bluuebunny/crossref_metadata_2025 huggingface dataset:
ECG-Based Semi-Supervised Anomaly Detection for Early Detection and Monitoring of Epileptic Seizures
Authors: Karasmanoglou Apostolos ,   Marios Antonakakis,   Michalis Zervakis
Published: March 2023

Epilepsy is one of the most common brain diseases, characterized by frequent recurrent seizures or “ictal” states. A patient experiences uncontrollable muscular contractions, inducing loss of mobility and balance, which may result in injury or even death during these ictal states. Extensive investigation is vital to establish a systematic approach for predicting and informing patients about oncoming seizures ahead of time. Most methodologies developed are focused on the detection of abnormalities using mostly electroencephalogram (EEG) recordings. In this regard, research has indicated that certain pre-ictal alterations in the Autonomic Nervous System (ANS) can be detected in patient electrocardiogram (ECG) signals. The latter could potentially provide the basis for a robust seizure prediction approach. The recently proposed ECG-based seizure warning systems utilize machine learning models to classify a patient’s condition. Such approaches require the incorporation of large, diverse, and thoroughly annotated ECG datasets, limiting their application potential. In this work, we investigate anomaly detection models in a patient-specific context with low supervision requirements. Specifically, we consider One-Class SVM (OCSVM), Minimum Covariance Determinant (MCD) Estimator, and Local Outlier Factor (LOF) models to quantify the novelty or abnormality of pre-ictal short-term (2–3 min) Heart Rate Variability (HRV) features of patients, trained on a reference interval considered to contain stable heart rate as the only form of supervision. Our models are evaluated against labels that were either hand-picked or automatically generated (weak labels) by a two-phase clustering procedure for samples of the “Post-Ictal Heart Rate Oscillations in Partial Epilepsy” (PIHROPE) dataset recorded by the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, achieving detection in 9 out of 10 cases, with average AUCs of over 93% across all models and warning times ranging from 6 to 30 min prior to seizure. The proposed anomaly detection and monitoring approach can potentially pave the way for early detection and warning of seizure incidents based on body sensor inputs.
Does Pain Acceptance Contribute to Improved Functionality through Walking in Women with Fibromyalgia? Looking at Depressive Comorbidity
Authors: Peñacoba Cecilia , Ecija Carmen , Gutiérrez Lorena , Catalá Patricia
Published: March 2023

In the last decade, research has pointed to physical exercise as an effective treatment in fibromyalgia patients. Some studies have highlighted the role of acceptance and commitment therapy in optimizing the benefits of exercise in patients. However, given the high comorbidity in fibromyalgia, it is necessary to value its possible influence on the effect of certain variables, such as acceptance, on the benefits of treatments, such as physical exercise. Our aim is to test the role of acceptance in the benefits of walking over functional limitation, further assessing whether this model is equally valid, considering depressive symptomatology as an additional differential diagnosis. A cross-sectional study with a convenience sample through contacting Spanish fibromyalgia associations was carried out. A total of 231 women with fibromyalgia (mean age 56.91 years) participated in the study. Data were analyzed with the Process program (Model 4, Model 58, Model 7). The results highlight the role of acceptance as a mediator between walking and functional limitation (B = −1.86, SE = 0.93, 95% CI = [−3.83, −0.15]). This model, when depression is incorporated as a moderator, is significant only in patients without depression, revealing the need for personalized treatments in fibromyalgia, considering their most prevalent comorbidity.
Major Determinants of Innovation Performance in the Context of Healthcare Sector
Authors: Nassani Abdelmohsen A. , Javed Asad , Rosak-Szyrocka Joanna , Pilar Ladislav , Yousaf Zahid , Haffar Mohamed
Published: March 2023

Through the innovation network (IN) and the use of artificial intelligence (AI), this study aims to look into the innovation performance (IP) of the healthcare industry. Digital innovation (DI) is also tested as a mediator. For the collection of data, cross-sectional methods and quantitative research designs were used. To test the study hypotheses, the SEM technique and multiple regression technique were used. Results reveal that AI and the innovation network support the attainment of innovation performance. The finding demonstrates that the relationship between INs and IP links and AI adoption and IP links is mediated through DI. The healthcare industry plays a vital role in facilitating public health and improving the living standards of the people. This sector’s growth and development are largely dependent on its innovativeness. This study highlights the major determinants of IP in the healthcare industry in terms of IN and AI adoption. This study adds to the literature’s knowledge via an innovative proposal in which the mediation role of DI among IN-IP and AI adoption-innovation links is investigated.
Hospice Caregivers’ Perception of Family and Non-Family Social Support and Stress over Time: Associations with Reports of General Support
Authors: Reblin Maija , Tay Djin L. , Iacob Eli , Cloyes Kristin G. , Hebdon Megan C. Thomas , Ellington Lee
Published: March 2023

