bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Mental Health Challenges and Coping Behaviour of Lesbian, Gay, and Bisexual Students at an Institution of Higher Learning
Authors: Sumbane Gsakani Olivia , Makua Nogwane Maureen
Published: March 2023

The South African university community is predominantly heterosexual, which fosters stigmatisation and discrimination against LGBTQI students despite the efforts to create conditions where LGBTQI students can succeed academically, socially, and personally. The study aimed to explore and describe the challenges experienced by LGBTQI students and their mental well-being as well as the coping behaviours adopted in a university in South Africa. This was accomplished using a descriptive phenomenological approach. A snowballing sampling method was used to select ten students who identified themselves as gay, lesbian, and bisexual (LGB). Semi-structured one-on-one interviews were conducted, and data were analysed thematically. The students perceived character defects stigma from fellow students and lecturers in and out of class. The mental health challenges experienced included a diminished sense of safety, lack of a sense of belonging, low self-esteem, and acting out of character. As a result, confrontation, passive withdrawal, and active dependent behaviour were utilised as different types of coping behaviour. The LGB students were subjected to stigma that negatively affected their mental health. Therefore, creating awareness about the rights of LGBTQI students to education, safety, and self-determination is recommended.
Does China’s Carbon Trading Pilot Policy Reduce Carbon Emissions? Empirical Analysis from 285 Cities
Authors: Yang Xuehui , Zhang Jiaping , Bi Lehua , Jiang Yiming
Published: March 2023

This article studies the influence of the Carbon Trading Pilot Policy (CTPP) on carbon emissions by constructing the balanced panel data from 2003 to 2020 for 285 cities in China above the prefecture level. Difference-in-Difference (DID) method is used to test the influence and the mechanism. (1) The findings suggested that CTPP has dramatically reduced China’s carbon emissions by 6.21%. The parallel trend test shows that the premise of DID is reliable. (2) A variety of robustness tests, such as the instrumental variable method for endogeneity, Propensity Score Matching (PSM) for sample selection bias, variable substitution, time–bandwidth change, and exclusion of policy intervention, show that the conclusion is still robust. (3) The mediation mechanism test indicates that CTPP can promote the reduction in carbon emissions by promoting Green Consumption Transformation (GCT), improving Ecological Efficiency (EE), and promoting Industrial Structure Upgrading (ISU). GCT contributes the most, followed by EE and ISU. (4) The analysis of the heterogeneity reveals that CTPP has a greater effect on carbon emission reduction in central and peripheral cities in China. This study provides policy implications for China and similar developing countries in the face of carbon reduction.
Health Communication in the Time of COVID-19 Pandemic: A Qualitative Analysis of Italian Advertisements
Authors: Scardigno Rosa , Musso Pasquale , Cicirelli Paolo Giovanni , D’Errico Francesca
Published: March 2023

In the climate of great uncertainty characterizing the COVID-19 pandemic, health communication played a significant role: several communicative strategies and channels were used to inform, educate and alert. Entropy-related risks were soon translated into the “infodemic”, a wide-spread phenomenon with psychosocial and cultural roots. Therefore, new challenges for public institutions occurred: public health communication, especially expressed through advertising and audiovisual spots, was engaged to offer key support in combatting the disease, mitigating its effects and supporting health and psychological wellbeing. This work aims to investigate how the Italian public institutions addressed those challenges by employing institutional spots. We tried to answer two main research questions: (a) in line with the literature concerning persuasive communication, what were the main variables that social advertising concerning health attitudes and behaviors relied on; and (b) how the different variables were combined to propose specific communicative pathways following both the different waves/phases of the COVID-19 pandemic and the elaboration likelihood model. To answer these questions, 34 Italian spots were analyzed by means of qualitative multimodal analysis (including scopes, major narratives themes, central and peripheral cues). The results enabled us to individuate different communicative pathways, oriented by inclusivity, functionality and contamination, in line with different rounds as well as with the holistic configurations of cultural narratives, central and peripheral cues.
Ecological Risk Assessment of Geological Disasters Based on Probability-Loss Framework: A Case Study of Fujian, China
Authors: Zong Leli , Zhang Ming , Chen Zi , Niu Xiaonan , Chen Guoguang , Zhang Jie , Zhou Mo , Liu Hongying
Published: March 2023

