bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
Authors: Kaur Tanpreet , Brooks Allen F. , Lapsys Alex , Desmond Timothy J. , Stauff Jenelle , Arteaga Janna , Winton Wade P. , Scott Peter J. H.
Published: December 2021

Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity 18F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) imaging. Herein, we report the first synthesis of fluorine-18 imaging agent, 6-(5-((5-(2,2-difluoro-2-(fluoro-18F)ethoxy)pyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one ([18F]1), a radioligand for HD and its preclinical evaluation in vitro (autoradiography of post-mortem HD brains) and in vivo (rodent and non-human primate brain PET). [18F]1 was synthesized in a 4.1% RCY (decay corrected) and in an average molar activity of 16.5 ± 12.5 GBq/μmol (445 ± 339 Ci/mmol). [18F]1 penetrated the blood-brain barrier of both rodents and primates, and specific saturable binding in post-mortem brain slices was observed that correlated to mHTT aggregates identified by immunohistochemistry.
Psychobiological Consequences of Childhood Sexual Abuse: Current Knowledge and Clinical Implications
Authors: Lo Iacono Luisa , Trentini Cristina , Carola Valeria
Published: December 2021

A large body of research has documented the long-term harms of childhood sexual abuse (CSA) on an individual’s emotional-adaptive function and mental health. Recent studies have also provided evidence of the biological impact of CSA, implicating specific alterations in many systems, including the endocrine and immune systems, and in DNA and chromatin, in the pathogenesis of medical disorders. Although the effects of CSA are often examined with regard to the general impact of early-life traumatic experiences, the study of CSA per sè, as a trigger of specific pathogenic pathways, would be more appropriate to understand their long-term implications and develop tailored diagnostic and therapeutic strategies. Based on these premises, this narrative minireview summarizes the research on the short-term and long-term sequelae of CSA, focusing on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the effects on the immune system, and the changes to DNA through altered methylation. Also, we discuss the literature that examines dysfunctional DNA telomere erosion and oxidative stress markers as a sign of CSA. Finally, recent evidence of the intergenerational transmission of the effects of CSA is reported. The impact of CSA on brain connectivity and functions is out of the scope of this review, thus brain imaging studies are not included. The results of this minireview are discussed, considering their implications for prevention and clinical practice.
DPP4 Regulates DHCR24-Mediated Cholesterol Biosynthesis to Promote Methotrexate Resistance in Gestational Trophoblastic Neoplastic Cells
Authors: Yuan Weijie , Yong Wenjing , Zhu Jing , Shi Dazun
Published: December 2021

Metabolic reprogramming could promote cellular adaptation in response to chemotherapeutic drugs in cancer cells. Herein, we aimed to characterize the metabolomic profiles regulated by Dipeptidyl Peptidase 4 (DPP4) in methotrexate (MTX)-resistant gestational trophoblastic neoplastic (GTN) cells. A total of eighty metabolites were found to be commonly altered in DPP4-depleted JAR/MTX and JEG3/MTX cells. Cholesterol biosynthesis-related metabolites were markedly impacted by DPP4 knockdown in MTX-resistant sublines. Manipulation of DPP4 expression remarkably affected the level of cellular cholesterol in GTN cells. Our analysis also identified 24-Dehydrocholesterol Reductase (DHCR24) as a potential downstream effector of DPP4. Manipulation of DHCR24 expression affected cellular cholesterol level, reactive oxygen species (ROS) accumulation, and chemosensitivity to MTX in GTN cell models. In addition, over-expression of DHCR24 could markedly restore cellular cholesterol level and rescue cell survival in DPP4-depleted MTX-resistant GTN cells. Highly correlated expression of DPP4 and DHCR24 was observed in clinical GTN specimens. Further, DPP4 inhibitor sitagliptin effectively inhibited cholesterol biosynthesis, reduced DHCR24 expression and enhanced MTX-induced cytotoxicity in vitro and in vivo. In conclusion, our findings suggested that DPP4 might regulate DHCR24-mediated cholesterol biosynthesis to promote methotrexate resistance in GTN cells. Targeting DPP4/DHCR24 signaling might help to sensitize MTX-resistant GTN to MTX treatment.
Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
Authors: Tyumentseva Anna , Averchuk Anton , Palkina Nadezhda , Zinchenko Ivan , Moshev Anton , Savchenko Andrey , Ruksha Tatiana
Published: December 2021