Social support has been identified as a key factor to protect wellbeing for home hospice cancer caregivers. However, few studies have assessed social support over time in this context, and measures of support are often limited to general assessments of perceived support. Our goal was to (1) describe change in cancer home hospice caregivers’ social support over time during care and into bereavement and (2) explore the impact of perceived stress and support from family and non-family members on caregivers’ perceived general social support. We conducted a secondary analysis of longitudinal prospective questionnaire data. Forty caregivers completed measures of general perceived support, family and non-family support and stress during hospice enrollment and 2 and 6 months post the patient’s death. Linear mixed models were used to determine change in support over time and the contribution of specific support/stress ratings to general support assessments. Caregivers overall had moderate and stable levels of social support over time, though there was significant variation between and within individuals. Family and non-family support and stress from family predicted general perceptions of social support, while no effects were found for non-family stress. This work suggests a need for more specific measures of support and stress, and the need for research to focus on improving baseline levels of caregiver perceived support.
Vulnerability and Agency in the Time of COVID-19: The Narratives of Child and Youth Care Workers in South Africa
Authors: Masuku Andile Samkele , Hlengwa Reggiswindis Thobile , Mkhize Lindelwa Vernon , Sibiya Maureen Nokuthula
Published: March 2023

In this paper, we use data generated through one-on-one interviews with 12 purposively sampled Child and Youth Care Workers to examine their narratives of work and life-related vulnerabilities and agency during the peak of the COVID-19 global pandemic in KwaZulu-Natal, South Africa. Our findings show that Child and Youth Care Workers were vulnerable to poor mental health. Indeed, working and socialising during the height of COVID-19 posed a mental toll on the Child and Youth Care Workers in this study, who experienced fear, uncertainty, anxiety and stress. Moreover, these workers faced challenges with working under the so-called new normal, which was instituted as part of a non-pharmaceutical response to slow and curb the spread of COVID-19. Finally, our findings show that Child and Youth Care Workers actively identified and applied specific emotionally-focused and physically-focused coping mechanisms to deal with the burden brought on by the pandemic. The study has implications for CYCWs working during crisis periods.
The Role of Impulsivity and Self-Control in Suicidal Ideation and Suicide Attempt
Authors: Martin Aleena , Oehlman Mitchell , Hawgood Jacinta , O’Gorman John
Published: March 2023

Two studies are reported examining the relation of self-control, as measured by self-report inventories, to indices of suicidal ideation and suicide attempts. In the first study (n = 113), self-control related significantly (p < 0.05) and negatively to both indices (r = −0.37 and r = −0.26), and, in a hierarchical regression analysis, added significantly to the variance in the suicidal ideation index accounted for by a measure of impulsivity. The second study (n = 223) replicated the findings of the bivariate correlations (r = −0.55 and r = −0.59) with the suicidality indices in the first study, both with the earlier measures and with alternative measures of self-control and impulsivity. Results indicated self-control added to the prediction of both indices and not just the ideation index. The second study also demonstrated that self-control acts as a moderator for perceived stress, a known risk factor for suicidality, such that, at low levels of perceived stress, there is little difference between those high and low in measured self-control, but that at high stress levels, those with high self-control had lower scores on suicidal ideation. The results are interpreted as showing that self-control is a protective factor for suicidality.
Identifying Anthropogenic Sources of Heavy Metals in Alpine Peatlands over the Past 150 Years: Examples from Typical Peatlands in Altay Mountains, Northwest China
Authors: Luo Nana , Yu Rui , Wen Bolong , Li Xiaoyu , Liu Xingtu , Li Xiujun
Published: March 2023

Alpine mountain peatlands are valuable archives of climatic and anthropogenic impact. However, the impacts of human activities on the Altay peatlands are poorly documented. Therefore, studying heavy metal (HM) concentrations, evaluating HM pollution levels, and identifying the sources in the Altay Mountain peatlands are crucial for revealing the intensity of human activities. The present study was performed on two peatland profiles: Jiadengyu (JDY) and Heihu (HH). The contents of HM and 210Pb and 137Cs dating technologies were used to construct a profile of anthropogenic pollutant distributions in the peatlands. Furthermore, the enrichment factor (EF) and geo-accumulation index (Igeo) of selected HMs were used to evaluate the risk assessment of HMs. The association of metals and assignment of their probable sources were examined using principal component analysis (PCA) and a positive matrix factorization model (PMF). The results showed that the concentrations of elements Cu, Zn, Cr, Pb, Ni, and As were at high levels in the two peatlands of the Altay Mountains, while the elements Hg and Cd were in low concentrations. Moreover, the concentrations of Cu, Cd, Hg, and Sb were higher than the background values of local element and posed a high environmental risk to the ecosystem. Combined with the results of the chronology, the peatland records indicated considerable growth in HMs concentrations from 1970 to 1990 related to recent anthropogenic activities. Additionally, the main sources of HMs are mining activities, domestic waste, and traffic sources in the two peatlands. Due to the environmental protection policies implemented since 2010, the natural processes have been the primary origin of HMs in peatlands, while emissions of industrial, agricultural, and domestic waste were still fundamental sources. The results of this study describe the sedimentary features of HMs in alpine mountains, and the data provide an essential theoretical basis for the evolutionary process through the characteristics of HM deposition.
Exploring the Predictive Potential of Physiological Measures of Human Thermal Strain in Outdoor Environments in Hot and Humid Areas in Summer—A Case Study of Shanghai, China
Authors: Lian Zefeng , Liu Binyi , Brown Robert D.
Published: March 2023