Geological disaster could pose a great threat to human development and ecosystem health. An ecological risk assessment of geological disasters is critical for ecosystem management and prevention of risks. Herein, based on the “probability-loss” theory, a framework integrating the hazard, vulnerability, and potential damage for assessing the ecological risk of geological disasters was proposed and applied to Fujian Province. In the process, a random forest (RF) model was implemented for hazard assessment by integrating multiple factors, and landscape indices were adopted to analyze vulnerability. Meanwhile, ecosystem services and spatial population data were used to characterize the potential damage. Furthermore, the factors and mechanisms that impact the hazard and influence risk were analyzed. The results demonstrate that (1) the regions exhibiting high and very high levels of geological hazard cover an area of 10.72% and 4.59%, respectively, and are predominantly concentrated in the northeast and inland regions, often distributed along river valleys. Normalized difference vegetation index (NDVI), precipitation, elevation, and slope are the most important factors for the hazard. (2) The high ecological risk of the study area shows local clustering and global dispersion. Additionally, human activities have a significant influence on ecological risk. (3) The assessment results based on the RF model have high reliability with a better performance compared with the information quantity model, especially when identifying high-level hazard areas. Our study will improve research on the ecological risk posed by geological disasters and provide effective information for ecological planning and disaster mitigation.
Preventive Measures among Healthcare Workers (HCWs) during the COVID-19 Pandemic
Authors: Rodríguez-González Robert , Galloza Aleksis , Medina Edgar J. , Oliver Valeria , Rodríguez Natalia I. , Ramos-Colón Elizabeth , Velázquez-Ferrer Mileily , Rivera-Alers Dayaneira , Vargas Wanda , Rivera-Amill Vanessa
Published: March 2023

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), placed health systems worldwide under immense pressure, and healthcare workers (HCWs) were at the front lines. The Puerto Rico Department of Health confirmed the first case of COVID-19 in March 2020. We aimed to assess whether COVID-19 preventive measures implemented by HCWs were effective in a work scenario before vaccine availability. We conducted a descriptive cross-sectional study from July to December 2020 to evaluate the use of personal protective equipment (PPE), hygiene guidelines, and other measures taken by HCWs to prevent the spread of SARS-CoV-2. We collected nasopharyngeal specimens for molecular testing at the beginning of the study and follow-up. We recruited 62 participants aged 30–59 (79% women). Participants recruited from hospitals, clinical laboratories, and private practice included medical technologists (33%), nurses (28%), respiratory therapists (2%), physicians (11%), and others (26%). Among our participants, nurses were at higher risk (p < 0.05) of infection. We identified that 87% of participants followed the hygiene recommendation guidelines. In addition, all participants practiced handwashing or disinfection before or after caring for each patient. All participants tested negative for SARS-CoV-2 during the study period. On follow-up, all study participants reported being vaccinated against COVID-19. The implementation of PPE and hygiene measures showed high efficacy as a prevention method against SARS-CoV-2 infection when vaccines and treatment were not widely available in Puerto Rico.
The Combination of Hearing Impairment and Frailty Is Associated with Cognitive Decline among Community-Dwelling Elderly in Japan
Authors: Kawamura Akie , Kamide Naoto , Ando Masataka , Murakami Takeshi , Shahzad Machiko T. , Takahashi Kayoko
Published: March 2023

Hearing impairment and frailty are associated with cognitive decline in older people. This study aimed to investigate the effect of the interaction between hearing impairment and frailty on cognitive decline in community-dwelling older people. A mail survey of community-dwelling, older people (age ≥ 65 years) who lived independently was conducted. Cognitive decline was defined using the self-administered dementia checklist (≥18 out of 40 points). Hearing impairment was assessed using a validated self-rated questionnaire. Furthermore, frailty was assessed using the Kihon checklist, and robust, pre-frailty, and frailty groups were identified. Multivariate logistic regression analysis, adjusted for potential confounding factors, was performed to determine the association of the interaction between hearing impairment and frailty with cognitive decline. Data obtained from 464 participants were analyzed. Hearing impairment was independently associated with cognitive decline. Additionally, the interaction term of hearing impairment and frailty was significantly related to cognitive decline. For participants in the robust group, hearing impairment was not associated with cognitive decline. In contrast, for participants in the pre-frailty or frailty groups, hearing impairment was associated with cognitive decline. The association between hearing impairment and cognitive decline was affected by frailty status in community-dwelling, older people.
“What If Others Think I Look Like…” The Moderating Role of Social Physique Anxiety and Sex in the Relationship between Physical Activity and Life Satisfaction in Swiss Adolescents
Authors: Meyer Silvia , Lang Christin , Ludyga Sebastian , Grob Alexander , Gerber Markus
Published: March 2023