Melanoma is highly heterogeneous type of malignant neoplasm that is responsible for the majority of deaths among other types of skin cancer. In the present study, we screened a list of differentially expressed genes in two primary, drug-naïve melanoma cell lines derived from patients with melanoma following treatment of the cells with the chemotherapeutic agent dacarbazine. The aim was to determine the transcriptomic profiles and associated alterations in the cell phenotype. We found the vascular endothelial growth factor A/vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase/protein kinase B and focal adhesion signaling pathways to be top altered after dacarbazine treatment. In addition, we observed the expression levels of genes associated with tumor dissemination, integrin β8 and matrix metalloproteinase-1, to be diminished in both cell lines studied, the results of which were confirmed by reverse transcription-quantitative polymerase chain reaction. By contrast, plexin A2 expression was found to be upregulated in K2303 cells, where reduced migration and invasion were also observed, following dacarbazine treatment. Plexin A2 downregulation was associated with the promotion of migrative and invasive capacities in B0404 melanoma cells. Since plexin A2 is semaphorin co-receptor that is involved in focal adhesion and cell migration regulation, the present study suggested that plexin A2 may be implicated in the dacarbazine-mediated phenotypic shift of melanoma cells. We propose that the signature of cancer cell invasiveness can be revealed by using a combination of transcriptomic and functional approaches, which should be applied in the development of personalized therapeutic strategies for each patient with melanoma.
GDPLichi: a DNA Damage Repair-Related Gene Classifier for Predicting Lung Adenocarcinoma Immune Checkpoint Inhibitors Response
Authors: Leng Yang , Dang Shiying , Yin Fei , Gao Tianshun , Xiao Xing , Zhang Yi , Chen Lin , Qin Changfei , Lai Nannan , Zhan Xiao-Yong , Huang Ke , Luo Chuanming , Kang Yang , Wang Nan , Li Yun , Liang Yuhong , Huang Bihui
Published: December 2021

Lung cancer is one of the most common and mortal malignancies, usually with a poor prognosis in its advanced or recurrent stages. Recently, immune checkpoint inhibitors (ICIs) immunotherapy has revolutionized the treatment of human cancers including lung adenocarcinoma (LUAD), and significantly improved patients’ prognoses. However, the prognostic and predictive outcomes differ because of tumor heterogeneity. Here, we present an effective method, GDPLichi (Genes of DNA damage repair to predict LUAD immune checkpoint inhibitors response), as the signature to predict the LUAD patient’s response to the ICIs. GDPLichi utilized only 7 maker genes from 8 DDR pathways to construct the predictive model and classified LUAD patients into two subgroups: low- and high-risk groups. The high-risk group was featured by worse prognosis and decreased B cells, CD8+ T cells, CD8+ central memory T cells, hematopoietic stem cells (HSC), myeloid dendritic cells (MDC), and immune scores as compared to the low-risk group. However, our research also suggests that the high-risk group was more sensitive to ICIs, which might be explained by increased TMB, neoantigen, immune checkpoint molecules, and immune suppression genes’ expression, but lower TIDE score as compared to the low-risk group. This conclusion was verified in three other LUAD cohort datasets (GSE30219, GSE31210, GSE50081).
hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
Authors: Zhan Bo , Dong Xiao , Yuan Yulin , Gong Zheng , Li Bohan
Published: December 2021

Purpose

Accumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.

Methods

HIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.

Results

HIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.

Conclusion

Our work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway.
Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
Authors: Ruggiero Maria Rosaria , Baroni Simona , Bitonto Valeria , Ruiu Roberto , Rapisarda Smeralda , Aime Silvio , Geninatti Crich Simonetta
Published: December 2021

This study aims to explore whether the water exchange rate constants in tumor cells can act as a hallmark of pathology status and a reporter of therapeutic outcomes. It has been shown, using 4T1 cell cultures and murine allografts, that an early assessment of the therapeutic effect of doxorubicin can be detected through changes in the cellular water efflux rate constant kio. The latter has been estimated by analyzing the magnetization recovery curve in standard NMR T1 measurements when there is a marked difference in the proton relaxation rate constants (R1) between the intra- and the extra-cellular compartments. In cellular studies, T1 measurements were carried out on a relaxometer working at 0.5 T, and the required difference in R1 between the two compartments was achieved via the addition of a paramagnetic agent into the extracellular compartment. For in-vivo experiments, the large difference in the R1 values of the two-compartments was achieved when the T1 measurements were carried out at low magnetic field strengths. This task was accomplished using a Fast Field Cycling (FFC) relaxometer that was properly modified to host a mouse in its probe head. The decrease in kio upon the administration of doxorubicin is the result of the decreased activity of Na+/K+-ATPase, as shown in an independent test on the cellular uptake of Rb ions. The results reported herein suggest that kio can be considered a non-invasive, early and predictive biomarker for the identification of responsive patients immediately from the first doxorubicin treatment.
Ribosomal Protein L23 Drives the Metastasis of Hepatocellular Carcinoma via Upregulating MMP9
Authors: Yang Minli , Zhou Yujiao , Deng Haijun , Zhou Hongzhong , Cheng Shengtao , Zhang Dapeng , He Xin , Mai Li , Chen Yao , Chen Juan
Published: December 2021

