bluuebunny/crossref_metadata_2025 huggingface dataset:
An Observational Study of Trifluridine/Tipiracil-Containing Regimen Versus Regorafenib-Containing Regimen in Patients With Metastatic Colorectal Cancer
Authors: Hsieh Meng-Che , Rau Kun-Ming , Lin Shung-Eing , Liu Kuang-Wen , Chiu Chong-Chi , Chen Chih-I , Song Ling-Chiao , Chen Hsin-Pao
Published: May 2022

Background

There are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC.

Material and method

Patients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR).

Results

A total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months (P = 0.006) and 9.2 versus 6.8 months (P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% (P < 0.001) and 72% versus 43% (P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival.

Conclusions

Our results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results.
Resistance Mechanisms of the Metastatic Tumor Microenvironment to Anti-Angiogenic Therapy
Authors: Schiffmann Lars M. , Bruns Christiane J. , Schmidt Thomas
Published: May 2022

Angiogenesis describes the formation of blood vessels from an existing vascular network. Anti-angiogenic drugs that target tumor blood vessels have become standard of care in many cancer entities. Though very promising results in preclinical evaluation, anti-angiogenic treatments fell short of expectations in clinical trials. Patients develop resistance over time or are primarily refractory to anti-angiogenic therapies similar to conventional chemotherapy. To further improve efficacy and outcome to these therapies, a deeper understanding of mechanisms that mediate resistance to anti-angiogenic therapies is needed. The field has done tremendous efforts to gain knowledge about how tumors engage tumor cell and microenvironmental mechanisms to do so. This review highlights the current state of knowledge with special focus on the metastatic tumor site and potential therapeutic relevance of this understanding from a translational and clinical perspective.
Neurodevelopmental Outcomes of Extremely Low Birth Weight Survivors in Johannesburg, South Africa
Authors: Ramdin Tanusha D. , Saggers Robin T. , Bandini Rossella M. , Magadla Yoliswa , Mphaphuli Aripfani V. , Ballot Daynia E.
Published: May 2022

Background:

Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes.

Objectives

To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa.

Methods

This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months.

Results

There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2–877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1–27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2–18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1–101.7), language 89.9 (95% CI 87.3–92.5) and motor 97.6 (95% CI 94.5–100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be “at risk” for neurodevelopmental delay.

Conclusion

Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.
Synergistic Inhibition of Pro-Inflammatory Pathways by Ginger and Turmeric Extracts in RAW 264.7 Cells
Authors: Zhou Xian , Münch Gerald , Wohlmuth Hans , Afzal Sualiha , Kao Ming-Hui (Tim) , Al-Khazaleh Ahmad , Low Mitchell , Leach David , Li Chun Guang
Published: May 2022

Synergy plays a prominent role in herbal medicines to increase potency and widen the therapeutic windows. The mechanism of synergy in herbal medicines is often associated with multi-targeted behavior and complex signaling pathways which are challenging to elucidate. This study aims to investigate the synergistic mechanism of a combination (GT) of ginger (G) and turmeric (T) extracts by exploring the modulatory activity in lipopolysaccharides (LPS)-induced inflammatory pathways and key molecular targets. A Bioplex ProTM mouse cytokine 23-plex assay was utilized to assess the broad anti-cytokine activity of GT in LPS and interferon (IFN)-ɣ (both at 50 ng/mL)-activated RAW 264.7 cells. The inhibitory effects of individual and combined G and T on major proinflammatory mediators including nitric oxide (NO), tumor necrosis factor (TNF) and interleukin (IL)-6 were tested using Griess reagents and ELISA assays, respectively. Immunofluorescent staining and Western blot were used to investigate the modulatory effect of GT on key proteins in the LPS/TLR4 signaling transduction. The regulation of murine microRNA miR-155-5p was tested using real-time PCR. The IC50 value and combination index (CI) values were used to demonstrate potency and synergistic interaction, respectively. GT synergistically attenuated a range of pro-inflammatory mediators including inducible NO, major cytokines (TNF and IL-6) and secondary inflammatory cytokines (GM-CSF and MCP-1). GT significantly inhibited LPS-induced NF-kB p65 translocation, the activation of TLR4, TRAF6, and phosphorylation of JNK and c-JUN. Moreover, the suppressive effect of GT on each of the protein targets in this axis was stronger than that of the individual components. Real-time PCR analysis showed that GT suppressed miR-155-5p to a greater extent than G or T alone in LPS-stimulated cells. Our study demonstrates the synergistic mechanism of GT in downregulating LPS-induced proinflammatory pathways at the miRNA and protein levels. Our results establish a scientific basis for the combined application of G and T as an advanced therapeutic candidate in inflammatory diseases with broad and synergistic anti-inflammatory activity and multi-targeted mechanisms.
The Combination of a Novel GLUT1 Inhibitor and Cisplatin Synergistically Inhibits Breast Cancer Cell Growth By Enhancing the DNA Damaging Effect and Modulating the Akt/mTOR and MAPK Signaling Pathways
Authors: Weng Hao-Cheng , Sung Chieh-Ju , Hsu Jui-Ling , Leu Wohn-Jenn , Guh Jih-Hwa , Kung Fan-Lu , Hsu Lih-Ching
Published: May 2022

