bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of Respite Services on the Psycho-Emotional State of Families of Children Admitted to Hospice Palliative Care Unit: Preliminary Study on Parents’ Perceptions
Authors: Hizanu (Dumitrache) Mihaela , Boeriu Estera , Tanasescu Sonia , Balan Ada , Oprisoni Licinia Andrada , Popa Maria Valentina , Gutu Cristian , Vulcanescu Dan Dumitru , Bagiu Iulia Cristina , Bagiu Radu Vasile , Dragomir Tiberiu Liviu , Boru Casiana , Avram Cecilia Roberta , Duceac Letiția Doina
Published: March 2024

Background: In children’s palliative care, the term “respite” refers to a temporary break offered to primary caregivers of a child with a life-limiting illness. The aim of this study was to assess the perceptions of parents who have benefited from respite care services in the Lumina Association, Bacău hospice unit and the benefits it can bring in improving their psycho-emotional state. Methods: The study consisted of quantitative research involving 34 parents/caregivers who responded to a questionnaire with 26 questions, and qualitative research which involved the organization of a focus group with 12 parents who benefited from respite services. Results: The use of respite services was associated with a significant reduction of psycho-emotional distress on the part of primary caregivers; 91% of respondents said that this type of service reduces the level of psycho-emotional stress. Conclusions: All participants in the study confirmed that the most important benefit of respite is the time gained to care for family and health. The development of respite services could reduce the risk of emotional exhaustion and mental health problems.
Systematic Review and Meta-Analysis of the Financial Impact of 30-Day Readmissions for Selected Medical Conditions: A Focus on Hospital Quality Performance
Authors: Kum Ghabowen Iwimbong , Epane Josue Patien , Shen Jay J. , Goodman Xan , Ramamonjiarivelo Zo , Zengul Ferhat Devrim
Published: March 2024

Background: The Patient Protection and Affordable Care Act (ACA) established the Hospital Quality Initiative in 2010 to enhance patient safety, reduce hospital readmissions, improve quality, and minimize healthcare costs. In response, this study aims to systematically review the literature and conduct a meta-analysis to estimate the average cost of procedure-specific 30-day risk-standardized unplanned readmissions for Acute Myocardial Infarction (AMI), Heart Failure (HF), Pneumonia, Coronary Artery Bypass Graft (CABG), and Total Hip Arthroplasty and/or Total Knee Arthroplasty (THA/TKA). Methods: Eligibility Criteria: This study included English language original research papers from the USA, encompassing various study designs. Exclusion criteria comprise studies lacking empirical evidence on hospital financial performance. Information Sources: A comprehensive search using relevant keywords was conducted across databases from January 1990 to December 2019 (updated in March 2021), covering peer-reviewed articles and gray literature. Risk of Bias: Bias in the included studies was assessed considering study design, adjustment for confounding factors, and potential effect modifiers. Synthesis of Results: The review adhered to PRISMA guidelines. Employing Monte Carlo simulations, a meta-analysis was conducted with 100,000 simulated samples. Results indicated mean 30-day readmission costs: USD 16,037.08 (95% CI, USD 15,196.01–16,870.06) overall, USD 6852.97 (95% CI, USD 6684.44–7021.08) for AMI, USD 9817.42 (95% CI, USD 9575.82–10,060.43) for HF, and USD 21,346.50 (95% CI, USD 20,818.14–21,871.85) for THA/TKA. Discussion: Despite the financial challenges that hospitals face due to the ACA and the Hospital Readmissions Reduction Program, this meta-analysis contributes valuable insights into the consistent cost trends associated with 30-day readmissions. Conclusions: This systematic review and meta-analysis provide comprehensive insights into the financial implications of 30-day readmissions for specific medical conditions, enhancing our understanding of the nexus between healthcare quality and financial performance.
Minimally Invasive Treatment of Stress Urinary Incontinence in Women: A Prospective Comparative Analysis between Bulking Agent and Single-Incision Sling
Authors: Campanella Lorenzo , Gabrielli Gianluca , Chiodo Erika , Stefanachi Vitaliana , Pennacchini Ermelinda , Grilli Debora , Grossi Giovanni , Cignini Pietro , Morciano Andrea , Zullo Marzio Angelo , Palazzetti Pierluigi , Rappa Carlo , Calcagno Marco , Spina Vincenzo , Cervigni Mauro , Schiavi Michele Carlo
Published: March 2024

