bluuebunny/crossref_metadata_2025 huggingface dataset:
BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors
Authors: Dudnik Elizabeth , Bar Jair , Moore Assaf , Gottfried Teodor , Moskovitz Mor , Dudnik Julia , Shochat Tzippy , Allen Aaron M. , Zer Alona , Rotem Ofer , Peled Nir , Urban Damien
Published: March 2021

Objectives

Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).

Materials and Methods

Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne® CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016–2018) MPM patients selected from the electronic databases of two ICC—of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1st-line platinum/pemetrexed+/−antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.

Results

There were no differences in ORR or mPFS with CT between the groups: ORR-50% vs. 47% vs. 50% vs. 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2–16.1) vs. 9.2mo (95% CI, 2.9–13.3) vs. 7.2mo (95% CI, 2.3-NR) vs. 10.9mo (95% CI, 2.9–20.3) (p>0.8) in groups A, B, B1, and B2, respectively. There were no differences in ORR or mPFS with ICPi between the groups: ORR-0% vs. 27% vs. 33% vs. 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4–3.7) vs. 3.0mo (95% CI, 1.3–10.5) vs. 2.0mo (95% CI, 1.9-NR) vs. 4.5mo (95% CI, 0.3–10.5) (p>0.3) in groups A, B, B1, and B2, respectively. In group A, no responses were seen with PARPi; mPFS with PARPi was 1.8mo (95% CI, 1.8-NR). OSDx was 98.3mo (95% CI, 9.7–98.3) vs. 19.4mo (95% CI, 9.7–47.3) vs. 18.8mo (95% CI, 8.5-NR) vs. 19.5mo (95% CI, 8.3–82.2) in groups A, B, B1, and B2, respectively (p>0.3).

Conclusions

BAP1-altered MPM, as compared to non-selected MPM, is characterized by similar efficacy of CT and ICPi. Numerically longer OS in BAP1-altered MPM may reflect favorable tumor biology. No responses were observed with PARPi.
Circulating Tumor Cells for Glioma
Authors: Zhang Huikai , Yuan Fanen , Qi Yangzhi , Liu Baohui , Chen Qianxue
Published: March 2021

Liquid biopsy has entered clinical applications for several cancers, including metastatic breast, prostate, and colorectal cancer for CTC enumeration and NSCLC for EGFR mutations in ctDNA, and has improved the individualized treatment of many cancers, but relatively little progress has been made in validating circulating biomarkers for brain malignancies. So far, data on circulating tumor cells about glioma are limited, the application of circulating tumor cells as biomarker for glioma patients has only just begun. This article reviews the research status and application prospects of circulating tumor cells in gliomas. Several detection methods and research results of circulating tumor cells about clinical research in gliomas are briefly discussed. The wide application prospect of circulating tumor cells in glioma deserves further exploration, and the research on more sensitive and convenient detection methods is necessary.
Asparagine Synthetase-Mediated l-Asparagine Metabolism Disorder Promotes the Perineural Invasion of Oral Squamous Cell Carcinoma
Authors: Fu Yong , Ding Liang , Yang Xihu , Ding Zhuang , Huang Xiaofeng , Zhang Lei , Chen Sheng , Hu Qingang , Ni Yanhong
Published: March 2021

Dysregulated amino acids metabolism reciprocally interplays with evolutionary phenotypic characteristics of cancer cells to enhance metastasis. The high metastasis potential of oral squamous cell carcinoma (OSCC) can manifest with perineural invasion (PNI). We here aimed to determine the role of amino acids metabolism in OSCCs with different PNI statuses. Targeted metabolomics was used to quantify 48 amino acids in 20 fresh OSCC samples and 25 amino acids were successfully detected, within which 9 were significantly up-regulated in PNI positive (PNI+) samples. As its highest area under the curve value (0.9063), l-asparagine was selected as the biomarker to distinguish PNI+ from PNI negative (PNI−). Then, the key enzyme of l-asparagine, asparagine synthetase (ASNS), was investigated using immunohistochemistry with 86 OSCC patients. The results showed that ASNS mainly expressed in tumor epitheliums and positively correlated with lymph node metastasis and PNI. Moreover, subgroup survival analysis revealed that ASNS expression combined with PNI status significantly improved their prognostic value, which was confirmed by the TCGA OSCC cohort (n = 279). To validate whether ASNS promotes PNI, we determined ASNS expression levels in five OSCC cell lines and one normal oral keratinocyte, and HSC3 showed the lowest ASNS level but CAL33 had the highest. Therefore, HSC3 and CAL33 (or PBS as control) were selected and injected separately into sciatic nerves to construct the in vivo PNI mouse models. Although both models eventually developed the hind-limb paralysis, nerve dysfunction in the CAL33 model progressed significantly earlier than HSC3 (Day 9 vs. Day 24). Besides, CAL33 migrated significantly farther than HSC3 in the nerve microenvironment (P = 0.0003), indicating high ASNS expression is indispensable for OSCC progression, especially PNI formation, through l-asparagine metabolism alteration. This study provides novel insights into how amino acids metabolism disorders alter tumor neurotropism which helps cancer metastasis.
Single-Cell Transcriptome Analysis Identifies Ligand–Receptor Pairs Associated With BCP-ALL Prognosis
Authors: Wu Liang , Jiang Minghao , Yu Ping , Li Jianfeng , Ouyang Wen , Feng Chong , Zhao Wei Li , Dai Yuting , Huang Jinyan
Published: March 2021