Breast cancer is the most prevalent cancer and the second leading cause of cancer death in women. Cisplatin is a commonly used chemotherapeutic drug for breast cancer treatment. Owing to serious side effects, the combination of cisplatin with other drugs is an effective strategy to simultaneously reduce side effects and increase the anticancer efficacy. GLUT1 is an emerging target for cancer treatment since cancer cells usually consume more glucose, a phenomenon called the Warburg effect. In this study, we found that the combination of cisplatin and a novel GLUT1 inhibitor #43 identified from our previous high-throughput screening exerted a synergistic anticancer effect in MCF-7 and MDA-MB-231 breast cancer cells. Mechanism studies in MCF-7 cells revealed that combination of cisplatin and #43 significantly induced apoptosis, intracellular reactive oxygen species, and loss of mitochondrial membrane potential. Furthermore, #43 enhanced the DNA damaging effect of cisplatin. Akt/mTOR downstream signaling and the ERK signaling pathway usually involved in cell growth and survival were inhibited by the combination treatment. On the other hand, phosphorylation of p38 and JNK, which may be associated with apoptosis, was induced by the combination treatment. Altogether, our data indicate that oxidative stress, DNA damage, the Akt/mTOR and MAPK signaling pathways, and apoptosis may be involved in the synergism of cisplatin and #43 in breast cancer cells.
NOX4 Mediates Epithelial Cell Death in Hyperoxic Acute Lung Injury Through Mitochondrial Reactive Oxygen Species
Authors: Harijith Anantha , Basa Prathima , Ha Alison , Thomas Jaya , Jafri Anjum , Fu Panfeng , MacFarlane Peter M. , Raffay Thomas M. , Natarajan Viswanathan , Sudhadevi Tara
Published: May 2022

Management of acute respiratory distress involves O2 supplementation, which is lifesaving, but causes severe hyperoxic acute lung injury (HALI). NADPH oxidase (NOX) could be a major source of reactive oxygen species (ROS) in hyperoxia (HO). Epithelial cell death is a crucial step in the development of many lung diseases. Alveolar type II (AT2) cells are the metabolically active epithelial cells of alveoli that serve as a source of AT1 cells following lung injury. The aim of this study was to determine the possible role of AT2 epithelial cell NOX4 in epithelial cell death from HALI. Wild type (WT), Nox4fl/fl (control), and Nox4−/−Spc-Cre mice were exposed to room air (NO) or 95% O2 (HO) to investigate the structural and functional changes in the lung. C57BL/6J WT animals subjected to HO showed increased expression of lung NOX4 compared to NO. Significant HALI, increased bronchoalveolar lavage cell counts, increased protein levels, elevated proinflammatory cytokines and increased AT2 cell death seen in hyperoxic Nox4fl/fl control mice were attenuated in HO-exposed Nox4−/−Spc-Cre mice. HO-induced expression of NOX4 in MLE cells resulted in increased mitochondrial (mt) superoxide production and cell apoptosis, which was reduced in NOX4 siRNA silenced cells. This study demonstrates a novel role for epithelial cell NOX4 in accelerating lung epithelial cell apoptosis from HALI. Deletion of the Nox4 gene in AT2 cells or silencing NOX4 in lung epithelial cells protected the lungs from severe HALI with reduced apoptosis and decreased mt ROS production in HO. These results suggest NOX4 as a potential target for the treatment of HALI.
Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function
Authors: Li Lanzhou , Zhao Chenfei , Kong Fange , Li Yi-Cong , Wang Chunxia , Chen Shanshan , Tan Hor-Yue , Liu Yang , Wang Di
Published: May 2022

Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e−NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of ApcMin/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of ApcMin/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-β (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of ApcMin/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.
Genotyping-by-Sequencing and QTL Mapping of Biomass Yield in Two Switchgrass F1 Populations (Lowland x Coastal and Coastal x Upland)
Authors: Razar Rasyidah M. , Qi Peng , Devos Katrien M. , Missaoui Ali M.
Published: May 2022