Introduction: The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Material and methods: Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents (PAHG Bulkamid®) and 75 with a single-incision sling (Altis®). The ICIQ-UI-SF (Incontinence Questionnaire-Urine Incontinence-Short Form), PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaires short form), FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Scale), and PGI-I (Patient Global Improvement Index) were used to assess efficiency and quality of life. Results: The bulking agents showed high efficacy and safety during the 29-month follow-up. Post-operative complications were recorded in both groups, with only two significant differences. The Bulkamid group experienced no pain, while 10.8% of the ALTIS group experienced groin pain and 5% experienced de novo urgency. Furthermore, patients treated with bulking agents experienced reduced nicturia (0.78 vs. 0.92 in patients treated with single-incision slings.). In both groups, we noticed a significant improvement in QoL (quality of life), with a halved ICIQ-UI-SF (International Consultation on Incontinence Questionnaire-Urine Incontinence-Short Form) score which was completed to assess the impact of urine symptoms. After 24 months of therapy, the Bulkamid group saw a decrease from 14.58 ± 5.11 at baseline to 5.67 ± 1.90 (p < 0.0001), whereas the ALTIS group experience a decrease from 13.75 ± 5.89 to 5.83 ± 1.78. Similarly, we observed an improvement in sexual function, with the number of sexually active patients increasing from 29 to 44 (56.4%) in the Bulkamid group (p = 0.041) and from 31 to 51 (61.7%) in the ALTIS group (p = 0.034). According to the most recent statistics, the PISQ-12, FSFI, and FSDS scores all demonstrated an improvement in women’s sexual function. Conclusions: In terms of efficacy and safety, bulking agents had notable results over the 29-month follow-up period. Furthermore, the patients treated with bulking agents reported a lower incidence of postoperative complications and a no discernible difference in terms of quality of life and sexual activity compared to the ones treated with single-incision slings. Bulking agents can be considered a very reliable therapeutic option based on accurate patient selection.
Living and Coping with Olfactory and Taste Disorders: A Qualitative Study of People with Long-COVID-19
Authors: Moro-López-Menchero Paloma , Martín-Sanz María Belén , Fernandez-de-las-Peñas César , Gómez-Sanchez Stella Maris , Gil-Crujera Antonio , Ceballos-García Laura , Escribano-Mediavilla Nuria I. , Fuentes-Fuentes Mª Victoria , Palacios-Ceña Domingo
Published: March 2024

Taste and smell disorders are common symptoms of SARS-CoV-2 acute infection. In post-COVID-19 condition, symptoms can persist leading to disruption in patients’ lives, to changes in their coping skills, and to the need to develop strategies for everyday life. This study aimed to describe the perspective of a group of patients with Long-COVID-19, a condition where loss of taste and/or smell was the most predominant symptom. A qualitative descriptive study was conducted. Participants who had suffered SARS-CoV-2 infection and had Long-COVID-19 loss of taste and/or smell were recruited. Purposive sampling was applied, and participants were recruited until data redundancy was reached. In-depth interviews were used for data collection and thematic analysis was applied. Twelve COVID-19 survivors (75% women) were recruited. The mean age of the participants was 55 years, and the mean duration of post-COVID-19 symptoms was 25 months. Three themes were identified: (a) Living with taste and smell disorders, describing the disorders they experience on a daily basis, how their life has changed and the accompanying emotions, (b) Changes and challenges resulting from the loss of taste and smell, changes in habits, self-care and risk in certain jobs or daily activities, (c) Coping with taste and smell disorders, describing the daily strategies used and the health care received. In conclusion, Long-COVID-19 taste and/or smell disorders limit daily life and involve changes in habits, meal preparation, and the ability to detect potentially dangerous situations.
Development of Integrated Supportive Care Nursing Competence Scale for Cancer Survivors
Authors: Bae Eun-Jung , Kim Yun-Hee
Published: March 2024

Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson’s correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach’s α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.
Associations of Sleep Quality and Physical Activity with Diabetes Quality of Life in Korean Americans with Type 2 Diabetes: A Cross-Sectional Study
Authors: Jeong Mihyun
Published: March 2024

The cross-sectional study aimed to examine the associations of sleep quality and physical activity with diabetes quality of life in Korean Americans with type 2 diabetes. A total of 119 Korean American adults with type 2 diabetes were recruited from Korean communities in Arizona, USA. The Pittsburgh Sleep Quality Index for sleep quality, the International Physical Activity Questionnaire for physical activity, and the Diabetes Quality of Life (DQOL) for quality of life were assessed. Descriptive statistics, bivariate correlations, and multiple linear regressions were conducted. The mean score of the total DQOL was 1.85 (SD = 0.28). Approximately 70% of those had poor sleep quality and a third showed low physical activity. The findings demonstrated that both sleep quality and low physical activity were independent predictors of overall DQOL scores, indicating that poor sleep quality and low physical activity are associated with reduced Diabetes Quality of Life in this demographic. Specifically, the satisfaction subscale of DQOL showed significant associations with low physical activity levels, suggesting that enhancing physical activity could potentially improve satisfaction within DQOL. Furthermore, the impact subscale was positively related to sleep quality, suggesting that better sleep quality might significantly lower the perceived negative impact of diabetes on daily life. No significant associations were found between sleep quality, physical activity, and the worry subscale of DQOL in the adjusted models. The study indicates that addressing sleep quality and promoting physical activity are essential components of diabetes management strategies aimed at improving the quality of life for Korean Americans with type 2 diabetes. This underlines the need for tailored interventions that consider cultural preferences and individual needs to enhance diabetes outcomes and quality of life in this population.
Individualized Prediction of SARS-CoV-2 Infection in Mexico City Municipality during the First Six Waves of the Pandemic
Authors: Victorino-Aguilar Mariel , Lerma Abel , Badillo-Alonso Humberto , Ramos-Lojero Víctor Manuel , Ledesma-Amaya Luis Israel , Ruiz-Velasco Acosta Silvia , Lerma Claudia
Published: March 2024

After COVID-19 emerged, alternative methods to laboratory tests for the individualized prediction of SARS-CoV-2 were developed in several world regions. The objective of this investigation was to develop models for the individualized prediction of SARS-CoV-2 infection in a large municipality of Mexico. The study included data from 36,949 patients with suspected SARS-CoV-2 infection who received a diagnostic tested at health centers of the Alvaro Obregon Jurisdiction in Mexico City registered in the Epidemiological Surveillance System for Viral Respiratory Diseases (SISVER-SINAVE). The variables that were different between a positive test and a negative test were used to generate multivariate binary logistic regression models. There was a large variation in the prediction variables for the models of different pandemic waves. The models obtained an overall accuracy of 73% (63–82%), sensitivity of 52% (18–71%), and specificity of 84% (71–92%). In conclusion, the individualized prediction models of a positive COVID-19 test based on SISVER-SINAVE data had good performance. The large variation in the prediction variables for the models of different pandemic waves highlights the continuous change in the factors that influence the spread of COVID-19. These prediction models could be applied in early case identification strategies, especially in vulnerable populations.
Quasi-Seniors’ Perception, Response, and Planning from the Perspective of Successful Aging
Authors: Wen Ming-Shien , Chuang Miao-Hsien , Lin Jinkwan
Published: March 2024