Background: Physical activity has been shown to have a positive effect on life satisfaction in adolescents. Despite these benefits, physical activity levels constantly drop during adolescence, suggesting potential interfering factors in this link. Since worries about physical appearance are an important issue at this age, this study aims to examine the relationship between physical activity and life satisfaction in adolescents and explores possible moderating effects of social physique anxiety and sex. Methods: We used data from a longitudinal study with N = 864 vocational students (mean age = 17.87 years, range: 16–25, 43% female) from Switzerland. To test our hypotheses, we used multiple hierarchical regression analyses as well as simple slope analyses. Results: We did not find a significant direct effect of physical activity on life satisfaction. However, we found a significant two-way interaction between physical activity and social physique anxiety. An additional significant three-way interaction occurred, indicating that a positive effect of physical activity on life satisfaction holds only for female adolescents with low social physique anxiety levels. Conclusions: This study highlights the importance of developing a healthy relationship with one’s body to fully benefit from physical activity, especially for female adolescents. Taken together, these results reveal important considerations for physical activity educators.
Bracket Bond Failures: Incidence and Association with Different Risk Factors—A Retrospective Study
Authors: Jakavičė Reda , Kubiliūtė Kristina , Smailienė Dalia
Published: March 2023

Background: Bracket bonding failure is one of the relevant problems in fixed orthodontics therapy, which affects the total treatment and quality of treatment results. The purpose of this retrospective study was to evaluate the frequency of bracket bond failure and find out risk factors. Methods: A total of 101 patients with an age range of 11–56 years were included in this retrospective study and treated for a mean period of 30.2 months. Inclusion criteria were: males and females with permanent dentition and completed orthodontic treatment in both fully bonded dental arches. Risk factors were calculated using binary logistic regression analysis. Results: The overall bracket failure rate was 14.65%. The bracket failure rate was significantly higher in the younger patients’ group (p = 0.003). In most cases, patients experienced bracket failures in the first month of the treatment. Most of the bracket bond failures occurred on the left lower first molar (29.1%) and were twice as common in the lower dental arch (66.98%). Patients with increased overbite had an increased likelihood of bracket loss (p = 0.042). Class II malocclusion increased the relative risk of bracket failure, while Class III decreased the rate of bracket failure, but the difference was not statistically significant (p = 0.093). Conclusions: The bracket bond failure rate was higher in younger patients than in older patients. Brackets placed on mandibular molars and premolars had the highest failure rate. Class II was associated with an increased bracket failure rate. Increased overbite statistically significantly increases bracket failure rate.
Validity and Reliability of Short-Term Heart Rate Variability Parameters in Older People in Response to Physical Exercise
Authors: Castillo-Aguilar Matías , Mabe Castro Matías , Mabe Castro Diego , Valdés-Badilla Pablo , Herrera-Valenzuela Tomás , Guzmán-Muñoz Eduardo , Lang Morin , Niño Méndez Oscar , Núñez-Espinosa Cristian
Published: March 2023

Background: Currently, and to the best of our knowledge, there is no standardized protocol to measure the effect of low- to moderate-intensity physical exercise on autonomic modulation focused in older people. Aim: Validate a test–retest short-term exercise protocol for measuring the autonomic response through HRV in older people. Methods: A test–retest study design was used. The participants were selected through intentional non-probabilistic sampling. A total of 105 older people (male: 21.9%; female: 78.1%) were recruited from a local community. The assessment protocol evaluated HRV before and immediately after the 2-min step test. It was performed twice on the same day, considering a time of three chronological hours between the two measurements. Results: The posterior distribution of estimated responses in the Bayesian framework suggests moderate to strong evidence favoring a null effect between measurements. In addition, there was moderate to robust agreement between heart rate variability (HRV) indices and assessments, except for low frequency and very low frequency, which showed weak agreement. Conclusions: Our results provide moderate to strong evidence for using HRV to measure cardiac autonomic response to moderate exercise, suggesting that it is sufficiently reliable to show similar results to those shown in this test–retest protocol.
How Did the COVID-19 Pandemic Increase Salience of Intimate Partner Violence on the Policy Agenda?
Authors: Lebrun Luce , Thiry Aline , Fallon Catherine
Published: March 2023

Belgian authorities, like most authorities in European countries, resorted to unprecedented measures in response to the spread of the COVID-19 pandemic between March 2020 and May 2022. This exceptional context highlighted the issue of intimate partner violence (IPV) in an unprecedented way. At a time when many other issues are being put on hold, IPV is being brought to the fore. This article investigated the processes that have led to increasing political attention to domestic violence in Belgium. To this end, a media analysis and a series of semi-structured interviews were conducted. The materials, collected and analyzed by mobilizing the framework of Kingdon’s streams theory, allowed us to present the agenda-setting process in its complexity and the COVID-19 as a policy window. The main policy entrepreneurs were NGOs and French-speaking feminist women politicians. Together, they rapidly mobilized sufficient resources to implement public intervention that had already been proposed in the preceding years, but which had been waiting for funding. By doing so, they responded during the peak of the pandemic to requests and needs that had already been expressed in a “non-crisis” context.
When the Going Gets Tough and the Environment Is Rough: The Role of Departmental Level Hostile Work Climate in the Relationships between Job Stressors and Workplace Bullying
Authors: Zahlquist Lena , Hetland Jørn , Notelaers Guy , Rosander Michael , Einarsen Ståle Valvatne
Published: March 2023