The prevalence of genetic diversity in switchgrass germplasm can be exploited to capture favorable alleles that increase its range of adaptation and biomass yield. The objectives of the study were to analyze the extent of polymorphism and patterns of segregation distortion in two F1 populations and use the linkage maps to locate QTL for biomass yield. We conducted genotyping-by-sequencing on two populations derived from crosses between the allotetraploid lowland genotype AP13 (a selection from “Alamo”) and coastal genotype B6 (a selection from PI 422001) with 285 progeny (AB population) and between B6 and the allotetraploid upland VS16 (a selection from “Summer”) with 227 progeny (BV population). As predictable from the Euclidean distance between the parents, a higher number of raw variants was discovered in the coastal × upland BV cross (6 M) compared to the lowland × coastal AB cross (2.5 M). The final number of mapped markers was 3,107 on the BV map and 2,410 on the AB map. More segregation distortion of alleles was seen in the AB population, with 75% distorted loci compared to 11% distorted loci in the BV population. The distortion in the AB population was seen across all chromosomes in both the AP13 and B6 maps and likely resulted from zygotic or post-zygotic selection for increased levels of heterozygosity. Our results suggest lower genetic compatibility between the lowland AP13 and the coastal B6 ecotype than between B6 and the upland ecotype VS16. Four biomass QTLs were mapped in the AB population (LG 2N, 6K, 6N, and 8N) and six QTLs in the BV population [LG 1N (2), 8N (2), 9K, and 9N]. The QTL, with the largest and most consistent effect across years, explaining between 8.4 and 11.5% of the variation, was identified on 6N in the AP13 map. The cumulative effect of all the QTLs explained a sizeable portion of the phenotypic variation in both AB and BV populations and the markers associated with them may potentially be used for the marker-assisted improvement of biomass yield. Since switchgrass improvement is based on increasing favorable allele frequencies through recurrent selection, the transmission bias within individuals and loci needs to be considered as this may affect the genetic gain if the favorable alleles are distorted.
Impacts of Fertilization Optimization on Soil Nitrogen Cycling and Wheat Nitrogen Utilization Under Water-Saving Irrigation
Authors: Zhang Zhen , Yu Zhenwen , Zhang Yongli , Shi Yu
Published: May 2022

Scholars have proposed the practice of split nitrogen fertilizer application (SNFA), which has proven to be an effective approach for enhancing nitrogen use efficiency. However, the combined effects of SNFA on wheat plant nitrogen use efficiency, ammonia (NH3) emission flux, as well as the rates of nitrification and denitrification in different ecosystems remain unclear. Meanwhile, few studies have sought to understand the effects of the split nitrogen fertilizer method under water-saving irrigation technology conditions on nitrogen loss. The current study assessed soil NH3 volatilization, nitrification, and denitrification intensities, as well as the abundance of nitrogen cycle-related functional genes following application of different treatments. Specifically, we applied a nitrogen rate of 240 kg⋅ha–1, and the following fertilizer ratios of the percent base to that of topdressing under water-saving irrigation: N1 (basal/dressing, 100/0%), N2 (basal/dressing, 70/30%), N3 (basal/dressing, 50/50%), N4 (basal/dressing, 30/70%), and N5 (basal/dressing, 0/100%). N3 treatment significantly reduced NH3 volatilization, nitrification, and denitrification intensities, primarily owing to the reduced reaction substrate concentration (NO3– and NH4+) and abundance of functional genes involved in the nitrogen cycle (amoA-AOB, nirK, and nirS) within the wheat-land soil. 15N tracer studies further demonstrated that N3 treatments significantly increased the grain nitrogen accumulation by 9.50–28.27% compared with that under other treatments. This increase was primarily due to an increase in the amount of nitrogen absorbed by wheat from soil and fertilizers, which was caused by an enhancement in total nitrogen uptake (7.2–21.81%). Overall, N3 treatment (basal/dressing, 50/50%) was found to effectively reduce nitrogen loss through NH3 volatilization, nitrification and denitrification while improving nitrogen uptake by wheat. Thus, its application will serve to further maximize the yield and provide a fertilization practice that will facilitate cleaner wheat production in the North China Plain.
Water-Soluble Trichogin GA IV-Derived Peptaibols Protect Tomato Plants From Botrytis cinerea Infection With Limited Impact on Plant Defenses
Authors: Baccelli Ivan , Luti Simone , Bernardi Rodolfo , Favaron Francesco , De Zotti Marta , Sella Luca
Published: May 2022