With the coming of a rapidly aging society, individuals born in the baby boom era after World War II are now facing the challenges of aging. From late middle age to successful aging, what are the perceptions and responses of these quasi-seniors? With this in mind, referring to Phelan’s successful aging scale, the researchers developed the 4P Strategies (Physical, Psychological, Prospect, and Place and Relationships) tailored for quasi-seniors. Based on grounded theory, the results of 12 sessions of focused interviews (involving a total of 93 interviewees between the ages of 55 and 75; 41 males and 52 females; 48 not retired and 45 retired) were matched with the 4P Strategies. The results were the following: (1) regarding the Physical factor, the interviewees were shocked by their physical decline, and they had begun to devise strategies for health preservation and exercise; (2) regarding the Psychological factor, in order to mentally adapt, the interviewees agreed that moderate stress relief was absolutely necessary; (3) regarding the Prospect factor: the interviewees felt that one should make financial plans early, contemplate the value of life, and more actively learn and realize one’s dreams; and (4) regarding the Place and Relationships factor, the interviewees aimed to rebuild their close relationships with their spouses, family members, and old friends and had polarized views regarding where to live in their old age. On the whole, the most discussed issue among the interviewees was where to live in their old age. Many had their own views and plans and did not stick to traditional views; however, they took the opinions of their significant others into account. During the interviews, interviewees wished to understand the responses of their peers to serve as a reference for their own decisions, and they realized that successful aging also required learning. This study aimed to encourage quasi-seniors about to enter their old age and help them to learn how to positively respond to aging as well as work towards a happy life with successful aging. This study could fill in gaps in research involving individuals in this age group and provide a reference for relevant policies.
Enhancing Post-Harvest Resilience: Investigating the Synergistic Effects of Essential Oil Combinations on Biochemical Profiles in Botrytis cinerea-Infected Apples
Authors: Karakus Sinem
Published: March 2024

This study explored the impact of essential oil combinations on Botrytis cinerea-infected apples, focusing on how these treatments affect the levels of amino acids, anthocyanins, organic acids, phenolic compounds, and hormones. We discovered significant differences in amino acid concentrations, particularly asparagine, serine, histidine, glycine, and arginine, between control and fungus-treated apples. Preventive measures notably increased anthocyanins like delphinidin-3-glycoside and peonidin-3-glycoside, while combinations such as thymol + fungus balanced anthocyanin profiles effectively. Organic acid and phenolic compound analyses showed that curative strategies generally increased concentrations, with the thymol + cineole + fungus treatment being especially effective. Hormonal analysis highlighted the benefits of preventive measures in raising indole-3-acetic acid and gibberellic acid levels, whereas curative treatments increased abscisic acid and salicylic acid concentrations. The combination of cineole and thymol with fungicide emerged as a potent strategy for enhancing phenolic content. These findings underscore the potential of specific essential oil combinations in improving the biochemical composition of B. cinerea-infected apples, offering new avenues for enhancing fruit quality and sustainability in the agriculture sector.
Durian (Durio zibethinus L.): Nutritional Composition, Pharmacological Implications, Value-Added Products, and Omics-Based Investigations
Authors: Khaksar Gholamreza , Kasemcholathan Sudarat , Sirikantaramas Supaart
Published: March 2024

Durian (Durio zibethinus L.), a tropical fruit celebrated in Southeast Asia for its distinct flavor, is the focus of this comprehensive review. The fruit’s pulp is rich in high-value bioactive compounds, including gamma-glutamylcysteine, a precursor to the essential antioxidant glutathione. With durian cultivation gaining prominence in Southeast Asia due to its economic potential through cultivar enhancement, an in-depth examination of durian-related research becomes crucial. This review explores the health benefits of durian, analyzing the nutritional compositions and bioactive compounds present in the pulp, peel, and seed. It also underscores durian-based food products and the potential for valorizing durian waste. This review encapsulates the significant advancements made in omics-based research, aimed at deciphering the molecular complexities of durian fruit post-harvest ripening and the metabolic shifts impacting its sensory attributes. It is the first to summarize studies across genome, transcriptome, and metabolome levels. Future research should prioritize the development of molecular markers to accelerate the breeding of elite cultivars with preferred traits. It also proposes the exploration of durian waste valorization, including underexplored parts like flowers and leaves for their bioactive compounds, to promote a sustainable bioeconomy. Finally, it suggests the development of innovative durian products catering to the tastes of health-conscious consumers.
Examining Teacher Concerns and Anxiety on the Implementation of a Universal Body Image Program
Authors: Hidalgo Sarah G. , Henning Taryn , Gomez Francesca , Perez Marisol
Published: March 2024