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Tumor metastasis is one of the major causes of high mortality of HCC. Identifying underlying key factors contributing to invasion and metastasis is critical to understand the molecular mechanisms of HCC metastasis. Here, we identified RNA binding protein L23 (RPL23) as a tumor metastasis driver in HCC. RPL23 was significantly upregulated in HCC tissues compared to adjacent normal tissues, and closely related to poor clinical outcomes in HCC patients. RPL23 depletion inhibited HCC cell proliferation, migration and invasion, and distant metastasis. Mechanistically, RPL23 directly associated with 3’UTR of MMP9, therefore positively regulated MMP9 expression. In conclusion, we identified that RPL23 might play an important role in HCC metastasis in an MMP9-dependent manner and be a potential therapeutic target for HCC tumorigenesis and metastasis.
Transarterial Chemoembolization Combined With Endoscopic Therapy Is Beneficial for Unresectable Hepatocellular Carcinoma With Esophagogastric Varices
Authors: Tao Ziwen , Ruan Yuying , Peng Zhi , Zhang Kai , Gao Yanjing
Published: December 2021

Background

The efficacy of transarterial chemoembolization (TACE) combined with endoscopic therapy for unresectable hepatocellular carcinoma with esophagogastric varices remains unclear.

Methods

The study has been registered on ClinicalTrials.gov with the number NCT05017922 (https://register.clinicaltrials.gov). Eligible patients were divided into combined group (received TACE plus endoscopic therapy) and control group (only received TACE). The occurrence of death and bleeding episodes during the follow-up was recorded. Kaplan–Meier analysis was used to compare outcomes between the two groups. Cox proportional hazard model was used to determine independent predictors for the survival.

Results

Eighty-nine patients were included, 42 in the combined group, others in the control group. During the follow-up, 51 patients died, the 1-year, 2-year, and 3-year survival rates were 64.9%, 45.5%, and 34.5%. The cumulative survival was significantly higher in the combined group than in the control group (p = 0.027); the 1-year, 2-year, and 3-year survival rates were 75.5%, 55.9%, 43.8% and 55.0%, 35.9%, 26.6%, respectively. Forty-four patients experienced bleeding, the bleeding rate was significantly higher in the control group than in the combined group (77.4% vs. 56.8%, p = 0.016). Multivariate analysis showed that treatment, hemoglobin, portal vein tumor thrombosis, and aspartate aminotransferase were independent predictors for overall survival; the first three factors were also independent predictors for bleeding-free survival. Patients who received primary prophylaxis had longer overall survival (p = 0.042) and bleeding-free survival (p = 0.029) than those who received secondary prophylaxis.

Conclusions

TACE combined with endoscopic therapy significantly improved survival and reduced bleeding rates in unresectable hepatocellular carcinoma with esophagogastric varices patients. Portal vein tumor thrombosis was a strong negative prognostic factor for both overall survival and bleeding-free survival. Primary prophylaxis improved survival benefits compared with secondary prophylaxis.
Inadequate Vaccine Responses in Children With Multiple Sclerosis
Authors: Santoro Jonathan D. , Saucier Laura E. , Tanna Runi , Wiegand Sarah E. , Pagarkar Dania , Tempchin Adam F. , Khoshnood Mellad , Ahsan Nusrat , Van Haren Keith
Published: December 2021

Objective: Immunizations against Hepatitis B virus (HBV) and Varicella Zoster virus (VZV), are recommended for patients with pediatric onset multiple sclerosis (POMS) and may be required prior to initiation of some disease modifying therapies. However, the efficacy of routine vaccine administration in POMS has never been studied. We sought to assess the humoral mediated vaccine response to HBV and VZV in children with POMS.

Methods: A multi-center retrospective chart-based review of 62 patients with POMS was performed. Clinical data and antibody titers against HBV and VZV were collected prior to initiation of disease modifying therapy or steroids and compared to institutional control data, using t-test and chi squared analysis.

Results: There were low rates of immunity against both HBV and VZV (33 and 25% respectively) among individuals with POMS. Fifteen individuals (24%) were non-immune to both. Compared to institutional control data, individuals with POMS were significantly less likely to be immune to and HBV (p = 0.003, 95% CI: 0.22–0.75) and VZV (p < 0.001, 95% CI: 0.09–0.39).