Peptaibols are non-ribosomal linear peptides naturally produced by a wide variety of fungi and represent the largest group of peptaibiotic molecules produced by Trichoderma species. Trichogin GA IV is an 11-residue lipopeptaibol naturally produced by Trichoderma longibrachiatum. Peptaibols possess the ability to form pores in lipid membranes or perturb their surface, and have been studied as antibiotics or anticancer drugs in human medicine, or as antimicrobial molecules against plant pathogens. When applied to plants, peptaibols may also elicit defense responses. A major drawback to the exploitation and application of peptaibols in agriculture is their poor water solubility. In a previous study, we designed water-soluble Lys-containing Trichogin GA IV analogs, which were able to inhibit the growth of several fungal plant pathogens in vitro. In the present study, we shed light on the mechanism underpinning their efficacy on plants, focusing on six Trichogin GA IV analogs. Our results highlighted peptide hydrophilicity, rather than helix stability, as the major determinant of their activity against B. cinerea infection in tomato leaves. The peptides showed preventive but not curative efficacy against infection, and lack of translaminar activity, with results reproducible on two tomato cultivars, Marmande and Micro-Tom. Reactive oxygen species (ROS) detection analysis in tomato and Arabidopsis, and expression of defense genes in tomato, highlighted a transient and limited impact of the peptides on the plant defense system. The treatment did not result in significant modulation of defense genes or defense priming. The antimicrobial effect thus emerges as the only mechanism behind the plant protection ability exerted by water-soluble Trichogin GA IV analogs, and limited effects on the plant metabolism are expected to occur.
Improve the Deep Learning Models in Forestry Based on Explanations and Expertise
Authors: Cheng Ximeng , Doosthosseini Ali , Kunkel Julian
Published: May 2022

In forestry studies, deep learning models have achieved excellent performance in many application scenarios (e.g., detecting forest damage). However, the unclear model decisions (i.e., black-box) undermine the credibility of the results and hinder their practicality. This study intends to obtain explanations of such models through the use of explainable artificial intelligence methods, and then use feature unlearning methods to improve their performance, which is the first such attempt in the field of forestry. Results of three experiments show that the model training can be guided by expertise to gain specific knowledge, which is reflected by explanations. For all three experiments based on synthetic and real leaf images, the improvement of models is quantified in the classification accuracy (up to 4.6%) and three indicators of explanation assessment (i.e., root-mean-square error, cosine similarity, and the proportion of important pixels). Besides, the introduced expertise in annotation matrix form was automatically created in all experiments. This study emphasizes that studies of deep learning in forestry should not only pursue model performance (e.g., higher classification accuracy) but also focus on the explanations and try to improve models according to the expertise.
A Tissue-Chopping Based Immunofluorescence Staining Method for Chloroplast Proteins
Authors: Wang Lulu , Tang Mingdong , Huang Wenwen , An Jinjie , Liu Xiaomin , Gao Hongbo
Published: May 2022

Immunofluorescence staining is an important method for detecting the localization of proteins in the cell. It is also frequently used in the localization study of chloroplast-division proteins. Although this method has been improved before by using protoplasts, it still has some limitations. Now we developed a new method to make it much easier. We just broke the plant leaf tissue with a serrated blade, stained the samples directly, and simply lysed the tissue into separatable cells. The localization of the target protein can then be observed with a clear view. Since this method directly uses broken leaf pieces, it is very fast. It can also be applied to the plants in which protoplasts are difficult to prepare. We first used this method to observe the localization of a chloroplast division protein FtsZ1 in the wild-type Arabidopsis. A ring was clearly seen in the middle of chloroplasts. In addition, we used this method to analyze the localization of FtsZ1 in arc3 and pdv2 mutants, as well as in dozens of other species, including some woody plants. This new immunofluorescence staining method is not only easy to use, but also has a wide applicability in various plants.
Tackling the Electro-Topography of the Selves Through the Sphere Model of Consciousness
Authors: Paoletti Patrizio , Leshem Rotem , Pellegrino Michele , Ben-Soussan Tal Dotan
Published: May 2022

In the current hypothesis paper, we propose a novel examination of consciousness and self-awareness through the neuro-phenomenological theoretical model known as the Sphere Model of Consciousness (SMC). Our aim is to create a practical instrument to address several methodological issues in consciousness research. We present a preliminary attempt to validate the SMC via a simplified electrophysiological topographic map of the Self. This map depicts the gradual shift from faster to slower frequency bands that appears to mirror the dynamic between the various SMC states of Self. In order to explore our hypothesis that the SMC’s different states of Self correspond to specific frequency bands, we present a mini-review of studies examining the electrophysiological activity that occurs within the different states of Self and in the context of specific meditation types. The theoretical argument presented here is that the SMC’s hierarchical organization of three states of the Self mirrors the hierarchical organization of Focused Attention, Open Monitoring, and Non-Dual meditation types. This is followed by testable predictions and potential applications of the SMC and the hypotheses derived from it. To our knowledge, this is the first integrated electrophysiological account that combines types of Self and meditation practices. We suggest this electro-topographic framework of the Selves enables easier, clearer conceptualization of the connections between meditation types as well as increased understanding of wakefulness states and altered states of consciousness.
A Reinforcement Sensitivity Theory of Violent Extremist Propaganda: The Motivational Pathways Underlying Movement Toward and Away From Violent Extremist Action
Authors: Shortland Neil , Portnoy Jill , McGarry Presley , Perliger Arie , Gordon Thomas , Anastasio Natalie
Published: May 2022