In the past 30 years, there have been numerous positive body image and eating disorder prevention programs targeting youth developed for school-based settings. Frequently, teachers are used as interventionists to increase dissemination, decrease costs relative to researchers, and increase scalability. However, little is known about teacher concerns and barriers that may hinder successful uptake and implementation. The current study recruited a total of 269 teachers who consented to implement a universal body image and appearance-related bullying and teasing prevention program in their classrooms as part of a randomized controlled trial. Teachers expressed some worry that they may say the wrong thing, and concern about feeling uncomfortable teaching the program due to their own body dissatisfaction. Teacher’s ethnicity, gender, years teaching, dieting behaviors and other weight control behaviors, and self-efficacy were not associated with concerns related to teaching the curriculum. Teachers with lower body esteem reported higher concerns and anxiety related to teaching a body image curriculum. In free response items, teachers worried about handling student comments that were beyond the scope of the curriculum. Teacher self-efficacy was the only variable associated with the number of program sessions implemented. Findings suggest avenues to increase implementation.
Forecasting Selected Commodities’ Prices with the Bayesian Symbolic Regression
Authors: Drachal Krzysztof , Pawłowski Michał
Published: March 2024

This study firstly applied a Bayesian symbolic regression (BSR) to the forecasting of numerous commodities’ prices (spot-based ones). Moreover, some features and an initial specification of the parameters of the BSR were analysed. The conventional approach to symbolic regression, based on genetic programming, was also used as a benchmark tool. Secondly, various other econometric methods dealing with variable uncertainty were estimated including Bayesian Model Averaging, Dynamic Model Averaging, LASSO, ridge, elastic net, and least-angle regressions, etc. Therefore, this study reports a concise and uniform comparison of an application of several popular econometric models to forecasting the prices of numerous commodities. Robustness checks and statistical tests were performed to strengthen the obtained conclusions. Monthly data beginning from January 1988 and ending in August 2021 were analysed.
Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer’s Disease
Authors: Pulliam Lynn , Sun Bing , McCafferty Erin , Soper Steven A. , Witek Malgorzata A. , Hu Mengjia , Ford Judith M. , Song Sarah , Kapogiannis Dimitrios , Glesby Marshall J. , Merenstein Daniel , Tien Phyllis C. , Freasier Heather , French Audrey , McKay Heather , Diaz Monica M. , Ofotokun Igho , Lake Jordan E. , Margolick Joseph B. , Kim Eun-Young , Levine Steven R. , Fischl Margaret A. , Li Wei , Martinson Jeremy , Tang Norina
Published: March 2024

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.
The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID)
Authors: Hu Yizhou , Zhang Feng , Ikonomovic Milos , Yang Tuo
Published: March 2024

Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of cognitive decline secondary to cerebral vascular aging and injury. It is the second most common type of dementia, and the prevalence continues to increase. Nuclear factor erythroid 2-related factor 2 (NRF2) is enriched in the cerebral vasculature and has diverse roles in metabolic balance, mitochondrial stabilization, redox balance, and anti-inflammation. In this review, we first briefly introduce cerebrovascular aging in VCID and the NRF2 pathway. We then extensively discuss the effects of NRF2 activation in cerebrovascular components such as endothelial cells, vascular smooth muscle cells, pericytes, and perivascular macrophages. Finally, we summarize the clinical potential of NRF2 activators in VCID.
Circadian Gene Variants: Effects in Overweight and Obese Pregnant Women
Authors: Franzago Marica , Borrelli Paola , Cavallo Pierluigi , Di Tizio Luciano , Gazzolo Diego , Di Nicola Marta , Stuppia Liborio , Vitacolonna Ester
Published: March 2024

