bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial
Authors: Jackson Philippa A. , Forster Joanne , Khan Julie , Pouchieu Camille , Dubreuil Séverine , Gaudout David , Moras Benjamin , Pourtau Line , Joffre Florent , Vaysse Carole , Bertrand Karène , Abrous Hélène , Vauzour David , Brossaud Julie , Corcuff Jean Benoit , Capuron Lucile , Kennedy David O.
Published: February 2021

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron—identified as promising following preliminary beneficial effects in major depressive disorder—represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18–54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders.

Clinical trials number: NCT03639831.
ST3Gal IV Mediates the Growth and Proliferation of Cervical Cancer Cells In Vitro and In Vivo Via the Notch/p21/CDKs Pathway
Authors: Wu Yinshuang , Chen Xixi , Dong Weijie , Xu Zhongyang , Jian Yuli , Xu Chunyan , Zhang Lin , Wei Anwen , Yu Xiao , Wang Shidan , Wang Yue , Liu Gang , Sun Xiaoxin , Wang Shujing
Published: February 2021

ST3Gal IV is one of the principal sialyltransferases responsible for the biosynthesis of α2, 3-sialic acid to the termini N-glycans or O-glycans of glycoproteins and glycolipids. It has been reported that ST3Gal IV expression is associated with gastric carcinoma, pancreatic adenocarcinoma and breast cancer. While the expression and functions of ST3Gal IV in cervical cancer are still poorly understood. In this study, we found that ST3Gal IV was downregulated in human cervical cancer tissues compared to normal cervix tissues, and ST3Gal IV expression was negatively associated with the pathological grade of cervical cancer. ST3Gal IV upregulation inhibited the growth and proliferation of cervical cancer HeLa and SiHa cells in vitro and in vivo. Furthermore, ST3Gal IV overexpression enhanced the expression of several Notch pathway components such as Jagged1, Notch1, Hes1 and Hey1, while cell cycle protein expression like Cyclin D1, Cyclin E1, CDK2 and CDK4 were decreased. These results indicate that expression of ST3Gal IV is reduced in cervical cancer and plays a negative role in cell proliferation via Notch/p21/CDKs signaling pathway. Thus, sialyltransferase ST3Gal IV might be a target for the diagnosis and therapy of cervical cancer.
Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases
Authors: Zhang Qingfu , Han Yunan , Zhang Yao , Liu Dan , Ming Jian , Huang Bo , Qiu Xueshan
Published: February 2021

Purpose

This study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).

Materials and Methods

We collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate-specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.

Results

Among the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 months, 95% CI: 15.3–19.9 months) had significantly worse survival compared with usual CRPC patients (median OS: 23.6 months, 95% CI: 21.3-25.9 months, log-rank P = 0.001), especially in metastasis cases (median OS: 15.7 months, 95% CI: 13.3-18.0 months) and patients with small cell carcinoma component (median OS: 9.7 months, 95% CI: 8.2–11.2 months). Prostate adenocarcinoma with diffuse NE differentiation (median OS: 18.8 months, 95% CI: 15.3–22.3 months) had poor outcome than those with usual CRPC (P = 0.027), while there was no significant change in the focal NE differentiation (median OS: 22.9 months, 95% CI: 18.1–27.7 months, P = 0.136). In the unadjusted model, an excess risk of overall death was observed in T-NEPC with PSA negative (HR = 2.86, 95% CI = 1.39–6.73). Among 476 NEPC cases in the SEER database from 2004 to 2017, we observed a higher hazard of overall death in patients aged 65 years and older (HR = 1.35, 95% CI = 1.08–1.69), patients with PSA ≤ 2.5 ng/ml (HR = 1.90, 95%CI = 1.44–2.52), patients with PSA 2.6–4.0 ng/ml (HR = 2.03, 95%CI = 1.38–2.99), stage IV tumor (HR = 2.13, 95%CI = 1.47–3.08) and other races (HR = 1.85, 95%CI = 1.17–2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.

Conclusion

T-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.
Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy
Authors: Liu Shousheng , Lai Jinfa , Lyu Ning , Xie Qiankun , Cao Huijiao , Chen Dabiao , He Meng , Zhang Bei , Zhao Ming
Published: February 2021

Background

This study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients.

Methods

We enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups.

Results

A total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36–0.91; p<0.05).

Conclusions

HBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients.

Name of the Trial Register

HAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC.

