitors for the treatment of COVID-19.
Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
Authors: Luo Yuan-Yuan , Tao Ke-Gong , Lu Yi-Ting , Li Bin-Bin , Wu Kai-Ming , Ding Chen-Hong , Yan Fang-Zhi , Liu Yue , Lin Yong , Zhang Xin , Zeng Xin
Published: February 2022

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs and 88 upregulated circRNAs in human HCC tissues, including hsa_circ_0098181, hsa_circ_0072309, hsa_circ_0000831, and hsa_circ_0000231. The reduction of hsa_circ_0098181 was confirmed in eight paired human HCC tissues, hepatoma cell lines, and CCL4/DEN-induced mouse HCC models by RT-qPCR. The FISH assay revealed that hsa_circ_0098181 is mainly located in the cytoplasm of hepatocytes in the paratumor tissues. Further log-rank analysis performed in 91 HCC patients demonstrated that low expression of hsa_circ_0098181 was related to poor prognosis. The plasmid and lentivirus overexpressing hsa_circ_0098181 were delivered into HCC cell lines. After hsa_circ_0098181 was upregulated, the proliferation, invasion, migration, and colony formation of HCC cell lines were inhibited, and the apoptosis was promoted. Moreover, exogenous hsa_circ_0098181 delivery mitigated the tumor formation ability of Huh7 in Balb/C nude mice. The dual-luciferase reporter assay and the RIP assay verified that hsa_circ_0098181 sponged miR-18a-3p to regulate PPARA. In addition, a rescue experiment found miR-18a-3p mimic partly reversed the suppression of hsa_circ_0098181 on proliferation, invasion, and migration of HCC cell lines. In conclusion, hsa_circ_0098181 can repress the development of HCC through sponging miR-18a-3p and promoting the expression of PPARA in vitro and in vivo, and hsa_circ_0098181 might be a therapeutic target for HCC.
Progress on the Elucidation of the Antinociceptive Effect of Ginseng and Ginsenosides in Chronic Pain
Authors: Li Mei-Xian , Wei Qian-Qi , Lu Huan-Jun
Published: February 2022

Ginseng (Panax ginseng C.A. Meyer) is a traditional Oriental herbal drug widely used in East Asia. Its main active ingredients are ginsenosides whose constituents are known to have various pharmacological activities such as anticancer, antinociception, and neuroprotection. The analgesic effects of ginsenosides, such as Rg1, Rg2, and Rb1, as well as compound K, are well known and the analgesic mechanism of action in inflammatory pain models is thought to be the down regulation of pro-inflammatory cytokine expression (TNF-α IL-1β, and IL-6). Several studies have also demonstrated that ginsenosides regulate neuropathic pain through the modulation of estrogen receptors. Recently, an increasing number of pathways have emerged in relation to the antinociceptive effect of ginseng and ginsenosides. Therefore, this review presents our current understanding of the effectiveness of ginseng in chronic pain and how its active constituents regulate nociceptive responses and their mechanisms of action.
Sporoderm-Broken Spores of Ganoderma lucidum Sensitizes Ovarian Cancer to Cisplatin by ROS/ERK Signaling and Attenuates Chemotherapy-Related Toxicity
Authors: Cen Kaili , Chen Ming , He Mengye , Li Zhenhao , Song Yinjing , Liu Pu , Jiang Qi , Xu Suzhen , Jia Yunlu , Shen Peng
Published: February 2022

Although platinum-based chemotherapeutics such as cisplatin are the cornerstone of treatment for ovarian cancer, their clinical application is profoundly limited due to chemoresistance and severe adverse effects. Sporoderm-broken spores of Ganoderma lucidum (SBSGL) have been reported to possess antitumor effects. However, the function and mechanism of SBSGL and its essential composition, ganoderic acid D (GAD), in the cisplatin therapy on ovarian cancer have yet to be investigated. Here, we investigated the combined effect of SBSGL and cisplatin in an ovarian tumor xenograft model. The results showed that combining SBSGL with cisplatin reduced tumor growth and ameliorated cisplatin-induced intestinal injury and myelosuppression. We also confirmed that GAD could enhance the therapeutic effect of cisplatin in SKOV3 and cisplatin-resistant SKOV3/DDP cells by increasing the intracellular reactive oxygen species (ROS). Mechanistically, we proved that ROS-mediated ERK signaling inhibition played an important role in the chemo-sensitization effect of GAD on cisplatin in ovarian cancer. Taken together, combining SBSGL with cisplatin provides a novel therapeutic strategy against ovarian cancer.
The Bioflavonoids Rutin and Rutin Succinate Neutralize the Toxins of B. jararaca Venom and Inhibit its Lethality
Authors: Sachetto Ana Teresa Azevedo , Miyamoto Jackson Gabriel , Tashima Alexandre Keiji , de Souza Ana Olívia , Santoro Marcelo Larami
Published: February 2022