Interpretation: Individuals with POMS have low rates of antibody-mediated immunity against HBV and VZV, despite receiving the appropriate vaccinations. This suggests an association between POMS and systemic immune dysregulation although further study is needed.
Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism
Authors: Ling Yun , Shi Jiajun , Ma Quanxin , Yang Qinqin , Rong Yili , He Jiangmin , Chen Minli
Published: December 2021

Vasodilatory therapy plays an important role in the treatment of cardiovascular diseases, especially hypertension and coronary heart disease. Previous research found that Guanxinning tablet (GXNT), a traditional Chinese compound preparation composed of Salvia miltiorrhiza (Danshen) and Ligusticum chuanxiong (Chuanxiong), increase blood flow in the arteries, but whether vasodilation plays a role in this effect remains unclear. Here, we found that GXNT significantly alleviated the vasoconstriction of isolated rabbit thoracic aorta induced by phenylephrine (PE), norepinephrine (NE), and KCl in a dose-dependent manner with or without endothelial cells (ECs). Changes in calcium ion levels in vascular smooth muscle cells (VSMCs) showed that both intracellular calcium release and extracellular calcium influx through receptor-dependent calcium channel (ROC) declined with GXNT treatment. Experiments to examine potassium channels suggested that endothelium-denuded vessels were also regulated by calcium-activated potassium channels (Kca) and ATP-related potassium channels (KATP) but not voltage-gated potassium channels (kv) and inward rectifying potassium channels (KIR). For endothelium-intact vessels, the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contents in vascular tissue obviously increased after GXNT treatment, and pretreatment with the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) or guanylyl cyclase inhibitor methylthionine chloride (MB) significantly inhibited vasodilation. An assessment of NO-related pathway protein expression revealed that GXNT enhanced the expression of phosphorylated endothelial NO synthase (eNOS) in a dose-dependent manner but had no effect on total eNOS, p-Akt, Akt, or PI3K levels in human umbilical vein ECs (HUVECs). In addition to PI3K/AKT signaling, Ca2+/calmodulin (CaM)-Ca2+/CaM-dependent protein kinase II (CaMKII) signaling is a major signal transduction pathway involved in eNOS activation in ECs. Further results showed that free calcium ion levels were decreased in HUVECs with GXNT treatment, accompanied by an increase in p-CaMKII expression, implying an increase in the Ca2+/CaM-Ca2+/CaMKII cascade. Taken together, these findings suggest that the GXNT may have exerted their vasodilative effect by activating the endothelial CaMKII/eNOS signaling pathway in endothelium-intact rings and calcium-related ion channels in endothelium-denuded vessels.
Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
Authors: Tao Yali , Zhou Hui , Niu Ting
Published: December 2021

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.

Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).

Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs.

Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.
In Vitro Red Blood Cell Segregation in Sickle Cell Anemia
Authors: Clavería Viviana , Connes Philippe , Lanotte Luca , Renoux Céline , Joly Philippe , Fort Romain , Gauthier Alexandra , Wagner Christian , Abkarian Manouk
Published: December 2021

Red blood cells in sickle cell anemia (sRBC) are more heterogeneous in their physical properties than healthy red blood cells, spanning adhesiveness, rigidity, density, size, and shape. sRBC with increased adhesiveness to the vascular wall would trigger vaso-occlusive like complications, a hallmark of sickle cell anemia. We investigated whether segregation occurs among sRBC flowing in micron-sized channels and tested the impact of aggregation on segregation. Two populations of sRBC of different densities were separated, labeled, and mixed again. The mixed suspension was flowed within glass capillary tubes at different pressure-drops, hematocrit, and suspending media that promoted or not cell aggregation. Observations were made at a fixed channel position. The mean flow velocity was obtained by using the cells as tracking particles, and the cell depleted layer (CDL) by measuring the distance from the cell core border to the channel wall. The labeled sRBC were identified by stopping the flow and scanning the cells within the channel section. The tube hematocrit was estimated from the number of fluorescence cells identified in the field of view. In non-aggregating media, our results showed a heterogeneous distribution of sRBC according to their density: low-density sRBC population remained closer to the center of the channel, while the densest cells segregated towards the walls. There was no impact of the mean flow velocity and little impact of hematocrit. This segregation heterogeneity could influence the ability of sRBC to adhere to the vascular wall and slow down blood flow. However, promoting aggregation inhibited segregation while CDL thickness was enhanced by aggregation, highlighting a potential protective role against vaso-occlusion in patients with sickle cell anemia.
The European Forest Condition Monitor: Using Remotely Sensed Forest Greenness to Identify Hot Spots of Forest Decline
Authors: Buras Allan , Rammig Anja , Zang Christian S.
Published: December 2021