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a blood cancer that originates from the abnormal proliferation of B-lymphoid progenitors. Cell population components and cell–cell interaction in the bone marrow microenvironment are significant factors for progression, relapse, and therapy resistance of BCP-ALL. In this study, we identified specifically expressed genes in B cells and myeloid cells by analyzing single-cell RNA sequencing data for seven BCP-ALL samples and four healthy samples obtained from a public database. Integrating 1356 bulk RNA sequencing samples from a public database and our previous study, we found a total of 57 significant ligand–receptor pairs (24 upregulated and 33 downregulated) in the autocrine crosstalk network of B cells. Via assessment of the communication between B cells and myeloid cells, another 29 ligand–receptor pairs were discovered, some of which notably affected survival outcomes. A score-based model was constructed with least absolute shrinkage and selection operator (LASSO) using these ligand–receptor pairs. Patients with higher scores had poorer prognoses. This model can be applied to create predictions for both pediatric and adult BCP-ALL patients.
Psychological Outcomes in Children and Early Adolescents With Type 1 Diabetes Following Pediatric Diabetes Summer Camp: A 3-Month Follow-Up Study
Authors: Troncone Alda , Chianese Antonietta , Cascella Crescenzo , Zanfardino Angela , Iafusco Dario
Published: March 2021

Objective:The aim of this study was to assess general psychosocial adjustment to diabetes and perceived disease management among patients with type 1 diabetes (T1D) and their parents before and after patients' participation in a diabetes summer camp.

Methods:In this follow-up study, 20 children and adolescents with T1D (eight boys; mean age = 11.01 ± 0.94 years; mean diabetes duration = 3.02 ± 2.27) attending a southern Italian diabetic center, along with their parents, were assessed prior to and 3 months after the youths participated in a 1 week camp-based intervention involving didactic and interactive child-centered education and recreational activities. Patients and their parents completed measures assessing patients' quality of life and strategies employed by patients to cope with pain. Patients also completed measures evaluating their diabetes psychosocial adjustment, diabetes self-efficacy management, and illness perception; also, their parents completed measures of caregivers' perceived diabetes burden and treatment satisfaction. Youths' glycated hemoglobin (HbA1c) and standardized body mass index (z-BMI) values were also assessed. Within-subjects repeated-measures analyses of variance evaluated pre- and post-camp changes.

Results:Camp attendance showed no beneficial effects on glycemic control, as indicated by HbA1c values both before (7.02%) and after (7.28%) camp being lower than 7.5%. HbA1c values were found to have increased after camp (pre-camp = 7.02%, post-camp = 7.28%;p= 0.010), but since they still fell within an acceptable range, they did not reveal clinically relevant changes in glycemic control. No substantial significant improvement in psychosocial measures was observed in children or parents (allp> 0.05). According to the parents' evaluation, social support-seeking as a patient pain-coping strategy was slightly increased (p= 0.044) after attending the camp.

Conclusions:This study does not provide empirical evidence of benefits of participating in a diabetes camp for either patients or their parents. These findings suggest that healthcare providers rethink such camps as an experience for youths with T1D that actively involves parents and that includes both youth- and parent-focused psychological interventions.
Viral Infections and Cutaneous Drug-Related Eruptions
Authors: Anci Eleonora , Braun Camille , Marinosci Annalisa , Rodieux Frédérique , Midun Elise , Torres Maria-Jose , Caubet Jean-Christoph
Published: March 2021

In the general population, up to 10% of children treated by antibiotics have cutaneous adverse drug reaction, but allergy is confirmed in less than 20% of patients. Most of the non-allergic reactions are probably due to virus, such as enterovirus acute infection or Ebstein-Barr Virus (EBV) acute infection or reactivation. Especially in children, viruses have the propensity to induce skin lesions (maculopapular rash, urticaria) due to their skin infiltration or immunologic response. In drug-related skin eruptions, a virus can participate by activating an immune predisposition. The culprit antibiotic is then the trigger for reacting. Even in severe drug-induced reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, viruses take part in immune phenomena, especially herpes viruses. Understanding the mechanisms of both virus- and drug-induced skin reaction is important to develop our clinical reflection and give an adaptive care to the patient. Our aim is to review current knowledge on the different aspects and potential roles of viruses in the different type of drug hypersensitivity reactions (DHR). Although major advances have been made those past year, further studies are needed for a better understanding of the link between viruses and DHR, to improve management of those patients.
The Punicalagin Metabolites Ellagic Acid and Urolithin A Exert Different Strengthening and Anti-Inflammatory Effects on Tight Junction-Mediated Intestinal Barrier Function In Vitro
Authors: Hering Nina A. , Luettig Julia , Jebautzke Britta , Schulzke Jörg D. , Rosenthal Rita
Published: March 2021