Clinical Trial Registration

https://www.clinicaltrials.gov/, identifier NCT 02436044
The Predictive Value of Tumor Volume and Its Change on Short-Term Outcome for Esophageal Squamous Cell Carcinoma Treated With Radiotherapy or Chemoradiotherapy
Authors: Liang Shuai , Li Chengming , Gao Zhenhua , Shang Dongping , Yu Jinming , Meng Xue
Published: February 2021

Objectives

To investigate the tumor volume and its change on short-term outcome in esophageal squamous cell carcinoma (ESCC) patients who underwent definitive radiotherapy or chemoradiotherapy.

Methods and Materials

All data were retrospectively collected from 418 ESCC patients who received radiotherapy or chemoradiotherapy at our institution between 2015 and 2019. Short-term outcome using the treatment response evaluation was assessed according to the RECIST 1.1. The tumor volume change rate (TVCR) was defined as follows: TVCR = {1 − [gross tumor volume (GTV) at shrinking irradiation field planning)]/(GTV at the initial treatment planning)} ×100%. Chi square test was used to compare the clinic characteristics in different TVCR groups, and the difference between initial GTV (GTVi) and shrinking GTV (GTVs) was compared using Wilcoxon’s sign rank test. Logistic regression analysis and Spearman correlation was performed.

Results

There was a significant decrease in GTVi compared to GTVs (P < 0.001). In univariate analysis, age, cT-stage, TNM stage, treatment modality, GTVi, and TVCR were associated with short-term outcome (all P< 0.05). In multivariate analysis, gender and TVCR were statistically significant (P = 0.010, <0.001) with short-term outcome, and the combined predictive value of gender and TVCR exceeded that of TVCR (AUC, 0.876 vs 0.855).

Conclusions

TVCR could serve to forecast short-term outcome of radiotherapy or chemoradiotherapy in ESCC. It was of great significance to guide the individualized treatment of ESCC.
Methyladenosine Modification in RNAs: Classification and Roles in Gastrointestinal Cancers
Authors: Li Qinghai , He Weiling , Wan Guohui
Published: February 2021

Cellular ribonucleic acids (RNAs), including messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), harbor more than 150 forms of chemical modifications, among which methylation modifications are dynamically regulated and play significant roles in RNA metabolism. Recently, dysregulation of RNA methylation modifications is found to be linked to various physiological bioprocesses and many human diseases. Gastric cancer (GC) and colorectal cancer (CRC) are two main gastrointestinal-related cancers (GIC) and the most leading causes of cancer-related death worldwide. In-depth understanding of molecular mechanisms on GIC can provide important insights in developing novel treatment strategies for GICs. In this review, we focus on the multitude of epigenetic changes of RNA methlyadenosine modifications in gene expression, and their roles in GIC tumorigenesis, progression, and drug resistance, and aim to provide the potential therapeutic regimens for GICs.
Development and Validation of a Machine Learning Prognostic Model for Hepatocellular Carcinoma Recurrence After Surgical Resection
Authors: Huang Yao , Chen Hengkai , Zeng Yongyi , Liu Zhiqiang , Ma Handong , Liu Jingfeng
Published: February 2021

Surgical resection remains primary curative treatment for patients with hepatocellular carcinoma (HCC) while over 50% of patients experience recurrence, which calls for individualized recurrence prediction and early surveillance. This study aimed to develop a machine learning prognostic model to identify high-risk patients after surgical resection and to review importance of variables in different time intervals. The patients in this study were from two centers including Eastern Hepatobiliary Surgery Hospital (EHSH) and Mengchao Hepatobiliary Hospital (MHH). The best-performed model was determined, validated, and applied to each time interval (0–1 year, 1–2 years, 2–3 years, and 3–5 years). Importance scores were used to illustrate feature importance in different time intervals. In addition, a risk heat map was constructed which visually depicted the risk of recurrence in different years. A total of 7,919 patients from two centers were included, of which 3,359 and 230 patients experienced recurrence, metastasis or died during the follow-up time in the EHSH and MHH datasets, respectively. The XGBoost model achieved the best discrimination with a c-index of 0.713 in internal validation cohort. Kaplan-Meier curves succeed to stratify external validation cohort into different risk groups (p < 0.05 in all comparisons). Tumor characteristics contribute more to HCC relapse in 0 to 1 year while HBV infection and smoking affect patients’ outcome largely in 3 to 5 years. Based on machine learning prediction model, the peak of recurrence can be predicted for individual HCC patients. Therefore, clinicians can apply it to personalize the management of postoperative survival.
Value of 11C-Choline PET/CT-Based Multi-Metabolic Parameter Combination in Distinguishing Early-Stage Prostate Cancer From Benign Prostate Diseases
Authors: Zhou Shuoming , Fu Hongliang , Liu Changming , Zhu Ziqiang , Zhang Jiabin , Weng Wubin , Kang Jian , Liu Qiang
Published: February 2021

Purpose

The most common disadvantage of 11C-choline positron emission tomography and computed tomography (PET/CT) in diagnosing early-stage prostate cancer (PCa) is its poor sensitivity. In spite of many efforts, this imaging modality lacks the ideal parameter of choline metabolism for the diagnosis of PCa, and the single metabolic parameter, that is, maximal standardized uptake value (SUVmax), based on this imaging modality is insufficient. 11C-choline PET/CT-based multi-metabolic parameter combination can help break this limitation.