The venom of the Brazilian pit viper Bothrops jararaca (BjV) is a complex mixture of molecules, and snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) are the most abundant protein families found therein. Toxins present in BjV trigger most of the deleterious disturbances in hemostasis observed in snakebites, i.e., thrombocytopenia, hypofibrinogenemia and bleedings. The treatment of patients bitten by snakes still poses challenges and the bioflavonoid rutin has already been shown to improve hemostasis in an experimental model of snakebite envenomation. However, rutin is poorly soluble in water; in this study, it was succinylated to generate its water-soluble form, rutin succinate (RS), which was analyzed comparatively regarding the chemical structure and characteristic features of rutin. Biological activities of rutin and RS were compared on hemostatic parameters, and against toxic activities of crude BjV in vitro. In vivo, C57BL/6 mice were injected i.p. with either BjV alone or pre-incubated with rutin, RS or 1,10-phenanthroline (o-phe, an SVMP inhibitor), and the survival rates and hemostatic parameters were analyzed 48 h after envenomation. RS showed the characteristic activities described for rutin – i.e., antioxidant and inhibitor of protein disulfide isomerase – but also prolonged the clotting time of fibrinogen and plasma in vitro. Differently from rutin, RS inhibited typical proteolytic activities of SVMP, as well as the coagulant activity of BjV. Importantly, both rutin and RS completely abrogated the lethal activity of BjV, in the same degree as o-phe. BjV induced hemorrhages, falls in RBC counts, thrombocytopenia and hypofibrinogenemia in mice. Rutin and RS also improved the recovery of platelet counts and fibrinogen levels, and the development of hemorrhages was totally blocked in mice injected with BjV incubated with RS. In conclusion, RS has anticoagulant properties and is a novel SVMP inhibitor. Rutin and RS showed different mechanisms of action on hemostasis. Only RS inhibited directly BjV biological activities, even though both flavonoids neutralized B. jararaca toxicity in vivo. Our results showed clearly that rutin and RS show a great potential to be used as therapeutic compounds for snakebite envenomation.
Segmented Point Cloud Gridding Method for a Full-Color Holographic System With Real Objects
Authors: Zhao Yu , Huang Yuan , Zhu Li-Ming , Bu Jing-Wen , Du Yu-Ren , Zhu Ming-Yu , Zhu Jin-Rong
Published: February 2022

The large amount of computing data from hologram calculations incurs a heavy computational load for realistic full-color holographic displays. In this research, we propose a segmented point-cloud gridding (S-PCG) method to enhance the computing ability of a full-color holographic system. A depth camera is used to collect the color and depth information from actual scenes, which are then reconstructed into the point-cloud model. Object points are categorized into depth grids with identical depth values in the red, green, and blue (RGB) channels. In each channel, the depth grids are segmented into M×N parts, and only the effective area of the depth grids will be calculated. Computer-generated holograms (CGHs) are generated from efficient depth grids by using a fast Fourier transform (FFT). Compared to the wavefront recording plane (WRP) and traditional PCG methods, the computational complexity is dramatically reduced. The feasibility of the S-PCG approach is established through numerical simulations and optical reconstructions.
All-Optical Polarization Manipulation Through Orbital Polarization Holography
Authors: Lyu Ziyao , Wang Changshun
Published: February 2022