Whenever people spend time outdoors during hot weather, they are putting themselves in potentially stressful situations. Being able to predict whether a person is overheating can be critical in preventing heat-health issues. There is a clear relationship between body core temperature and heat health. However, measuring body core temperature is expensive. Identifying a non-invasive measure that could indicate a person’s thermal strain would be valuable. This study investigated five physiological measures as possible surrogates: finger mean skin temperature (FSKT), finger maximum skin temperature (FMSKT), skin conductance level (SCL), heart rate (HR), and heart rate variability (HRV). Furthermore, they were compared against the results of participants’ subjective thermal sensation and thermal comfort in a range of hot microclimatic conditions in a hot and humid climate. Results showed that except for SCL, each of the other four physiological measures had a positive significant relationship with thermal sensation, but a negative relationship with thermal comfort. Furthermore, through testing by cumulative link mixed models, HRV was found to be the most suitable surrogate for predicting thermal sensation and thermal comfort through a simple, non-invasive measure in outdoor environment in summer in a hot and humid area. This study highlights the method for predicting human thermal strain and contributes to improve the public health and well-being of urban dwellers in outdoor environments.
Case Report: Acute Intoxication from Phosphine Inhalation
Authors: Shi Longke , Jian Tianzi , Tao Yiming , Li Yaqian , Yu Guangcai , Zhao Liwen , Wen Zixin , Kan Baotian , Jian Xiangdong
Published: March 2023

Aluminum phosphide is a highly effective insecticide for fumigation in granaries and is often used in rural grain storage. However, people’s awareness of its toxicity is not strong. A case of acute inhalation toxicity of phosphine caused by the use of aluminum phosphide to fumigate a granary is reported here. The case presented with aspiration pneumonia and acute left heart failure. The patient was cured using comprehensive life support treatment, including respiratory support, antiarrhythmic treatment, and blood pressure maintenance with vasoactive drugs. There is no specific antidote for phosphine poisoning at present, and the comprehensive application of restricted fluid resuscitation, high-dose glucocorticoid shock, vasoactive drugs and bedside hemofiltration is significant in improving the prognosis of patients. It is also important to remind people to pay attention to their own protection in the process of using aluminum phosphide.
Why Do Customers Want to Buy COVID-19 Medicines? Evidence from Thai Citizens
Authors: Kim Long , Pongsakornrungsilp Siwarit , Pongsakornrungsilp Pimlapas , Jindabot Teerasak , Kumar Vikas
Published: March 2023

Purchase intention has been acknowledged as an important factor influencing businesses’ sales performances and sustainability. Thus, finding factors that influence purchase intention is essential to all relevant businesses. Based on the current importance of purchase intention to businesses, the main objective of this research was to investigate how country of origin, brand image, and perceived value influenced intentions to purchase COVID-19 medicines among Thai consumers. To accomplish this objective, researchers created a Google Form to survey 862 people around Thailand. However, researchers found only 653 valid data, which were analyzed through the structural equation model. The research findings revealed that perceived COVID-19 medicine value increased once the values of country of origin and brand image were highly considered by consumers. At the same time, consumers attempted to buy COVID-19 medicines for their COVID-19 treatments if the products contained high country of origin and perceived values. Finally, the perceived value was found to be a full mediator between brand image and purchase intention. In comparison, despite country of origin and perceived value being the significant factors in purchase intention, consumers’ intention to purchase COVID-19 medicines depended significantly on the degree of the consumers’ perceived value because perceived value contributed the highest impact on purchase intention. These results revealed that COVID-19 medicines were highly valued by many consumers because these medicines could help prevent heavy illness in consumers. As a result, consumers had a higher intention to purchase these medicines for their future COVID-19 treatments.
Low Behavioral Intention to Use Any Type of HIV Testing and HIV Self-Testing among Migrant Male Factory Workers Who Are at High Risk of HIV Infection in China: A Secondary Data Analysis
Authors: Zhang Kechun , Chan Paul Shing-fong , Li Xinyue , Fang Yuan , Cai Yong , Zou Huachun , Cao Bolin , Cao He , Hu Tian , Chen Yaqi , Wang Zixin
Published: March 2023