Materials and Methods

Before surgery, SUVmax of choline, which is the most common metabolic parameter of 11C-choline PET/CT, mean standardized uptake value (SUVmean), prostate-to-muscle (P/M) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 74 patients with histologically proven PCa were quantified. A total of 13 patients with focal chronic prostatitis without severe features and 30 patients with benign prostate hyperplasia were used for comparison. Univariable and multivariable analyses were performed to compare the patient characteristics and metabolic parameters of 11C-choline PET/CT. The performance of single parameters and the combination of parameters were assessed by using logistic regression models.

Results

The comparable c-statistics, which mean the area under the ROC curve in the logistic regression model, of SUVmax, SUVmean, and P/M ratio are 0.657, 0.667, and 0.672, respectively. The c-statistic significantly rose to 0.793 when SUVmax and SUVmean were combined with the P/M ratio. This parameter combination performed the best for PCa cases with all biochemical recurrence risks and for PCa patients grouped by different risk. The greatest improvement over a single parameter, such as P/M ratio, was noted in the group of low-risk PCa, with values of 0.535 to 0.772 for the three-parameter combination. And in the histopathological level, the Ki-67 index is positively correlated with the P/M ratio (r=0.491, p=0.002).

Conclusion

P/M ratio is a more ideal parameter than SUVmax as a single parameter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of 11C-choline PET/CT.
Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients
Authors: Yu Hao , Lam Ka-On , Wu Huanmei , Green Michael , Wang Weili , Jin Jian-Yue , Hu Chen , Jolly Shruti , Wang Yang , Kong Feng-Ming Spring
Published: February 2021

Background

Radiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.

Methods

This is a secondary analysis of prospective studies from two academic cancer centers. The primary endpoint was grade≥2 (RILF2), classified according to a system consistent with the consensus recommendation of an expert panel of the AAPM task for normal tissue toxicity. Eligible patients must have at least 6 months’ follow-up after radiotherapy commencement. Baseline levels of 30 cytokines, dosimetric, and clinical characteristics were analyzed. Support vector machine (SVM) algorithm was applied for model development. Data from one center was used for model training and development; and data of another center was applied as an independent external validation.

Results

There were 57 and 37 eligible patients in training and validation datasets, with 14 and 16.2% RILF2, respectively. Of the 30 plasma cytokines evaluated, SVM identified baseline circulating CCL4 as the most significant cytokine associated with RILF2 risk in both datasets (P = 0.003 and 0.07, for training and test sets, respectively). An SVM classifier predictive of RILF2 was generated in Cohort 1 with CCL4, mean lung dose (MLD) and chemotherapy as key model features. This classifier was validated in Cohort 2 with accuracy of 0.757 and area under the curve (AUC) of 0.855.

Conclusions

Using machine learning, this study constructed and validated a weighted-SVM classifier incorporating circulating CCL4 levels with significant dosimetric and clinical parameters which predicts RILF2 risk with a reasonable accuracy. Further study with larger sample size is needed to validate the role of CCL4, and this SVM classifier in RILF2.
Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux
Authors: Saha Jhuma , Kim Jong Hyuk , Amaya Clarissa N. , Witcher Caleb , Khammanivong Ali , Korpela Derek M. , Brown David R. , Taylor Josephine , Bryan Brad A. , Dickerson Erin B.
Published: February 2021