Obesity and overweight are common and complex conditions influenced by multiple genetic and environmental factors. Several genetic variants located in the genes involved in clock systems and fat taste perception can affect metabolic health. In particular, the polymorphisms in CLOCK and BMAL1 genes were reported to be significantly related to cardiovascular disease, metabolic syndrome, sleep reduction, and evening preference. Moreover, genetic variants in the CD36 gene have been shown to be involved in lipid metabolism, regulation of fat intake, and body weight regulation. The aim of this study is to evaluate, for the first time, the association between variants in some candidate genes (namely, BMAL1 rs7950226 (G>A), CLOCK rs1801260 (A>G), CLOCK rs4864548 (G>A), CLOCK rs3736544 (G>A), CD36 rs1984112 (A>G), CD36 rs1761667 (G>A)) and overweight/obesity (OB) in pregnant women. A total of 163 normal-weight (NW) and 128 OB participants were included. A significant correlation was observed between A-allele in CLOCK rs4864548 and an increased risk of obesity (OR: 1.97; 95% CI 1.22–3.10, p = 0.005). In addition, we found that subjects carrying the haplotype of rs1801260-A, rs4864548-A, and rs3736544-G are likely to be overweight or obese (OR 1.47, 95% CI 1.03–2.09, p = 0.030), compared with those with other haplotypes. Moreover, a significant relation was observed between third-trimester lipid parameters and genetic variants—namely, CD36 rs1984112, CD36 rs1761667, BMAL1 rs7950226, and CLOCK rs1801260. A multivariate logistic regression model revealed that CLOCK rs4864548 A-allele carriage was a strong risk factor for obesity (OR 2.05, 95% CI 1.07–3.93, p = 0.029); on the other hand, greater adherence to Mediterranean diet (OR 0.80, 95% CI 0.65–0.98, p = 0.038) and higher HDL levels (OR 0.96, 95% CI 0.94–0.99, p = 0.021) were related to a reduced risk of obesity. Interestingly, an association between maternal CLOCK rs4864548 and neonatal birthweight was detected (p = 0.025). These data suggest a potential role of the polymorphisms in clock systems and in fat taste perception in both susceptibility to overweight/obesity and influencing the related metabolic traits in pregnant women.
Chagas Disease: A Silent Threat for Dogs and Humans
Authors: Durães-Oliveira João , Palma-Marques Joana , Moreno Cláudia , Rodrigues Armanda , Monteiro Marta , Alexandre-Pires Graça , da Fonseca Isabel Pereira , Santos-Gomes Gabriela
Published: March 2024

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.
Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women
Authors: Turska-Kozłowska Monika , Pedraz-Petrozzi Bruno , Paluszkiewicz Piotr , Parada-Turska Jolanta
Published: March 2024

Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc’s inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA/TRP ratio and KYN/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.
Applications of Flow Cytometry in Drug Discovery and Translational Research
Authors: Ullas Sumana , Sinclair Charles
Published: March 2024

Flow cytometry is a mainstay technique in cell biology research, where it is used for phenotypic analysis of mixed cell populations. Quantitative approaches have unlocked a deeper value of flow cytometry in drug discovery research. As the number of drug modalities and druggable mechanisms increases, there is an increasing drive to identify meaningful biomarkers, evaluate the relationship between pharmacokinetics and pharmacodynamics (PK/PD), and translate these insights into the evaluation of patients enrolled in early clinical trials. In this review, we discuss emerging roles for flow cytometry in the translational setting that supports the transition and evaluation of novel compounds in the clinic.
Anionic Methacrylate Copolymer Microparticles for the Delivery of Myo-Inositol Produced by Spray-Drying: In Vitro and In Vivo Bioavailability
Authors: Caruana Roberto , Zizzo Maria Grazia , Caldara Gaetano Felice , Montalbano Francesco , Fasciano Silvia , Arena Dora , Salamone Marida , Di Fazio Gaetano , Bottino Alessandro , Licciardi Mariano
Published: March 2024

