bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
Authors: Liu Weixi , Yang Zhicheng , Chen Yan , Yang Haoyu , Wan Xiaoxian , Zhou Xindie , Liu Ruiping , Zhang Yunkun
Published: February 2021

Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial.

Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility.

Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the CTLA-4 genes and RA for more robust conclusions.

Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms.

Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.
Oxidative Imbalance in Candida tropicalis Biofilms and Its Relation With Persister Cells
Authors: da Silva María A. , Baronetti José L. , Páez Paulina L. , Paraje María G.
Published: February 2021

Background

Persister cells (PCs) make up a small fraction of microbial population, can survive lethal concentrations of antimicrobial agents. In recent years, Candida tropicalis has emerged as being a frequent fungal agent of medical devices subject to biofilm infections. However, PCs are still poorly understood.

Objectives

This study aimed to investigate the relation of PCs on the redox status in C. tropicalis biofilms exposed to high doses of Amphotericin B (AmB), and alterations in surface topography and the architecture of biofilms.

Methods

We used an experimental model of two different C. tropicalis biofilms exposed to AmB at supra minimum inhibitory concentration (SMIC80), and the intra- and extracellular reactive oxygen species (iROS and eROS), reactive nitrogen species (RNS) and oxidative stress response were studied. Light microscopy (LM) and confocal laser scanning microscopy (CLSM) were also used in conjunction with the image analysis software COMSTAT.

Results

We demonstrated that biofilms derived from the PC fraction (B2) showed a higher capacity to respond to the stress generated upon AmB treatment, compared with biofilms obtained from planktonic cells. In B2, a lower ROS and RNS accumulation was observed in concordance with higher activation of the antioxidant systems, resulting in an oxidative imbalance of a smaller magnitude compared to B1. LM analysis revealed that the AmB treatment provoked a marked decrease of biomass, showing a loss of cellular aggrupation, with the presence of mostly yeast cells. Moreover, significant structural changes in the biofilm architecture were noted between both biofilms by CLSM—COMSTAT analysis. For B1, the quantitative parameters bio-volume, average micro-colony volume, surface to bio-volume ratio and surface coverage showed reductions upon AmB treatment, whereas increases were observed in roughness coefficient and average diffusion distance. In addition, untreated B2 was substantially smaller than B1, with less biomass and thickness values. The analysis of the above-mentioned parameters also showed changes in B2 upon AmB exposure.

Conclusion

To our knowledge, this is the first study that has attempted to correlate PCs of Candida biofilms with alterations in the prooxidant-antioxidant balance and the architecture of the biofilms. The finding of regular and PCs with different cellular stress status may help to solve the puzzle of biofilm resistance, with redox imbalance possibly being an important factor.
Reversible Tau Phosphorylation Induced by Synthetic Torpor in the Spinal Cord of the Rat
Authors: Hitrec Timna , Squarcio Fabio , Cerri Matteo , Martelli Davide , Occhinegro Alessandra , Piscitiello Emiliana , Tupone Domenico , Amici Roberto , Luppi Marco
Published: February 2021

Tau is a key protein in neurons, where it affects the dynamics of the microtubule system. The hyperphosphorylation of Tau (PP-Tau) commonly leads to the formation of neurofibrillary tangles, as it occurs in tauopathies, a group of neurodegenerative diseases, including Alzheimer's. Hypothermia-related accumulation of PP-Tau has been described in hibernators and during synthetic torpor (ST), a torpor-like condition that has been induced in rats, a non-hibernating species. Remarkably, in ST PP-Tau is reversible and Tau de-phosphorylates within a few hours following the torpor bout, apparently not evolving into pathology. These observations have been limited to the brain, but in animal models of tauopathies, PP-Tau accumulation also appears to occur in the spinal cord (SpCo). The aim of the present work was to assess whether ST leads to PP-Tau accumulation in the SpCo and whether this process is reversible. Immunofluorescence (IF) for AT8 (to assess PP-Tau) and Tau-1 (non-phosphorylated Tau) was carried out on SpCo coronal sections. AT8-IF was clearly expressed in the dorsal horns (DH) during ST, while in the ventral horns (VH) no staining was observed. The AT8-IF completely disappeared after 6 h from the return to euthermia. Tau-1-IF disappeared in both DH and VH during ST, returning to normal levels during recovery. To shed light on the cellular process underlying the PP-Tau pattern observed, the inhibited form of the glycogen-synthase kinase 3β (the main kinase acting on Tau) was assessed using IF: VH (i.e., in motor neurons) were highly stained mainly during ST, while in DH there was no staining. Since tauopathies are also related to neuroinflammation, microglia activation was also assessed through morphometric analyses, but no ST-induced microglia activation was found in the SpCo. Taken together, the present results show that, in the DH of SpCo, ST induces a reversible accumulation of PP-Tau. Since during ST there is no motor activity, the lack of AT8-IF in VH may result from an activity-related process at a cellular level. Thus, ST demonstrates a newly-described physiological mechanism that is able to resolve the accumulation of PP-Tau and apparently avoid the neurodegenerative outcome.
A Susceptible Period of Photic Day-Night Rhythm Loss in Common Marmoset Social Behavior Development
Authors: Koshiba Mamiko , Watarai-Senoo Aya , Karino Genta , Ozawa Shimpei , Kamei Yoshimasa , Honda Yoshiko , Tanaka Ikuko , Kodama Tohru , Usui Setsuo , Tokuno Hironobu
Published: February 2021