In line with the work environment hypothesis, the present study investigates whether department-level perceptions of hostile work climate moderate the relationship between psychosocial predictors of workplace bullying (i.e., role conflicts and workload) and exposure to bullying behaviours in the workplace. The data were collected among all employees in a Belgian university and constitutes of 1354 employees across 134 departments. As hypothesized, analyses showed positive main effects of role conflict and workload on exposure to bullying behaviours. In addition, the hypothesized strengthening effect of department-level hostile work climate on the relationship between individual-level job demands and individual exposure to bullying behaviours was significant for role conflict. Specifically, the positive relationship between role conflict and exposure to bullying behaviours was stronger among employees working in departments characterized by a pronounced hostile work climate. In contrast to our predictions, a positive relationship existed between workload and exposure to bullying behaviours, yet only among individuals in departments with low hostile work climate. These findings contribute to the bullying research field by showing that hostile work climate may strengthen the impact of role stress on bullying behaviours, most likely by posing as an additional distal stressor, which may fuel a bullying process. These findings have important theoretical as well as applied implications.
Real-Time PCR Quantification of 87 miRNAs from Cerebrospinal Fluid: miRNA Dynamics and Association with Extracellular Vesicles after Severe Traumatic Brain Injury
Authors: Seršić Lara Valenčić , Alić Vedrana Krušić , Biberić Maša , Zrna Siniša , Jagoić Tin , Tarčuković Janja , Grabušić Kristina
Published: March 2023

Severe traumatic brain injury (sTBI) is an intracranial damage triggered by external force, most commonly due to falls and traffic accidents. The initial brain injury can progress into a secondary injury involving numerous pathophysiological processes. The resulting sTBI dynamics makes the treatment challenging and prompts the improved understanding of underlying intracranial processes. Here, we analysed how extracellular microRNAs (miRNAs) are affected by sTBI. We collected thirty-five cerebrospinal fluids (CSF) from five sTBI patients during twelve days (d) after the injury and combined them into d1–2, d3–4, d5–6 and d7–12 CSF pools. After miRNA isolation and cDNA synthesis with added quantification spike-ins, we applied a real-time PCR-array targeting 87 miRNAs. We detected all of the targeted miRNAs, with totals ranging from several nanograms to less than a femtogram, with the highest levels found at d1–2 followed by decreasing levels in later CSF pools. The most abundant miRNAs were miR-451a, miR-16-5p, miR-144-3p, miR-20a-5p, let-7b-5p, miR-15a-5p, and miR-21-5p. After separating CSF by size-exclusion chromatography, most miRNAs were associated with free proteins, while miR-142-3p, miR-204-5p, and miR-223-3p were identified as the cargo of CD81-enriched extracellular vesicles, as characterised by immunodetection and tunable resistive pulse sensing. Our results indicate that miRNAs might be informative about both brain tissue damage and recovery after sTBI.
Inhibitory Effects of Loganin on Adipogenesis In Vitro and In Vivo
Authors: Jeon Hyoju , Lee Chang-Gun , Jeong Hyesoo , Yun Seong-Hoon , Kim Jeonghyun , Uprety Laxmi Prasad , Oh Kang-Il , Singh Shivani , Yoo Jisu , Park Eunkuk , Jeong Seon-Yong
Published: March 2023

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity.
Application of Bioelectrochemical Systems and Anaerobic Additives in Wastewater Treatment: A Conceptual Review
Authors: Madondo Nhlanganiso Ivan , Rathilal Sudesh , Bakare Babatunde Femi , Tetteh Emmanuel Kweinor
Published: March 2023