Scope: Ellagitannins are polyphenols found in numerous fruits, nuts and seeds. The elagitannin punicalagin and its bioactive metabolites ellagic acid and urolithins are discussed to comprise a high potential for therapeutically or preventive medical application such as in intestinal diseases. The present study characterizes effects of punicalagin, ellagic acid and urolithin A on intestinal barrier function in the absence or presence of the proinflammatory cytokine tumor necrosis factor-α (TNFα).

Methods and Results: Transepithelial resistance (TER), fluorescein and ion permeability, tight junction protein expression and signalling pathways were examined in Caco-2 and HT-29/B6 intestinal epithelial cell models. Punicalagin had less or no effects on barrier function in both cell models. Ellagic acid was most effective in ileum-like Caco-2 cells, where it increased TER and reduced fluorescein and sodium permeabilities. This was paralleled by myosin light chain kinase two mediated expression down-regulation of claudin-4, -7 and -15. Urolithin A impeded the TNFα-induced barrier loss by inhibition of claudin-1 and -2 protein expression upregulation and claudin-1 delocalization in HT-29/B6.

Conclusion: Ellagic acid and urolithin A affect intestinal barrier function in distinct ways. Ellagic acid acts preventive by strengthening the barrier per se, while urolithin A protects against inflammation-induced barrier dysfunction.
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing
Authors: Kern Charlotte , Schöning Verena , Chaccour Carlos , Hammann Felix
Published: March 2021

Several repurposed drugs are currently under investigation in the fight against coronavirus disease 2019 (COVID-19). Candidates are often selected solely by their effective concentrations in vitro, an approach that has largely not lived up to expectations in COVID-19. Cell lines used in in vitro experiments are not necessarily representative of lung tissue. Yet, even if the proposed mode of action is indeed true, viral dynamics in vivo, host response, and concentration-time profiles must also be considered. Here we address the latter issue and describe a model of human SARS-CoV-2 viral kinetics with acquired immune response to investigate the dynamic impact of timing and dosing regimens of hydroxychloroquine, lopinavir/ritonavir, ivermectin, artemisinin, and nitazoxanide. We observed greatest benefits when treatments were given immediately at the time of diagnosis. Even interventions with minor antiviral effect may reduce host exposure if timed correctly. Ivermectin seems to be at least partially effective: given on positivity, peak viral load dropped by 0.3–0.6 log units and exposure by 8.8–22.3%. The other drugs had little to no appreciable effect. Given how well previous clinical trial results for hydroxychloroquine and lopinavir/ritonavir are explained by the models presented here, similar strategies should be considered in future drug candidate prioritization efforts.
Catalpol Protects Against High Glucose-Induced Bone Loss by Regulating Osteoblast Function
Authors: Zhao Lu , Du Wei , Zhao Dandan , Ji Xueyan , Huang Yanfei , Pang Yong , Guo Kaijin , Yin Xiaoxing
Published: March 2021

Objective: The overall objective of this study was to investigate the effects of catalpol on bone remodeling of diabetic osteoporosis by regulating osteoblast differentiation and migration.

Method: Using a murine model of diabetic osteoporosis, to detect the protective effects of catalpol on bone loss, architectural deterioration of trabecular bone and bone metabolism biomarkers were tested. A model of MC3T3-E1 cells was established by treatment with high glucose; the regulatory role of catalpol in the differentiation and migration was tested by Western blot, ALP staining, and Alizarin Red staining.

Results: Catalpol treatment markedly ameliorated trabecular bone deterioration by reducing degenerative changes of the trabecular structure by improving the bone formation marker levels of ALP, osteopontin, type I collagen, and osteocalcin, as well as the level of OPG/RANKL. Catalpol enhanced cell motility and scattering following gap formation of MC3T3-E1 cells.

Conclusion: The results indicated that catalpol exhibits a protective effect against diabetic osteoporosis by regulating the differentiation and migration of osteoblast.
4-Chlorothymol Exerts Antiplasmodial Activity Impeding Redox Defense System in Plasmodium falciparum
Authors: Kumar Saurabh , Mina Pooja Rani , Kumar Ravi , Pal Anirban , Ahmad Ateeque , Tandon Sudeep , Darokar Mahendra P.
Published: March 2021