The prevalence of neurodevelopmental psychiatric disorders such as pervasive developmental disorders is rapidly increasing worldwide. Although these developmental disorders are known to be influenced by an individual’s genetic background, the potential biological responses to early life’s environmental exposure to both physical and psychological factors must also be considered. Many studies have acknowledged the influence of shorter time for rest at night and the simultaneous occurrence of various kinds of complications involving developmental disorders. In a prior study, we examined how a common marmoset’s (Callithrix jacchus) psychosocial development was affected when it was reared under constant daylight from birth and then reared individually by humans nursing them under constant light (LL) during their juvenile development stages. The behaviors of these marmosets were compared with those of normal day-night cycle (LD) marmosets using a multivariate analysis based on principal component analysis (PCA). That study found that LL marmosets relatively elicited egg-like calls (Ecall) and side-to-side shakes of the upper body with rapid head rotation through adulthood frequently. Based on the PCA, these behaviors were interpreted as “alert” or “hyperactive” states. However, we did not clarify susceptible periods of the photic rhythm loss experience and the psychological development output. In this study we summarize the following studies in our model animal colonies involving 30 animals (11 female, 19 males) to further explore critical age states of inquiry about each social behavior profiling. We compared social behaviors of three age stages, juvenile, adolescent and young adult equivalent to one another in four LL experience conditions, LL (postnatal day (P) 0 to around 150), Middle (P60–149, 90 days), Late (P150–239, 90 days), and LD (no experience). In the most representative 1st and 2nd principal component scores, the shifting to higher frequency of alert behaviors developed at the adult stage in LL, Middle, then Late in turn. The no LL experience group, LD, generally featured higher frequency of local preference of high position compared to LL experience present groups, in adulthood. This limited model primate study might inspire different developmental age sensitive mechanisms of neuronal network to control socio-emotional functions by utilizing the multivariate visualization method, BOUQUET. This study could potentially contribute to nurturing educational designs for social developmental disorders.
Chloroquine and Hydroxychloroquine Myopathy: Clinical Spectrum and Treatment Outcomes
Authors: Naddaf Elie , Paul Pritikanta , AbouEzzeddine Omar F.
Published: February 2021

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. In this retrospective study, we aimed to define the clinical phenotype, laboratory features, and treatment outcomes of CQ/HCQ myopathy, as well as the safety profile of these drugs. We identified 13 patients seen between 2000 and 2019, with a median age at presentation of 66 years (range 53–89); 11 were females. At onset of symptoms, patients were on CQ or HCQ for a minimum of 6 months and up to 21 years. Diagnosis was often delayed by a median of 6 months (range 3–48). At presentation, 13 patients reported limb weakness, with five requiring assistance in walking. Ten reported dysphagia, often severe, resulting in marked weight loss or aspiration pneumonia. Nine reported respiratory symptoms, which were multifactorial in four, and four reported severe neck weakness. Myopathy clinical phenotype showed predominant involvement of one or more of the following: proximal limb muscle weakness (12 patients), dysphagia (9), axial weakness (4), and respiratory failure (5). Eleven patients had a cardiac evaluation showing prolonged QT interval in 10 and CQ/HCQ cardiomyopathy (CMP) in four. Ten out of 12 patients markedly improved after discontinuing the medication, but most were left with some residual weakness. Eleven patients had a muscle biopsy showing a myopathy with rimmed vacuoles and marked acid phosphatase reactivity. Nine had elevated creatine kinase level up to 1,199 U/L. Twelve patients had an electromyography (EMG), which showed myopathic motor unit potentials with fibrillation potentials in 11 and myotonic discharges in 3. Higher cumulative dose and longer exposure duration were associated with more severe disability and more common cardiac and swallow involvement, indicating a cumulative dose effect. Herein, we demonstrate that long-term exposure to CQ and HCQ may result in a myopathy with a wide spectrum of clinical presentation and predilection for swallowing, respiratory, and cardiac muscles, often with marked associated morbidity. Once accurately diagnosed and the drug is discontinued, patients usually improve but often fail to return to baseline.
Identification of Key Gene Signatures Associated With Bone Metastasis in Castration-Resistant Prostate Cancer Using Co-Expression Analysis
Authors: Yu Zhongxiang , Zou Hanlin , Wang Huihao , Li Qi , Yu Dong
Published: February 2021