Anecdotal evidence supports than engaging with violent extremist content online facilitates the radicalization process. However, there is a consistent lack of empirically grounded research to provide insight into the psychological process through which this influence occurs (if at all). As such, most theories often fail to accommodate both the multifinality (the concept that many people are exposed to violent extremist material, yet never engage in violent extremism), and equifinality (the concept that people can view a range violent extremist content, yet all end up engaging in violent extremism) that naturally is observed in those who engage with violent extremist content online and those who engage in violent extremist behavior. This paper presents Reinforcement Sensitivity Theory (RST) as a theoretical framework to inform understanding of the process that governs the interaction between violent extremist material online and engaging with violent extremism. RST is a motivational theory which has been applied to a range of benevolent and deviant behaviors. Specifically, we argue that RST is suitable to explain the effect of violent extremist content online because (1) it outlines multiple differentiated motivational pathways that can account for multifinality and equifinality observed in those who engage in violent extremist behavior and (2) the extant neurological and psychophysiological research using RST provides a empirically supported framework for developing both research methods and verifiable hypotheses to advance our understanding of how, if at all, violent extremist content online contributes to the process of radicalization.
Do Attitudes, Mental Health Status, and Interpersonal Factors Predict COVID-19 Vaccine Hesitancy at the Early Phase of the Pandemic? A Longitudinal Study in Chinese College Students
Authors: Wu Zhipeng , Wang Xin , Zhang Sha , Ding Nani , Zhang Guohua , Zhao Chengjia , Xu Huihui , Lai Xinyi , Tu Xiaolian , Yang Xue
Published: May 2022

Purpose

The present study examined whether and how attitudes toward the COVID-19 vaccine (i.e., safety, efficacy, and price), mental health statuses (i.e., perceived stress and depression), and interpersonal factors (i.e., online social support, perceived social support) would predict COVID-19 vaccine hesitancy.

Patients and methods

The two-wave longitudinal surveys were conducted in December 2019 and 2020 in Chinese medical college students (N = 194). Well- validated measures were used, including the Perceived Stress Scale, the Center for Epidemiologic Studies Depression Scale, the Online Social Support Questionnaire, and the Perceived Social Support Scale. Perceived safety, efficacy, price of COVID-19 vaccine, vaccine hesitancy, and actual intake were also measured.

Results

Only 2.1% of participants had been vaccinated against COVID-19 in the early stages of the pandemic; 13.4% intended to get vaccinated in the next 3 months, and 66% intended to have it in the next 12 months upon follow-up. Multiple regression analyses revealed that perceived stress (βm = −0.15, p < 0.05) and depression (βm = −0.15, p < 0.05) were risk factors for positive attitudes toward the COVID-19 vaccine; online social support (ORm = 1.41, p < 0.01) and positive attitudes toward the COVID-19 vaccine (ORm = 1.83, p < 0.01) were protective factors of intention to get vaccinated in future.

Conclusion

Findings suggest that intervention efforts should be made to reduce negative attitudes toward the COVID-19 vaccine among people with poor mental health and enhance online social support to promote COVID-19 vaccination.
Encouraging Brand Evangelism Through Failure Attribution and Recovery Justice: The Moderating Role of Emotional Attachment
Authors: Zhu Tingting , Park Sung Kyu
Published: May 2022

Brand evangelism is essential to the profitability of e-shops, but the effects of failure attribution and recovery justice in encouraging brand evangelism in the online service recovery context are not straightforward. Grounded on a framework integrating Attribution theory, Justice theory, and Attachment theory, this study explores whether failure attribution and recovery justice affect brand evangelism through recovery satisfaction with emotional attachment as a moderator. We gathered 400 samples from e-shoppers who encountered a service failure and recovery in the past year to verify the hypotheses using structural equation modeling and multiple-group analysis. Results declare that failure attribution (locus, stability, and controllability) and recovery justice (distributive, procedural, and interactional justice) are significantly related to recovery satisfaction and subsequent brand evangelism. Moreover, failure attribution (locus, stability, and controllability) correlates significantly with recovery justice (distributive, procedural, and interactional justice). In addition, emotional attachment plays a moderating role on the relationships between distributive and procedural justice on recovery satisfaction. This work contributes to brand evangelism research by giving a different perspective (i.e., service recovery) to comprehend what stimulate or deter brand evangelism. In addition, this work develops service recovery research through the combination of the third dimension of attribution (locus) and fourth dimension of justice (informational justice) into a framework, investigating the effect of failure attribution on recovery justice, and revealing the moderating effect of emotional attachment in the recovery process.
The Transfer Model and Guidance Strategy of Netizens' Emotions
Authors: Wen Zhitao , Xia Yixue , Liu Mo , Lan Yuexin
Published: May 2022