Malaria remains one of the major health concerns due to the resistance of Plasmodium species toward the existing drugs warranting an urgent need for new antimalarials. Thymol derivatives were known to exhibit enhanced antimicrobial activities; however, no reports were found against Plasmodium spp. In the present study, the antiplasmodial activity of thymol derivatives was evaluated against chloroquine-sensitive (NF-54) and -resistant (K1) strains of Plasmodium falciparum. Among the thymol derivatives tested, 4-chlorothymol showed potential activity against sensitive and resistant strains of P. falciparum. 4-Chlorothymol was found to increase the reactive oxygen species and reactive nitrogen species level. Furthermore, 4-chlorothymol could perturb the redox balance by modulating the enzyme activity of GST and GR. 4-Chlorothymol also showed synergy with chloroquine against chloroquine-resistant P. falciparum. 4-Chlorothymol was found to significantly suppress the parasitemia and increase the mean survival time in in vivo assays. Interestingly, in in vivo assay, 4-chlorothymol in combination with chloroquine showed higher chemosuppression as well as enhanced mean survival time at a much lower concentration as compared to individual doses of chloroquine and 4-chlorothymol. These observations clearly indicate the potential use of 4-chlorothymol as an antimalarial agent, which may also be effective in combination with the existing antiplasmodial drugs against chloroquine-resistant P. falciparum infection. In vitro cytotoxicity/hemolytic assay evidently suggests that 4-chlorothymol is safe for further exploration of its therapeutic properties.
Novel Insights Linking lncRNAs and Metabolism With Implications for Cardiac Regeneration
Authors: Correia Magda , Bernardes de Jesus Bruno , Nóbrega-Pereira Sandrina
Published: March 2021

Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellular and organismal carbohydrate and lipid metabolism and play multifaceted functions in the cardiovascular system. Still, our understanding of the metabolic determinants and pathways that can promote cardiac regeneration in the injured hearth remains limited. Here, we will discuss the emerging concepts that provide evidence for a molecular interplay between lncRNAs and metabolic signaling in cardiovascular function and whether exploiting this axis could provide ground for improved regenerative strategies in the heart.
Impact of Low Hemoglobin on Body Composition, Strength, and Redox Status of Older Hemodialysis Patients Following Resistance Training
Authors: da Silva Victor , Corrêa Hugo , Neves Rodrigo , Deus Lysleine , Reis Andrea , Souza Michel , dos Santos Cláudio , de Castro Danilo , Honorato Fernando , Simões Herbert , Moraes Milton , Schoenfeld Brad , Prestes Jonato , Rosa Thiago
Published: March 2021

Introduction

The purpose of this study was to: (i) investigate the effect of six months of resistance training (RT) on body composition, muscle strength, hematological patterns, and redox profile in maintenance hemodialysis (HD) patients, and; (ii) evaluate the effects of baseline concentrations of hemoglobin on the RT response.

Methods

One hundred fifty-seven subjects with chronic kidney disease (CKD) were randomly allocated into two groups: Control [CTL, (n= 76)] and RT (n= 81). A first visit was required for anamnesis and anthropometric measurements. Venous blood samples were collected at baseline and after twenty-four weeks of training in all patients for the analysis of clinical and redox balance markers. The RT program spanned six months and consisted of three sets of 8–12 repetitions with a rating of perceived exertion between 5 and 8 for three weekly sessions. Each exercise session was performed in twelve resistance exercises and it least for approximately 40 min.

Results

The main results demonstrated that RT decreased waist circumference by 3%, and decreased thiobarbituric reactive species (TBARS) by 28%. Moreover, RT increased handgrip strength by 28.4%, fat-free mass by 4.1%, hemoglobin by 5%, iron by 33.4%, glutathione by 121%, and Trolox equivalent antioxidant capacity by 14.2% (p< 0.05). Low hemoglobin concentrations impaired the effect of RT on fat-free mass gain.

Conclusion

Six months of RT in HD patients improved clinical parameters, such as hemoglobin, iron, body composition, and redox balance, while low hemoglobin concentration impaired exercise-benefits on fat-free mass in patients with CKD. These findings can contribute to a better clinical application of RT in the maintenance of hemodialysis patients.
The Distribution of Onion Virulence Gene Clusters Among Pantoea spp.
Authors: Stice Shaun P. , Shin Gi Yoon , De Armas Stefanie , Koirala Santosh , Galván Guillermo A. , Siri María Inés , Severns Paul M. , Coutinho Teresa , Dutta Bhabesh , Kvitko Brian H.
Published: March 2021