This study investigated the prevalence of and factors associated with behavioral intention to take up any type of HIV testing and HIV self-testing (HIVST) in the next six months among male migrant workers, who were at high risk of HIV infection, in Shenzhen, China. This was a secondary data analysis. A total of 363 subjects who had sexual intercourse with non-regular female sex partners and/or female sex workers in the past six months were selected. Logistic regression models were fitted for data analysis. About 16.5% of participants reported having used HIV testing in their lifetime and 12.7% for HIVST. Among the participants, 25.6% and 23.7% intended to take up any type of HIV testing and HIVST in the next six months, respectively. Significant factors associated with the behavioral intention to take up HIV testing and HIVST included individual-level factors based of the Health Belief Model (e.g., perceived benefit, perceived cue to action, perceived self-efficacy) and interpersonal-level factors (e.g., frequency of exposure to health-related content or HIV and STI-related content on short video apps). This study provided practical implications for designing interventions to increase the uptake of HIV testing and HIVST among migrant workers.
Procrastination and Stress: A Conceptual Review of Why Context Matters
Authors: Sirois Fuschia M.
Published: March 2023

Research over the past two decades has continued to highlight the robust associations between procrastination and stress across multiple populations and contexts. Despite this burgeoning evidence base and theory linking procrastination to higher levels of stress, as well as the reverse, the role of context in this potentially dynamic association has received relatively little attention. In this conceptual review I argue that from a mood regulation perspective of procrastination, stressful contexts necessarily increase risk for procrastination because they deplete coping resources and lower the threshold for tolerating negative emotions. Drawing on insights from coping and emotion regulation theory, the new stress context vulnerability model of procrastination proposes that the risk for procrastination increases in stressful contexts primarily because procrastination is a low-resource means of avoiding aversive and difficult task-related emotions. The new model is then applied to evidence on the primary and secondary sources of stress during the COVID-19 pandemic and how they may have increased vulnerability for procrastination. After discussing potential applications of the new model for understanding how and why risk for procrastination may increase in other stressful contexts, approaches that might mitigate vulnerability for procrastination in high-stress contexts are discussed. Overall, this new stress context vulnerability model underscores the need for taking a more compassionate view of the antecedents and factors that may increase the risk for procrastination.
Psychometric Properties of the Brazilian Version of the Quality of Dying and Death for Adult Family Members of ICU Patients
Authors: Benichel Cariston Rodrigo , Meneguin Silmara , Pollo Camila Fernandes , Oliveira Mariele Gobo , de Oliveira Cesar
Published: March 2023

Death is a complex, subjective phenomenon that requires an understanding of experiences to be qualified to provide care during the end-of-life process. This study aimed to analyze the psychometric properties of the Portuguese version (Brazil) of the Quality of Dying and Death (QODD) scale on family members of patients who died in adult intensive care units. A methodological study was conducted with 326 family members of patients that died in three ICUs of public hospitals in the state of São Paulo, Brazil. For this study, the QODD 3.2a (25 items and six domains) was administered during the period from December 2020 to March 2022. The analysis was performed using the classic theory of the tests and the goodness of fit of the model was tested using confirmatory factor analysis. We have used Spearman’s correlation coefficients between the scores of the overall scale and domains. Cronbach’s alpha coefficient and the intraclass correlation coefficient (ICC) were used for the evaluation of internal consistency and temporal stability, respectively. The Horn’s parallel analysis indicated two factors that were not confirmed in the exploratory factor analysis. A single factor retained 18 of the initial 25 items and the analysis of the goodness of fit to the unidimensional model resulted in the following: CFI = 0.7545, TLI = 0.690, chi-squared = 767.33, df = 135, RMSEA = 0.121 with 90%CI, and p = 5.04409. The inter-item correlations indicated a predominance of weak correlations among the items of the instrument. The items with the largest number of moderate correlations were questions 13b, 9b, and 10b and a strong correlation was found between questions 15b and 16b. Cronbach’s alpha coefficient was 0.8 and the ICC was 0.9. The Quality of Dying and Death—Version 3.2a (intensive therapy) in Brazilian Portuguese has a unidimensional structure and acceptable reliability. However, it did not obtain a good fit to the proposed factorial model.
Comparing Health Workforce Policy during a Major Global Health Crisis: A Critical Conceptual Debate and International Empirical Investigation
Authors: Kuhlmann Ellen , Denis Jean-Louis , Côté Nancy , Lotta Gabriela , Neri Stefano
Published: March 2023