About 80–90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis. However, the molecular mechanisms of bone metastasis are still not clear. This study aimed to detect the differences between the tumor and normal samples in bone after metastatic colonization. Four transcriptional datasets (GSE32269, GSE101607, GSE29650, and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between tumor and normal marrow samples in GSE32269. Most of the top 10 up-regulated DEGs are related with prostate cancer, and the top 10 down-regulated DEGs are mainly related with bone development. Seven co-expression modules were then detected based on the 1469 DEGs shared by the four datasets. Three of them were found highly preserved among the four datasets. Enrichment analysis showed that the three modules were respectively enriched in Cell adhesion molecules (CAMs), Leukocyte transendothelial migration and cell cycle, which might play significantly important roles in the tumor development in bone marrow. Ten, 17, and 99 hub genes for each module were then identified. And four genes (C3AR1, IL10RA, LY86, and MS4A6A) were detect to be tightly related to progression of bone metastatic CRPC. ROC curve was plotted and AUC was calculated to distinguish tumor and normal bone marrow samples as well as bone and non-bone metastatic CRPCs. The present study identified key genes and modules involved in bone metastatic CRPCs, which may provide new insights and biomarkers for understanding of the molecular mechanisms of bone metastatic CRPC.
Prognostic and Therapeutic Roles of the Insulin Growth Factor System in Glioblastoma
Authors: Tirrò Elena , Massimino Michele , Romano Chiara , Martorana Federica , Pennisi Maria Stella , Stella Stefania , Pavone Giuliana , Di Gregorio Sandra , Puma Adriana , Tomarchio Cristina , Vitale Silvia Rita , Manzella Livia , Vigneri Paolo
Published: February 2021

Glioblastoma multiforme (GBM) is the most common primary brain malignancy and is often resistant to conventional treatments due to its extensive cellular heterogeneity. Thus, the overall survival of GBM patients remains extremely poor. Insulin-like growth factor (IGF) signaling entails a complex system that is a key regulator of cell transformation, growth and cell-cycle progression. Hence, its deregulation is frequently involved in the development of several cancers, including brain malignancies. In GBM, differential expression of several IGF system components and alterations of this signaling axis are linked to significantly worse prognosis and reduced responsiveness to temozolomide, the most commonly used pharmacological agent for the treatment of the disease. In the present review we summarize the biological role of the IGF system in the pathogenesis of GBM and comprehensively discuss its clinical significance and contribution to the development of resistance to standard chemotherapy and experimental treatments.
Maintenance Therapy in AML
Authors: Reville Patrick K. , Kadia Tapan M.
Published: February 2021

Recent advances in therapeutics coupled with steady improvements in supportive care for patients with acute myeloid leukemia (AML) have led to improved outcomes. Despite these advances, even in patients that achieve a complete remission with initial therapy high rates of relapse remain a clinical dilemma. For decades, investigators have attempted strategies of maintenance therapy to prolong both remission duration and overall survival in patients with AML. These approaches have included cytotoxic chemotherapy, immunotherapy, hypomethylating agents, and targeted small molecule therapy. Overall, the evidence in favor of maintenance therapy is limited. Recent strategies, especially with hypomethylating agents have begun to show promise as maintenance therapy in improving clinical outcomes. Ongoing and future studies will continue to elucidate the true role for maintenance therapy options in patients with AML. In this review we summarize prior and ongoing maintenance therapy approaches in AML and highlight some of the most promising strategies.
Outcomes of Non-anesthesiologist-Administered Propofol in Pediatric Gastroenterology Procedures
Authors: Lee Frances C. , Queliza Karen , Chumpitazi Bruno P. , Rogers Amber P. , Seipel Catherine , Fishman Douglas S.
Published: February 2021

Background and Aims: Non-anesthesiologist-administered propofol (NAAP) has been found to have an acceptable safety profile in adult endoscopy, but its use remains controversial and pediatric data is limited. Our aim was to examine the safety and efficacy of NAAP provided by pediatric hospitalists in pediatric endoscopy.