Pantoea ananatis is a gram-negative bacterium and the primary causal agent of center rot of onions in Georgia. Previous genomic studies identified two virulence gene clusters, HiVir and alt, associated with center rot. The HiVir gene cluster is required to induce necrosis on onion tissues via synthesis of pantaphos, (2-hydroxy[phosphono-methyl)maleate), a phosphonate phytotoxin. The alt gene cluster aids in tolerance to thiosulfinates generated during onion tissue damage. Whole genome sequencing of other Pantoea species suggests that these gene clusters are present outside of P. ananatis. To assess the distribution of these gene clusters, two PCR primer sets were designed to detect the presence of HiVir and alt. Two hundred fifty-two strains of Pantoea spp. were phenotyped using the red onion scale necrosis (RSN) assay and were genotyped using PCR for the presence of these virulence genes. A diverse panel of strains from three distinct culture collections comprised of 24 Pantoea species, 41 isolation sources, and 23 countries, collected from 1946–2019, was tested. There is a significant association between the alt PCR assay and Pantoea strains recovered from symptomatic onion (P < 0.001). There is also a significant association of a positive HiVir PCR and RSN assay among P. ananatis strains but not among Pantoea spp., congeners. This may indicate a divergent HiVir cluster or different pathogenicity and virulence mechanisms. Last, we describe natural alt positive [RSN+/HiVir+/alt+] P. ananatis strains, which cause extensive bulb necrosis in a neck-to-bulb infection assay compared to alt negative [RSN+/HiVir+/alt–] P. ananatis strains. A combination of assays that include PCR of virulence genes [HiVir and alt] and an RSN assay can potentially aid in identification of onion-bulb-rotting pathogenic P. ananatis strains.
Polyploidy Expands the Range of Centaurium (Gentianaceae)
Authors: Maguilla Enrique , Escudero Marcial , Jiménez-Lobato Vania , Díaz-Lifante Zoila , Andrés-Camacho Cristina , Arroyo Juan
Published: March 2021

The Mediterranean region is one of the most important worldwide hotspots in terms of number of species and endemism, and multiple hypotheses have been proposed to explain how diversification occurred in this area. The contribution of different traits to the diversification process has been evaluated in different groups of plants. In the case ofCentaurium(Gentianaceae), a genus with a center of diversity placed in the Mediterranean region, polyploidy seems to have been an important driver of diversification as more than half of species are polyploids. Moreover, ploidy levels are strongly geographically structured across the range of the genus, with tetraploids distributed towards more temperate areas in the north and hexaploids in more arid areas towards the south. We hypothesize that the diversification processes and biodiversity patterns inCentauriumare explained by the coupled formation of polyploid lineages and the colonization of different areas. A MCC tree from BEAST2 based on three nuclear DNA regions of a total of 26 taxa (full sampling, of 18 species and 8 subspecies) was used to perform ancestral area reconstruction analysis in “BioGeoBEARS.” Chromosome evolution was analyzed in chromEvol and diversification in BAMM to estimate diversification rates. Our results suggest that two major clades diverged early from the common ancestor, one most likely in the western Mediterranean and the other in a widespread area including west and central Asia (but with high uncertainty in the exact composition of this widespread area). Most ancestral lineages in the western clade remained in or around the western Mediterranean, and dispersal to other areas (mainly northward and eastward), occurred at the tips. Contrarily, most ancestral lineages in the widespread clade had larger ancestral areas. Polyploidization events in the western clade occurred at the tips of the phylogeny (with one exception of a polyploidization event in a very shallow node) and were mainly tetraploid, while polyploidization events occurred in the widespread clade were at the tips and in an ancestral node of the phylogeny, and were mainly hexaploid. We show how ancestral diploid lineages remained in the area of origin, whereas recent and ancestral polyploidization could have facilitated colonization and establishment in other areas.
Behavioral and Neurodynamic Effects of Word Learning on Phonotactic Repair
Authors: Gow David W. , Schoenhaut Adriana , Avcu Enes , Ahlfors Seppo P.
Published: March 2021

Processes governing the creation, perception and production of spoken words are sensitive to the patterns of speech sounds in the language user’s lexicon. Generative linguistic theory suggests that listeners infer constraints on possible sound patterning from the lexicon and apply these constraints to all aspects of word use. In contrast, emergentist accounts suggest that these phonotactic constraints are a product of interactive associative mapping with items in the lexicon. To determine the degree to which phonotactic constraints are lexically mediated, we observed the effects of learning new words that violate English phonotactic constraints (e.g., srigin) on phonotactic perceptual repair processes in nonword consonant-consonant-vowel (CCV) stimuli (e.g., /sre/). Subjects who learned such words were less likely to “repair” illegal onset clusters (/sr/) and report them as legal ones (/∫r/). Effective connectivity analyses of MRI-constrained reconstructions of simultaneously collected magnetoencephalography (MEG) and EEG data showed that these behavioral shifts were accompanied by changes in the strength of influences of lexical areas on acoustic-phonetic areas. These results strengthen the interpretation of previous results suggesting that phonotactic constraints on perception are produced by top-down lexical influences on speech processing.
Social Support and Hope Mediate the Relationship Between Gratitude and Depression Among Front-Line Medical Staff During the Pandemic of COVID-19
Authors: Feng Lijuan , Yin Rong
Published: March 2021

Background

The pandemic of Coronavirus Disease 2019 (COVID-19) has burdened an unprecedented psychological stress on the front-line medical staff, who are at high risk of depression. While existing studies and theories suggest that factors such as gratitude, social support, and hope play a role in the risk of depression, few studies have combined these factors to explore the relationship between them.

Objective

This study examined the mediating roles of social support and hope in the relationship between gratitude and depression among front-line medical staff during the pandemic of COVID-19.