Background: The health workforce is central to healthcare systems and population health, but marginal in comparative health policy. This study aims to highlight the crucial relevance of the health workforce and contribute comparative evidence to help improve the protection of healthcare workers and prevention of inequalities during a major public health crisis. Methods: Our integrated governance framework considers system, sector, organizational and socio-cultural dimensions of health workforce policy. The COVID-19 pandemic serves as the policy field and Brazil, Canada, Italy, and Germany as illustrative cases. We draw on secondary sources (literature, document analysis, public statistics, reports) and country expert information with a focus on the first COVID-19 waves until the summer of 2021. Results: Our comparative investigation illustrates the benefits of a multi-level governance approach beyond health system typologies. In the selected countries, we found similar problems and governance gaps concerning increased workplace stress, lack of mental health support, and gender and racial inequalities. Health policy across countries failed to adequately respond to the needs of HCWs, thus exacerbating inequalities during a major global health crisis. Conclusions: Comparative health workforce policy research may contribute new knowledge to improve health system resilience and population health during a crisis.
Quantitative Assessment of Water Quality Improvement by Reducing External Loadings at Lake Erhai, Southwest China
Authors: Gong Falu , Luo Liancong , Li Huiyun , Chen Lan , Zhang Rufeng , Wu Guizhu , Zhang Jian , Shi Weiqiang , Zhang Fan , Zhang Hao , Sun Ting
Published: March 2023

To quantitatively evaluate the effects on water quality improvement caused by reducing external loadings entering Lake Erhai through inflow rivers, a one-dimensional hydrodynamic and ecological model (DYRESM–CAEDYM) was set up to simulate the water quality and water level variations. The calibrated and validated model was used to conduct six scenarios for evaluating the water quality responses to different amounts of external loading reduction at Lake Erhai. The results show (1) the total nitrogen (TN) concentration of Lake Erhai will be higher than 0.5 mg/L without any watershed pollution control during April–November 2025, which cannot meet Grade II standard of the China Surface Water Environmental Quality Standards (GB3838-2002). (2) External loading reductions can significantly reduce the concentrations of nutrients and Chla at Lake Erhai. The effects of water quality improvement will be proportional to the reduction rate of external loading reductions. (3) Internal release might be an important source of pollution It needs to be seriously considered as well as external loading for mitigating the eutrophication at Lake Erhai in the future.
Relationship between Diet Quality and Periodontal Disease in South Korean Adults Aged ≥40 Years
Authors: Lee Mi-Ra
Published: March 2023

The purpose of this study was to investigate the relationship between diet quality and periodontal disease, in adults aged ≥40 years, using data from the 7th (2016–2018) Korea National Health and Nutrition Survey (KNHANES), representing South Koreans. The subjects of this study were 7935 people aged ≥40 years, who responded to the items in the Korea Healthy Eating Index (KHEI) and underwent periodontal examination. Complex sample univariate and multivariate logistic regression analyses were conducted, to analyze the relationship between the diet quality and periodontal disease. The group with a low diet quality for energy intake balance, showed a higher risk of periodontal disease than the group with a high diet quality for energy intake balance, and it was confirmed that the diet quality in adults aged ≥40 years was related to periodontal disease. Therefore, regular diet evaluations, and the counseling of gingivitis and periodontitis patients by dental experts, will have a positive effect on the restoration and improvement of periodontal health in adults.
Decision Analytic Modeling for Global Clinical Trial Planning: A Case for HIV-Positive Patients at High Risk for Mycobacterium tuberculosis Sepsis in Uganda
Authors: Keim-Malpass Jessica , Heysell Scott K. , Thomas Tania A. , Lobo Jennifer M. , Mpagama Stellah G. , Muzoora Conrad , Moore Christopher C.
Published: March 2023

Sepsis is a significant cause of mortality among people living with human immunodeficiency virus (HIV) in sub-Saharan Africa. In the planning period prior to the start of a large multi-country clinical trial studying the efficacy of the immediate empiric addition of anti-tuberculosis therapy to standard-of-care antibiotics for sepsis in people living with HIV, we used decision analysis to assess the costs and potential health outcome impacts of the clinical trial design based on preliminary data and epidemiological parameter estimates. The purpose of this analysis was to highlight this approach as a case example where decision analysis can estimate the cost effectiveness of a proposed clinical trial design. In this case, we estimated the impact of immediate empiric anti-tuberculosis (TB) therapy versus the diagnosis-dependent standard of care using three different TB diagnostics: urine TB-LAM, sputum Xpert-MTB/RIF, and the combination of LAM/Xpert. We constructed decision analytic models comparing the two treatment strategies for each of the three diagnostic approaches. Immediate empiric-therapy demonstrated favorable cost-effectiveness compared with all three diagnosis-dependent standard of care models. In our methodological case exemplar, the proposed randomized clinical trial intervention demonstrated the most favorable outcome within this decision simulation framework. Applying the principles of decision analysis and economic evaluation can have significant impacts on study design and clinical trial planning.
Leaving No Women Behind: Evaluating the Impact of the COVID-19 Pandemic on Livelihood Outcomes in Kenya and Ethiopia
Authors: Makate Marshall , Makate Clifton
Published: March 2023