Spin-orbital optical phenomena are closely related with light-matter interactions and have been of great interest in the last few years. Here, the effect of optical orbital angular momentum (OAM) on polarized waves carrying spin angular momentum (SAM) has been investigated experimentally by means of orbital polarization holography and analyzed with Jones matrices theoretically. We report that all-optical OAM-to-polarization manipulation can be realized with a controllable holographic grating recorded through the interference of orthogonally polarized beams in various helical modes in a kind of photo-alignment supermolecular liquid-crystalline films. The polarization states of diffraction beams can be controlled through adjusting the spatial degree of freedom of the recording light field. The OAM-controlled polarization manipulation is discussed in terms of Jones matrices and photoinduced birefringence. Because of the realization of OAM-to-SAM conversion, this work may find applications in a variety of devices.
Effects of Three Different Modes of Resistance Training on Appetite Hormones in Males With Obesity
Authors: Ataeinosrat Ali , Haghighi Marjan Mosalman , Abednatanzi Hossein , Soltani Mohammad , Ghanbari-Niaki Abbass , Nouri-Habashi Akbar , Amani-Shalamzari Sadegh , Mossayebi Ali , Khademosharie Mitra , Johnson Kelly E. , VanDusseldorp Trisha A. , Saeidi Ayoub , Zouhal Hassane
Published: February 2022

Purpose

This study explored the effect of three different modes of resistance training on appetite hormones [leptin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine–tyrosine (PYY)], cardiometabolic and anthropometric measures in males with obesity.

Methods

Forty-four males with obesity (age: 27.5 ± 9.4 yrs.; mean weight: 93.2 ± 2.2 kg, body mass index: 32.9 ± 1.2 kg/m2) were randomized to traditional resistance training (TRT, n = 11), circuit resistance training (CRT, n = 11), interval resistance training (IRT, n = 11) or control (C, n = 11) groups. All resistance training groups received 50 min of supervised training per session, three days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of training.

Results

Plasma levels of leptin, ghrelin, CCK, and PYY decreased significantly in all three different modalities of resistance training groups when compared to the control group (p < 0.05). GLP-1 increased significantly in both CRT and IRT groups compared to TRT and C groups (p < 0.05). Glucose-dependent insulinotropic polypeptide decreased significantly in CRT and IRT groups compared to the C group (p < 0.05). Adiponectin levels increased significantly in all resistance training groups compared to the C group (p < 0.05).

Conclusion

Overall, CRT and IRT protocols had the greatest impact on appetite hormones compared to individuals who engaged in TRT or did not exercise (C).
Dynamics of Etiolation Monitored by Seedling Morphology, Carotenoid Composition, Antioxidant Level, and Photoactivity of Protochlorophyllide in Arabidopsis thaliana
Authors: Jedynak Pawel , Trzebuniak Kamil Filip , Chowaniec Magdalena , Zgłobicki Piotr , Banaś Agnieszka Katarzyna , Mysliwa-Kurdziel Beata
Published: February 2022

Although etiolated Arabidopsis thaliana seedlings are widely used as a model to study the de-etiolation process, the etiolation itself at the molecular level still needs elucidation. Here, we monitored the etiolation dynamics for wild type A. thaliana seedlings and lutein-deficient (lut2) mutant between 2 and 12 days of their growth in the absence of light. We analyzed the shape of the apex, the growth rate, the carotenoids and protochlorophyllide (Pchlide) accumulation, and the light-dependent protochlorophyllide oxidoreductase (LPOR) transcripts. Differences concerning the apical hook curvature and cotyledon opening among seedlings of the same age were observed, mostly after day 6 of the culture. We categorized the observed apex shapes and presented quantitatively how distribution among the categories changed during 12 days of seedling growth. The Pchlide654/Pchlide633 ratio, corresponding to the amount of the photoactive Pchlide, was the highest in the youngest seedlings, and decreased with their age. LPORA, LPORB, and LPORC transcripts were detected in etiolated seedlings, and their content decreased during seedling growth. Expression of SAG12 or SAG13 senescence markers, depletion in antioxidants, and excess ion leakage were not observed during the etiolation. Lack of lutein in the lut2 mutant resulted in slow Pchlide accumulation and affected other xanthophyll composition.
Genome-Wide Expression Analysis of Root Tips in Contrasting Rice Genotypes Revealed Novel Candidate Genes for Water Stress Adaptation
Authors: Abdirad Somayeh , Ghaffari Mohammad Reza , Majd Ahmad , Irian Saeed , Soleymaniniya Armin , Daryani Parisa , Koobaz Parisa , Shobbar Zahra-Sadat , Farsad Laleh Karimi , Yazdanpanah Parisa , Sadri Amirhossein , Mirzaei Mehdi , Ghorbanzadeh Zahra , Kazemi Mehrbano , Hadidi Naghmeh , Haynes Paul A. , Salekdeh Ghasem Hosseini
Published: February 2022