Forest decline, in course of climate change, has become a frequently observed phenomenon. Much of the observed decline has been associated with an increasing frequency of climate change induced hotter droughts while decline induced by flooding, late-frost, and storms also play an important role. As a consequence, tree mortality rates have increased across the globe. Despite numerous studies that have assessed forest decline and predisposing factors for tree mortality, we still lack an in-depth understanding of (I) underlying eco-physiological mechanisms, (II) the influence of varying environmental conditions related to soil, competition, and micro-climate, and (III) species-specific strategies to cope with prolonged environmental stress. To deepen our knowledge within this context, studying tree performance within larger networks seems a promising research avenue. Ideally such networks are already established during the actual period of environmental stress. One approach for identifying stressed forests suitable for such monitoring networks is to assess measures related to tree vitality in near real-time across large regions by means of satellite-borne remote sensing. Within this context, we introduce the European Forest Condition monitor (EFCM)—a remote-sensing based, freely available, interactive web information tool. The EFCM depicts forest greenness (as approximated using NDVI from MODIS at a spatial resolution of roughly 5.3 hectares) for the pixel-specific growing season across Europe and consequently allows for guiding research within the context of concurrent forest performance. To allow for inter-temporal comparability and account for pixel-specific features, all observations are set in relation to normalized difference vegetation index (NDVI) records over the monitoring period beginning in 2001. The EFCM provides both a quantile-based and a proportion-based product, thereby allowing for both relative and absolute comparison of forest greenness over the observational record. Based on six specific examples related to spring phenology, drought, late-frost, tree die-back on water-logged soils, an ice storm, and windthrow we exemplify how the EFCM may help identifying hotspots of extraordinary forest greenness. We discuss advantages and limitations when monitoring forest condition at large scales on the basis of moderate resolution remote sensing products to guide users toward an appropriate interpretation.
Identification of Key Genes in ‘Luang Pratahn’, Thai Salt-Tolerant Rice, Based on Time-Course Data and Weighted Co-expression Networks
Authors: Sonsungsan Pajaree , Chantanakool Pheerawat , Suratanee Apichat , Buaboocha Teerapong , Comai Luca , Chadchawan Supachitra , Plaimas Kitiporn
Published: December 2021

Salinity is an important environmental factor causing a negative effect on rice production. To prevent salinity effects on rice yields, genetic diversity concerning salt tolerance must be evaluated. In this study, we investigated the salinity responses of rice (Oryza sativa) to determine the critical genes. The transcriptomes of ‘Luang Pratahn’ rice, a local Thai rice variety with high salt tolerance, were used as a model for analyzing and identifying the key genes responsible for salt-stress tolerance. Based on 3' Tag-Seq data from the time course of salt-stress treatment, weighted gene co-expression network analysis was used to identify key genes in gene modules. We obtained 1,386 significantly differentially expressed genes in eight modules. Among them, six modules indicated a significant correlation within 6, 12, or 48h after salt stress. Functional and pathway enrichment analysis was performed on the co-expressed genes of interesting modules to reveal which genes were mainly enriched within important functions for salt-stress responses. To identify the key genes in salt-stress responses, we considered the two-state co-expression networks, normal growth conditions, and salt stress to investigate which genes were less important in a normal situation but gained more impact under stress. We identified key genes for the response to biotic and abiotic stimuli and tolerance to salt stress. Thus, these novel genes may play important roles in salinity tolerance and serve as potential biomarkers to improve salt tolerance cultivars.
Formation and Development of Taproots in Deciduous Tree Species
Authors: Kościelniak Paulina , Glazińska Paulina , Kȩsy Jacek , Zadworny Marcin
Published: December 2021

Trees are generally long-lived and are therefore exposed to numerous episodes of external stimuli and adverse environmental conditions. In certain trees e.g., oaks, taproots evolved to increase the tree’s ability to acquire water from deeper soil layers. Despite the significant role of taproots, little is known about the growth regulation through internal factors (genes, phytohormones, and micro-RNAs), regulating taproot formation and growth, or the effect of external factors, e.g., drought. The interaction of internal and external stimuli, involving complex signaling pathways, regulates taproot growth during tip formation and the regulation of cell division in the root apical meristem (RAM). Assuming that the RAM is the primary regulatory center responsible for taproot growth, factors affecting the RAM function provide fundamental information on the mechanisms affecting taproot development.
Omics-Facilitated Crop Improvement for Climate Resilience and Superior Nutritive Value
Authors: Zenda Tinashe , Liu Songtao , Dong Anyi , Li Jiao , Wang Yafei , Liu Xinyue , Wang Nan , Duan Huijun
Published: December 2021