Methods: We retrospectively reviewed 929 esophagogastroduodenoscopy (EGD), colonoscopy, and combined EGD/colonoscopy cases in children aged 5–20 years between April 2015 and December 2016 at a large children's hospital. We analyzed the data for adverse events in relation to demographics and anthropometrics, American Society of Anesthesiologists physical classification score, presence of a trainee, comorbid conditions, and procedure time.

Results: A total of 929 cases were included of which 496 (53%) were completed with NAAP. Seventeen (3.4%) of NAAP cases had an adverse event including the following: 12 cases of hypoxia, 2 cardiac, and 3 gastrointestinal adverse events. General anesthesia cases had 62 (14.3%) adverse events including the following: 54 cases of hypoxia, 1 cardiac, 7 gastrointestinal, and 1 urologic adverse event. No adverse events in either group required major resuscitation. NAAP vs. general anesthesia had a lower overall adverse event rate (3.4 vs. 14.3%, p < 0.0004) and respiratory adverse event rate (2.4% vs. 12.5%, p < 0.0004). Overall, cardiac and gastrointestinal adverse event rates between the two groups were comparable. When accounting for all captured factors via logistic regression, both younger age (P < 0.001) and general anesthesia (P < 0.0001) remained risk factors for an adverse event.

Conclusion: The overall adverse event rate of NAAP was low (3.4%) with none requiring major resuscitation or hospitalization. This is comparable to studies of NAAP in adult endoscopy and suggests that NAAP provided by pediatric hospitalists has an acceptable safety profile.
Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology
Authors: Zhu Ning , Huang Bingwu , Jiang Wenbing
Published: February 2021

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.
Glycyrrhetinic Acid Protects Renal Tubular Cells against Oxidative Injury via Reciprocal Regulation of JNK-Connexin 43-Thioredoxin 1 Signaling
Authors: Zhou Yao , Gao Leiping , Xia Ping , Zhao Jing , Li Wei , Zhou Yufeng , Wei Qingxue , Wu Qijing , Wu Qi , Sun Dongdong , Gao Kun
Published: February 2021

Background and Objective: The incidence of chronic kidney disease (CKD) is steadily increasing. Although renal tubular epithelium injury is closely correlated with the prognosis of CKD, the underlying mechanism is not fully understood and therapeutic strategies are limited. The main bioactive component of the Chinese medicine herb, glycyrrhiza, is 18α-glycyrrhetinic acid (Ga), which is also a pharmacological inhibitor of gap junctions. Our previous studies indicated that Ga is able to ameliorate renal cell injury. The present study explored the regulatory role of Ga in redox signaling in renal tubular epithelial cells with oxidative injury.

Methods: Rat renal tubular epithelial cells, NRK-52E, were incubated with Px-12, a thioredoxin inhibitor, to mimic thioredoxin deficiency and induce oxidative injury in vitro. A Cell Counting Kit-8 was used to analyze cell viability while a reactive oxygen species (ROS)/superoxide (O2−) fluorescence probe was employed to determine oxidative stress. Apoptosis was evaluated using DT-mediated dUTP nick end labeling/4,6-diamidino-2-phenylindole staining and cleaved caspase 3 protein analysis. Western blot analysis was used to analyze the expression of specific proteins while siRNA transfection was performed to downregulate targeted proteins.

Results: Inhibition of thioredoxin 1 by Px-12 triggered renal tubular cell oxidative injury as evidenced by morphological change, loss of cellular viability, over production of ROS and O2−, and appearance of cleaved caspase-3. Ga significantly attenuated cell oxidative injury, as indicated by the parameters mentioned above. Px-12 induced phosphorylation of c-Jun N-terminal kinase (JNK) and subsequently the expression of connexin 43 (Cx43) in NRK-52E cells. Ga and the JNK inhibitor, sp600125, markedly suppressed Px-12-induced generation of intracellular ROS and O2−. Inhibition of JNK improved Px-12-elicited NRK-52E cell injury. Moreover, sp600125 inhibited Cx43 expression. After downregulation of Cx43 via Cx43 siRNA transfection, the phosphorylation of JNK was markedly reduced. Furthermore, Ga restored the expression of thioredoxin 1 inhibited by Px-12.