Root system architecture (RSA) is an important agronomic trait with vital roles in plant productivity under water stress conditions. A deep and branched root system may help plants to avoid water stress by enabling them to acquire more water and nutrient resources. Nevertheless, our knowledge of the genetics and molecular control mechanisms of RSA is still relatively limited. In this study, we analyzed the transcriptome response of root tips to water stress in two well-known genotypes of rice: IR64, a high-yielding lowland genotype, which represents a drought-susceptible and shallow-rooting genotype; and Azucena, a traditional, upland, drought-tolerant and deep-rooting genotype. We collected samples from three zones (Z) of root tip: two consecutive 5 mm sections (Z1 and Z2) and the following next 10 mm section (Z3), which mainly includes meristematic and maturation regions. Our results showed that Z1 of Azucena was enriched for genes involved in cell cycle and division and root growth and development whereas in IR64 root, responses to oxidative stress were strongly enriched. While the expansion of the lateral root system was used as a strategy by both genotypes when facing water shortage, it was more pronounced in Azucena. Our results also suggested that by enhancing meristematic cell wall thickening for insulation purposes as a means of confronting stress, the sensitive IR64 genotype may have reduced its capacity for root elongation to extract water from deeper layers of the soil. Furthermore, several members of gene families such as NAC, AP2/ERF, AUX/IAA, EXPANSIN, WRKY, and MYB emerged as main players in RSA and drought adaptation. We also found that HSP and HSF gene families participated in oxidative stress inhibition in IR64 root tip. Meta-quantitative trait loci (QTL) analysis revealed that 288 differentially expressed genes were colocalized with RSA QTLs previously reported under drought and normal conditions. This finding warrants further research into their possible roles in drought adaptation. Overall, our analyses presented several major molecular differences between Azucena and IR64, which may partly explain their differential root growth responses to water stress. It appears that Azucena avoided water stress through enhancing growth and root exploration to access water, whereas IR64 might mainly rely on cell insulation to maintain water and antioxidant system to withstand stress. We identified a large number of novel RSA and drought associated candidate genes, which should encourage further exploration of their potential to enhance drought adaptation in rice.
RNA Binding Protein OsTZF7 Traffics Between the Nucleus and Processing Bodies/Stress Granules and Positively Regulates Drought Stress in Rice
Authors: Guo Chiming , Chen Lingli , Cui Yuchao , Tang Ming , Guo Ying , Yi Yin , Li Yan , Liu Liqing , Chen Liang
Published: February 2022

Tandem CCCH zinc finger (TZF) proteins are the essential components of processing bodies (PBs) and stress granules (SGs), which play critical roles in growth development and stress response in both animals and plants through posttranscriptional regulation of target mRNA. In this study, we characterized the biological and molecular functions of a novel tandem zinc finger protein, OsTZF7. The expression of OsTZF7 was upregulated by abiotic stresses, including polyethylene glycol (PEG) 4000, NaCl, and abscisic acid (ABA) in rice. Accordingly, the overexpression of OsTZF7 increased drought tolerance and enhanced sensitivity to exogenous ABA in rice, whereas the knockdown of OsTZF7 resulted in the opposite phenotype. RNA-seq analysis revealed that genes related to “response to stress,” “abscisic acid signaling,” “methylated histone binding,” and “cytoplasmic mRNA processing body” are regulated by OsTZF7. We demonstrated that OsTZF7 can traffic between the nucleus and PBs/SGs, and the leucine-rich nuclear export signal (NES) mediates the nuclear export of OsTZF7. Additionally, we revealed that OsTZF7 can bind adenine- and uridine-rich (AU-rich) element (ARE) or ARE-like motifs within the 3′ untranslated region of downregulated mRNAs, and interact with PWWP family proteins in vitro. Together, these results indicate that OsTZF7 positively regulates drought response in rice via ABA signaling and may be involved in mRNA turnover.
Exploring Relationships Between L2 Chinese Character Writing and Reading Acquisition From Embodied Cognitive Perspectives: Evidence From HSK Big Data
Authors: Chai Xingsan , Ma Mingzhu
Published: February 2022