The interspecies electron transfer (IET) between microbes and archaea is the key to how the anaerobic digestion process performs. However, renewable energy technology that utilizes the application of a bioelectrochemical system together with anaerobic additives such as magnetite-nanoparticles can promote both direct interspecies electron transfer (DIET) as well as indirect interspecies electron transfer (IIET). This has several advantages, including higher removal of toxic pollutants present in municipal wastewater, higher biomass to renewable energy conversion, and greater electrochemical efficiencies. This review explores the synergistic influence of bioelectrochemical systems and anaerobic additives on the anaerobic digestion of complex substrates such as sewage sludge. The review discussions present the mechanisms and limitations of the conventional anaerobic digestion process. In addition, the applicability of additives in syntrophic, metabolic, catalytic, enzymatic, and cation exchange activities of the anaerobic digestion process are highlighted. The synergistic effect of bio-additives and operational factors of the bioelectrochemical system is explored. It is elucidated that a bioelectrochemical system coupled with nanomaterial additives can increase biogas–methane potential compared to anaerobic digestion. Therefore, the prospects of a bioelectrochemical system for wastewater require research attention.
Dynasore Protects Corneal Epithelial Cells Subjected to Hyperosmolar Stress in an In Vitro Model of Dry Eye Epitheliopathy
Authors: Martinez-Carrasco Rafael , Fini M. Elizabeth
Published: March 2023

Epitheliopathy at the ocular surface is a defining sign of dry eye disease, a common disorder that affects 10% to 30% of the world’s population. Hyperosmolarity of the tear film is one of the main drivers of pathology, with subsequent endoplasmic reticulum (ER) stress, the resulting unfolded protein response (UPR), and caspase-3 activation implicated in the pathway to programmed cell death. Dynasore, is a small molecule inhibitor of dynamin GTPases that has shown therapeutic effects in a variety of disease models involving oxidative stress. Recently we showed that dynasore protects corneal epithelial cells exposed to the oxidant tBHP, by selective reduction in expression of CHOP, a marker of the UPR PERK branch. Here we investigated the capacity of dynasore to protect corneal epithelial cells subjected to hyperosmotic stress (HOS). Similar to dynasore’s capacity to protect against tBHP exposure, dynasore inhibits the cell death pathway triggered by HOS, protecting against ER stress and maintaining a homeostatic level of UPR activity. However, unlike with tBHP exposure, UPR activation due to HOS is independent of PERK and mostly driven by the UPR IRE1 branch. Our results demonstrate the role of the UPR in HOS-driven damage, and the potential of dynasore as a treatment to prevent dry eye epitheliopathy.
MiR-199a-5p-Regulated SMARCA4 Promotes Oral Squamous Cell Carcinoma Tumorigenesis
Authors: Xu Mingyan , Zhang Junling , Lu Xuemei , Liu Fan , Shi Songlin , Deng Xiaoling
Published: March 2023

SWI/SNF related, matrix associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1), an ATPase subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, plays an important regulatory role in many cytogenetic and cytological processes during cancer development. However, the biological function and mechanism of SMARCA4 in oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to investigate the role of SMARCA4 in OSCC and its potential mechanism. Using a tissue microarray, SMARCA4 expression was found to be highly upregulated in OSCC tissues. In addition, SMARCA4 upregulate expression led to increased migration and invasion of OSCC cells in vitro, as well as tumor growth and invasion in vivo. These events were associated with the promotion of epithelial–mesenchymal transition (EMT). Bioinformatic analysis and luciferase reporter assay confirmed that SMARCA4 is a target gene of microRNA miR-199a-5p. Further mechanistic studies showed that the miR-199a-5p regulated SMARCA4 can promote the invasion and metastasis of tumor cells through EMT. These findings indicate that the miR-199a-5p- SMARCA4 axis plays a role in tumorigenesis by promoting OSCC cell invasion and metastasis through EMT regulation. Our findings provide insights into the role of SMARCA4 in OSCC and the mechanism involved, which may have important implications for therapeutic purposes.
Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity and Rehabilitation
Authors: Raciti Loredana , Formica Caterina , Raciti Gianfranco , Quartarone Angelo , Calabrò Rocco Salvatore
Published: March 2023

Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the extracellular pathway. The synthesis of neurosteroids occurs in peripheral tissues such as gonads tissues, liver, and skin; then, because of their high lipophilia, they cross the blood–brain barrier and are stored in the brain structure. Neurosteroidogenesis occurs in brain regions such as the cortex, hippocampus, and amygdala by enzymes necessary for the in situ synthesis of progesterone from cholesterol. Neurosteroids could be considered the main players in both sexual steroid-induced hippocampal synaptic plasticity and normal transmission in the hippocampus. Moreover, they show a double function of increasing spine density and enhancing long term potentiation, and have been related to the memory-enhancing effects of sexual steroids. Estrogen and progesterone affect neuronal plasticity differently in males and females, especially regarding changes in the structure and function of neurons in different regions of the brain. Estradiol administration in postmenopausal women allowed for improving cognitive performance, and the combination with aerobic motor exercise seems to enhance this effect. The paired association between rehabilitation and neurosteroids treatment could provide a boosting effect in order to promote neuroplasticity and therefore functional recovery in neurological patients. The aim of this review is to investigate the mechanisms of action of neurosteroids as well as their sex-dependent differences in brain function and their role in neuroplasticity and rehabilitation.
Crosstalk between Mesenchymal Stem Cells and Cancer Stem Cells Reveals a Novel Stemness-Related Signature to Predict Prognosis and Immunotherapy Responses for Bladder Cancer Patients
Authors: Ma Lin , Chen Hualin , Yang Wenjie , Ji Zhigang
Published: March 2023