The SARS-CoV-2 pandemic has revolutionised our lives, bringing with it the twin crises of illness and the need for an optimal mix of policies to alleviate its impact on the population. There needs to be more evidence on the effects of the pandemic on livelihood outcomes, including an understanding of whether female-headed families in low-income countries fare worse than their male-headed counterparts during pandemics. Using high-frequency phone surveys conducted in Ethiopia and Kenya, we examine the aggregate impact of the pandemic on income and consumption losses, as well as food insecurity. The empirical analysis estimates linear probability models that relate livelihood outcomes with household headship and other socioeconomic characteristics as controls. Overall, the pandemic increased the likelihood of food insecurity while decreasing income and consumption, particularly among female-headed households. In Kenya, living in a female-headed home increased the possibility of an adult going without food by about 10%, an adult skipping a meal by about 9.9%, and a child missing a meal by about 17% in the seven days preceding the telephone survey. In Ethiopia, living in a female-headed household increased the likelihood of an adult going hungry, skipping a meal, and running out of food by about 24.35%, 18.9%, and 26.7%, respectively. Salient pre-existing socioeconomic inequalities further exacerbated the effects of the pandemic on livelihoods. The findings have important implications for public policy and preparations by governments and other organisations interested in developing suitable gender-sensitive measures to lessen the impact of future pandemics in low- and middle-income countries.
Inactivation of HAP4 Accelerates RTG-Dependent Osmoadaptation in Saccharomyces cerevisiae
Authors: Di Noia Maria Antonietta , Scarcia Pasquale , Agrimi Gennaro , Ocheja Ohiemi Benjamin , Wahid Ehtisham , Pisano Isabella , Paradies Eleonora , Palmieri Luigi , Guaragnella Cataldo , Guaragnella Nicoletta
Published: March 2023

Mitochondrial RTG (an acronym for ReTroGrade) signaling plays a cytoprotective role under various intracellular or environmental stresses. We have previously shown its contribution to osmoadaptation and capacity to sustain mitochondrial respiration in yeast. Here, we studied the interplay between RTG2, the main positive regulator of the RTG pathway, and HAP4, encoding the catalytic subunit of the Hap2-5 complex required for the expression of many mitochondrial proteins that function in the tricarboxylic acid (TCA) cycle and electron transport, upon osmotic stress. Cell growth features, mitochondrial respiratory competence, retrograde signaling activation, and TCA cycle gene expression were comparatively evaluated in wild type and mutant cells in the presence and in the absence of salt stress. We showed that the inactivation of HAP4 improved the kinetics of osmoadaptation by eliciting both the activation of retrograde signaling and the upregulation of three TCA cycle genes: citrate synthase 1 (CIT1), aconitase 1 (ACO1), and isocitrate dehydrogenase 1 (IDH1). Interestingly, their increased expression was mostly dependent on RTG2. Impaired respiratory competence in the HAP4 mutant does not affect its faster adaptive response to stress. These findings indicate that the involvement of the RTG pathway in osmostress is fostered in a cellular context of constitutively reduced respiratory capacity. Moreover, it is evident that the RTG pathway mediates peroxisomes–mitochondria communication by modulating the metabolic function of mitochondria in osmoadaptation.
PPAR Alpha Activation by Clofibrate Alleviates Ischemia/Reperfusion Injury in Metabolic Syndrome Rats by Decreasing Cardiac Inflammation and Remodeling and by Regulating the Atrial Natriuretic Peptide Compensatory Response
Authors: Sánchez-Aguilar María , Ibarra-Lara Luz , Cano-Martínez Agustina , Soria-Castro Elizabeth , Castrejón-Téllez Vicente , Pavón Natalia , Osorio-Yáñez Citlalli , Díaz-Díaz Eulises , Rubio-Ruíz María Esther
Published: March 2023

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs’ signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.
Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study
Authors: Uberti Francesca , Trotta Francesco , Pagliaro Pasquale , Bisericaru Daniel Mihai , Cavalli Roberta , Ferrari Sara , Penna Claudia , Matencio Adrián
Published: March 2023

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.
Deletion of pbpC Enhances Bacterial Pathogenicity on Tomato by Affecting Biofilm Formation, Exopolysaccharides Production, and Exoenzyme Activities in Clavibacter michiganensis
Authors: Li Yao , Chen Xing , Xu Xiaoli , Yu Chengxuan , Liu Yan , Jiang Na , Li Jianqiang , Luo Laixin
Published: March 2023