Chinese characters are central to understanding how learners learn to read a logographic script. However, researchers know little about the role of character writing in reading Chinese as a second language (CSL). Unlike an alphabetic script, a Chinese character symbol transmits semantic information and is a cultural icon bridging embodied experience and text meaning. As a unique embodied practice, writing by hand contributes to cognitive processing in Chinese reading. Therefore, it is essential to clarify how Chinese character writing (bodily activity), language distance (past language usage), and cultural background (bodily coupling with the environment) influence CSL reading proficiency. Based on extant research on L2 reading acquisition and strength of key theoretical perspectives of embodied cognition theory (ECT), this study tested a regression model for CSL reading involving individual-level factors (Chinese character writing proficiency [CCWP]) and group-level predictors (language distance and cultural background). This study collected big data in a sample of 74,362 CSL learners with 67 diverse L1s. Results of hierarchical linear modeling showed a significant effect of CCWP and significant language distance × CCWP interaction effect on reading proficiency; however, cultural background × CCWP interaction effect was not significant. These results conform to the ECT and indicate that bodily activity, past language usage, and cultural background aided reading. CCWP may benefit from withstanding the negative transfer from L1s. Furthermore, CCWP and cultural background are not synergistic predictors of reading. This study may open novel avenues for explorations of CSL reading development.
Older Women’s Loneliness and Depression Decreased by a Reminiscence Program in Times of COVID-19
Authors: Pinazo-Hernandis Sacramento , Sales Alicia , Martinez Dolores
Published: February 2022

The confinement caused by the current COVID-19 pandemic protects physical health, but in turn, has a long-lasting and far-reaching negative psychosocial impact; anxiety, stress, fear and depressive symptoms. All of these have a particular impact on vulnerable older people, putting them at serious risk of loneliness. Women report feeling lonelier than men, affecting women to a greater extent. The present study aims to analyze the efficacy of an integrative reminiscence intervention in older women living in nursing homes to reduce the effects of loneliness and depression after COVID-19. 34 older women living in nursing homes are included into study and were divided into intervention group (N = 14) and control group (N = 20). Results showed a significant reduction in perception of loneliness, depression and better positive affects, after the intervention. The pandemic has not yet finished and the most affected group has been the people living in nursing homes. These results show the need for evidence of interventions that can help the recovery of these people who have been so affected. The effects of loneliness during confinement and its psychological effects can be mitigated through such programs.
Promoting Pre-service Teacher Students’ Learning Engagement: Design-Based Research in a Flipped Classroom
Authors: Gu Jianjun , Tang Lin , Liu Xiaohong , Xu Jinlei
Published: February 2022

Students’ learning engagement is recognized as one of the main components of effective instruction and a necessary prerequisite for learning, but students’ learning engagement in flipped classroom poses some pedagogical challenges. This study aimed to promote students’ learning engagement via the flipped classroom approach. Design-based research (DBR) was adopted in this study to conduct an experiment involving three iterations in a Modern Educational Technology (MET) course in a Chinese university. The participants included 36 third-year pre-service teacher undergraduates. Classroom observations and a learning engagement questionnaire were used to measure the effectiveness of the flipped instruction in terms of students’ learning engagement. Data analysis applied descriptive statistics, ANOVA, and paired samples t tests. The results showed that after three rounds of iterative experiments, students’ learning engagement (behavioral, cognitive, and emotional) significantly improved. Several principles are provided as guidelines for instructors to implement flipped classroom approach to promote students’ learning engagement.
Flipped Presentation of Authentic Audio-Visual Materials: Impacts on Intercultural Sensitivity and Intercultural Effectiveness in an EFL Context
Authors: Khabir Masoud , Jabbari Ali Akbar , Razmi Mohammad Hasan
Published: February 2022