Methods

This study used the Gratitude Questionnaire, the Perceived Social Support Scale (PSSS), the State Hope Scale (SHS), and the Center for Epidemiologic Studies Depression Scale to examine the gratitude, social support, hope, and depression among 344 front-line medical workers in Wuhan, which was the hardest-hit area of COVID-19 in China.

Results

The results showed that the prevalence of mild depressive disorder was 40.12% and the prevalence of major depressive disorder was 9.59% among front-line medical staff during the pandemic of COVID-19; gratitude has a direct and negative effect on depression. Gratitude was negative predictors of depression through the mediating variables of social support and hope [βgratitude–social support–depression = −0.096, 95%CI(−0.129 to −0.064); βgratitude–hope–depression = −0.034, 95%CI(−0.055 to −0.013)], as well as via an indirect path from social support to hope [βgratitude–social support–hope–depression = −0.089, 95%CI (−0.108 to −0.070)].

Conclusion

The study findings indicate that gratitude as a positive emotion can reduce depression in medical staff by promoting social support and hope, respectively. Gratitude also reduced depression in health care workers through a chain mediating effect of social support and hope. Overall, gratitude can directly foster social support and hope, and protect people from stress and depression, which has implications for clinical interventions among front-line medical staff during the pandemic of COVID-19.
Longitudinal Trajectories of Study Characteristics and Mental Health Before and During the COVID-19 Lockdown
Authors: van Zyl Llewellyn E. , Rothmann Sebastiaan , Zondervan-Zwijnenburg Maria A. J.
Published: March 2021

The COVID-19 lockdown has significantly disrupted the higher education environment within the Netherlands and led to changes in available study-related resources and study demands of students. These changes in study resources and study demands, the uncertainty and confusion about educational activities, the developing fear and anxiety about the disease, and the implementation of the COVID-19 lockdown measures may have a significant impact on the mental health of students. As such, this study aimed to investigate the trajectory patterns, rate of change, and longitudinal associations between study resources–demands and mental health of 141 university students from the Netherlands before and during the COVID-19 lockdown. The present study employed a longitudinal design and a piecewise latent growth modeling strategy to investigate the changes in study resources and mental health over a 3 month period. The results showed that moderate levels of student resources significantly decreased before, followed by a substantial rate of increase during, lockdown. In contrast, study demands and mental health were reported to be moderate and stable throughout the study. Finally, the growth trajectories of study resources–demands and mental health were only associated before the lockdown procedures were implemented. Despite growing concerns relating to the negative psychological impact of COVID-19 on students, our study shows that the mental health during the initial COVID-19 lockdown remained relatively unchanged.
Affective Benefits of Nature Contact: The Role of Rumination
Authors: Bratman Gregory N. , Young Gerald , Mehta Ashish , Lee Babineaux Ihno , Daily Gretchen C. , Gross James J.
Published: March 2021

Mounting evidence shows that nature contact is associated with affective benefits. However, the psychological mechanisms responsible for these effects are not well understood. In this study, we examined whether more time spent in nature was associated with higher levels of positive affect in general, and lower levels of negative affect and rumination in general. We also conducted a cross-sectional mediation analysis to examine whether rumination mediated the association of nature contact with affect. Participants (N = 617) reported their average time spent in nature each week, as well as their general levels of positive and negative affect, and the degree to which they typically engaged in rumination in daily life. We then used structural equation modeling to test our hypotheses. Our results support the hypothesis that nature contact is associated with general levels of affect, and that rumination mediates this association for negative affect, and marginally mediates this association for positive affect.
Expression of Dopamine D1−4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia
Authors: Wysokiński Adam , Kozłowska Elżbieta , Szczepocka Ewa , Łucka Anna , Agier Justyna , Brzezińska-Błaszczyk Ewa , Sobierajska Katarzyna
Published: March 2021

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D1, D2, D3, D4 and serotonin 5-HT1A, 5-HT2A, and 5-HT3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects.

Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D1−4 and serotonin 5-HT1A−3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC50, half of IC50, and one-quarter of IC50 concentrations.

Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D1, D2 and D4 receptors (p < 0.001), and significantly lower mRNA expression of 5-HT3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D1 lost its significance, while that of D3, 5-HT1A, 5-HT2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors.

Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.
Integrating a Positron Emission Tomography/Computed Tomography Into the National Health System of Cyprus: Will It Return on Its Investment?
Authors: Kefallonitou Dimitra , Polycarpou Irene , Souliotis Kyriakos , Giannakou Konstantinos
Published: March 2021

A European Union (EU) member state, Cyprus is a country with a population of ~850,000 citizens. According to the Cyprus Ministry of Health, since 2009, more than 3,000 new incidents with neoplasm are diagnosed every year (i.e., 3% increasing rate). Projections estimate an average annual increase of 2.2% of new incidents until 2040. However, the National Health System (NHS) of Cyprus lacks a Positron Emission Tomography/Computed Tomography (PET/CT) care framework and infrastructure. Patients can only have a PET/CT exam in the private sector, either in Cyprus or a neighboring country (e.g., Greece or Israel). This requires the government of Cyprus to cover financial expenses related to medical treatments while the patients may also need to cover their expenses for traveling to a neighboring country. This study presents a cost analysis to examine whether the integration of a PET/CT with, or without, an F18-FDG cyclotron unit in the NHS of Cyprus is an efficient investment that can be recovered within the unit's service life. To perform this study, we estimated necessary resources for purchasing and operating such unit for a period of 15 years. The results of this study indicate that an investment in a PET/CT unit is not financially viable. Alternatives, such as the reimbursement of PET/CT operated by the private sector is recommended.
Environmental Inequalities in Flood Exposure: A Matter of Scale
Authors: Poussard Clémence , Dewals Benjamin , Archambeau Pierre , Teller Jacques
Published: March 2021

Studies on inequalities in exposure to flood risk have explored whether population of a lower socio-economic status are more exposed to flood hazard. While evidence exist for coastal flooding, little is known on inequalities for riverine floods. This paper addresses two issues: (1) is the weakest population, in socio-economic terms, more exposed to flood hazard, considering different levels of exposure to hazard? (2) Is the exposure to flood risk homogeneous across the territory, considering different scales of analysis? An analysis of the exposure of inhabitants of Liège province to flood risk was conducted at different scales (province, districts, and municipalities), considering three levels of exposure to flood hazard (level 1- low hazard, level 3- high hazard), and five socio-economic classes (class 1-poorest, class 5-wealthiest households). Our analysis confirms that weaker populations (classes 2 and 3) are usually more exposed to flood hazards than the wealthiest (classes 4 and 5). Still it should be stressed that the most precarious households (class 1) are less exposed than low to medium-range ones (classes 2 and 3). Further on the relation between socio-economic status and exposure to flood hazard varies along the spatial scale considered. At the district level, it appears that classes 4 and 5 are most exposed to flood risk in some peripheral areas. In municipalities located around the center of the city, differences of exposure to risk are not significant.
LGBTQs and LAW’S Violence Within a Heteronormative Landscape
Authors: Donnelly-Drummond Anthony
Published: March 2021

This article raises concerns as to the way in which specific exemptions within equality law across the United Kingdom may be viewed as a form of violence against LGBTQs.1 The overarching concept of heteronormativity and its impact is aired. The possible impact of exemptions for religious organisations to legally discriminate on grounds of sexual orientation under Northern Ireland’s Equality Act 2006 acting as a catalyst for the Asher’s cake incident, is reviewed. Similarly, the effect of exemptions under the Equality Act 2010 feasibly lending support for protestors against inclusion of LGBTQ issues in a Birmingham school is made clear. Thereafter the invisibility of LGBTQs within curricula is raised alongside the legacy of section 28. Overall, the article raises the spectre that specific aspects of equality legislation, designed to protect individuals on a range of grounds, may be perceived as not only flawed but inherently violent due to the dehumanizing impact on LGBTQ people. In addition, concerns are raised that against this background, within the United Kingdom there has been a failure to educate all students as to contemporary issues of diversity, potentially harming their development as citizens in our diverse contemporary society.
Immune and Nervous Systems Interaction in Endocrine Disruptors Toxicity: The Case of Atrazine
Authors: Galbiati Valentina , Buoso Erica , d'Emmanuele di Villa Bianca Roberta , Paola Rosanna Di , Morroni Fabiana , Nocentini Giuseppe , Racchi Marco , Viviani Barbara , Corsini Emanuela
Published: March 2021

Endocrine disruptors (ED) are natural and anthropogenic chemicals that can interfere with hormonal systems at different levels. As such, ED-induced alterations in hormone functions have been implicated in many diseases and pathological conditions, including adverse developmental, reproductive, neurological, cardiovascular, and immunological effects in mammals. The fact that ED may compete with several endogenous hormones for multiple receptors and pathways is not always fully considered. This results in a complex response that depends on the cellular context in terms of receptors and interacting proteins and, thus, may differ between tissues and circumstances. Microglia, neurons, and other immune cells are potential targets and still underappreciated actors in endocrine disruption. Due to the large scale of this topic, this review is not intended to provide a comprehensive review nor a systematic review of chemicals identified as endocrine disruptors. It focuses on the immune-neuro-endocrine network in ED toxicity and research gaps, using atrazine as an example to highlight this complexity and the interrelationship between the immune, endocrine, and nervous systems, and ED.
Fluid Resuscitation for Refractory Hypotension
Authors: Valverde Alexander
Published: March 2021