In the context of the COVID-19 pandemic, a large amount of information is gathered on Internet platforms, through which people express their opinions and vent their emotions. Emotional guidance of netizens has become an important part of social governance during turbulences caused by a so-called “infodemic”. This study focuses on the evolution and interaction of netizens' emotions after the occurrence of network public opinion events. First, the transfer model of netizens' emotions is constructed, and the significance of each parameter in the model is studied through simulation. Then, based on the model, we put forward the optimization method and quantitative method of guidance strategy of netizens' emotions. Finally, the empirical study proves the effectiveness of the model, which can provide a theoretical basis for the emotional guidance strategies after the outbreak of network public opinion events.
Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Perspectives on the Use of Hypnosis
Authors: Anlló Hernán , Larue François , Herer Bertrand
Published: May 2022

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent and debilitating respiratory condition, characterized by chronic airflow limitation, breathlessness, and other persistent respiratory symptoms. Critically, patients suffering from COPD often find themselves trapped in a vicious comorbidity cycle: while breathlessness and increased respiratory rate are known inducers of anxiety, the latter have been shown in turn to exacerbate breathlessness and chest discomfort. Hypnosis holds great potential for the simultaneous complementary management of anxiety and breathlessness in COPD. It is an inexpensive psychological intervention tailored to the patient’s own experience, convenient in terms of logistics and implementation. In this short qualitative review, we present hypnosis’ structural, cognitive, and neural fundamentals, and assess existing instances of hypnosis use in the treatment of anxiety, depression, and respiratory disease. We then discuss its potential as a tool for improving health-related quality of life and the self-management of COPD within (and beyond) pulmonary rehabilitation.
Hierarchical Structure of Depression Knowledge Network and Co-word Analysis of Focus Areas
Authors: Yu Qingyue , Wang Zihao , Li Zeyu , Liu Xuejun , Oteng Agyeman Fredrick , Wang Xinxing
Published: May 2022

Contemporarily, depression has become a common psychiatric disorder that influences people’s life quality and mental state. This study presents a systematic review analysis of depression based on a hierarchical structure approach. This research provides a rich theoretical foundation for understanding the hot spots, evolutionary trends, and future related research directions and offers further guidance for practice. This investigation contributes to knowledge by combining robust methodological software for analysis, including Citespace, Ucinet, and Pajek. This paper employed the bibliometric methodology to analyze 5,000 research articles concerning depression. This current research also employed the BibExcel software to bibliometrically measure the keywords of the selected articles and further conducted a co-word matrix analysis. Additionally, Pajek software was used to conduct a co-word network analysis to obtain a co-word network diagram of depression. Further, Ucinet software was utilized to calculate K-core values, degree centrality, and mediated centrality to better present the research hotspots, sort out the current status and reveal the research characteristics in the field of depression with valuable information and support for subsequent research. This research indicates that major depressive disorder, anxiety, and mental health had a high occurrence among adolescents and the aged. This present study provides policy recommendations for the government, non-governmental organizations and other philanthropic agencies to help furnish resources for treating and controlling depression orders.
Shorter Telomeres Related to Posttraumatic Stress Disorder Re-experiencing Symptoms in Sexually Assaulted Civilian Women
Authors: Carvalho Carolina Muniz , Coimbra Bruno Messina , Xavier Gabriela , Bugiga Amanda V. G. , Fonseca Tamiris , Olff Miranda , Polimanti Renato , Mello Andrea Feijó , Ota Vanessa Kiyomi , Mello Marcelo Feijó , Belangero Sintia Iole
Published: May 2022

Telomeres are short tandem repeats of “TTAGGG” that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls – HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = −0.16; confidence interval (CI) 95% = −0.027—−0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.
COVID-19 and Youth Psychopathological Distress in Umbria, Central Italy: A 2-Year Observational Study in a Real-World Setting
Authors: Menculini Giulia , Pomili Giorgio , Brufani Francesca , Minuti Agnese , Mancini Niccolò , D’Angelo Martina , Biscontini Sonia , Mancini Enrico , Savini Andrea , Orsolini Laura , Volpe Umberto , Tortorella Alfonso , Steardo Luca
Published: May 2022

Introduction

Adolescents and young adults represent a vulnerable population in the context of the Coronavirus disease 2019 (COVID-19) pandemic. The present retrospective study aims to investigate the pandemic’s psychological impact on adolescents and young adults by analyzing data from an outpatient mental health service dedicated to youths in Umbria, central Italy.

Materials and Methods

The clinical charts of subjects aged 14–24 who first accessed the service in the timeframe between March 1st, 2019, and February 28th, 2021, were reviewed. Subjects were divided into two subgroups according to the period of time when they accessed the service (pre-COVID-19 vs. during- COVID-19 outbreak). Bivariate analyses were performed using the Chi-square test and the Welch’s t-test. A secondary analysis was performed considering only subjects suffering from psychiatric disorders. Furthermore, data concerning individuals who were already followed by the service before the pandemic were analyzed by the McNemar’s test and the t-paired test to assess changes in treatment features.