Utilizing a pre-experimental pre-test post-test design, this study investigated the effect of an authentic audio-visual American sitcom (Friends) on the intercultural sensitivity (ICS) and intercultural effectiveness (ICE) of a sample of male and female upper-intermediate English students. To this aim, 34 Iranian EFL students were selected through convenient non-random sampling. In order to assure the participants' homogeneity in English proficiency, the selected students were given the Oxford Quick Placement Test prior to the intervention. Over a 10-week period, the participants were presented with nearly 30-min-long episodes ofFriendsin a flipped context, two episodes every week uploaded to the accompanying website. An online 10-item quiz on the day of watching and a next-day meeting were held. During the online discussion meetings, the participants discussed cultural questions tailored to the aims of the study. The required data were collected through the administration of the intercultural sensitivity scale (ISS) and intercultural effectiveness scale (IES) in pre- and post-test assessments. The analyses of the data indicated that both ICS and ICE improved significantly during the intervention. However, ICS indicated more improvement. In addition, a semi-structured interview was administered to the participants to examine their perception of the flipped classroom experience. Having analyzed the data using MAXQDA 2020, some significant themes emerged which are reported. On the whole, the participants portrayed positive attitudes toward using technology in flipped classes. The educational and practical implications are discussed.
Sex Difference in Global Burden of Major Depressive Disorder: Findings From the Global Burden of Disease Study 2019
Authors: Li Sangzi , Xu Yufeng , Zheng Leilei , Pang Hu , Zhang Qianni , Lou Lixia , Huang Xingru
Published: February 2022

Objectives

Globally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs).

Methods

Global and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden.

Results

Sex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10–24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P < 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P < 0.001; standardized β = 0.300, P < 0.001).

Conclusion

Although some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD.
Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial
Authors: Steenen Serge A. , Su Naichuan , van Westrhenen Roos , van Wijk Arjen J. , Tjia Daniël S. L. , de Lange Jan , de Jongh Ad
Published: February 2022

Background

Promising results from a trauma reactivation study on post-traumatic stress disorder suggest that propranolol is capable of attenuating symptoms of traumatically induced mental disorders by blocking memory reconsolidation.

Methods

A randomized, parallel, placebo-controlled, quadruple-blind trial was designed to determine the effectiveness of perioperative propranolol during exposure to dental extractions in reducing dental anxiety in patients with dental anxiety or dental phobia. Between November 2014 and December 2018, 52 patients with high levels of fear in anticipation of dental extractions who were referred to a department of oral and maxillofacial surgery for at least two tooth and/or molar removals with 1 month in between were included. On the first visit participants received either 120 mg of perioperative oral propranolol (n = 19) or placebo (n = 17), and a core fear memory was reactivated 1 h preoperatively. The primary outcome was change in severity of dental anxiety from baseline to 1-month follow-up, as indexed by the short version of the dental anxiety inventory (S-DAI). Secondary outcome measures were change in intra-operative state anxiety and specific phobia diagnoses.

Results

Linear mixed model (LMM) yielded no statistically significant difference in change of dental trait anxiety from baseline to 1-month follow-up between propranolol and placebo groups (Cohen's d = 0.23). S-DAI scores decreased in both study arms from baseline to follow-up (propranolol arm: from 32.1 [SD = 7.3] to 29.1 [SD = 8.8]; placebo arm: from 31.6 [SD = 7.5] to 27.1 [SD = 6.5]). Also, administering propranolol was not associated with a significant difference in change of intra-operative state anxiety or phobia diagnoses between groups over time.

Conclusions

The results do not concur with earlier findings regarding post-traumatic stress disorder, and suggest that individuals with traumatically induced fears or phobias do not benefit from the application of perioperative propranolol.
The Impact of the COVID-19 Pandemic on Head and Neck Cancer Diagnosis in the Piedmont Region, Italy: Interrupted Time-Series Analysis
Authors: Popovic Maja , Fiano Valentina , Moirano Giovenale , Chiusa Luigi , Conway David I. , Garzino Demo Paolo , Gilardetti Marco , Iorio Giuseppe Carlo , Moccia Chiara , Ostellino Oliviero , Pecorari Giancarlo , Ramieri Guglielmo , Ricardi Umberto , Riva Giuseppe , Virani Shama , Richiardi Lorenzo
Published: February 2022

Background

The COVID-19 pandemic has likely affected the most vulnerable groups of patients and those requiring time-critical access to healthcare services, such as patients with cancer. The aim of this study was to use time trend data to assess the impact of COVID-19 on timely diagnosis and treatment of head and neck cancer (HNC) in the Italian Piedmont region.

