bluuebunny/crossref_metadata_2025 huggingface dataset:
Process Mapping of the Sol–Gel Transition in Acid-Initiated Sodium Silicate Solutions
Authors: Matinfar Marzieh , Nychka John A.
Published: October 2024

Fabricating large-scale porous bioactive glass bone scaffolds presents significant challenges. This study aims to develop formable, in situ setting scaffolds with a practical gelation time of about 10 min by mixing 45S5 bioactive glass with sodium silicate (waterglass) and an acid initiator. The effects of pH (2–11), waterglass concentration (15–50 wt.%), and acid initiator type (phosphoric or boric acid) were examined to optimize gelation kinetics and microstructure. A 10 min gelation time was achieved with boric acid and phosphoric acid at various pH levels by adjusting the waterglass concentration. Exponential and polynomial models were proposed to predict gelation times in basic and acidic environments, respectively. The optical properties of the gels were studied qualitatively and quantitatively, providing insights into gelation kinetics and structure. Acidic gels formed smaller particles in a dense network (pores < 550 nm) with higher light transmittance, while basic gels had larger aggregates (pores ~5 µm) and lower transmittance. As the waterglass concentration decreased, pore size and transmittance converged in both groups. The onset of gelation was detected around 8 min using the derivative of light transmittance. This work identifies the key factors controlling waterglass gelation and their impact on gel structure, enabling the tailored creation of formable, in situ setting bioactive glass bone scaffolds.
Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome
Authors: Trabacca Antonio , Ferrante Camilla , Oliva Maria Carmela , Fanizza Isabella , Gallo Ivana , De Rinaldis Marta
Published: October 2024

Background: Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype. Methods: We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases. Results: The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy. Conclusion: This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.
A Study of JUN’s Promoter Region and Its Regulators in Chickens
Authors: Kong Ruihong , Shi Jieyao , Xie Ke , Wu Han , Wang Xu , Zhang Yani , Wang Yingjie
Published: October 2024

Background: The Jun proto-oncogene (JUN), also referred to as C-JUN, is an integral component of the JNK signaling pathway, which is crucial for the formation and differentiation of spermatogonial stem cells (SSCs). Investigations into the transcriptional regulation of chicken JUN can offer a molecular foundation for elucidating its mechanistic role in SSCs. Methods: In this study, we successfully cloned a 2000 bp upstream sequence of the JUN transcription start site and constructed a series of pGL3 recombinant vectors containing JUN promoters of varying lengths. Results: We verified the promoter activity of the 2000 bp upstream sequence by assessing the fluorescence intensity of DF-1 and identified the promoter activities of different regions via dual-luciferase assays. The transcription of JUN and its promoter region spanning −700 to 0 bp was modulated by an activator of the JNK signaling pathway. Bioinformatics analysis revealed that this −700 to 0 bp region was highly conserved among avian species and predicted the presence of binding sites for Wilms tumor 1 (WT1) and CCAAT/enhancer binding protein alpha (CEBPA). The JNK signaling pathway activator was found to upregulate the expression of these transcription factors in DF-1 cells. Through the deletion of binding sites and the overexpression of WT1 and CEBPA, we demonstrated that WT1 inhibited the transcription of JUN, while CEBPA promoted it. Conclusions: In conclusion, the −700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs.
Oral Function, Loneliness, Depression, and Social Participation Among Physically Disabled Middle-Aged and Older Adult Individuals: Insights from a Japanese Cross-Sectional Study
Authors: Maki Naoki , Sakamoto Harumi , Taniguchi Keisuke , Mutsukura Yuhki , Nomura Shoko , Oh Sechang , Yanagi Hisako , Mayers Thomas
Published: October 2024