Penicillin-binding proteins (PBPs) are considered essential for bacterial peptidoglycan biosynthesis and cell wall assembly. Clavibacter michiganensis is a representative Gram-positive bacterial species that causes bacterial canker in tomato. pbpC plays a significant role in maintaining cell morphological characteristics and stress responses in C. michiganensis. The current study demonstrated that the deletion of pbpC commonly enhances bacterial pathogenicity in C. michiganensis and revealed the mechanisms through which this occurs. The expression of interrelated virulence genes, including celA, xysA, xysB, and pelA, were significantly upregulated in △pbpC mutants. Compared with those in wild-type strains, exoenzyme activities, the formation of biofilm, and the production of exopolysaccharides (EPS) were significantly increased in △pbpC mutants. It is noteworthy that EPS were responsible for the enhancement in bacterial pathogenicity, with the degree of necrotic tomato stem cankers intensifying with the injection of a gradient of EPS from C. michiganensis. These findings highlight new insights into the role of pbpC affecting bacterial pathogenicity, with an emphasis on EPS, advancing the current understanding of phytopathogenic infection strategies for Gram-positive bacteria.
Time-Series Transcriptome Analysis Reveals the Molecular Mechanism of Ethylene Reducing Cold Sensitivity of Postharvest ‘Huangguan’ Pear
Authors: Wei Chuangqi , Wu Yanyan , Ma Zhenyu , Cheng Yudou , Guan Yeqing , Zhang Yang , Feng Yunxiao , Li Xueling , Guan Junfeng
Published: March 2023

‘Huangguan’ pear (Pyrus bretschneideri Rehd) fruit is susceptible to cold, characterized by developing peel browning spots (PBS) during cold storage. Additionally, ethylene pretreatment reduces chilling injury (CI) and inhibits PBS occurrence, but the mechanism of CI remains unclear. Here, we deciphered the dynamic transcriptional changes during the PBS occurrence with and without ethylene pretreatment via time-series transcriptome. We found that ethylene suppressed the cold-signaling gene expression, thereby decreasing the cold sensitivity of the ‘Huangguan’ fruit. Moreover, the “Yellow” module closely correlated with PBS occurrence was identified via weighted gene co-expression network analysis (WGCNA), and this module was related to plant defense via Gene Ontology (GO) enrichment analysis. Local motif enrichment analysis suggested that the “Yellow” module genes were regulated by ERF and WRKY transcription factors. Functional studies demonstrated that PbWRKY31 has a conserved WRKY domain, lacks transactivation activity, and localizes in the nucleus. PbWRKY31-overexpressed Arabidopsis were hypersensitive to cold, with higher expression levels of cold signaling and defense genes, suggesting that PbWRKY31 participates in regulating plant cold sensitivity. Collectively, our findings provide a comprehensive transcriptional overview of PBS occurrence and elucidate the molecular mechanism by which ethylene reduces the cold sensitivity of ‘Huangguan’ fruit as well as the potential role of PbWRKY31 in this process.
MMR Deficiency Defines Distinct Molecular Subtype of Breast Cancer with Histone Proteomic Networks
Authors: Hacking Sean , Chou Charissa , Baykara Yigit , Wang Yihong , Uzun Alper , Gamsiz Uzun Ece D.
Published: March 2023

Mismatch repair (MMR) alterations are important prognostic and predictive biomarkers in a variety of cancer subtypes, including colorectal and endometrial. However, in breast cancer (BC), the distinction and clinical significance of MMR are largely unknown. This may be due in part to the fact that genetic alterations in MMR genes are rare and only seen to occur in around 3% of BCs. In the present study, we analyzed TCGA data using a multi-sample protein–protein interaction (PPI) analysis tool, Proteinarium, and showed a distinct separation between specific MMR-deficient and -intact networks in a cohort of 994 BC patients. In the PPI networks specific to MMR deficiency, highly connected clusters of histone genes were identified. We also found the distribution of MMR-deficient BC to be more prevalent in HER2-enriched and triple-negative (TN) BC subtypes compared to luminal BCs. We recommend defining MMR-deficient BC by next-generation sequencing (NGS) when any somatic mutation is detected in one of the seven MMR genes.
Searching for Mechanisms Underlying the Assembly of Calcium Entry Units: The Role of Temperature and pH
Authors: Girolami Barbara , Serano Matteo , Di Fonso Alessia , Paolini Cecilia , Pietrangelo Laura , Protasi Feliciano
Published: March 2023

Store-operated Ca2+ entry (SOCE) is a mechanism that allows muscle fibers to recover external Ca2+, which first enters the cytoplasm and then, via SERCA pump, also refills the depleted intracellular stores (i.e., the sarcoplasmic reticulum, SR). We recently discovered that SOCE is mediated by Calcium Entry Units (CEUs), intracellular junctions formed by: (i) SR stacks containing STIM1; and (ii) I-band extensions of the transverse tubule (TT) containing Orai1. The number and size of CEUs increase during prolonged muscle activity, though the mechanisms underlying exercise-dependent formation of new CEUs remain to be elucidated. Here, we first subjected isolated extensor digitorum longus (EDL) muscles from wild type mice to an ex vivo exercise protocol and verified that functional CEUs can assemble also in the absence of blood supply and innervation. Then, we evaluated whether parameters that are influenced by exercise, such as temperature and pH, may influence the assembly of CEUs. Results collected indicate that higher temperature (36 °C vs. 25 °C) and lower pH (7.2 vs. 7.4) increase the percentage of fibers containing SR stacks, the n. of SR stacks/area, and the elongation of TTs at the I band. Functionally, assembly of CEUs at higher temperature (36 °C) or at lower pH (7.2) correlates with increased fatigue resistance of EDL muscles in the presence of extracellular Ca2+. Taken together, these results indicate that CEUs can assemble in isolated EDL muscles and that temperature and pH are two of the possible regulators of CEU formation.
The SLC9C2 Gene Product (Na+/H+ Exchanger Isoform 11; NHE11) Is a Testis-Specific Protein Localized to the Head of Mature Mammalian Sperm
Authors: Gardner Cameron C. , James Paul F.
Published: March 2023

Na+/H+ exchangers (NHEs) are a family of ion transporters that regulate the pH of various cell compartments across an array of cell types. In eukaryotes, NHEs are encoded by the SLC9 gene family comprising 13 genes. SLC9C2, which encodes the NHE11 protein, is the only one of the SLC9 genes that is essentially uncharacterized. Here, we show that SLC9C2 exhibits testis/sperm-restricted expression in rats and humans, akin to its paralog SLC9C1 (NHE10). Similar to NHE10, NHE11 is predicted to contain an NHE domain, a voltage sensing domain, and finally an intracellular cyclic nucleotide binding domain. An immunofluorescence analysis of testis sections reveals that NHE11 localizes with developing acrosomal granules in spermiogenic cells in both rat and human testes. Most interestingly, NHE11 localizes to the sperm head, likely the plasma membrane overlaying the acrosome, in mature sperm from rats and humans. Therefore, NHE11 is the only known NHE to localize to the acrosomal region of the head in mature sperm cells. The physiological role of NHE11 has yet to be demonstrated but its predicted functional domains and unique localization suggests that it could modulate intracellular pH of the sperm head in response to changes in membrane potential and cyclic nucleotide concentrations that are a result of sperm capacitation events. If NHE11 is shown to be important for male fertility, it will be an attractive target for male contraceptive drugs due to its exclusive testis/sperm-specific expression.
Activation of TLRs Triggers GLP-1 Secretion in Mice
Authors: Lebrun Lorène J. , Dusuel Alois , Xolin Marion , Le Guern Naig , Grober Jacques
Published: March 2023

The gastrointestinal tract constitutes a large interface with the inner body and is a crucial barrier against gut microbiota and other pathogens. As soon as this barrier is damaged, pathogen-associated molecular patterns (PAMPs) are recognized by immune system receptors, including toll-like receptors (TLRs). Glucagon-like peptide 1 (GLP-1) is an incretin that was originally involved in glucose metabolism and recently shown to be rapidly and strongly induced by luminal lipopolysaccharides (LPS) through TLR4 activation. In order to investigate whether the activation of TLRs other than TLR4 also increases GLP-1 secretion, we used a polymicrobial infection model through cecal ligation puncture (CLP) in wild-type and TLR4-deficient mice. TLR pathways were assessed by intraperitoneal injection of specific TLR agonists in mice. Our results show that CLP induces GLP-1 secretion both in wild-type and TLR4-deficient mice. CLP and TLR agonists increase gut and systemic inflammation. Thus, the activation of different TLRs increases GLP-1 secretion. This study highlights for the first time that, in addition to an increased inflammatory status, CLP and TLR agonists also strongly induce total GLP-1 secretion. Microbial-induced GLP-1 secretion is therefore not only a TLR4/LPS-cascade.
Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review
Authors: Abdul Ghani Muhamad Adib , Ugusman Azizah , Latip Jalifah , Zainalabidin Satirah
Published: March 2023

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.
Endocrine-Disrupting Chemicals and Disease Endpoints
Authors: Ahn Changhwan , Jeung Eui-Bae
Published: March 2023

Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems, and have been shown to interfere with physiological systems, especially by disrupting the hormone balance. During the last few decades, EDCs have been shown to affect reproductive, neurological, and metabolic development and function and even stimulate tumor growth. EDC exposure during development can disrupt normal development patterns and alter susceptibility to disease. Many chemicals have endocrine-disrupting properties, including bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols, and phthalates. These compounds have gradually been elucidated as risk factors for many diseases, such as reproductive, neural, and metabolic diseases and cancers. Endocrine disruption has been spread to wildlife and species that are connected to the food chains. Dietary uptake represents an important source of EDC exposure. Although EDCs represent a significant public health concern, the relationship and specific mechanism between EDCs and diseases remain unclear. This review focuses on the disease-EDC relationship and the disease endpoints associated with endocrine disruption for a better understanding of the relationship between EDCs-disease and elucidates the development of new prevention/treatment opportunities and screening methods.