Methods

This study was based on two different data sources. First, regional hospital discharge register data were used to identify incident HNC in patients ≥18 years old during the period from January 1, 2015, to December 31, 2020. Interrupted time-series analysis was used to model the long-time trends in monthly incident HNC before COVID-19 while accounting for holiday-related seasonal fluctuations in the HNC admissions. Second, in a population of incident HNC patients eligible for recruitment in an ongoing clinical cohort study (HEADSpAcE) that started before the COVID-19 pandemic, we compared the distribution of early-stage and late-stage diagnoses between the pre-COVID-19 and the COVID-19 period.

Results

There were 4,811 incident HNC admissions in the 5-year period before the COVID-19 outbreak and 832 admissions in 2020, of which 689 occurred after the COVID-19 outbreak in Italy. An initial reduction of 28% in admissions during the first wave of the COVID-19 pandemic (RR 0.72, 95% CI 0.62–0.84) was largely addressed by the end of 2020 (RR 0.96, 95% CI 0.89–1.03) when considering the whole population, although there were some heterogeneities. The gap between observed and expected admissions was particularly evident and had not completely recovered by the end of the year in older (≥75 years) patients (RR: 0.88, 0.76–1.01), patients with a Romano-Charlson comorbidity index below 2 (RR 0.91, 95% CI: 0.84–1.00), and primary surgically treated patients (RR 0.88, 95% CI 0.80–0.97). In the subgroup of patients eligible for the ongoing active recruitment, we observed no evidence of a shift toward a more advanced stage at diagnosis in the periods following the first pandemic wave.

Conclusions

The COVID-19 pandemic has affected differentially the management of certain groups of incident HNC patients, with more pronounced impact on older patients, those treated primarily surgically, and those with less comorbidities. The missed and delayed diagnoses may translate into worser oncological outcomes in these patients.
Presence and Plant Uptake of Heavy Metals in Tidal Marsh Wetland Soils
Authors: Chintapenta Lathadevi K. , Ommanney Katharine I. , Ozbay Gulnihal
Published: February 2022

Marsh grasses have been used as efficient tools for phytoremediation and are known to play key roles in maintaining ecosystem functions by reducing the contamination of coastlines. This study was initiated to understand how human activities in wetlands can impact ion-heavy metal concentrations in relation to native and invasive marsh grasses. The study site, Blackbird Creek (BBC) is a tidal wetland that experiences agricultural, fishing, recreational, residential and other anthropogenic activities throughout the year. Heavy metals cadmium, arsenic, and lead in the soils and marsh grasses were monitored along with the ion compositions of soils. The main objective of this study was to understand if the marsh soils containing monotypic stands of native (Spartina) and non-native (Phragmites) vegetation display similar levels of heavy metals. Differences were observed in the concentrations of heavy metals at study sites with varying marsh vegetation types, and in soils containing vegetation and no vegetation. The soils with denseSpartinaandPhragmitesstands were anaerobic whereas soil at the boat ramp site was comparatively less anaerobic and also had increased levels of cadmium. Heavy metal concentrations in soil andPhragmitesleaves were inversely correlated whereas they were positively correlated inSpartinasites. Electrical conductivity and pH levels in soil also showed increased cadmium and arsenic concentrations. These findings collectively infer that human activities and seasonal changes can increase soil complexities affecting the bioavailability of metals.
Transfer Learning Approaches for Neuroimaging Analysis: A Scoping Review
Authors: Ardalan Zaniar , Subbian Vignesh
Published: February 2022