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and clinical data have corroborated the increased therapeutic potential of propranolol with chemotherapy in angiosarcoma patients. Because propranolol is also a weak base and accumulates in lysosomes, we sought to determine whether propranolol enhanced doxorubicin cytotoxicity via antagonism of β-ARs or by preventing the lysosomal accumulation of doxorubicin. β-AR-like immunoreactivities were confirmed in primary tumor tissues and cell lines; receptor function was verified by monitoring downstream signaling pathways of β-ARs in response to receptor agonists and antagonists. Mechanistically, propranolol increased cytoplasmic doxorubicin concentrations in sarcoma cells by decreasing the lysosomal accumulation and cellular efflux of this chemotherapeutic agent. Equivalent concentrations of the receptor-active S-(−) and -inactive R-(+) enantiomers of propranolol produced similar effects, supporting a β-AR-independent mechanism. Long-term exposure of hemangiosarcoma cells to propranolol expanded both lysosomal size and number, yet cells remained sensitive to doxorubicin in the presence of propranolol. In contrast, removal of propranolol increased cellular resistance to doxorubicin, underscoring lysosomal doxorubicin sequestration as a key mechanism of resistance. Our results support the repurposing of the R-(+) enantiomer of propranolol with weak base chemotherapeutics to increase cytotoxicity and reduce the development of drug-resistant cell populations without the cardiovascular and other side effects associated with antagonism of β-ARs.
Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression
Authors: Cerda-Troncoso Cristóbal , Varas-Godoy Manuel , Burgos Patricia V.
Published: February 2021

Cancer progression involves a variety of pro-tumorigenic biological processes including cell proliferation, migration, invasion, and survival. A cellular pathway implicated in these pro-tumorigenic processes is autophagy, a catabolic route used for recycling of cytoplasmic components to generate macromolecular building blocks and energy, under stress conditions, to remove damaged cellular constituents to adapt to changing nutrient conditions and to maintain cellular homeostasis. During autophagy, cells form a double-membrane sequestering a compartment termed the phagophore, which matures into an autophagosome. Following fusion with the lysosome, the cargo is degraded inside the autolysosomes and the resulting macromolecules released back into the cytosol for reuse. Cancer cells use this recycling system during cancer progression, however the key autophagy players involved in this disease is unclear. Accumulative evidences show that autophagy receptors, crucial players for selective autophagy, are overexpressed during cancer progression, yet the mechanisms whereby pro-tumorigenic biological processes are modulated by these receptors remains unknown. In this review, we summarized the most important findings related with the pro-tumorigenic role of autophagy receptors p62/SQSTM1, NBR1, NDP52, and OPTN in cancer progression. In addition, we showed the most relevant cargos degraded by these receptors that have been shown to function as critical regulators of pro-tumorigenic processes. Finally, we discussed the role of autophagy receptors in the context of the cellular pathways implicated in this disease, such as growth factors signaling, oxidative stress response and apoptosis. In summary, we highlight that autophagy receptors should be considered important players of cancer progression, which could offer a niche for the development of novel diagnosis and cancer treatment strategies.
Role of 1,25-Dihydroxyvitamin D3 on Osteogenic Differentiation and Mineralization of Chicken Mesenchymal Stem Cells
Authors: Chen Chongxiao , Adhikari Roshan , White Dima Lynn , Kim Woo Kyun
Published: February 2021

1,25-dihydroxyvitamin D3 (1,25OHD) has been suggested to play an important role in osteogenic differentiation and mineralization. However, limited data have been reported in avian species. In the present study, the direct role of 1,25OHD on osteogenic differentiation and mineralization in chicken mesenchymal stem cells (cMSCs) derived from day-old broiler bones was investigated. cMSCs were treated with control media (C), osteogenesis media (OM), OM with 1, 5, 10, and 50 nM 1,25OHD, respectively. The messenger RNA (mRNA) samples were obtained at 24 and 48 h and 3 and 7 days to examine mRNA expression of key osteogenic genes [runt related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen type I alpha 2 chain (COL1A2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and alkaline phosphatase (ALP)]. Cells were stained at 7, 14, and 21 days using Von Kossa (mineralization), Alizarin Red (AR; mineralization), and Alkaline Phosphatase (early marker) staining methods. From the mRNA expression results, we found a time-dependent manner of 1,25OHD on osteoblast differentiation and mineralization. In general, it showed an inhibitory effect on differentiation and mineralization during the early stage (24 and 48 h), and a stimulatory effect during the late cell stage (3 and 7 days). The staining showed 1,25OHD had an inhibitory effect on ALP enzyme activities and mineralization in a dosage-dependent manner up to 14 days. However, at 21 days, there was no difference between the treatments. This study provides a novel understanding of the effects of 1,25OHD on osteogenic differentiation and mineralization of cMSCs depending on cell stage and maturity.
A Review of Strawberry Photobiology and Fruit Flavonoids in Controlled Environments
Authors: Warner Rachael , Wu Bo-Sen , MacPherson Sarah , Lefsrud Mark
Published: February 2021