Novel crop improvement approaches, including those that facilitate for the exploitation of crop wild relatives and underutilized species harboring the much-needed natural allelic variation are indispensable if we are to develop climate-smart crops with enhanced abiotic and biotic stress tolerance, higher nutritive value, and superior traits of agronomic importance. Top among these approaches are the “omics” technologies, including genomics, transcriptomics, proteomics, metabolomics, phenomics, and their integration, whose deployment has been vital in revealing several key genes, proteins and metabolic pathways underlying numerous traits of agronomic importance, and aiding marker-assisted breeding in major crop species. Here, citing several relevant examples, we appraise our understanding on the recent developments in omics technologies and how they are driving our quest to breed climate resilient crops. Large-scale genome resequencing, pan-genomes and genome-wide association studies are aiding the identification and analysis of species-level genome variations, whilst RNA-sequencing driven transcriptomics has provided unprecedented opportunities for conducting crop abiotic and biotic stress response studies. Meanwhile, single cell transcriptomics is slowly becoming an indispensable tool for decoding cell-specific stress responses, although several technical and experimental design challenges still need to be resolved. Additionally, the refinement of the conventional techniques and advent of modern, high-resolution proteomics technologies necessitated a gradual shift from the general descriptive studies of plant protein abundances to large scale analysis of protein-metabolite interactions. Especially, metabolomics is currently receiving special attention, owing to the role metabolites play as metabolic intermediates and close links to the phenotypic expression. Further, high throughput phenomics applications are driving the targeting of new research domains such as root system architecture analysis, and exploration of plant root-associated microbes for improved crop health and climate resilience. Overall, coupling these multi-omics technologies to modern plant breeding and genetic engineering methods ensures an all-encompassing approach to developing nutritionally-rich and climate-smart crops whose productivity can sustainably and sufficiently meet the current and future food, nutrition and energy demands.
A Deep Learning Method for Fully Automatic Stomatal Morphometry and Maximal Conductance Estimation
Authors: Gibbs Jonathon A. , Mcausland Lorna , Robles-Zazueta Carlos A. , Murchie Erik H. , Burgess Alexandra J.
Published: December 2021

Stomata are integral to plant performance, enabling the exchange of gases between the atmosphere and the plant. The anatomy of stomata influences conductance properties with the maximal conductance rate, gsmax, calculated from density and size. However, current calculations of stomatal dimensions are performed manually, which are time-consuming and error prone. Here, we show how automated morphometry from leaf impressions can predict a functional property: the anatomical gsmax. A deep learning network was derived to preserve stomatal morphometry via semantic segmentation. This forms part of an automated pipeline to measure stomata traits for the estimation of anatomical gsmax. The proposed pipeline achieves accuracy of 100% for the distinction (wheat vs. poplar) and detection of stomata in both datasets. The automated deep learning-based method gave estimates for gsmax within 3.8 and 1.9% of those values manually calculated from an expert for a wheat and poplar dataset, respectively. Semantic segmentation provides a rapid and repeatable method for the estimation of anatomical gsmax from microscopic images of leaf impressions. This advanced method provides a step toward reducing the bottleneck associated with plant phenotyping approaches and will provide a rapid method to assess gas fluxes in plants based on stomata morphometry.
Suppression of the Lycopene Cyclase Gene Causes Downregulation of Ascorbate Peroxidase Activity and Decreased Glutathione Pool Size, Leading to H2O2 Accumulation in Euglena gracilis
Authors: Tamaki Shun , Sato Ryosuke , Koshitsuka Yuki , Asahina Masashi , Kodama Yutaka , Ishikawa Takahiro , Shinomura Tomoko
Published: December 2021