In this study, a new micro delivery system based on an anionic methacrylate copolymer, able to improve the biological response of myo-inositol by daily oral administration, was manufactured by spray-drying. It has an ideal dose form for oral administration, with an experimental drug loading (DL)% of 14% and a regulated particle size of less than 15 µm. The new formulation features an improvement on traditional formulations used as a chronic therapy for the treatment of polycystic ovary syndrome. The microparticles’ release profile was studied and ex vivo porcine intestinal mucosa permeation experiments were performed to predict potential improvements in oral absorption. Batch n. 3, with the higher Eudragit/MI weight ratio (ratio = 6), showed the best-modified release profiles of the active ingredient, ensuring the lowest myo-inositol loss in an acidic environment. The in vivo evaluation of the myo-inositol micro delivery system was carried out in a rat animal model to demonstrate that the bioavailability of myo-inositol was increased when compared to the administration of the same dosage of the pure active ingredient. The AUC and Cmax of the loaded active molecule in the micro delivery system was improved by a minimum of 1.5 times when compared with the pure substance, administered with same dosage and route. Finally, the increase of myo-inositol levels in the ovary follicles was assessed to confirm that a daily administration of the new formulation improves myo-inositol concentration at the site of action, resulting in an improvement of about 1.25 times for the single administration and 1.66 times after 7 days of repeated administration when compared to pure MI.
The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis
Authors: Guan Xiaoyue , Wang Yuting , Li Wenlan , Mu Wenli , Tang Yifei , Wang Mingfei , Seyam Abdelrahman , Yang Yao , Pan Lifei , Hou Tiezhou
Published: March 2024

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis–apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.
Localized Expression of Olfactory Receptor Genes in the Olfactory Organ of Common Minke Whales
Authors: Hirose Ayumi , Nakamura Gen , Nikaido Masato , Fujise Yoshihiro , Kato Hidehiro , Kishida Takushi
Published: March 2024

Baleen whales (Mysticeti) possess the necessary anatomical structures and genetic elements for olfaction. Nevertheless, the olfactory receptor gene (OR) repertoire has undergone substantial degeneration in the cetacean lineage following the divergence of the Artiodactyla and Cetacea. The functionality of highly degenerated mysticete ORs within their olfactory epithelium remains unknown. In this study, we extracted total RNA from the nasal mucosae of common minke whales (Balaenoptera acutorostrata) to investigate ORs’ localized expression. All three sections of the mucosae examined in the nasal chamber displayed comparable histological structure. However, the posterior portion of the frontoturbinal region exhibited notably high OR expression. Neither the olfactory bulb nor the external skin exhibited the expression of these genes. Although this species possesses four intact non-class-2 ORs, all the ORs expressed in the nasal mucosae belong to class-2, implying the loss of aversion to specific odorants. These anatomical and genomic analyses suggest that ORs are still responsible for olfaction within the nasal region of baleen whales, enabling them to detect desirable scents such as prey and potential mating partners.
Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses
Authors: Lee Hyun-Joo , Kim Dong-Kyu
Published: March 2024

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin−CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.
Exosomal miRNA Changes Associated with Restoration to Sinus Rhythm in Atrial Fibrillation Patients
Authors: Tsai Pei-Chien , Ko Albert Min-Shan , Chen Yu-Lin , Chiu Cheng-Hsun , Yeh Yung-Hsin , Tsai Feng-Chun
Published: March 2024

We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.
Endoplasmic Reticulum Stress Induces Vasodilation in Liver Vessels That Is Not Mediated by Unfolded Protein Response
Authors: Zavadskis Sergejs , Shiganyan Anna , Müllebner Andrea , Oesterreicher Johannes , Holnthoner Wolfgang , Duvigneau Johanna Catharina , Kozlov Andrey V.
Published: March 2024