Rapid technology development in controlled environment (CE) plant production has been applied to a large variety of plants. In recent years, strawberries have become a popular fruit for CE production because of their high economic and nutritional values. With the widespread use of light-emitting diode (LED) technology in the produce industry, growers can manipulate strawberry growth and development by providing specific light spectra. Manipulating light intensity and spectral composition can modify strawberry secondary metabolism and highly impact fruit quality and antioxidant properties. While the impact of visible light on secondary metabolite profiles for other greenhouse crops is well documented, more insight into the impact of different light spectra, from UV radiation to the visible light spectrum, on strawberry plants is required. This will allow growers to maximize yield and rapidly adapt to consumer preferences. In this review, a compilation of studies investigating the effect of light properties on strawberry fruit flavonoids is provided, and a comparative analysis of how light spectra influences strawberry’s photobiology and secondary metabolism is presented. The effects of pre-harvest and post-harvest light treatments with UV radiation and visible light are considered. Future studies and implications for LED lighting configurations in strawberry fruit production for researchers and growers are discussed.
Effect of Grafting on Viral Resistance of Non-transgenic Plum Scion Combined With Transgenic PPV-Resistant Rootstock
Authors: Sidorova Tatiana , Miroshnichenko Dmitry , Kirov Ilya , Pushin Alexander , Dolgov Sergey
Published: February 2021

In stone fruit trees, resistance to Plum pox virus (PPV) can be achieved through the specific degradation of viral RNA by the mechanism of RNA interference (RNAi). Transgenic virus-resistant plants, however, raise serious biosafety concerns due to the insertion and expression of hairpin constructs that usually contain various selective foreign genes. Since a mature stone tree represents a combination of scion and rootstock, grafting commercial varieties onto transgenic virus-tolerant rootstocks is a possible approach to mitigate biosafety problems. The present study was aimed at answering the following question: To what extent are molecular RNAi silencing signals transmitted across graft junctions in transgrafted plum trees and how much does it affect PPV resistance in genetically modified (GM)/non-transgenic (NT) counterparts? Two combinations, NT:GM and GM:NT (scion:rootstock), were studied, with an emphasis on the first transgrafting scenario. Viral inoculation was carried out on either the scion or the rootstock. The interspecific rootstock “Elita” [(Prunus pumila L. × P. salicina Lindl.) × (P. cerasifera Ehrh.)] was combined with cv. “Startovaya” (Prunus domestica L.) as a scion. Transgenic plum lines of both cultivars were transformed with a PPV-coat protein (CP)-derived intron-separate hairpin-RNA construct and displayed substantial viral resistance. High-throughput sequence data of small RNA (sRNA) pools indicated that the accumulation of construct-specific small interfering RNA (siRNA) in transgenic plum rootstock reached over 2%. The elevated siRNA level enabled the resistance to PPV and blocked the movement of the virus through the GM tissues into the NT partner when the transgenic tissues were inoculated. At the same time, the mobile siRNA signal was not moved from the GM rootstock to the target NT tissue to a level sufficient to trigger silencing of PPV transcripts and provide reliable viral resistance. The lack of mobility of transgene-derived siRNA molecules was accompanied by the transfer of various endogenous rootstock-specific sRNAs into the NT scion, indicating the exceptional transitivity failure of the studied RNAi signal. The results presented here indicate that transgrafting in woody fruit trees remains an unpredictable practice and needs further in-depth examination to deliver molecular silencing signals.
Potential Effects of Microplastic on Arbuscular Mycorrhizal Fungi
Authors: Leifheit Eva F. , Lehmann Anika , Rillig Matthias C.
Published: February 2021

Microplastics (MPs) are ubiquitously found in terrestrial ecosystems and are increasingly recognized as a factor of global change (GCF). Current research shows that MP can alter plant growth, soil inherent properties, and the composition and activity of microbial communities. However, knowledge about how microplastic affects arbuscular mycorrhizal fungi (AMF) is scarce. For plants it has been shown that microplastic can both increase and decrease the aboveground biomass and reduce the root diameter, which could indirectly cause a change in AMF abundance and activity. One of the main direct effects of microplastic is the reduction of the soil bulk density, which translates to an altered soil pore structure and water transport. Moreover, especially fibers can have considerable impacts on soil structure, namely the size distribution and stability of soil aggregates. Therefore, microplastic alters a number of soil parameters that determine habitat space and conditions for AMF. We expect that this will influence functions mediated by AMF, such as soil aggregation, water and nutrient transport. We discuss how the impacts of microplastic on AMF could alter how plants deal with other GCFs in the context of sustainable food production. The co-occurrence of several GCFs, e.g., elevated temperature, drought, pesticides, and microplastic could modify the impact of microplastic on AMF. Furthermore, the ubiquitous presence of microplastic also relates to earth system processes, e.g., net primary production (NPP), carbon and nitrogen cycling, which involve AMF as key soil organisms. For future research, we outline which experiments should be prioritized.
Perfectionism and Burnout During the COVID-19 Crisis: A Two-Wave Cross-Lagged Study
Authors: Spagnoli Paola , Buono Carmela , Kovalchuk Liliya Scafuri , Cordasco Gennaro , Esposito Anna
Published: February 2021