Results

The number of new accesses during the pandemic period remained stable. After the emergency onset, youths accessing the service showed a higher prevalence of anxiety disorders (p = 0.022). During the COVID-19 period, services were more frequently delivered by using a digital mental health approach (p = 0.001). Psychopharmacological treatment was more frequently prescribed among subjects that were referred to the service after the pandemic onset (p = 0.033). As for substance use, a highly significant reduction in opioid use was observed (p = 0.003). Family therapy was delivered less frequently in the during-COVID-19 subgroup, especially in the subpopulation of subjects suffering from psychiatric disorders (p = 0.013). When considering subjects referred to the service in the pre-COVID-19 period, the number of interventions provided to this population increased after the pandemic outbreak (p = 0.038).

Conclusion

In the context of the COVID-19-related public health crisis, youths represent an at-risk population for which pathways to care should be reinforced, and targeted interventions, including psychosocial treatments, should be implemented.
Decreased Serum Brain-Derived Neurotrophic Factor in Poststroke Depression: A Systematic Review and Meta-Analysis
Authors: Zhang Chunhui , Wang Xuefang , Zhu Qinghua , Mei Yongxia , Zhang Zhenxiang , Xu Hui
Published: May 2022

Backgrounds

There were conflicting results on the comparison of brain-derived neurotrophic factor (BDNF) levels between poststroke depression (PSD) patients and stroke patients without PSD among previous studies. Thus, we conducted this systemic review and meta-analysis to explore the alteration of serum BDNF levels in PSD.

Methods

This study included articles from the Web of Science and PubMed databases that were published before December 2021. STATA 12.0 software was used to compute the standardized mean difference (SMD) and 95% confidence interval (CI) regarding the comparison of serum BDNF in PSD and stroke patients without PSD.

Results

We collected the mean value and standard deviation (SD) of serum BDNF in PSD and stroke patients without PSD from six studies (PSD: n = 268, stroke patients without PSD: n = 425). The present meta-analysis showed decreased serum BDNF level in patients with PSD, compared to stroke patients without PSD with a random-effects model (mean value of BDNF level [PSD vs. stroke patients without PSD]: 14.106 vs. 17.995 ng/ml; SMD = –1.578; 95% CI: –2.820, –0.337; I2 = 97.8%, p-value for Q test < 0.001).

Conclusion

Brain-derived neurotrophic factor may work as a potential biomarker to predict the risk of PSD among stroke survivors. More large-sample clinical trials exploring the alteration of serum BDNF levels in PSD among stroke patients need to be conducted to verify this result.
Venlafaxine as an Adjuvant Therapy for Inflammatory Bowel Disease Patients With Anxious and Depressive Symptoms: A Randomized Controlled Trial
Authors: Liang Chang , Chen Pingrun , Tang Yu , Zhang Chuheng , Lei Na , Luo Ying , Duan Shihao , Zhang Yan
Published: May 2022

Background and Aims

The effect of antidepressant therapy on Inflammatory Bowel Disease (IBD) remains controversial. This trial aimed to assess whether adding venlafaxine to standard therapy for IBD improved the quality of life (QoL), mental health, and disease activity of patients with IBD with anxious and depressive symptoms.

Methods

A prospective, randomized, double-blind, and placebo-controlled clinical trial was conducted. Participants diagnosed with IBD with symptoms of anxiety or depression were randomly assigned to receive either venlafaxine 150 mg daily or equivalent placebo and followed for 6 months. Inflammatory Bowel Disease Questionnaire (IBDQ), Mayo score, Crohn's disease activity index (CDAI), Hospital Anxiety and Depression Scale (HADS), and blood examination were completed before the enrollment, during, and after the follow-up. Mixed linear models and univariate analyses were used to compare groups.

Results

Forty-five patients with IBD were included, of whom 25 were randomized to receive venlafaxine. The mean age was 40.00 (SD = 13.12) years old and 25 (55.6%) were male. Venlafaxine showed a significant improvement on QoL (p < 0.001) and disease course (p = 0.035), a greater reduction in HADS (anxiety: p < 0.001, depression: p < 0.001), Mayo scores (p < 0.001), and CDAI (p = 0.006) after 6 months. Venlafaxine had no effect on IL-10 expression, endoscopic scores, relapse rate, and use rate of biologics and corticosteroids, but did reduce serum level of erythrocyte estimation rate (ESR; p = 0.003), C-reactive protein (CRP; p < 0.001) and tumor necrosis factor-α (TNF-α; p = 0.009).