Conclusion: ROS-JNK-Cx43-thioredoxin 1 signaling plays a crucial role in renal tubular cell injury. JNK is involved in the regulation of thioredoxin 1 and Cx43, and Cx43 reciprocally regulates thioredoxin 1. Inhibition of gap junctions by Ga alleviated renal tubular oxidative injury via improvement of thioredoxin 1-mediated redox signaling.
Quantifying Key Points of Hydraulic Vulnerability Curves From Drought-Rewatering Experiment Using Differential Method
Authors: Liu Xiao , Wang Ning , Cui Rong , Song Huijia , Wang Feng , Sun Xiaohan , Du Ning , Wang Hui , Wang Renqing
Published: February 2021

Precise and accurate estimation of key hydraulic points of plants is conducive to mastering the hydraulic status of plants under drought stress. This is crucial to grasping the hydraulic status before the dieback period to predict and prevent forest mortality. We tested three key points and compared the experimental results to the calculated results by applying two methods. Saplings (n= 180) ofRobinia pseudoacaciaL. were separated into nine treatments according to the duration of the drought and rewatering. We established the hydraulic vulnerability curve and measured the stem water potential and loss of conductivity to determine the key points. We then compared the differences between the calculated [differential method (DM) and traditional method (TM)] and experimental results to identify the validity of the calculation method. From the drought-rewatering experiment, the calculated results from the DM can be an accurate estimation of the experimental results, whereas the TM overestimated them. Our results defined the hydraulic status of each period of plants. By combining the experimental and calculated results, we divided the hydraulic vulnerability curve into four parts. This will generate more comprehensive and accurate methods for future research.
Differential Tissue-Specific Jasmonic Acid, Salicylic Acid, and Abscisic Acid Dynamics in Sweet Cherry Development and Their Implications in Fruit-Microbe Interactions
Authors: Fresno David H. , Munné-Bosch Sergi
Published: February 2021

Sweet cherry is an important non-climacteric fruit with a high commercial interest, but exploitation of sweet cherry trees (Prunus avium L.) in orchards is usually subject to important economic losses due to fruit decay by pathogenic fungi and other microorganisms. Sweet cherries development and ripening are characterized by profound physiological changes in the fruit, among which the phytohormone abscisic acid (ABA) plays a pivotal role. In addition, sweet cherries are usually affected by fruit decay pathogens, and the role of other stress-related hormones such as jasmonic acid (JA) and salicylic acid (SA) may also be of paramount importance, not only from a developmental point of view, but also from a fruit-microbe interaction perspective. Here, a tissue-specific hormone quantification by LC-MS/MS, including the contents of JA, SA, and ABA, in the fruit exocarp and mesocarp of sweet cherries during fruit development from trees growing in a commercial orchard was carried out. Additionally, this study was complemented with the characterization of the culturable epiphytic and endophytic microbial communities of sweet cherries at various stages of fruit development and during cracking lesion formation. Our results revealed a completely differential behavior of phytohormones between both tissues (the exocarp and mesocarp), with a more dynamic exocarp in front of a more stable mesocarp, and with marked variations during fruit development. Microbial epiphytic community was mainly composed by yeasts, although rot-causing fungi like Alternaria spp. were always also present throughout fruit development. Endophytic colonization was poor, but it increased throughout fruit development. Furthermore, when the exocarp was naturally disrupted in sweet cherries suffering from cracking, the colonization by Alternaria spp. markedly increased. Altogether, results suggest that the fruit exocarp and mesocarp are very dynamic tissues in which endogenous phytohormones not only modulate fruit development and ripening but also fruit-microbe interactions.
“Test Your Spirituality in One Minute or Less” Structural Validity of the Multidimensional Inventory for Religious/Spiritual Well-Being Short Version (MI-RSWB 12)
Authors: Fuchshuber Jürgen , Unterrainer Human F.
Published: February 2021

Background: The Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB 48) was developed in order to address a religious/spiritual dimension as being an important part of psychological well-being. In the meantime, the instrument has been successfully applied in numerous studies. Subsequently, a short version, the MI-RSWB 12 was constructed, especially for the use in clinical assessment. Here it is intended to contribute to the further development of the MI-RSWB 12 by investigating its structural validity through structural equation modeling.

Materials and Methods: A total sample of 1,097 German-speaking adults (744 females; 67.8%; Age range: 18–69 years) from the normal population filled in the MI-RSWB 12 via an online-survey. In line with theoretical assumptions 5 different factor structure models for the MI-RSWB 12 were tested: (1) a single-factor model, (2) a model with four correlated RSWB dimensions, (3) a single higher-order model with four lower order factors, (4) a two higher-order model with four lower order factors, (5) a bifactor model, which includes four specific RSWB dimensions.

Results: The single-factor model provided the poorest model fit, with no indices falling within the acceptable range. The four-factor, two higher-order factors and the bifactor models showed overall acceptable fit indices. With regard to the Akaike information criterion (AIC), the four-factor model demonstrated superiority compared to both the two higher-order factor model and the bifactor model, which in turn showed did not differ from each other.

Conclusion: Four different MI-RSWB 12 sub-scales should be calculated in future studies, while a general factor and two higher order factors are statistically valid as well. Further applications of the MI-RSWB 12, especially in the clinical patient groups, are encouraged.
Physical Activity, Loneliness, and Meaning of Friendship in Young Individuals – A Mixed-Methods Investigation Prior to and During the COVID-19 Pandemic With Three Cross-Sectional Studies
Authors: Lippke Sonia , Fischer Marie Annika , Ratz Tiara
Published: February 2021

Meaningful social interactions and regular physical activity are inversely associated with loneliness. Using a mixed-methods research design employing quantitative and qualitative research approaches, this research aimed to explore loneliness, physical activity, friendship, and experiences relating to the COVID-19 pandemic both prior to and during the pandemic. Quantitative data of (1) n = 363 first-year university students assessed in 2018/2019 and of (2) n = 175 individuals aged 18–29 years assessed in 2020 were gathered using independent self-administered online surveys. In addition, (3) n = 4 students were recruited for semi-structured, qualitative interviews in 2020 during the onset phase of the COVID-19 pandemic. Correlation and regression analyses as well as analyses of variance were conducted. Thematic analysis as a qualitative method was used to explore the role physical activity, friendship, and social interactions played in loneliness, particularly in times of social isolation and social distancing. Results revealed associations of varying strength between physical activity and loneliness in 2018/2019 (r = −0.09, p ≤ 0.05) and 2020 (r = −0.20, p < 0.01). In 2020, n = 73 (41.7%) participants felt that their loneliness had increased since the COVID-19 social and physical distancing guidelines were introduced, but this was not associated with a perceived change in physical activity (r = −0.05, p > 0.05). Analyses of qualitative data revealed three main themes: (1) the lack of deep friendships at university, (2) the positive perceived impact of team sports on feelings of loneliness, and (3) the need for real connection in times of crisis. Thus, with regard to feelings of loneliness during the pandemic, being physically active seems to be a small but potentially relevant factor among young individuals. The qualitative study suggests that first-year university students might buffer the lack of deep friendships and meaningful interactions by building social bonds in team sports. In times of physical distancing, young individuals vulnerable to loneliness may therefore require special support such as doing sports with physical distance and perceiving connected with their team for instance by digital devices and emotional coping.
Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia
Authors: Sehatpour Pejman , Avissar Michael , Kantrowitz Joshua T. , Corcoran Cheryl M. , De Baun Heloise M. , Patel Gaurav H. , Girgis Ragy R. , Brucato Gary , Lopez-Calderon Javier , Silipo Gail , Dias Elisa , Martinez Antigona , Javitt Daniel C.
Published: February 2021

Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types.
Reduced Activity in an Inpatient Liaison Psychiatry Service During the First Wave of the COVID-19 Pandemic: Comparison With 2019 Data and Characterization of the SARS-CoV-2 Positive Cohort
Authors: Butler Matthew , Delvi Afraa , Mujic Fedza , Broad Sophie , Pauli Lucy , Pollak Thomas A. , Gibbs Soraya , Fai Lam Chun Chiang Sin , Calcia Marilia A. , Posporelis Sotirios
Published: February 2021

Background: The COVID-19 pandemic led to changes in the way that healthcare was accessed and delivered in the United Kingdom (UK), particularly during the peak of the first lockdown period (the “first wave”) beginning in March 2020. In some patients, COVID-19 is associated with acute neuropsychiatric manifestations, and there is suggestion that there may also be longer term neuropsychiatric complications. Despite this, at the time of writing there are only emerging data on the direct effects of the COVID-19 pandemic on psychiatric care.

Methods: In this retrospective study we analyzed referrals to an inpatient liaison psychiatry department of a large acute teaching hospital during the first wave of covid-19 in the UK and compared this data to the same period in 2019.

Results: We saw a 40% reduction in the number of referrals in 2020, with an increase in the proportion of referrals for both psychosis or mania and delirium. Almost one third (28%) of referred patients tested positive for COVID-19 at some point during their admission, with 40% of these presenting with delirium as a consequence of their COVID-19 illness. Save delirium, we did not find evidence for high prevalence of new-onset acute mental illness in COVID-19 positive patients.