Background/Objectives: In the context of an aging society, physical disability and its relationship with frailty is of growing concern. The aim of this study was to examine the associations between oral function, social participation, and loneliness among community-dwelling middle-aged and older adult physically disabled individuals. Methods: In this cross-sectional study, the participants were 140 individuals with certified physical disabilities living in the studied area. Demographic characteristics, outing activities, loneliness (Three-Item Loneliness (TIL) Scale), and frailty/ability to live independently (Kihon Checklist (KCL)) were assessed using a questionnaire survey. The participants were divided into two groups based on the presence or absence of oral dysfunction (OD), and statistical analyses were performed to compare the groups. Results: The group with OD had significantly higher TIL and KCL total scores and significantly lower mobility, confinement, cognitive function, greater levels of depression, and fewer outing activities (volunteering, movies, festivals, sports) compared to the group without OD. In a multivariate, age- and sex-adjusted binomial logistic regression analysis, outing activities (OR = 0.011, 95% CI: 0.000–0.529, p = 0.023) and loneliness (OR = 6.174, 95%CI: 1.292-29.502, p = 0.023) were identified as significant factors. Conclusions: An association was found between OD, loneliness, and social activities among middle-aged and older individuals with physical disabilities. The results suggest that future interventions should consider the relationship between oral function and factors such as depression, loneliness, social isolation, and social engagement as a means to mitigate frailty and other health and well-being concerns for physically disabled individuals.
Global Community in James Welch’s The Heartsong of Charging Elk
Authors: Liu Kedong , Zhao Yutong , Li Limin
Published: October 2024

Human beings have had beautiful dreams for a harmonious world since centuries ago; this can be termed cosmopolitanism, shijie datong, or global community. Based on theories expounded by Confucius, Tönnies, Anderson, Bauman, Derrida, and Appiah, we closely examine the concept of “global cultural community” or “international community”, that is, the community involving individuals or groups of two or more countries by way of textual analysis, with James Welch’s The Heartsong of Charging Elk as an example. Through an analysis of the plot in the novel, we find that the American Indian protagonist Charging Elk integrates into the local French culture, while retaining his indigenous cultural identity, and thus negotiates a global community. This finding is also evaluated in the context of all five novels by Welch and in a broader scope of American Indian literature with inter-continental themes. The studies on cosmopolitanism or global community in American Indian literature can play an important role in exploring the construction of a global community for humanity for a shared future.
Blue Öyster Cult’s “Godzilla”: An American Kaiju Anthem
Authors: Compora Daniel Patrick
Published: October 2024

In 1978, the American hard rock band Blue Öyster Cult released the song “Godzilla” as the first single from the fifth studio album Spectres. Despite not registering on popular charts, it would eventually evolve into an iconic song of its era. “Godzilla” continues to receive airplay on classic rock stations, and it remains a staple of the band’s touring performances. In 2019, a cover of the song, more than forty years after its release, made its film debut in Godzilla: King of the Monsters. Though the song is primarily a tribute to the Japanese monster from which it gets its name, “Godzilla” also reflects the nuclear fear and paranoia of the 1970s Cold War era. “Godzilla’s” cultural impact, the song’s lyrics, the Cold War context in which it was written, and its connection to the kaiju films featuring the famous monster are examined. While this is the most popular and well-known song dedicated to Godzilla, it is not the only one. Other compositions have, but they have failed to achieve the iconic status that Blue Öyster Cult’s version has attained. This song has evolved into an unofficial anthem for the great monster.
Hybrid: Reading Godzilla Through Posthumanism
Authors: Pagnoni Berns Fernando Gabriel , Aguilar Emiliano , Traversa Jorge Eduardo
Published: October 2024

This essay proposes to read the classic cycle of Godzilla films (roughly, 1954–1995) using a posthuman perspective that makes its emphasis on animal, vegetal and mineral life. We will use posthuman and materialist philosophy to analyze hybrid monsters as part of new interdisciplinary studies about non-human agencies and their creepy potential. As such, we want to offer the first posthumanist readings of the Godzilla franchise, in time to celebrate its 70 years of existence and, in consequence, highlight how posthumanist the series has always been.
Challenging Childhood Obesity: The Influence of Education and Close Monitoring on Obesity-Related Behaviors
Authors: Sunnetci Silistre Eda , Yesil Alihan , Kozanoglu Tugba , Balci Mehmet Cihan , Karaca Meryem , Gokcay Gulden Fatma
Published: October 2024