Conclusions

Venlafaxine has a significantly beneficial effect on QoL, IBD activity, and mental health in patients with IBD with comorbid anxious or depressive symptoms. (Chinese Clinical Trial Registry, ID: ChiCTR1900021496).
Predicting the Risk Factors Associated With Severe Outcomes Among COVID-19 Patients–Decision Tree Modeling Approach
Authors: Kumaran Mahalakshmi , Pham Truong-Minh , Wang Kaiming , Usman Hussain , Norris Colleen M. , MacDonald Judy , Oudit Gavin Y. , Saini Vineet , Sikdar Khokan C.
Published: May 2022

Background

The COVID-19 pandemic has seen a large surge in case numbers over several waves, and has critically strained the health care system, with a significant number of cases requiring hospitalization and ICU admission. This study used a decision tree modeling approach to identify the most important predictors of severe outcomes among COVID-19 patients.

Methods

We identified a retrospective population-based cohort (n = 140,182) of adults who tested positive for COVID-19 between 5th March 2020 and 31st May 2021. Demographic information, symptoms and co-morbidities were extracted from a communicable disease and outbreak management information system and electronic medical records. Decision tree modeling involving conditional inference tree and random forest models were used to analyze and identify the key factors(s) associated with severe outcomes (hospitalization, ICU admission and death) following COVID-19 infection.

Results

In the study cohort, nearly 6.37% were hospitalized, 1.39% were admitted to ICU and 1.57% died due to COVID-19. Older age (>71Y) and breathing difficulties were the top two factors associated with a poor prognosis, predicting about 50% of severe outcomes in both models. Neurological conditions, diabetes, cardiovascular disease, hypertension, and renal disease were the top five pre-existing conditions that altogether predicted 29% of outcomes. 79% of the cases with poor prognosis were predicted based on the combination of variables. Age stratified models revealed that among younger adults (18–40 Y), obesity was among the top risk factors associated with adverse outcomes.

Conclusion

Decision tree modeling has identified key factors associated with a significant proportion of severe outcomes in COVID-19. Knowledge about these variables will aid in identifying high-risk groups and allocating health care resources.
Anxiety and Coping Stress Strategies in Researchers During COVID-19 Pandemic
Authors: Batista Patrícia , Afonso Anabela , Lopes Manuel , Fonseca César , Oliveira-Silva Patrícia , Pereira Anabela , Pinho Lara
Published: May 2022

The current COVID-19 pandemic has affected the whole world, leading to changes in one's personal and working life. Researchers have undergone extensive changes in their roles, mainly in the area of health care, with research into the virus now the priority.

Aim

To assess the anxiety, depression, stress, fears, and coping strategies of Portuguese researchers during the COVID-19 pandemic.

Participants and Methods

A total of 243 researchers, with an average age of 37.9 ± 9.6, participated in an online questionnaire. The study was performed between 1 June 2021 and 11 August 2021. The questionnaire included depression, anxiety, and stress (DASS-21), fear of COVID-19 scale (FCV-19S), and coping inventory for stressful situations (CISS).

Results

The findings suggest being female and younger seem to be related to more significant fears. Singles and younger researchers showed higher values of stress, depression, and anxiety. Research areas, such as medical and health sciences, presented higher levels in the DASS-21 depression and stress scale (p < 0.05). Also, the results showed a moderate or moderate strong significant positive linear relationship between the scales (p < 0.001): DASS-21 stress, DASS-21 anxiety, and DASS-21 depression (r > 0.70); CISS-21 emotional-oriented with DASS-21 stress (r = 0.683), DASS-21 depression (r = 0.622), and DASS-21 anxiety (r = 0.557); and emotional fear and cognitive fear (r = 0.652).

Conclusion

The findings of this study support the growing concern for the psychological well-being of researchers and the need for intervention with more extensive and diverse studies.
Tracing the Phonetic Space of Prosodic Focus Marking
Authors: Roessig Simon , Winter Bodo , Mücke Doris
Published: May 2022

Focus is known to be expressed by a wide range of phonetic cues but only a few studies have explicitly compared different phonetic variables within the same experiment. Therefore, we presented results from an analysis of 19 phonetic variables conducted on a data set of the German language that comprises the opposition of unaccented (background) vs. accented (in focus), as well as different focus types with the nuclear accent on the same syllable (broad, narrow, and contrastive focus). The phonetic variables are measures of the acoustic and articulographic signals of a target syllable. Overall, our results provide the highest number of reliable effects and largest effect sizes for accentuation (unaccented vs. accented), while the differentiation of focus types with accented target syllables (broad, narrow, and contrastive focus) are more subtle. The most important phonetic variables across all conditions are measures of the fundamental frequency. The articulatory variables and their corresponding acoustic formants reveal lower tongue positions for both vowels /o, a/, and larger lip openings for the vowel /a/ under increased prosodic prominence with the strongest effects for accentuation. While duration exhibits consistent mid-ranked results for both accentuation and the differentiation of focus types, measures related to intensity are particularly important for accentuation. Furthermore, voice quality and spectral tilt are affected by accentuation but also in the differentiation of focus types. Our results confirm that focus is realized via multiple phonetic cues. Additionally, the present analysis allows a comparison of the relative importance of different measures to better understand the phonetic space of focus marking.