Conclusion: Our data indicate decreased clinical activity in our inpatient psychiatry liaison department during the first wave of the COVID-19 pandemic, although a relative increase in relative increase in referrals for psychosis or mania, suggesting less of a relative decrease in more severe cases of mental illness. The reasons for this are likely multifactorial, including structural changes in the NHS and patient reluctance to present to emergency departments (ED) due to infection fears and Government advice. Our data also supports the literature suggesting the high relative prevalence of delirium in COVID-19, and we support integration of psychiatry liaison teams in acute general hospital wards to optimize delirium management. Finally, consideration should be given to adequate staffing of community and crisis mental health teams to safely manage the mental health of people reluctant to visit EDs.
Listener Modeling and Context-Aware Music Recommendation Based on Country Archetypes
Authors: Schedl Markus , Bauer Christine , Reisinger Wolfgang , Kowald Dominik , Lex Elisabeth
Published: February 2021

Music preferences are strongly shaped by the cultural and socio-economic background of the listener, which is reflected, to a considerable extent, in country-specific music listening profiles. Previous work has already identified several country-specific differences in the popularity distribution of music artists listened to. In particular, what constitutes the “music mainstream” strongly varies between countries. To complement and extend these results, the article at hand delivers the following major contributions: First, using state-of-the-art unsupervized learning techniques, we identify and thoroughly investigate (1) country profiles of music preferences on the fine-grained level of music tracks (in contrast to earlier work that relied on music preferences on the artist level) and (2) country archetypes that subsume countries sharing similar patterns of listening preferences. Second, we formulate four user models that leverage the user’s country information on music preferences. Among others, we propose a user modeling approach to describe a music listener as a vector of similarities over the identified country clusters or archetypes. Third, we propose a context-aware music recommendation system that leverages implicit user feedback, where context is defined via the four user models. More precisely, it is a multi-layer generative model based on a variational autoencoder, in which contextual features can influence recommendations through a gating mechanism. Fourth, we thoroughly evaluate the proposed recommendation system and user models on a real-world corpus of more than one billion listening records of users around the world (out of which we use 369 million in our experiments) and show its merits vis-à-vis state-of-the-art algorithms that do not exploit this type of context information.
MIND-VR: Design and Evaluation Protocol of a Virtual Reality Psychoeducational Experience on Stress and Anxiety for the Psychological Support of Healthcare Workers Involved in the COVID-19 Pandemic
Authors: Pallavicini Federica , Orena Eleonora , di Santo Simona , Greci Luca , Caragnano Chiara , Ranieri Paolo , Vuolato Costanza , Pepe Alessandro , Veronese Guido , Dakanalis Antonios , Rossini Angelo , Caltagirone Carlo , Clerici Massimo , Mantovani Fabrizia
Published: February 2021

To ensure the continuity of healthcare and to counter the spread of the COVID-19 pandemic, doctors and nursing staff at hospitals must face an insidious, invisible danger that is stretching the healthcare system far past its capacity. Excessive workload, inadequate protection from contamination, the need to manage patients experiencing extreme suffering and being kept apart from their families put medical personnel at high risk to experience stress and anxiety. Numerous scientific studies have shown that, among various therapeutic programs, virtual reality represents a highly specialized and effective tool for the prevention and treatment of stress and anxiety. However, the solutions developed using this technology for the management of stress and anxiety induced by the COVID-19 pandemic are still very limited, and none of these have been developed specifically for use with healthcare professionals. Therefore, this paper will detail the design and evaluation protocol of MIND-VR, a virtual reality-based psychoeducational experience on stress and anxiety developed following a user-centered design approach. The virtual experience will be tested on a sample of Italian hospital healthcare personnel involved in the COVID-19 pandemic emergency. MIND-VR is available free of charge, both in Italian and English, on the project website (https://mind-vr.com/).
The Impact of the Closure and Reopening of Golf Courses in the United Kingdom on Wellbeing During the COVID-19 Pandemic: A Multi-Study Approach
Authors: Sorbie Graeme G. , Beaumont Alexander J. , Williams Ashley K. , Glen Jonathan , Hardie Scott M. , Lavallee David
Published: February 2021