Deep learning algorithms have been moderately successful in diagnoses of diseases by analyzing medical images especially through neuroimaging that is rich in annotated data. Transfer learning methods have demonstrated strong performance in tackling annotated data. It utilizes and transfers knowledge learned from a source domain to target domain even when the dataset is small. There are multiple approaches to transfer learning that result in a range of performance estimates in diagnosis, detection, and classification of clinical problems. Therefore, in this paper, we reviewed transfer learning approaches, their design attributes, and their applications to neuroimaging problems. We reviewed two main literature databases and included the most relevant studies using predefined inclusion criteria. Among 50 reviewed studies, more than half of them are on transfer learning for Alzheimer's disease. Brain mapping and brain tumor detection were second and third most discussed research problems, respectively. The most common source dataset for transfer learning was ImageNet, which is not a neuroimaging dataset. This suggests that the majority of studies preferred pre-trained models instead of training their own model on a neuroimaging dataset. Although, about one third of studies designed their own architecture, most studies used existing Convolutional Neural Network architectures. Magnetic Resonance Imaging was the most common imaging modality. In almost all studies, transfer learning contributed to better performance in diagnosis, classification, segmentation of different neuroimaging diseases and problems, than methods without transfer learning. Among different transfer learning approaches, fine-tuning all convolutional and fully-connected layers approach and freezing convolutional layers and fine-tuning fully-connected layers approach demonstrated superior performance in terms of accuracy. These recent transfer learning approaches not only show great performance but also require less computational resources and time.
Validation of dMEREM, the Detailed Mars Energetic Radiation Environment Model, with RAD Data from the Surface of Mars
Authors: Gonçalves Patrícia , Arruda Luísa , Pinto Marco
Published: February 2022

The detailed Martian Energetic Radiation Environment Model (dMEREM) is a Geant4 based model developed for the European Space Agency, which enables to predict the radiation environment expected at different locations on the Martian orbit, atmosphere and surface, as a function of epoch, latitude and longitude, taking into account the specific atmospheric and soil composition, based on different particle propagation codes for primary Galactic Cosmic Rays or Solar Particle Events. This work describes the validation of dMEREM with differential proton fluxes measured with the NASA Curiosity rover Radiation Assessment Detector (RAD) at the Gale Crater, at the surface of Mars, from 15 November 2015 to 15 January 2016 and in the beginning of September 2017, using two different Galactic Cosmic Ray (GCR) models, the ISO-15 390 and the Badhwar-O’Neill 2014 models. This work includes a comparative study of the available Geant4 physics lists in describing the RAD measured proton spectrum, and an investigation of the proton directional spectrum at the Martian surface, and on its effect on the comparisons between models and data, which are necessarily measured within a limited field-of-view. For both GCR models and data periods there was a good agreement between the proton fluxes in the energy range between 10 and 90 MeV measured at the surface of Mars with RAD and the corresponding dMEREM predictions. Therefore, although the RAD only measures a limited field-of-view in zenith angle of the Martian Particle Radiation Field, and this effect has to be taken into account, the results obtained constitute an important benchmark in the use of dMEREM in the assessment of the expected ionising radiation field on the surface of Mars.
The State of US Farm Operator Livelihoods
Authors: Burchfield Emily K. , Schumacher Britta L. , Spangler Kaitlyn , Rissing Andrea
Published: February 2022

In nine of the last 10 years, the United States Department of Agriculture (USDA) has reported that the average funds generated on-farm for farm operators to meet living expenses and debt obligations have been negative. This paper pieces together disparate data to understand why farm operators in the most productive agricultural systems on the planet are systematically losing money. The data-driven narrative we present highlights some troubling trends in US farm operator livelihoods. Though US farms are more productive than ever before, rising input costs, volatile production values, and rising land rents have left farmers with unprecedented levels of farm debt, low on-farm incomes, and high reliance on federal programs. For many US farm operators, the indicators of a “good livelihood”—stability, security, equitable rewards for work—are largely absent. We conclude by proposing three axes of intervention that would help US agriculture better sustain all farmers' livelihoods, a crucial step toward improving overall agricultural sustainability: (1) increase the diversity of people, crops, and cropping systems, (2) improve equity in access to land, support, and capital, and (3) improve the quality, accessibility, and content of data to facilitate monitoring of multiple indicators of agricultural “success.”