The current study aims at examining the relationship between the perfectionism two-factor model (i.e., concerns and strivings) and burnout dimensions measured by using the BAT (Burnout Assessment Tool) through a longitudinal study. A two-wave cross-lagged study was conducted using path analysis in SEM (Structural Equation Modeling) of 191 workers. Results confirmed the predictive role of perfectionistic concerns on the burnout dimensions, whereas perfectionistic strivings were not significantly related, suggesting that perfectionism should be monitored by employers and clinicians to prevent employee burnout. Limitations and future research directions are envisaged.
Emotion Regulation, Physical Diseases, and Borderline Personality Disorders: Conceptual and Clinical Considerations
Authors: Cavicchioli Marco , Barone Lavinia , Fiore Donatella , Marchini Monica , Pazzano Paola , Ramella Pietro , Riccardi Ilaria , Sanza Michele , Maffei Cesare
Published: February 2021

This perspective paper aims at discussing theoretical principles that could explain how emotion regulation and physical diseases mutually influence each other in the context of borderline personality disorder (BPD). Furthermore, this paper discusses the clinical implications of the functional relationships between emotion regulation, BPD and medical conditions considering dialectical behavior therapy (DBT) as a well-validated therapeutic intervention, which encompasses these issues. The inflexible use of maladaptive emotion regulation strategies (e.g., suppression, experiential avoidance, and rumination) might directly increase the probability of developing physical diseases through a physiological pathway, or indirectly through a behavioral pathway. Some metabolic and chronic medical conditions could significantly impact emotional functioning through biological alterations involved in emotion regulation. Several empirical studies have shown high co-occurrence rates between BPD and several chronic physical diseases, especially ones linked to emotion-based maladaptive behaviors. DBT addresses physical diseases reported by individuals with BPD reducing problematic behaviors functionally associated to emotion dysregulation and identifying physical health as a goal forBuilding a Life Worth Living.
A Recurrent Neural Network for Attenuating Non-cognitive Components of Pupil Dynamics
Authors: Koorathota Sharath , Thakoor Kaveri , Hong Linbi , Mao Yaoli , Adelman Patrick , Sajda Paul
Published: February 2021

There is increasing interest in how the pupil dynamics of the eye reflect underlying cognitive processes and brain states. Problematic, however, is that pupil changes can be due to non-cognitive factors, for example luminance changes in the environment, accommodation and movement. In this paper we consider how by modeling the response of the pupil in real-world environments we can capture the non-cognitive related changes and remove these to extract a residual signal which is a better index of cognition and performance. Specifically, we utilize sequence measures such as fixation position, duration, saccades, and blink-related information as inputs to a deep recurrent neural network (RNN) model for predicting subsequent pupil diameter. We build and evaluate the model for a task where subjects are watching educational videos and subsequently asked questions based on the content. Compared to commonly-used models for this task, the RNN had the lowest errors rates in predicting subsequent pupil dilation given sequence data. Most importantly was how the model output related to subjects' cognitive performance as assessed by a post-viewing test. Consistent with our hypothesis that the model captures non-cognitive pupil dynamics, we found (1) the model's root-mean square error was less for lower performing subjects than for those having better performance on the post-viewing test, (2) the residuals of the RNN (LSTM) model had the highest correlation with subject post-viewing test scores and (3) the residuals had the highest discriminability (assessed via area under the ROC curve, AUC) for classifying high and low test performers, compared to the true pupil size or the RNN model predictions. This suggests that deep learning sequence models may be good for separating components of pupil responses that are linked to luminance and accommodation from those that are linked to cognition and arousal.
Motivation-Enhancing Psychotherapy for Inpatients With Anorexia Nervosa (MANNA): A Randomized Controlled Pilot Study
Authors: Ziser Katrin , Rheindorf Nadine , Keifenheim Katharina , Becker Sandra , Resmark Gaby , Giel Katrin E. , Skoda Eva-Maria , Teufel Martin , Zipfel Stephan , Junne Florian
Published: February 2021