The purpose of this multi-study was to assess what impact the closure and reopening of golf courses had on: personal competence; sense of belonging; enjoyment; self-esteem; self-confidence; resilience; social connections; wellbeing and life satisfaction (hereafter referred to collectively as “key variables of interest”) during the COVID-19 pandemic. Golfers (Study 1: n = 298, Study 2: n = 124) ≥16 years old residing in the UK participated in this study which collected data using online surveys. Study 1 was conducted during a period of quarantine restrictions (4–12th May 2020), whilst study 2 took place following the easing of the COVID-19 quarantine restrictions (6–14th July 2020). Within study 1 and study 2, key variables of interest levels were also collected to investigate the association with golf related activities. The findings of study 1 highlighted that negligible and non-significant correlations were observed between golf physical and sedentary activities and key variables of interest (r < 0.3, p > 0.05) except sense of belonging and sedentary golf activities (r = 0.178, p = 0.003). Study 2 highlighted that sense of belonging, enjoyment and wellbeing were significantly associated with outdoor golf course activity (r = 0.186–0.252, p ≤ 0.05). Furthermore, when comparing study 1 and study 2, sense of belonging and life satisfaction significantly improved (p < 0.05, d = 0.2). Based on these findings, playing golf on outdoor golf courses appears to be positively related to sense of belonging, enjoyment and wellbeing. Also, with the reopening of golf courses life satisfaction improved which, together, highlights the beneficial impact that outdoor golf can impart.
Veterinary Herd Health Consultancy and Antimicrobial Use in Dairy Herds
Authors: Skjølstrup Nanna K. , Nielsen Liza R. , Jensen Carsten S. , Lastein Dorte B.
Published: February 2021

The globally increasing level of antimicrobial resistance affects both human and animal health, why it is necessary to identify ways to change our current use of antimicrobials. The veterinary herd health collaboration between veterinarians and dairy farmers provides a useful setting for changing antimicrobial use in livestock. However, farmers and veterinarians work in a complex agricultural setting influenced by socio-economic factors, which complicates their choices regarding antimicrobial usage. It is therefore necessary to be aware of the range of potential influencing factors and to integrate this knowledge in the relevant local settings. This manuscript presents a literature review of relevant factors relating to antimicrobial use within the veterinary herd health consultancy setting, including knowledge gaps of relevance for changing the use of antimicrobials. An enriched version of the framework of the Theory of Planned Behaviour was used to organise the literature review. We identified diverging attitudes on correct treatment practices and perceptions of antimicrobial resistance among veterinarians and farmers, influenced by individual risk perception as well as social norms. Furthermore, disagreements in terms of goal setting and in the frequency of herd visits in relation to herd health consultancy can negatively influence the collaboration and the intention to change antimicrobial use. Farmers and veterinarians emphasise the importance of legislation and the role of the dairy industry in changing antimicrobial use, but the relevance of specific factors depends on the country-specific context. Overall, farmers and veterinarians must communicate better to understand each other's perspectives and establish common goals within the collaboration if they are to work efficiently to reduce antimicrobial use. Farmers and veterinarians both requested changes in individual behaviour; however, they also called for national and structural solutions in terms of balanced legislation and the availability of better diagnostics to facilitate a change in antimicrobial use practices. These various paths to achieving the desired changes in antimicrobial use illustrate the need to bridge methodological research approaches of veterinary science and social sciences for a better understanding of our potential to change antimicrobial use within the dairy farm animal sector.
The Immense Functional Attributes of Maize Rhizosphere Microbiome: A Shotgun Sequencing Approach
Authors: Akinola Saheed , Ayangbenro Ayansina , Babalola Olubukola
Published: February 2021

The northwest (NW) province of South Africa is a semi-arid area, often disturbed by soil extremes such as drought and intense temperature. However, many functions possessed by the rhizosphere microbiome are still required, especially those inhabiting arid and semi-arid soils. This study involves a metagenomic comparison of the major metabolic attributes of two maize rhizosphere soils and their surrounding soils. Here, we hypothesized that there is a considerable difference between the functional diversity of maize rhizosphere and bulk soils and that the rhizosphere soil has distinct functional traits of agricultural importance. A high-throughput sequencing approach was used to assess the metabolic profile of rhizosphere soil microbiota of maize collected from the Gauteng and NW provinces of South Africa. The relative abundance of 13 functional hit categories was significantly different between the sampling sites. The diversity indices showed a considerable difference between the rhizosphere and surrounding soils. The difference in the chemical properties of the sampling sites was responsible for the variation in the microbial functional composition. Nevertheless, the presence of a high relative abundance of functional categories with unknown functions in SEED subsystem-2 coupled with the large number of functional hits conferring a response to soil stressors viz. oxidative stress, heat shock, osmotic stress, and cold shock noticed in the rhizosphere samples may indicate the presence of novel genes at the sampling sites. Exploring the plant growth-promoting traits of microorganisms present at these sites could eliminate the constraint posed by soil stressors on sustainable agriculture.