Mesenchymal stem cells (MSCs) and cancer stem cells (CSCs) maintain bladder cancer (BCa) stemness and facilitate the progression, metastasis, drug resistance, and prognosis. Therefore, we aimed to decipher the communication networks, develop a stemness-related signature (Stem. Sig.), and identify a potential therapeutic target. BCa single-cell RNA-seq datasets (GSE130001 and GSE146137) were used to identify MSCs and CSCs. Pseudotime analysis was performed by Monocle. Stem. Sig. was developed by analyzing the communication network and gene regulatory network (GRN) that were decoded by NicheNet and SCENIC, respectively. The molecular features of the Stem. Sig. were evaluated in TCGA-BLCA and two PD-(L)1 treated datasets (IMvigor210 and Rose2021UC). A prognostic model was constructed based on a 101 machine-learning framework. Functional assays were performed to evaluate the stem traits of the hub gene. Three subpopulations of MSCs and CSCs were first identified. Based on the communication network, the activated regulons were found by GRN and regarded as the Stem. Sig. Following unsupervised clustering, two molecular subclusters were identified and demonstrated distinct cancer stemness, prognosis, immunological TME, and response to immunotherapy. Two PD-(L)1 treated cohorts further validated the performance of Stem. Sig. in prognosis and immunotherapeutic response prediction. A prognostic model was then developed, and a high-risk score indicated a poor prognosis. Finally, the hub gene SLC2A3 was found exclusively upregulated in extracellular matrix-related CSCs, predicting prognosis, and shaping an immunosuppressive tumor microenvironment. Functional assays uncovered the stem traits of SLC2A3 in BCa by tumorsphere formation and western blotting. The Stem. Sig. derived from MSCs and CSCs can predict prognosis and response to immunotherapy for BCa. Besides, SLC2A3 may serve as a promising stemness target facilitating cancer effective management.
The Role of Physical Exercise in Opioid Substitution Therapy: Mechanisms of Sequential Effects
Authors: Psarianos Alexandros , Chryssanthopoulos Costas , Paparrigopoulos Thomas , Philippou Anastassios
Published: March 2023

It is generally accepted that chronic opioid use is associated with structural and functional changes in the human brain that lead to an enhancement of impulsive behavior for immediate satisfaction. Interestingly, in recent years, physical exercise interventions have been used as an adjunctive treatment for patients with opioid use disorders (OUDs). Indeed, exercise has positive effects on both the biological and psychosocial basis of addiction, modifying neural circuits such as the reward, inhibition, and stress systems, and thus causing behavioral changes. This review focuses on the possible mechanisms that contribute to the beneficial effects of exercise on the treatment of OUDs, with emphasis placed on the description of a sequential consolidation of these mechanisms. Exercise is thought to act initially as a factor of internal activation and self-regulation and eventually as a factor of commitment. This approach suggests a sequential (temporal) consolidation of the functions of exercise in favor of gradual disengagement from addiction. Particularly, the sequence in which the exercise-induced mechanisms are consolidated follows the pattern of internal activation—self-regulation—commitment, eventually resulting in stimulation of the endocannabinoid and endogenous opioid systems. Additionally, this is accompanied by modification of molecular and behavioral aspects of opioid addiction. Overall, the neurobiological actions of exercise in combination with certain psychological mechanisms appear to promote its beneficial effects. Given the positive effects of exercise on both physical and mental health, exercise prescription is recommended as a complement to conventional therapy for patients on opioid maintenance treatment.
Ceftazidime-Avibactam (C/A) Resistant, Meropenem Sensitive KPC-Producing Klebsiella pneumoniae in ICU Setting: We Are What We Are Treated with?
Authors: Corcione Silvia , De Benedetto Ilaria , Shbaklo Nour , Torsello Giulia , Lupia Tommaso , Bianco Gabriele , Cavallo Rossana , Brazzi Luca , Montrucchio Giorgia , De Rosa Francesco Giuseppe
Published: March 2023

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.
Depression and Its Phytopharmacotherapy—A Narrative Review
Authors: Dobrek Lukasz , Głowacka Krystyna
Published: March 2023

Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood disturbances, persistent sadness, loss of interest and impaired cognition, which causes distress to the patient and significantly affects the ability to function and have a satisfying family, social and professional life. Depression requires comprehensive management, including pharmacological treatment. Because pharmacotherapy of depression is a long-term process associated with the risk of numerous adverse drug effects, much attention is paid to alternative therapy methods, including phytopharmacotherapy, especially in treating mild or moderate depression. Preclinical studies and previous clinical studies confirm the antidepressant activity of active compounds in plants, such as St. John’s wort, saffron crocus, lemon balm and lavender, or less known in European ethnopharmacology, roseroot, ginkgo, Korean ginseng, borage, brahmi, mimosa tree and magnolia bark. The active compounds in these plants exert antidepressive effects in similar mechanisms to those found in synthetic antidepressants. The description of phytopharmacodynamics includes inhibiting monoamine reuptake and monoamine oxidase activity and complex, agonistic or antagonistic effects on multiple central nervous system (CNS) receptors. Moreover, it is noteworthy that the anti-inflammatory effect is also important to the antidepressant activity of the plants mentioned above in light of the hypothesis that immunological disorders of the CNS are a significant pathogenetic factor of depression. This narrative review results from a traditional, non-systematic literature review. It briefly discusses the pathophysiology, symptomatology and treatment of depression, with a particular focus on the role of phytopharmacology in its treatment. It provides the mechanisms of action revealed in experimental studies of active ingredients isolated from herbal antidepressants and presents the results of selected clinical studies confirming their antidepressant effectiveness.
Pharmacokinetic Markers of Clinical Outcomes in Severe Mental Illness: A Systematic Review
Authors: Paribello Pasquale , Manchia Mirko , Pinna Federica , Isayeva Ulker , Squassina Alessio , Pisanu Claudia , Balderi Lorenzo , Contu Martina , Pinna Marco , Carpiniello Bernardo
Published: March 2023

The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals and their communities. Pharmacogenomic (PGx) approaches hold great promise in personalizing treatment selection and clinical outcomes, possibly reducing the burden of SMI. Here, we sought to review the literature in the field, focusing on PGx testing and particularly on pharmacokinetic markers. We performed a systematic review on PUBMED/Medline, Web of Science, and Scopus. The last search was performed on the 17 September 2022, and further augmented with a comprehensive pearl-growing strategy. In total, 1979 records were screened, and after duplicate removal, 587 unique records were screened by at least 2 independent reviewers. Ultimately, forty-two articles were included in the qualitative analysis, eleven randomized controlled trials and thirty-one nonrandomized studies. The observed lack of standardization in PGx tests, population selection, and tested outcomes limit the overall interpretation of the available evidence. A growing body of evidence suggests that PGx testing might be cost-effective in specific settings and may modestly improve clinical outcomes. More efforts need to be directed toward improving PGx standardization, knowledge for all stakeholders, and clinical practice guidelines for screening recommendations.
Lycium barbarum Berries (Solanaceae) as Source of Bioactive Compounds for Healthy Purposes: A Review
Authors: Teixeira Filipa , Silva Ana Margarida , Delerue-Matos Cristina , Rodrigues Francisca
Published: March 2023

Lycium barbarum L. is a species widely used in dietary supplements and natural healthcare products. The berries, also known as goji or wolfberries, mostly grow in China, but recent reports on their outstanding bioactive properties have increased their popularity and cultivation around the world. Goji berries are a remarkable source of phenolic compounds (such as phenolic acids and flavonoids), carotenoids, organic acids, carbohydrates (fructose and glucose), and vitamins (ascorbic acid). Several biological activities, such as antioxidant, antimicrobial, anti-inflammatory, prebiotic, and anticancer activities, have been associated with its consumption. Hence, goji berries were highlighted as an excellent source of functional ingredients with promising applications in food and nutraceutical fields. This review aims to summarize the phytochemical composition and biological activities, along with various industrial applications, of L. barbarum berries. Simultaneously, the valorization of goji berries by-products, with its associated economic advantages, will be emphasized and explored.
Nitric Oxide Acts as a Key Signaling Molecule in Plant Development under Stressful Conditions
Authors: Khan Murtaza , Ali Sajid , Al Azzawi Tiba Nazar Ibrahim , Yun Byung-Wook
Published: March 2023