Patients with anorexia nervosa (AN) are frequently characterized by an unstable readiness to change and high ambivalence toward treatment. Enhancing readiness to behavioral change therefore plays an essential role for adherence to treatment especially for severely ill patients treated in inpatient settings. Therefore, a novel 10 week program for the individual psychotherapy sessions was designed using elements from motivational interviewing to be applied within the multidisciplinary inpatient treatment for patients with AN. In a randomized controlled pilot trial, N = 22 patients with AN received either the new intervention or treatment as usual in one of two recruiting university hospitals. Readiness to change, eating disorder pathology, therapeutic alliance as well as acceptance and feasibility of the new intervention were measured from patients and therapists in week 1, 5, and 10 of inpatient treatment. Results confirm acceptance and feasibility of the MANNA intervention as evaluated by patients as well as therapists. Patients receiving the new intervention completed their inpatient treatment significantly more often on regular terms than patients receiving treatment as usual. No differences between the groups could be found concerning therapeutic alliance during and at the end of treatment and readiness to change. Absolute numbers of BMI increase indicate a larger increase in the intervention group albeit not significant in this pilot study sample. Limitations of the study such as the small sample size as well as possible adaptions and advancements of the intervention that need to be examined in a larger clinical trial of efficacy are discussed. This phase II study is registered with the German Clinical Trials Register (DRKS) under the trial number DRKS00015639.
Neighborhood Walkability as a Predictor of Incident Hypertension in a National Cohort Study
Authors: Jones Alana C. , Chaudhary Ninad S. , Patki Amit , Howard Virginia J. , Howard George , Colabianchi Natalie , Judd Suzanne E. , Irvin Marguerite R.
Published: February 2021

The built environment (BE) has been associated with health outcomes in prior studies. Few have investigated the association between neighborhood walkability, a component of BE, and hypertension. We examined the association between neighborhood walkability and incident hypertension in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Walkability was measured using Street Smart Walk Score based on participants' residential information at baseline (collected between 2003 and 2007) and was dichotomized as more (score ≥70) and less (score <70) walkable. The primary outcome was incident hypertension defined at the second visit (collected between 2013 and 2017). We derived risk ratios (RR) using modified Poisson regression adjusting for age, race, sex, geographic region, income, alcohol use, smoking, exercise, BMI, dyslipidemia, diabetes, and baseline blood pressure (BP). We further stratified by race, age, and geographic region. Among 6,894 participants, 6.8% lived in more walkable areas and 38% (N = 2,515) had incident hypertension. In adjusted analysis, neighborhood walkability (Walk Score ≥70) was associated with a lower risk of incident hypertension (RR [95%CI]: 0.85[0.74, 0.98], P = 0.02), with similar but non-significant trends in race and age strata. In secondary analyses, living in a more walkable neighborhood was protective against being hypertensive at both study visits (OR [95%CI]: 0.70[0.59, 0.84], P < 0.001). Neighborhood walkability was associated with incident hypertension in the REGARDS cohort, with the relationship consistent across race groups. The results of this study suggest increased neighborhood walkability may be protective for high blood pressure in black and white adults from the general US population.
A Central Clearing Clinic to Provide Mental Health Services for Refugees in Germany
Authors: Bajbouj Malek , Panneck Patricia , Winter Sibylle-Maria , Ajami Carlos , Alabdullah Jihad , Benedikt Burger Max , Haberlandner Anja , Hahn Eric , Heinz Andreas , Heuser Isabella , Hoyer Armin , Kluge Ulrike , Aichberger Marion , Repantis Dimitris , Schreiter Stefanie , Seybold Joachim , Sutej Igor
Published: February 2021

Objective: To determine migration related distress pattern in refugees and feasibility of a de novo established, central low-threshold outpatient clinic serving more than 80,000 newly arrived refugees in the metropole of Berlin.

Methods: In an observational cohort study the relative prevalence of major psychiatric disorders by age, place of living within berlin, language and region of origin were assessed in a refugee cohort from 63 nationalities speaking 36 languages.

Findings: Within 18 months, a total of 3,096 cases with a mean age of 29.7 years (11.7) have been referred from all 12 districts and 165 of 182 subdistricts of Berlin to the CCC. 33.7% of the patients were female. The three most frequent diagnoses were unipolar depression (40.4%), posttraumatic stress disorder (24.3%), and adjustment disorder (19.6%).