Carotenoids are photosynthetic pigments and hydrophobic antioxidants that are necessary for the survival of photosynthetic organisms, including the microalga Euglena gracilis. In the present study, we identified an uncharacterized gene encoding the E. gracilis β-carotene synthetic enzyme lycopene cyclase (EgLCY) and discovered a relationship between EgLCY-mediated carotenoid synthesis and the reactive oxygen species (ROS) scavenging system ascorbate-glutathione cycle. The EgLCY cDNA sequence was obtained via homology searching E. gracilis transcriptome data. An enzyme assay using Escherichia coli demonstrated that EgLCY converts lycopene to β-carotene. E. gracilis treated with EgLCY double-stranded RNA (dsRNA) produced colorless cells with hypertrophic appearance, inhibited growth, and marked decrease in carotenoid and chlorophyll content, suggesting that EgLCY is essential for the synthesis of β-carotene and downstream carotenoids, which are abundant and physiologically functional. In EgLCY dsRNA-treated cells, the ascorbate-glutathione cycle, composed of ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDAR), and glutathione reductase (GR), was unusually modulated; APX and GR activities significantly decreased, whereas DHAR and MDAR activities increased. Ascorbate content was significantly increased and glutathione content significantly decreased in EgLCY dsRNA-treated cells and was correlated with their recycling enzyme activities. Fluorescent imaging demonstrated that EgLCY dsRNA-treated cells accumulated higher levels of H2O2 compared to wild-type cells. Taken together, this study revealed that EgLCY-mediated synthesis of β-carotene and downstream carotenoid species upregulates APX activity and increases glutathione pool size for H2O2 scavenging. Our study suggests a possible relationship between carotenoid synthesis and the ascorbate-glutathione cycle for ROS scavenging in E. gracilis.
One Ring Fit to Rule Them All? An Analysis of Avatar Bodies and Customization in Exergames
Authors: Czerwonka Sara , Alvarez Adrian , McArthur Victoria
Published: December 2021

With the growing popularity of exergames, researchers have noted the importance of presenting players with customizable avatars to encourage the long-term adoption of healthy behaviors offline. However, the “idealized” avatar bodies presented in avatar customization interfaces can represent limited body types and often problematically represent gender as binary. In this paper, we present a systematic analysis of the avatar customization interfaces of six console-based exergames. Results of our analysis indicate that customization options tend to be limited in exergames, especially with regard to body type and gender. Implications for avatar self-priming, self-identification, and healthy behavior adoption are discussed.
Gender-Related Beliefs, Norms, and the Link With Green Consumption
Authors: Zhao Ziyue , Gong Yuanchao , Li Yang , Zhang Linxiu , Sun Yan
Published: December 2021

Although extant literature provided abundant evidence that men and women are different in their environmental behaviors, there is a lack of integration of gender differences in green consumption and the underlying mechanism that associates with these disparities. Therefore, to solve this existing gap, the current paper reviewed existing literature on green consumption with threefold purposes. First, presenting an integrated view of gender-different green consumption patterns along with the relationship of gender-related beliefs and individuals’ pro-environmental behavior based on existing evidence. Second, interpreting how gender differences are generated based on the value-belief-norm (VBN) theory, and the theory of social roles. Third, analyzing previous studies, providing implications for future research, and then proposing suggestions for marketing practitioners in the green products industry. Accordingly, this article compared men’s and women’s different behavior in green consumption and discussed how and why they behave differently. Generally, women show a more positive green consumption intention, consume less carbon, and purchase green products more frequently. Whereas men are doing better than women in terms of environmental knowledge, and in some regions, they express higher concerns about environmental problems. It interprets individual differences in green consumption based on VBN theory from a unique insight—gender. It also identified some barriers for both men and women to participate in green consumption, and then proposed several suggestions to improve the public willingness of engaging in green consumption.
The Influence of Undergraduate Entrepreneurship Education on Entrepreneurial Intention: Evidence From Universities in China’s Pearl River Delta
Authors: Li Jing , Huang Shi-zheng , Chau Ka Yin , Yu Liqiong
Published: December 2021

Entrepreneurship may be taught, and entrepreneurship education is flourishing at colleges and universities. However, previous documents show that entrepreneurship education is inconsistent with the research conclusions of entrepreneurial intention, which is a lack of discussion on the mediating effect of government subsidies from external resources. Based on the cognitive behavior theory, a mediating effect of entrepreneurship education on entrepreneurial strategy and entrepreneurial intention is built. By collecting the data of 334 questionnaires of college students in Pearl River Delta in China, a structural equation is used for empirical analysis. The result indicates that entrepreneurship education does not have a significant influence on entrepreneurial intention; exploration innovation and exploitation innovation have a positive influence on entrepreneurial intention, and exploration innovation and exploitation innovation have a mediating effect on entrepreneurship education and entrepreneurial intention; government subsidies have a positive regulating effect on exploration innovation, exploitation innovation, and entrepreneurial intention. In this article, the application of the cognitive behavior theory in the field of entrepreneurship research is expanded to provide the theoretical basis for building the entrepreneurship education ecosystem, which is conductive to innovation and entrepreneurship to promote regional economic development.
Motives for Studying and Student Wellbeing: Validation of the Motivational Mindset Model
Authors: Hudig Job , Scheepers Ad W. A. , Schippers Michaéla C. , Smeets Guus
Published: December 2021