Nitric oxide (NO), a colorless gaseous molecule, is a lipophilic free radical that easily diffuses through the plasma membrane. These characteristics make NO an ideal autocrine (i.e., within a single cell) and paracrine (i.e., between adjacent cells) signalling molecule. As a chemical messenger, NO plays a crucial role in plant growth, development, and responses to biotic and abiotic stresses. Furthermore, NO interacts with reactive oxygen species, antioxidants, melatonin, and hydrogen sulfide. It regulates gene expression, modulates phytohormones, and contributes to plant growth and defense mechanisms. In plants, NO is mainly produced via redox pathways. However, nitric oxide synthase, a key enzyme in NO production, has been poorly understood recently in both model and crop plants. In this review, we discuss the pivotal role of NO in signalling and chemical interactions as well as its involvement in the mitigation of biotic and abiotic stress conditions. In the current review, we have discussed various aspects of NO including its biosynthesis, interaction with reactive oxygen species (ROS), melatonin (MEL), hydrogen sulfide, enzymes, phytohormones, and its role in normal and stressful conditions.
A Unified Deep Learning Framework for Single-Cell ATAC-Seq Analysis Based on ProdDep Transformer Encoder
Authors: Wang Zixuan , Zhang Yongqing , Yu Yun , Zhang Junming , Liu Yuhang , Zou Quan
Published: March 2023

Recent advances in single-cell sequencing assays for the transposase-accessibility chromatin (scATAC-seq) technique have provided cell-specific chromatin accessibility landscapes of cis-regulatory elements, providing deeper insights into cellular states and dynamics. However, few research efforts have been dedicated to modeling the relationship between regulatory grammars and single-cell chromatin accessibility and incorporating different analysis scenarios of scATAC-seq data into the general framework. To this end, we propose a unified deep learning framework based on the ProdDep Transformer Encoder, dubbed PROTRAIT, for scATAC-seq data analysis. Specifically motivated by the deep language model, PROTRAIT leverages the ProdDep Transformer Encoder to capture the syntax of transcription factor (TF)-DNA binding motifs from scATAC-seq peaks for predicting single-cell chromatin accessibility and learning single-cell embedding. Based on cell embedding, PROTRAIT annotates cell types using the Louvain algorithm. Furthermore, according to the identified likely noises of raw scATAC-seq data, PROTRAIT denoises these values based on predated chromatin accessibility. In addition, PROTRAIT employs differential accessibility analysis to infer TF activity at single-cell and single-nucleotide resolution. Extensive experiments based on the Buenrostro2018 dataset validate the effeteness of PROTRAIT for chromatin accessibility prediction, cell type annotation, and scATAC-seq data denoising, therein outperforming current approaches in terms of different evaluation metrics. Besides, we confirm the consistency between the inferred TF activity and the literature review. We also demonstrate the scalability of PROTRAIT to analyze datasets containing over one million cells.
Acral Melanoma Is Infiltrated with cDC1s and Functional Exhausted CD8 T Cells Similar to the Cutaneous Melanoma of Sun-Exposed Skin
Authors: De Leon-Rodríguez Saraí G. , Aguilar-Flores Cristina , Gajón Julián A. , Mantilla Alejandra , Gerson-Cwilich Raquel , Martínez-Herrera José Fabián , Rodríguez-Soto Benigno E. , Gutiérrez-Quiroz Claudia T. , Pérez-Koldenkova Vadim , Muñoz-Cruz Samira , Bonifaz Laura C. , Fuentes-Pananá Ezequiel M.
Published: March 2023

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1+) CD8 T cells and PD-1 ligand (PD-L1+) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells’ capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy.
Catechin Versus MoS2 Nanoflakes Functionalized with Catechin: Improving the Sperm Fertilizing Ability—An In Vitro Study in a Swine Model
Authors: Cimini Costanza , Ramal-Sanchez Marina , Taraschi Angela , Della Pelle Flavio , Scroccarello Annalisa , Belda-Perez Ramses , Valbonetti Luca , Lanuti Paola , Marchisio Marco , D’Atri Mario , Ortolani Claudio , Papa Stefano , Capacchietti Giulia , Bernabò Nicola , Compagnone Dario , Barboni Barbara
Published: March 2023

Nowadays, the adoption of In Vitro Fertilization (IVF) techniques is undergoing an impressive increase. In light of this, one of the most promising strategies is the novel use of non-physiological materials and naturally derived compounds for advanced sperm preparation methods. Here, sperm cells were exposed during capacitation to MoS2/Catechin nanoflakes and catechin (CT), a flavonoid with antioxidant properties, at concentrations of 10, 1, 0.1 ppm. The results showed no significant differences in terms of sperm membrane modifications or biochemical pathways among the groups, allowing the hypothesis that MoS2/CT nanoflakes do not induce any negative effect on the parameters evaluated related to sperm capacitation. Moreover, the addition of CT alone at a specific concentration (0.1 ppm) increased the spermatozoa fertilizing ability in an IVF assay by increasing the number of fertilized oocytes with respect to the control group. Our findings open interesting new perspectives regarding the use of catechins and new materials obtained using natural or bio compounds, which could be used to implement the current strategies for sperm capacitation.