Conclusion: The present data gives insight into the distribution of mental disorders in a large sample of refugees and provides evidence that a CCC is an effective service to quickly and broadly provide psychiatric consultations and thus to overcome classical barriers refugees usually experience in the host communities. In Berlin, Germany, and Europe treatment resources for this population should focus on stress and trauma related disorders.
Fuel Tankering: Economic Benefits and Environmental Impact for Flights Up to 1500 NM (Full Tankering) and 2500 NM (Partial Tankering)
Authors: Tabernier Laurent , Fernández Esther Calvo , Tautz Andreas , Deransy Robin , Martin Peter
Published: February 2021

The majority of emissions from aviation come from the combustion of the fuel required to operate each flight. Keeping the fuel consumption required for a safe flight to the absolute minimum is therefore the simplest and most effective way to ensure that emissions from that flight are kept to a minimum. In practice, however, the fuel load is determined by each aircraft operator on the basis of a number of criteria maximizing first cost efficiency, rather than fuel savings. In this context, tankering is the practice of carrying more fuel than is necessary for the safe execution of the flight to avoid or minimize refueling at the destination airport. It offers an economic advantage when there is a significant difference in fuel prices between the departure and arrival airports, but considerably increases the amount of emissions produced, because the more fuel an aircraft carries, the heavier it is, and carrying this extra weight increases its fuel consumption. This paper presents the steps followed by EUROCONTROL in conducting a first study to estimate the number of times this practice would offer an economic benefit and the amount of extra CO2 emissions that would result. This study, limited to flights up to 1500 and 2500 NM, corresponding mainly to short and medium-haul flights, estimates that, in 2018, 21% of ECAC (In this paper, ECAC refers to the geographical region defined by the 44 member states that signed the European Civil Aviation Conference) flights would perform fuel tankering beneficially. This would represent a net saving of 265 M€ per year for the airlines, but the burning of 286,000 tonnes of additional fuel (equivalent to 0.54% of ECAC jet fuel used), or 901,000 tonnes of CO2 per year. At a time when aviation is challenged for its contribution to climate change, the use of fuel tankering for economic reasons is therefore highly questionable.
Updated Characterization of Races of Plasmopara halstedii and Entomopathogenic Fungi as Endophytes of Sunflower Plants in Axenic Culture
Authors: Miranda-Fuentes Pedro , García-Carneros Ana B. , Molinero-Ruiz Leire
Published: February 2021

The management of downy mildew (Plasmopara halstedii) in sunflower, is heavily dependent on genetic resistance, whilst entomopathogenic fungi (EF) can reduce other sunflower diseases. In this work, we characterized P. halstedii from Spain and other countries collected in the past few years. Twenty-three races were identified (the most frequent in Spain being 310, 304, 705 and 715), with an increasing proportion of highly virulent races. Five isolates from countries other than Spain overcame the resistance in RHA-340. In addition, we assessed the efficacy of five EF against downy mildew and their effects on sunflower growth in axenic conditions. None of the entomopathogens reduced disease severity, nor did they have any effect on plant growth when applied together with P. halstedii. In contrast, three EF reduced some of the plant growth variables in the absence of the pathogen. Microbiological and molecular diagnostics suggest that the axenic system and the short experimental time used in this study did not favor the successful establishment of EF in the plants or their potential biocontrol effect. Our results show a shift in P. halstedii racial patterns and suggest that soil as a growth substrate and long infection times are needed for EF effectiveness against downy mildew.
Short-Term Effect of Biochar on Microbial Biomass, Respiration and Enzymatic Activities in Wastewater Irrigated Soils in Urban Agroecosystems of the West African Savannah
Authors: Asirifi Isaac , Werner Steffen , Heinze Stefanie , Saba Courage K. S. , Lawson Innocent Y. D. , Marschner Bernd
Published: February 2021

Irrigated urban agriculture (UA) supports the economy and health of urban inhabitants in low-income countries. This system is often characterized by high nutrient inputs and mostly utilizes wastewater for irrigation. Biochar has been proposed to increase crop yields and improve soil properties. In this study, we assessed the transient effect of rice husk biochar (20 t ha−1) and/or fertilizer (NPK: 15-15-15) on microbial respiration, microbial biomass carbon and enzyme activities of irrigated (wastewater and tap water) soil from an UA field experiment in the Guinea savannah zones of Ghana. Our results showed an increase by up to 123% in soil organic carbon (SOC) after a year of biochar application, while hot water extractable carbon (HWEC) was increased by only 11 to 26% and microbial biomass carbon (MBC) by 34%. Basal respiration was significantly increased in mineral fertilized soil by up to 46% but decreased by 12–45% under wastewater irrigation. Overall, the metabolic quotient (qCO2) indicated less stress for the microbial community and increased carbon use efficiency with biochar application and wastewater irrigation. Total enzymes activity was increased under wastewater irrigation and biochar treated soils exhibit a more diverse composition of C-cycling enzymes and a higher activity of aminopeptidases. Biochar and wastewater showed positive effects on biological soil properties and contributed to soil fertility. Our results suggest beneficial effects of biochar on non-biochar SOC stocks in the long term.