There is a growing body of evidence that ER stress and the unfolded protein response (UPR) play a key role in numerous diseases. Impaired liver perfusion and ER stress often accompany each other in liver diseases. However, the exact impact of ER stress and UPR on the hepatic perfusion is not fully understood. The aim of this study was to disclose the effect of ER stress and UPR on the size of liver vessels and on the levels of Ca2+ and nitric oxide (NO), critical regulators of vascular tonus. This study was carried out in precisely cut liver tissue slices. Confocal microscopy was used to create 3D images of vessels. NO levels were determined either using either laser scan microscopy (LSM) in cells or by NO-analyser in medium. Ca2+ levels were analysed by LSM. We show that tunicamycin, an inducer of ER stress, acts similarly with vasodilator acetylcholine. Both exert a similar effect on the NO and Ca2+ levels; both induce significant vasodilation. Notably, this vasodilative effect persisted despite individual inhibition of UPR pathways—ATF-6, PERK, and IRE1—despite confirming the activation of UPR. Experiments with HUVEC cells showed that elevated NO levels did not result from endothelial NO synthase (eNOS) activation. Our study suggests that tunicamycin-mediated ER stress induces liver vessel vasodilation in an NO-dependent manner, which is mediated by intracellular nitrodilator-activatable NO store (NANOS) in smooth muscle cells rather than by eNOS.
Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring
Authors: Crocetto Felice , Falcone Alfonso , Mirto Benito , Sicignano Enrico , Pagano Giovanni , Dinacci Fabrizio , Varriale Domenico , Machiella Fabio , Giampaglia Gaetano , Calogero Armando , Varlese Filippo , Balsamo Raffaele , Trama Francesco , Sciarra Antonella , Del Giudice Francesco , Busetto Gian , Ferro Matteo , Lucarelli Giuseppe , Lasorsa Francesco , Imbimbo Ciro , Barone Biagio
Published: March 2024

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.
Gene Expression Profiling Reveals Fundamental Sex-Specific Differences in SIRT3-Mediated Redox and Metabolic Signaling in Mouse Embryonic Fibroblasts
Authors: Belužić Robert , Šimunić Ena , Podgorski Iva I. , Pinterić Marija , Hadžija Marijana Popović , Balog Tihomir , Sobočanec Sandra
Published: March 2024

Sirt-3 is an important regulator of mitochondrial function and cellular energy homeostasis, whose function is associated with aging and various pathologies such as Alzheimer’s disease, Parkinson’s disease, cardiovascular diseases, and cancers. Many of these conditions show differences in incidence, onset, and progression between the sexes. In search of hormone-independent, sex-specific roles of Sirt-3, we performed mRNA sequencing in male and female Sirt-3 WT and KO mouse embryonic fibroblasts (MEFs). The aim of this study was to investigate the sex-specific cellular responses to the loss of Sirt-3. By comparing WT and KO MEF of both sexes, the differences in global gene expression patterns as well as in metabolic and stress responses associated with the loss of Sirt-3 have been elucidated. Significant differences in the activities of basal metabolic pathways were found both between genotypes and between sexes. In-depth pathway analysis of metabolic pathways revealed several important sex-specific phenomena. Male cells mount an adaptive Hif-1a response, shifting their metabolism toward glycolysis and energy production from fatty acids. Furthermore, the loss of Sirt-3 in male MEFs leads to mitochondrial and endoplasmic reticulum stress. Since Sirt-3 knock-out is permanent, male cells are forced to function in a state of persistent oxidative and metabolic stress. Female MEFs are able to at least partially compensate for the loss of Sirt-3 by a higher expression of antioxidant enzymes. The activation of neither Hif-1a, mitochondrial stress response, nor oxidative stress response was observed in female cells lacking Sirt-3. These findings emphasize the sex-specific role of Sirt-3, which should be considered in future research.
Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation
Authors: Pinto Daniela , Themudo Gonçalo , Pereira André C. , Botelho Ana , Cunha Mónica V.
Published: March 2024

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention.