bluuebunny/crossref_metadata_2025 huggingface dataset:
Badminton Improves Executive Function in Adults Living with Mild Intellectual Disability
Authors: Wang Yifan , Wu Xueping , Chen Huawei
Published: February 2023

Background: Adults with intellectual disability have limited executive function—which includes working memory, cognitive flexibility, and inhibitory control subcomponents—making their ability to live independently challenging. The present study explored whether a badminton intervention program could improve the executive function of adults living with a mild intellectual disability, but with no physical disability. Methods: This randomized controlled study randomly assigned 30 adults with mild intellectual disabilities recruited from Shanghai Sunshine bases in Shanghai (20 males and 10 females; mean age, 35.80 (3.93) years) to a badminton intervention program (n = 15, training for 12 weeks, 3 times/week, 60 min each time) or the control group (n = 15), which received a typical physical education course consisting primarily of gymnastics. Correct response rates and response times on the Stroop test, n-back task, and task switching were analyzed using two-way analyses of variance, followed by simple effects tests to evaluate inhibitory control, working memory, and cognitive flexibility, respectively, before and after the badminton intervention. Results: No significant difference was detected between the badminton group and the control group (p > 0.05) for their pre-test scores on any subcomponent of executive function. A 2 × 2 repeated-measures analysis of variance showed a significant increase in accuracy in the inhibitory control task for the badminton group after the intervention (p < 0.05). In addition, the accuracy rate and reaction time in a working memory task were significantly improved in the badminton group after the intervention (p < 0.05). Although some improvement in cognitive flexibility was observed for this group after the intervention, it was not statistically significant (p > 0.05). In the control group, there was no significant difference in any executive function subcomponents after the intervention (p > 0.05). Conclusions: These results suggest that badminton may be used as an effective intervention to improve the executive function of adults with a mild intellectual disability and that our protocol may inform future badminton exercise intervention programs.
Occurrence, Risk, and Source of Heavy Metals in Lake Water Columns and Sediment Cores in Jianghan Plain, Central China
Authors: Wang Cong , Wang Kan , Zhou Wuquan , Li Yong , Zou Guoqing , Wang Zhi
Published: February 2023

Heavy metal pollution in lakes is an issue that endangers ecosystems worldwide; however, the vertical properties of heavy metals in the water columns and sediment cores of lakes have been rarely evaluated simultaneously. This study revealed the pollution, risks, and sources of heavy metals from surface water to deep sediments in four typical shallow lakes located in central China. The results showed that the concentrations of heavy metals, except Hg, had insignificant stratification in the water column. Heavy metals had three vertical profiles in sediment cores, i.e., the concentrations of As, Hg, Cd, Pb, and Mn in the surface sediment (0–9 cm) were higher than that in the bottom sediment (9–45 cm) (p < 0.05), the concentrations of Cr, Co, Fe, and Ni in the bottom sediment were higher than the surface sediment (p < 0.05), and the concentrations of Cu and Zn had no significant stratification. The Nemerow pollution index showed that heavy metal pollution dominated by Hg reached slight–moderate levels, and had higher levels in surface water than that in bottom water (p < 0.05). The Nemerow integrated risk index showed that the heavy metals had moderate–extreme potential ecological risks (Cd contributed 43.4%) in the sediments, and the ecological risk in surface sediment was significantly higher than that in bottom sediment (p < 0.01). Principal component analysis revealed that agriculture, transportation, and chemical industry were the major sources of heavy metals in water and surface sediments, while agriculture and steel-making were the primary sources in bottom sediments. This study provides valuable data and insight for the control of heavy metal pollution in lakes with high human activity loads.
Out-of-State Travel for Abortion among Texas Residents following an Executive Order Suspending In-State Services during the Coronavirus Pandemic
Authors: Sierra Gracia , Berglas Nancy F. , Hofler Lisa G. , Grossman Daniel , Roberts Sarah C. M. , White Kari
Published: February 2023

During the COVID-19 pandemic, existing and new abortion restrictions constrained people’s access to abortion care. We assessed Texas abortion patients’ out-of-state travel patterns before and during implementation of a state executive order that prohibited most abortions for 30 days in 2020. We received data on Texans who obtained abortions between February and May 2020 at 25 facilities in six nearby states. We estimated weekly trends in the number of out-of-state abortions related to the order using segmented regression models. We compared the distribution of out-of-state abortions by county-level economic deprivation and distance traveled. The number of Texas out-of-state abortions increased 14% the week after (versus before) the order was implemented (incidence rate ratio [IRR] = 1.14; 95% CI: 0.49, 2.63), and increased weekly while the order remained in effect (IRR = 1.64; 95% CI: 1.23, 2.18). Residents of the most economically disadvantaged counties accounted for 52% and 12% of out-of-state abortions before and during the order, respectively (p < 0.001). Before the order, 38% of Texans traveled ≥250 miles one way, whereas during the order 81% traveled ≥250 miles (p < 0.001). Texans’ long-distance travel for out-of-state abortion care and the socioeconomic composition of those less likely to travel reflect potential burdens imposed by future abortion bans.
Determinants of Depressive Symptoms in People Living with HIV: Findings from a Population-Based Study with a Gender Perspective
Authors: Bayes-Marin Ivet , Egea-Cortés Laia , Palacio-Vieira Jorge , Bruguera Andreu , Mesías-Gazmuri Jocelyn , Llibre Josep M. , Fernández Emma , Imaz Arkaitz , Forero Carlos G. , Agustí Cristina , Arbones-Fernández Laia , Miró José M. , Casabona Jordi , Reyes-Ureña Juliana
Published: February 2023

Depressive symptoms are common among people living with HIV (PLWH). The aim of this study was to identify the determinants of depressive symptoms in PLWH in Spain. A total of 1060 PLWH participated in this cross-sectional study and completed the Patient Health Questionnaire-9. The odds ratios for the presence of depressive symptoms were analyzed in a multivariable logistic regression model, including sociodemographic data, comorbidities, health-related behaviors, and social-environment-related variables. We found an overall prevalence of depressive symptoms of 21.42%; by subgroup, namely men, women, and transgender persons, prevalence was 18.13%, 32.81%, and 37.14%, respectively. Moreover, social isolation (OR = 1.05 [CI, 1.02–1.08]) and poor physical and mental quality of life (OR = 1.06 [CI, 1.02–1.09] and OR = 1.13 [CI, 1.09–1.17], respectively) were associated with depressive symptoms. As protective factors, we identified serodisclosure to more people (vs. none; OR = 0.39 [CI, 0.17–0.87]), satisfaction with social roles (OR = 0.86 [CI, 0.79–0.94]), better cognitive function (OR = 0.92 [CI, 0.89–0.95]), and sexualized drug use once in a lifetime (OR = 0.52 [CI, 0.29–0.93]). This study showed a high prevalence of depressive symptoms in PLWH, especially among women and transgender people. The association between psychosocial variables and depressive symptoms highlights the multidimensionality of the problem and identifies areas for intervention. This study found that the management of mental health issues is an area that needs to be improved and tailored to specific groups, with the aim of enhancing the well-being of PLWH.
Ethical, Legal, Organisational and Social Issues of Teleneurology: A Scoping Review
Authors: Torres-Castaño Alezandra , Abt-Sacks Analía , Toledo-Chávarri Ana , Suarez-Herrera José Carlos , Delgado-Rodríguez Janet , León-Salas Beatriz , González-Hernández Yadira , Carmona-Rodríguez Montserrat , Serrano-Aguilar Pedro
Published: February 2023

Background: Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. Teleneurology (TN) allows neurology to be applied when the doctor and patient are not present in the same place, and sometimes not at the same time. In February 2021, the Spanish Ministry of Health requested a health technology assessment report on the implementation of TN as a complement to face-to-face neurological care. Methods: A scoping review was conducted to answer the question on the ethical, legal, social, organisational, patient (ELSI) and environmental impact of TN. The assessment of these aspects was carried out by adapting the EUnetHTA Core Model 3.0 framework, the criteria established by the Spanish Network of Health Technology Assessment Agencies and the analysis criteria of the European Validate (VALues In Doing Assessments of healthcare TEchnologies) project. Key stakeholders were invited to discuss their concerns about TN in an online meeting. Subsequently, the following electronic databases were consulted from 2016 to 10 June 2021: MEDLINE and EMBASE. Results: 79 studies met the inclusion criteria. This scoping review includes 37 studies related to acceptability and equity, 15 studies developed during COVID and 1 study on environmental aspects. Overall, the reported results reaffirm the necessary complementarity of TN with the usual face-to-face care. Conclusions: This need for complementarity relates to factors such as acceptability, feasibility, risk of dehumanisation and aspects related to privacy and the confidentiality of sensitive data.
Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius’ Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia)
Authors: Speranskaya Anna S. , Artiushin Ilia V. , Samoilov Andrei E. , Korneenko Elena V. , Khabudaev Kirill V. , Ilina Elena N. , Yusefovich Alexander P. , Safonova Marina V. , Dolgova Anna S. , Gladkikh Anna S. , Dedkov Vladimir G. , Daszak Peter
Published: February 2023

Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius’ pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score −320.15) and the E. europaeus (docking score –294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.
Trajectories of Seroprevalence and Neutralizing Activity of Antibodies against SARS-CoV-2 in Southern Switzerland between July 2020 and July 2021: An Ongoing, Prospective Population-Based Cohort Study
Authors: Amati Rebecca , Piumatti Giovanni , Franscella Giovanni , Buttaroni Peter , Camerini Anne-Linda , Corna Laurie , Levati Sara , Fadda Marta , Fiordelli Maddalena , Annoni Anna Maria , Bezani Kleona , Amendola Antonio , Fragoso Corti Cristina , Sabatini Serena , Kaufmann Marco , Frei Anja , Puhan Milo Alan , Crivelli Luca , Albanese Emiliano ,   on behalf of the Corona Immunitas Ticino Study Group
Published: February 2023

Objectives: The COVID-19 pandemic continues, and evidence on infection- and vaccine-induced immunity is key. We assessed COVID-19 immunity and the neutralizing antibody response to virus variants across age groups in the Swiss population. Study Design: We conducted a cohort study in representative community-dwelling residents aged five years or older in southern Switzerland (total population 353,343), and we collected blood samples in July 2020 (in adults only, N = 646), November–December 2020 (N = 1457), and June–July 2021 (N = 885). Methods: We used a previously validated Luminex assay to measure antibodies targeting the spike (S) and the nucleocapsid (N) proteins of the virus and a high-throughput cell-free neutralization assay optimized for multiple spike protein variants. We calculated seroprevalence with a Bayesian logistic regression model accounting for the population’s sociodemographic structure and the test performance, and we compared the neutralizing activity between vaccinated and convalescent participants across virus variants. Results: The overall seroprevalence was 7.8% (95% CI: 5.4–10.4) by July 2020 and 20.2% (16.4–24.4) by December 2020. By July 2021, the overall seroprevalence increased substantially to 72.5% (69.1–76.4), with the highest estimates of 95.6% (92.8–97.8) among older adults, who developed up to 10.3 more antibodies via vaccination than after infection compared to 3.7 times more in adults. The neutralizing activity was significantly higher for vaccine-induced than infection-induced antibodies for all virus variants (all p values < 0.037). Conclusions: Vaccination chiefly contributed to the reduction in immunonaive individuals, particularly those in older age groups. Our findings on the greater neutralizing activity of vaccine-induced antibodies than infection-induced antibodies are greatly informative for future vaccination campaigns.
Offering and Asking for Help with Domestic Chores in Couple Relationships
Authors: Marici Marius , Clipa Otilia , Schipor Maria-Doina , Runcan Remus , Andrei Ana-Maria
Published: February 2023

Domestic chores are a topic of great interest for couple relationships since they are a source of conflict between intimate partners. The purpose of the present research is to investigate offering and asking for help with domestic chores and the respondents’ tendency to be intuitive or verbal or to do chores alone. A vignette applied to children and married adults. The respondents were 116 boys and 116 girls and 110 male partners and 300 female partners, who completed individual questionnaires, online using Google Forms, regarding helping behaviour. Research findings indicate that men are more verbal and women are more intuitive when offering help, but when asking for help with domestic chores, men and women are statistically similar. The present research raises questions about the role of gender differences in couple relationships, and about educational solutions for couples and provides opportunities for future research.
Characterization of Three Types of Recycled Aggregates from Different Construction and Demolition Waste: An Experimental Study for Waste Management
Authors: Saiz Martínez Pablo , Ferrández Daniel , Melane-Lavado Alberto , Zaragoza-Benzal Alicia
Published: February 2023

Achieving sustainable management and efficient use of natural resources stands out as one of the goals included in the Goals for Sustainable Development in the 2030 Agenda. The construction sector is currently far from presenting an efficient model in terms of treating waste generated by it. Variations in the physical and chemical properties of recycled aggregates coming from construction and demolition waste are one of the main reasons of their limited use in the production of construction materials. This research presents a physicochemical characterization of three different types of recycled aggregates coming from different types of waste: concrete, ceramic and mixed. Physical characterization shows that recycled concrete aggregate has better physical properties compared with mixed recycled aggregate and ceramic recycled aggregate, which makes it more suitable for use in masonry mortars and concrete, due to its higher dry density (2210.33 kg/m3), its lower content of fines (5.17%), its lower friability coefficient (24.60%), and its water absorption coefficient (6.70%). Chemical characterization shows that none of the tested recycled aggregates contains traces of harmful chemical agents that exceed the limits established by the reference regulations. Finally, the statistical analysis shows good homogeneity for these raw materials, obtaining low coefficients of variation and values within the recommended in each of the calculated confidence intervals.
Efficiency and Potential Evaluation to Promote Differentiated Low-Carbon Management in Chinese Counties
Authors: Zhang He , Peng Jingyi , Wang Rui , Guo Yuanyuan , He Jing , Yu Dahlia , Zhang Jianxun
Published: February 2023

Low-carbon management plays an important role in mitigating climate change and adapting to it. Localities should adopt differentiated low-carbon management policies according to the state of their environment. To help formulate specific and realistic low-carbon management policies, this paper took into account specific low-carbon management sectors. Likewise, it carefully considered the differences in various resource endowments and proposed a method for evaluating low-carbon management efficiency and potential. The method was applied to an empirical study from 2015 conducted on 1771 Chinese counties. Significant spatial heterogeneity was found during the research. The counties bordering central and Western China and the ones in the southeast coastal areas showed higher efficiency in the industrial sector. Southern and Northern China had higher efficiency in the housing and transportation sector, respectively. Moreover, counties in remote areas showed more potential in the industrial sector. Central China had higher potential in the housing sector, while counties bordering provinces had more potential in the transportation sector. Therefore, Chinese counties were divided into eight management zones where differentiated management strategies were identified to shape low-carbon management policies.
Prevalence of Burnout in Healthcare Workers of Tertiary-Care Hospitals during the COVID-19 Pandemic: A Cross-Sectional Survey from Two Central European Countries
Authors: Štěpánek Ladislav , Nakládalová Marie , Janošíková Magdaléna , Ulbrichtová Romana , Švihrová Viera , Hudečková Henrieta , Sovová Eliška , Sova Milan , Vévoda Jiří
Published: February 2023

COVID-19 has led to an unprecedented strain on healthcare workers (HCWs). This study aimed to determine the prevalence of burnout in hospital employees during a prolonged pandemic-induced burden on healthcare systems. An online survey among employees of a Czech and Slovak university hospital was conducted between November 2021 and January 2022, approximately when the incidence rates peaked in both countries. The Maslach Burnout Inventory—Human Services Survey was applied. We obtained 807 completed questionnaires (75.1% from Czech employees, 91.2% from HCWs, 76.2% from women; mean age of 42.1 ± 11 years). Burnout in emotional exhaustion (EE) was found in 53.2%, depersonalization (DP) in 33%, and personal accomplishment (PA) in 47.8% of respondents. In total, 148 (18.3%) participants showed burnout in all dimensions, 184 (22.8%) in two, and 269 (33.3%) in at least one dimension. Burnout in EE and DP (65% and 43.7%) prevailed in physicians compared to other HCWs (48.6% and 28.8%). Respondents from COVID-19-dedicated units achieved burnout in the EE and DP dimensions with higher rates than non-frontline HCWs (58.1% and 40.9% vs. 49.9% and 27.7%). Almost two years of the previous overloading of healthcare services, caused by the COVID-19 pandemic, resulted in the relatively high prevalence of burnout in HCWs, especially in physicians and frontline HCWs.
Severity and Management of Adverse Drug Reactions Reported by Patients and Healthcare Professionals: A Cross-Sectional Survey
Authors: Srisuriyachanchai Warisara , Cox Anthony R. , Kampichit Sirinya , Jarernsiripornkul Narumol
Published: February 2023

Adverse drug reaction (ADR) severity levels are mainly rated by healthcare professionals (HCPs), but patient ratings are limited. This study aimed to compare patient-rated and pharmacist-rated ADR severity levels and determined methods employed for ADR management and prevention by patients and HCPs. A cross-sectional survey was conducted in outpatients visiting two hospitals. Patients were asked about ADR experiences using a self-administered questionnaire, and additional information was retrieved from the medical records. In total, 617 out of 5594 patients had experienced ADRs (11.0%), but 419 patients were valid (68.0%). Patients commonly reported that their ADR severity level was moderate (39.4%), whereas pharmacists rated the ADRs as mild (52.5%). There was little agreement between patient-rated and pharmacist-rated ADR severity levels (κ = 0.144; p < 0.001). The major method of ADR management by physicians was drug withdrawal (84.7%), while for patients, it was physician consultation (67.5%). The main methods for ADR prevention by patients and HCPs were carrying an allergy card (37.2%) and recording drug allergy history (51.1%), respectively. A higher level of ADR bothersomeness was associated with higher ADR severity levels (p < 0.001). Patients and HCPs rated ADR severity and used ADR management and prevention methods differently. However, patient rating of ADR severity is a potential signal for severe ADR detection of HCPs.
Social and Behavioural Correlates of High Physical Activity Levels among Aboriginal Adolescent Participants of the Next Generation: Youth Wellbeing Study
Authors: Macniven Rona , McKay Christopher D. , Graham Simon , Gubhaju Lina , Williams Robyn , Williamson Anna , Joshy Grace , Evans John Robert , Roseby Robert , Porykali Bobby , Yashadhana Aryati , Ivers Rebecca , Eades Sandra
Published: February 2023

Physical activity typically decreases during teenage years and has been identified as a health priority by Aboriginal adolescents. We examined associations between physical activity levels and sociodemographic, movement and health variables in the Aboriginal led ‘Next Generation: Youth Well-being (NextGen) Study’ of Aboriginal people aged 10–24 years from Central Australia, Western Australia and New South Wales. Baseline survey data collected by Aboriginal researchers and Aboriginal youth peer recruiters from 2018 to 2020 examined demographics and health-related behaviours. Logistic regression was used to estimate odds ratios (OR) for engaging in high levels of physical activity in the past week (3–7 days; 0–2 days (ref), or ‘don’t remember’) associated with demographic and behavioural factors. Of 1170 adolescents, 524 (41.9%) had high levels of physical activity; 455 (36.4%) had low levels; 191 (15.3%) did not remember. Factors independently associated with higher odds of physical activity 3–7 days/week were low weekday recreational screen time [55.3% vs. 44.0%, OR 1.79 (1.16–2.76)], having non-smoking friends [50.4% vs. 25.0%, OR 2.27 (1.03–5.00)] and having fewer friends that drink alcohol [48.1% vs. 35.2%, OR 2.08 (1.05–4.14)]. Lower odds of high physical activity were independently associated with being female [40.2% vs. 50.9%, OR 0.57 (0.40–0.80)] and some findings differed by sex. The NextGen study provides evidence to inform the co-design and implementation of strategies to increase Aboriginal adolescent physical activity such as focusing on peer influences and co-occurring behaviours such as screen time.
Genome-Wide Identification and Abiotic Stress Response Analysis of PP2C Gene Family in Woodland and Pineapple Strawberries
Authors: Guo Lili , Lu Shixiong , Liu Tao , Nai Guojie , Ren Jiaxuan , Gou Huimin , Chen Baihong , Mao Juan
Published: February 2023

Protein phosphatase 2C (PP2C) is a negative regulator of serine/threonine residue protein phosphatase and plays an important role in abscisic acid (ABA) and abiotic-stress-mediated signaling pathways in plants. The genome complexity of woodland strawberry and pineapple strawberry is different due to the difference in chromosome ploidy. This study conducted a genome-wide investigation of the FvPP2C (Fragaria vesca) and FaPP2C (Fragaria ananassa) gene family. Fifty-six FvPP2C genes and 228 FaPP2C genes were identified from the woodland strawberry and pineapple strawberry genomes, respectively. FvPP2Cs were distributed on seven chromosomes, and FaPP2Cs were distributed on 28 chromosomes. The size of the FaPP2C gene family was significantly different from that of the FvPP2C gene family, but both FaPP2Cs and FvPP2Cs were localized in the nucleus, cytoplasm, and chloroplast. Phylogenetic analysis revealed that 56 FvPP2Cs and 228 FaPP2Cs could be divided into 11 subfamilies. Collinearity analysis showed that both FvPP2Cs and FaPP2Cs had fragment duplication, and the whole genome duplication was the main cause of PP2C gene abundance in pineapple strawberry. FvPP2Cs mainly underwent purification selection, and there were both purification selection and positive selection effects in the evolution of FaPP2Cs. Cis-acting element analysis found that the PP2C family genes of woodland and pineapple strawberries mainly contained light responsive elements, hormone responsive elements, defense and stress responsive elements, and growth and development-related elements. The results of quantitative real-time PCR (qRT-PCR) showed that the FvPP2C genes showed different expression patterns under ABA, salt, and drought treatment. The expression level of FvPP2C18 was upregulated after stress treatment, which may play a positive regulatory role in ABA signaling and abiotic stress response mechanisms. This study lays a foundation for further investigation on the function of the PP2C gene family.
Respiratory Infection and Inflammation in Cystic Fibrosis: A Dynamic Interplay among the Host, Microbes, and Environment for the Ages
Authors: Yu Christiaan , Kotsimbos Tom
Published: February 2023

The interplay between airway inflammation and infection is now recognized as a major factor in the pathobiology in cystic fibrosis (CF). A proinflammatory environment is seen throughout the CF airway resulting in classic marked and enduring neutrophilic infiltrations, irreversibly damaging the lung. Although this is seen to occur early, independent of infection, respiratory microbes arising at different timepoints in life and the world environment perpetuate this hyperinflammatory state. Several selective pressures have allowed for the CF gene to persist until today despite an early mortality. Comprehensive care systems, which have been a cornerstone of therapy for the past few decades, are now revolutionized by CF transmembrane conductance regulator (CTFR) modulators. The effects of these small-molecule agents cannot be overstated and can be seen as early as in utero. For an understanding of the future, this review looks into CF studies spanning the historical and present period.
Comparison of Tomato Transcriptomic Profiles Reveals Overlapping Patterns in Abiotic and Biotic Stress Responses
Authors: Amoroso Ciro Gianmaria , D’Esposito Daniela , Aiese Cigliano Riccardo , Ercolano Maria Raffaella
Published: February 2023

Until a few years ago, many studies focused on the transcriptomic response to single stresses. However, tomato cultivations are often constrained by a wide range of biotic and abiotic stress that can occur singularly or in combination, and several genes can be involved in the defensive mechanism response. Therefore, we analyzed and compared the transcriptomic responses of resistant and susceptible genotypes to seven biotic stresses (Cladosporium fulvum, Phytophthora infestans, Pseudomonas syringae, Ralstonia solanacearum, Sclerotinia sclerotiorum, Tomato spotted wilt virus (TSWV) and Tuta absoluta) and five abiotic stresses (drought, salinity, low temperatures, and oxidative stress) to identify genes involved in response to multiple stressors. With this approach, we found genes encoding for TFs, phytohormones, or participating in signaling and cell wall metabolic processes, participating in defense against various biotic and abiotic stress. Moreover, a total of 1474 DEGs were commonly found between biotic and abiotic stress. Among these, 67 DEGs were involved in response to at least four different stresses. In particular, we found RLKs, MAPKs, Fasciclin-like arabinogalactans (FLAs), glycosyltransferases, genes involved in the auxin, ET, and JA pathways, MYBs, bZIPs, WRKYs and ERFs genes. Detected genes responsive to multiple stress might be further investigated with biotechnological approaches to effectively improve plant tolerance in the field.
Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting
Authors: Seiberl Michael , Feige Julia , Hilpold Patrick , Hitzl Wolfgang , Machegger Lukas , Buchmann Arabella , Khalil Michael , Trinka Eugen , Harrer Andrea , Wipfler Peter , Moser Tobias
Published: February 2023

Serum neurofilament light chain (sNfL) is an intensely investigated biomarker in multiple sclerosis (MS). The aim of this study was to explore the impact of cladribine (CLAD) on sNfL and the potential of sNfL as a predictor of long-term treatment response. Data were gathered from a prospective, real-world CLAD cohort. We measured sNfL at baseline (BL-sNfL) and 12 months (12Mo-sNfL) after CLAD start by SIMOA. Clinical and radiological assessments determined fulfilment of “no evidence of disease activity” (NEDA-3). We evaluated BL-sNfL, 12M-sNfL and BL/12M sNfL ratio (sNfL-ratio) as predictors for treatment response. We followed 14 patients for a median of 41.5 months (range 24.0–50.0). NEDA-3 was fulfilled by 71%, 57% and 36% for a period of 12, 24 and 36 months, respectively. We observed clinical relapses in four (29%), MRI activity in six (43%) and EDSS progression in five (36%) patients. CLAD significantly reduced sNfL (BL-sNfL: mean 24.7 pg/mL (SD ± 23.8); 12Mo-sNfL: mean 8.8 pg/mL (SD ± 6.2); p = 0.0008). We found no correlation between BL-sNfL, 12Mo-sNfL and ratio-sNfL and the time until loss of NEDA-3, the occurrence of relapses, MRI activity, EDSS progression, treatment switch or sustained NEDA-3. We corroborate that CLAD decreases neuroaxonal damage in MS patients as determined by sNfL. However, sNfL at baseline and at 12 months failed to predict clinical and radiological treatment response in our real-world cohort. Long-term sNfL assessments in larger studies are essential to explore the predictive utility of sNfL in patients treated with immune reconstitution therapies.
Potent Therapeutic Strategies for COVID-19 with Single-Domain Antibody Immunoliposomes Neutralizing SARS-CoV-2 and Lip/cGAMP Enhancing Protective Immunity
Authors: Zhou Yajun , Lu Xing , Wang Xiaoqing , Ying Tianlei , Tan Xiangshi
Published: February 2023

The worldwide spread of COVID-19 continues to impact our lives and has led to unprecedented damage to global health and the economy. This highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. We modified a single-domain antibody, SARS-CoV-2 VHH, to the surface of the liposomes. These immunoliposomes demonstrated a good neutralizing ability, but could also carry therapeutic compounds. Furthermore, we used the 2019-nCoV RBD-SD1 protein as an antigen with Lip/cGAMP as the adjuvant to immunize mice. Lip/cGAMP enhanced the immunity well. It was demonstrated that the combination of RBD-SD1 and Lip/cGAMP was an effective preventive vaccine. This work presented potent therapeutic anti-SARS-CoV-2 drugs and an effective vaccine to prevent the spread of COVID-19.
The Effects of Interstitial Lung Diseases on Alveolar Extracellular Vesicles Profile: A Multicenter Study
Authors: d’Alessandro Miriana , Gangi Sara , Soccio Piera , Cantó Elisabet , Osuna-Gómez Rubén , Bergantini Laura , Cameli Paolo , Fabbri Gaia , Croce Sara , Scioscia Giulia , Montuori Giusy , Fanetti Matteo , Moriondo Giorgia , Mezzasalma Fabrizio , Castillo Diego , Lacedonia Donato , Vidal Silvia , Bargagli Elena
Published: February 2023

Diagnosis of interstitial lung diseases (ILD) is difficult to perform. Extracellular vesicles (EVs) facilitate cell-to-cell communication, and they are released by a variety of cells. Our goal aimed to investigate EV markers in bronchoalveolar lavage (BAL) from idiopathic pulmonary fibrosis (IPF), sarcoidosis and hypersensitivity pneumonitis (HP) cohorts. ILD patients followed at Siena, Barcelona and Foggia University Hospitals were enrolled. BAL supernatants were used to isolate the EVs. They were characterized by flow cytometry assay through MACSPlex Exsome KIT. The majority of alveolar EV markers were related to the fibrotic damage. CD56, CD105, CD142, CD31 and CD49e were exclusively expressed by alveolar samples from IPF patients, while HP showed only CD86 and CD24. Some EV markers were common between HP and sarcoidosis (CD11c, CD1c, CD209, CD4, CD40, CD44, CD8). Principal component analysis distinguished the three groups based on EV markers with total variance of 60.08%. This study has demonstrated the validity of the flow cytometric method to phenotype and characterize EV surface markers in BAL samples. The two granulomatous diseases, sarcoidosis and HP, cohorts shared alveolar EV markers not revealed in IPF patients. Our findings demonstrated the viability of the alveolar compartment allowing identification of lung-specific markers for IPF and HP.
Characterization of RAGE and CK2 Expressions in Human Fetal Membranes
Authors: Coste Karen , Bruet Shaam , Chollat-Namy Caroline , Filhol Odile , Cochet Claude , Gallot Denis , Marceau Geoffroy , Blanchon Loïc , Sapin Vincent , Belville Corinne
Published: February 2023

At the feto-maternal interface, fetal membranes (FM) play a crucial role throughout pregnancy. FM rupture at term implicates different sterile inflammation mechanisms including pathways activated by the transmembrane glycoprotein receptor for advanced glycation end-products (RAGE) belonging to the immunoglobulin superfamily. As the protein kinase CK2 is also implicated in the inflammation process, we aimed to characterize the expressions of RAGE and the protein kinase CK2 as a candidate regulator of RAGE expression. The amnion and choriodecidua were collected from FM explants and/or primary amniotic epithelial cells throughout pregnancy and at term in spontaneous labor (TIL) or term without labor (TNL). The mRNA and protein expressions of RAGE and the CK2α, CK2α′, and CK2β subunits were investigated using reverse transcription quantitative polymerase chain reaction and Western blot assays. Their cellular localizations were determined with microscopic analyses, and the CK2 activity level was measured. RAGE and the CK2α, CK2α′, and CK2β subunits were expressed in both FM layers throughout pregnancy. At term, RAGE was overexpressed in the amnion from the TNL samples, whereas the CK2 subunits were expressed at the same level in the different groups (amnion/choriodecidua/amniocytes, TIL/TNL), without modification of the CK2 activity level and immunolocalization. This work paves the way for future experiments regarding the regulation of RAGE expression by CK2 phosphorylation.
Combination of Copper Metallodendrimers with Conventional Antitumor Drugs to Combat Cancer in In Vitro Models
Authors: Hołota Marcin , Michlewska Sylwia , Garcia-Gallego Sandra , del Olmo Natalia Sanz , Ortega Paula , Bryszewska Maria , de la Mata Francisco Javier , Ionov Maksim
Published: February 2023

Copper carbosilane metallodendrimers containing chloride ligands and nitrate ligands were mixed with commercially available conventional anticancer drugs, doxorubicin, methotrexate and 5-fluorouracil, for a possible therapeutic system. To verify the hypothesis that copper metallodendrimers can form conjugates with anticancer drugs, their complexes were biophysically characterized using zeta potential and zeta size methods. Next, to confirm the existence of a synergetic effect of dendrimers and drugs, in vitro studies were performed. The combination therapy has been applied in two cancer cell lines: MCF-7 (human breast cancer cell line) and HepG2 (human liver carcinoma cell line). The doxorubicin (DOX), methotrexate (MTX) and 5-fluorouracil (5-FU) were more effective against cancer cells when conjugated with copper metallodendrimers. Such combination significantly decreased cancer cell viability when compared to noncomplexed drugs or dendrimers. The incubation of cells with drug/dendrimer complexes resulted in the increase of the reactive oxygen species (ROS) levels and the depolarization of mitochondrial membranes. Copper ions present in the dendrimer structures enhanced the anticancer properties of the whole nanosystem and improved drug effects, inducing both the apoptosis and necrosis of MCF-7 (human breast cancer cell line) and HepG2 (human liver carcinoma cell line) cancer cells.
Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells
Authors: Domijan Ana-Marija , Hercog Klara , Štampar Martina , Gajski Goran , Gerić Marko , Sokolović Marijana , Žegura Bojana
Published: February 2023

The study aimed to investigate toxicity and the mechanism of toxicity of two Fusarium mycotoxins, deoxynivalenol (DON) and zearalenone (ZEA). DON and ZEA were applied to HepG2 cells as single compounds and in combination at low environmentally relevant concentrations. HepG2 cells were exposed to DON (0.5, 1, and 2 µM), ZEA (5, 10, and 20 µM) or their combinations (1 µM DON + 5 µM ZEA, 1 µM DON + 10 µM ZEA and 1 µM DON + 20 µM ZEA) for 24 h and cell viability, DNA damage, cell cycle and proliferation were assessed. Both mycotoxins reduced cell viability, however, combined treatment with DON and ZEA resulted in higher reduction of cell viability. DON (1 µM) induced primary DNA damage, while DON (1 µM) in combination with higher ZEA concentrations showed antagonistic effects compared to DON alone at 1 µM. DON arrested HepG2 cells in G2 phase and significantly inhibited cell proliferation, while ZEA had no significant effect on cell cycle. The combined treatment with DON and ZEA arrested cells in G2 phase to a higher extend compared to treatment with single mycotoxins. Potentiating effect observed after DON and ZEA co-exposure at environmentally relevant concentrations indicates that in risk assessment and setting governments’ regulations, mixtures of mycotoxins should be considered.
Graft-versus-Host Disease Modulation by Innate T Cells
Authors: Fang Ying , Zhu Yichen , Kramer Adam , Chen Yuning , Li Yan-Ruide , Yang Lili
Published: February 2023

Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft-versus-host disease (GvHD), induced by the mismatched major histocompatibility complex (MHC) between healthy donors and recipients, leading to severe complications and death. To address this issue and increase the potential for allogeneic cell therapies in clinical practice, minimizing GvHD is a crucial challenge. Innate T cells, encompassing subsets of T lymphocytes including mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδ T) cells, offer a promising solution. These cells express MHC-independent T-cell receptors (TCRs), allowing them to avoid MHC recognition and thus GvHD. This review examines the biology of these three innate T-cell populations, evaluates research on their roles in GvHD modulation and allogeneic stem cell transplantation (allo HSCT), and explores the potential futures for these therapies.
TOMM40 Genetic Variants Cause Neuroinflammation in Alzheimer’s Disease
Authors: Chen Yi-Chun , Chang Shih-Cheng , Lee Yun-Shien , Ho Wei-Min , Huang Yu-Hua , Wu Yah-Yuan , Chu Yi-Chuan , Wu Kuan-Hsuan , Wei Li-Shan , Wang Hung-Li , Chiu Ching-Chi
Published: February 2023

Translocase of outer mitochondrial membrane 40 (TOMM40) is located in the outer membrane of mitochondria. TOMM40 is essential for protein import into mitochondria. TOMM40 genetic variants are believed to increase the risk of Alzheimer’s disease (AD) in different populations. In this study, three exonic variants (rs772262361, rs157581, and rs11556505) and three intronic variants (rs157582, rs184017, and rs2075650) of the TOMM40 gene were identified from Taiwanese AD patients using next-generation sequencing. Associations between the three TOMM40 exonic variants and AD susceptibility were further evaluated in another AD cohort. Our results showed that rs157581 (c.339T > C, p.Phe113Leu, F113L) and rs11556505 (c.393C > T, p.Phe131Leu, F131L) were associated with an increased risk of AD. We further utilized cell models to examine the role of TOMM40 variation in mitochondrial dysfunction that causes microglial activation and neuroinflammation. When expressed in BV2 microglial cells, the AD-associated mutant (F113L) or (F131L) TOMM40 induced mitochondrial dysfunction and oxidative stress-induced activation of microglia and NLRP3 inflammasome. Pro-inflammatory TNF-α, IL-1β, and IL-6 released by mutant (F113L) or (F131L) TOMM40-activated BV2 microglial cells caused cell death of hippocampal neurons. Taiwanese AD patients carrying TOMM40 missense (F113L) or (F131L) variants displayed an increased plasma level of inflammatory cytokines IL-6, IL-18, IL-33, and COX-2. Our results provide evidence that TOMM40 exonic variants, including rs157581 (F113L) and rs11556505 (F131L), increase the AD risk of the Taiwanese population. Further studies suggest that AD-associated mutant (F113L) or (F131L) TOMM40 cause the neurotoxicity of hippocampal neurons by inducing the activation of microglia and NLRP3 inflammasome and the release of pro-inflammatory cytokines.
Molecular Accounting and Profiling of Human Respiratory Microbial Communities: Toward Precision Medicine by Targeting the Respiratory Microbiome for Disease Diagnosis and Treatment
Authors: Alsayed Ahmad R. , Abed Anas , Khader Heba A. , Al-Shdifat Laith M. H. , Hasoun Luai , Al-Rshaidat Mamoon M. D. , Alkhatib Mohammad , Zihlif Malek
Published: February 2023

The wide diversity of microbiota at the genera and species levels across sites and individuals is related to various causes and the observed differences between individuals. Efforts are underway to further understand and characterize the human-associated microbiota and its microbiome. Using 16S rDNA as a genetic marker for bacterial identification improved the detection and profiling of qualitative and quantitative changes within a bacterial population. In this light, this review provides a comprehensive overview of the basic concepts and clinical applications of the respiratory microbiome, alongside an in-depth explanation of the molecular targets and the potential relationship between the respiratory microbiome and respiratory disease pathogenesis. The paucity of robust evidence supporting the correlation between the respiratory microbiome and disease pathogenesis is currently the main challenge for not considering the microbiome as a novel druggable target for therapeutic intervention. Therefore, further studies are needed, especially prospective studies, to identify other drivers of microbiome diversity and to better understand the changes in the lung microbiome along with the potential association with disease and medications. Thus, finding a therapeutic target and unfolding its clinical significance would be crucial.
The Gut–Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology
Authors: Guo Yuxi , Chen Xuefeng , Gong Pin , Li Guoliang , Yao Wenbo , Yang Wenjuan
Published: February 2023

The intestine is considered to be a vital digestive organ to absorb nutrients and is the largest immune organ, while numerous microorganisms coexist with the host. It is well known that the complex interactions between the gut microbiota and the host’s immune system inevitably affect the function of other organs, creating an “axis” between them. During the past few years, a new technique based mainly on microfluidics and cell biology has been developed to emulate the structure, function, and microenvironment of the human gut, called the “gut-on-chip”. This microfluidic chip provides insight into key aspects of gut function in health and disease, such as the gut–brain axis, gut–liver axis, gut–kidney axis, and gut–lung axis. In this review, we first describe the basic theory of the gut axis and the various composition and parameter monitoring of the gut microarray systems, as well as summarize the development and emerging advances in the gut–organ-on-chip, with a focus on the host-gut flora and nutrient metabolism, and highlight their role in pathophysiological studies. In addition, this paper discusses the challenges and prospects for the current development and further use of the gut–organ-on-chip platform.
Water Dynamics in Highly Concentrated Protein Systems—Insight from Nuclear Magnetic Resonance Relaxometry
Authors: Kruk Danuta , Kasparek Adam , Masiewicz Elzbieta , Kolodziejski Karol , Cybulski Radoslaw , Nowak Bartosz
Published: February 2023

1H spin-lattice relaxation experiments have been performed for water–Bovine Serum Albumin (BSA) mixtures, including 20%wt and 40%wt of BSA. The experiments have been carried out in a frequency range encompassing three orders of magnitude, from 10 kHz to 10 MHz, versus temperature. The relaxation data have been thoroughly analyzed in terms of several relaxation models with the purpose of revealing the mechanisms of water motion. For this purpose, four relaxation models have been used: the data have been decomposed into relaxation contributions expressed in terms of Lorentzian spectral densities, then three-dimensional translation diffusion has been assumed, next two-dimensional surface diffusion has been considered, and eventually, a model of surface diffusion mediated by acts of adsorption to the surface has been employed. In this way, it has been demonstrated that the last concept is the most plausible. Parameters describing the dynamics in a quantitative manner have been determined and discussed.
Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review
Authors: Fioretto Bianca Saveria , Rosa Irene , Matucci-Cerinic Marco , Romano Eloisa , Manetti Mirko
Published: February 2023

Systemic sclerosis (SSc, scleroderma) is a multifaceted rare connective tissue disease whose pathogenesis is dominated by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and both cutaneous and visceral fibrosis. Microvascular impairment represents the initial event of the disease, preceding fibrosis by months or years and accounting for the main disabling and/or life-threatening clinical manifestations, including telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy, ischemic digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. Despite a variety of available treatment options, treatment of SSc-related vascular disease remains problematic, even considering SSc etherogenity and the quite narrow therapeutic window. In this context, plenty of studies have highlighted the great usefulness in clinical practice of vascular biomarkers allowing clinicians to assess the evolution of the pathological process affecting the vessels, as well as to predict the prognosis and the response to therapy. The current narrative review provides an up-to-date overview of the main candidate vascular biomarkers that have been proposed for SSc, focusing on their main reported associations with characteristic clinical vascular features of the disease.