Research on the joint effect of multiple motives for studying was recently given a push in a new direction with the introduction of the motivational mindset model (MMM). This model contributes to a better understanding of study success and student wellbeing in higher education. The aim of the present study is to validate the newly developed model and the associated mindset classification tool (MCT). To this end, 662 first-year university students were classified in one of the four types of motivational mindset using the classification tool and three exploratory validation procedures were conducted through sense of purpose, study engagement, and students’ background characteristics in terms of gender and ethnicity. Both purpose and study engagement are central dimensions of student wellbeing and predictors of study success. The results show that (1) sense of purpose and study engagement differ across the four types of mindset, (2) students in the low-impact mindset show the least optimal pattern of study engagement and sense of purpose, (3) sense of purpose and study engagement are positively related and this relationship is consistent across mindsets, and (4) overall differences in purpose and study engagement between gender and ethnic subgroups stem from one specific type of motivational mindset. The results provide support for the validity of the MMM and the usefulness of the MCT. The implications of the findings are discussed as well as promising avenues for future research.
Perceptual-Motor and Perceptual-Cognitive Skill Acquisition in Soccer: A Systematic Review on the Influence of Practice Design and Coaching Behavior
Authors: Bergmann Fynn , Gray Rob , Wachsmuth Svenja , Höner Oliver
Published: December 2021

Facilitating players' skill acquisition is a major challenge within sport coaches' work which should be supported by evidence-based recommendations outlining the most effective practice and coaching methods. This systematic review aimed at accumulating empirical knowledge on the influence of practice design and coaching behavior on perceptual-motor and perceptual-cognitive skill acquisition in soccer. A systematic search was carried out according to the PRISMA guidelines across the databases SPORTDiscus, PsycInfo, MEDLINE, and Web of Science to identify soccer-specific intervention studies conducted in applied experimental settings (search date: 22ndNovember 2020). The systematic search yielded 8,295 distinct hits which underwent an independent screening process. Finally, 34 eligible articles, comprising of 35 individual studies, were identified and reviewed regarding their theoretical frameworks, methodological approaches and quality, as well as the interventions' effectiveness. These studies were classified into the following two groups: Eighteen studies investigated the theory-driven instructional approaches Differential Learning, Teaching Games for Understanding, and Non-linear Pedagogy. Another seventeen studies, most of them not grounded within a theoretical framework, examined specific aspects of practice task design or coaches' instructions. The Downs and Black checklist and the Template for Intervention Description and Replication were applied to assess the quality in reporting, risk of bias, and the quality of interventions' description. Based on these assessments, the included research was of moderate quality, however, with large differences across individual studies. The quantitative synthesis of results revealed empirical support for the effectiveness of coaching methodologies aiming at encouraging players' self-exploration within representative scenarios to promote technical and tactical skills. Nevertheless, “traditional” repetition-based approaches also achieved improvements with respect to players' technical outcomes, yet, their impact on match-play performance remains widely unexplored. In the light of the large methodological heterogeneity of the included studies (e.g., outcomes or control groups' practice activities), the presented results need to be interpreted by taking the respective intervention characteristics into account. Overall, the current evidence needs to be extended by theory-driven, high-quality studies within controlled experimental designs to allow more consolidated and evidence-based recommendations for coaches' work.
The Importance of Patient Expectations: A Mixed-Methods Study of U.S. Psychiatrists
Authors: Rosenfield Maayan N. , Bernstein Michael H.
Published: December 2021

Objective: To examine how psychiatrists think about and modulate non-specific factors (e.g., hope, expectations) in clinical practice.

Methods: U.S. psychiatrists were recruited for two studies assessing attitudes and behaviors related to non-specific factors. Study 1 entailed remote qualitative focus groups (k = 7) with n = 26 participants (36.0% female). Study 2 was a quantitative survey with n = 346 respondents (34.0% female) designed to assess the generalizability of focus group findings.

Results: Four themes were identified in Study 1 that were used to inform the survey (Study 2): (1) Expectations (2) Hope, (3) Placebo Effect, and (4) Aesthetic Features. Nearly all surveyed psychiatrists (92.2%) considered patient expectations at least “most of the time” when interacting with a patient. Focus groups revealed that psychiatrists often attempt to balance optimism and realism to improve outcomes. A majority of survey respondents believed office design and physician attire could at least somewhat influence expectations (72.5 and 77.3%, respectively) and even outcomes (51.5 and 58.7%, respectively). Focus group psychiatrists described how physical features may be used as therapeutic tools.

Conclusions: Psychiatrists are highly mindful of patient expectations. Although there is variability in the perceived importance of expectations, hope, the placebo effect, and aesthetic features, many utilize these factors in clinical practice.