Hypotension is a common occurrence, especially in anesthetized patients and in critical patients suffering from hypovolemia due to shock and sepsis. Hypotension can also occur in normovolemic animals, anesthetized or conscious, under conditions of vasodilation or decreased cardiac function. The main consequence of hypotension is decreased organ perfusion and tissue injury/dysfunction. In the human literature there is no consensus on what is the threshold value for hypotension, and ranges from < 80 to < 100 mmHg for systolic blood pressure and from < 50 to < 70 mmHg for mean arterial blood pressure have been referenced for intraoperative hypotension. In veterinary medicine, similar values are referenced, despite marked differences in normal arterial blood pressure between species and with respect to humans. Therapeutic intervention involves fluid therapy to normalize volemia and use of sympathomimetics to enhance cardiac function and regulate peripheral vascular resistance. Despite these therapeutic measures, there is a subset of patients that are seemingly refractory and exhibit persistent hypotension. This review covers the physiological aspects that govern arterial blood pressure control and blood flow to tissues/organs, the pathophysiological mechanisms involved in hypotension and refractory hypotension, and therapeutic considerations and expectations that include proper interpretation of cardiovascular parameters, fluid recommendations and therapy rates, use of sympathomimetics and vasopressors, and newer approaches derived from the human literature.
Factors Influencing the Transborder Transmission of Brucellosis in Cattle Between Côte d'Ivoire and Mali: Evidence From Literature and Current Key Stakeholders
Authors: Oyetola Wilfried Délé , Diallo Kanny , Kreppel Katharina , Kone Philippe Soumahoro , Schelling Esther , Bonfoh Bassirou , Bada Alambedji Rianatou
Published: March 2021

Brucellosis is one of the main zoonoses affecting ruminants. Cattle and small ruminants are involved in transhumance and trade between Côte d'Ivoire and Mali. The endemic nature of the disease in both countries, connected through transhumance, poses unique challenges and requires more information to facilitate disease surveillance and the development of integrated control strategies. This study aimed to assess the main factors influencing the historical and current transborder transmission of brucellosis between Côte d'Ivoire and Mali. A literature review was conducted and data collection was performed through a participatory, transdisciplinary process by holding focus group discussions and interviews with key stakeholders. Cattle breeders, herdsmen, professionals of animal and human health, border control agents and experts took part. The data was analyzed to generate essential new knowledge for transborder brucellosis transmission factors and control strategies. From the literature, the seroprevalence of brucellosis in both countries varied from 11% (1987) to 20% (2013) and 15% (1972–1973) to 5% (2012–2014) in Mali and Côte d'Ivoire, respectively. The reduction of seroprevalence in Côte d'Ivoire was the result of the annual vaccination campaigns which lowered it from 28% (1978) to 14% (1984) after an increase due to livestock policy implemented in 1976. The meta-analysis and interviews jointly showed that the cross-border mobility was associated with the livestock development policy in Côte d'Ivoire as well as the ECOWAS act on the free movement of people and goods. This act supported the seasonal transhumance of livestock for access to pasture land in southern humid zones in Côte d'Ivoire. The seasonal mobility for grazing and trade was the main risk factor for the spread of brucellosis between pastoral zones of both countries. The existing legal health framework and border control mechanism do not achieve transborder surveillance to control brucellosis. Existing sanitary regulations should be adapted at regional scale to integrate a joint surveillance of high priority zoonotic diseases like brucellosis at border controls.
Increasing Embryonic Morphogen Nodal Expression Suggests Malignant Transformation in Colorectal Lesions and as a Potential Marker for CMS4 Subtype of Colorectal Cancer
Authors: Wang Xiaopai , Liu Shousheng , Cao Huijiao , Li Xiubo , Rong Yuming , Liu Guorong , Du Hong , Shen Hong
Published: March 2021

Nodal, an embryonic morphogen in TGF-β family, is related with tumorigenicity and progression in various tumors including colorectal cancer (CRC). However, the difference of Nodal expression between CRC and colorectal polyps has not yet been investigated. Besides, whether Nodal can be used as a marker for consensus molecular subtype classification-4 (CMS4) of CRC is also worth studying. We analyzed Nodal expression in patients of CRC (161), high-grade intraepithelial neoplasia (HGIN, 28) and five types of colorectal polyps (116). The Nodal expression difference among groups and the association between Nodal expression and clinicopathological features were analyzed. Two categories logistic regression model was used to predict the odds ratio (OR) of risk factors for high tumor-stroma percentage (TSP), and ROC curve was used to assess the diagnostic value of Nodal in predicting high TSP in CRC. We found that Nodal expression was significantly elevated in CRC and HGIN (p < 0.0001). The increased expression of Nodal was related with high TSP, mismatch repair-proficient (pMMR) status, lymph node metastasis and advanced AJCC stage (p < 0.05). Besides, Nodal expression was the only risk factor for high TSP (OR = 6.94; p < 0.001), and ROC curve demonstrated that Nodal expression was able to efficiently distinguish high and low TSP. In conclusion, different expression of Nodal between CRC/HGIN and benign lesions is suggestive of a promoting role for Nodal in colorectal tumor progression. Besides, Nodal might also be used as a potential marker for CMS4 subtype of CRC.