Background: We aimed to evaluate the role of nutrition and behavior education intervention in the prevention and treatment of childhood obesity by comparing changes in obesity-related characteristics among obese children during a follow-up period of 12 months. Methods: This study was designed as a prospective cohort study in children aged between 6 and 18 years, with exogenous obesity who applied to Istanbul Research and Training Hospital, Pediatrics Department, between January 2018 and July 2019. Beginning at the sixth month, a program for nutrition and behavior education for obesity prevention and treatment was initiated and continued during the second half of the study period. Results: The mean age of 59 children (29 females, 30 males) was 11.73 ± 2.78. BMI levels did not show a significant difference in the first 6 months, but decreased significantly during the second 6 months of the study. Screen time, fast eating behavior, overeating behavior and food score index scores also demonstrated significant improvements during the intervention period of the study, between 6 and 12 months. Conclusion: It was concluded that nutrition and behavior education for the prevention and treatment of childhood obesity could be a successful intervention with close follow-up.
The Intersection of Sexual Orientation, Substance Use, and Mental Health: Findings from Hints 5
Authors: Bouraleh Saredo M. , Ghose Bishwajit
Published: October 2024

Objectives: In this study, we aimed to investigate (1) the association of tobacco and e-cigarette use with sexual orientation (LGBTQ and heterosexual individuals) and (2) the difference in the association of tobacco and e-cigarette use with self-reported depression by sexual orientation. Methods: The data for this study were obtained from the Health Information National Trends Survey (HINTS 5, Cycle 4). Sample participants included 3583 adults (93.87% heterosexuals). We used multinomial regression to measure the relative risk ratios (RRRs) of being a former and current user versus never a user of tobacco and e-cigarettes and binomial regression to measure the odds ratios of depression between the LGBTQ and heterosexuals. Results: Current smoking prevalence is higher among LGBTQ participants (17.3%) compared to heterosexuals (11.0%). The disparity is even greater for e-cigarette use, with 7.3% of LGBTQ participants being current users versus 2.8% of heterosexuals and 24.5% of LGBTQ participants being former users compared to 9.3% of heterosexuals. Compared to heterosexuals, the relative risk ratio of being a current tobacco user among the LGBTQ participants was about 1.75 times higher [RRR = 1.75, 95%CI = 1.16, 2.64], and that of e-cigarette use was about 2.8 times higher [RRR = 2.81, 95%CI = 1.57, 5.05]. Among current e-cigarette users, heterosexual participants had 1.9 percentage points [risk difference = 1.94, 95%CI = 1.20, 3.13] higher probability of depression, whereas among the LGBTQ participants, the risk was about 3.7 times higher [OR = 3.67, 95%CI = 1.06, 12.74]. Conclusions: Our findings conclude that the LGBTQ are more likely to use tobacco and e-cigarettes compared to heterosexuals and that the risk of depression from e-cigarette smoking is more pronounced among the LGBTQ participants.
Health-Related Experiences of Geophagia Among Women of Reproductive Age in Tshwane District, Gauteng Province: An Exploratory Qualitative Study
Authors: Malebatja Mohora Feida , Randa Moreoagae Bertha , Mokgatle Mpata Mathildah , Oguntibeju Oluwafemi Omoniyi
Published: October 2024

Background/Objectives: Women of reproductive age are reported to be the largest population that practises geophagia. The short-term and long-term health related conditions originating from the practise of geophagia are often not understood by geophagic women of reproductive age. This study has explored the health-related experiences of geophagia among women of reproductive age of Tshwane District, Gauteng Province. Methods: This was a qualitative study design following inductive thematic content analysis. In-depth interviews and focus group discussions were used to collect data using an interview guide and audio record. Data collection took place in 2023. Results: Mental health disorders, pregnancy complications, appendicitis, cancers, breathing complications, fatigue, premature deaths, worms, piles, and nutrients deficiencies were reported as some of the health-related challenges and diseases experienced by women of reproductive age of Tshwane District, Gauteng Province resulting from the practise of geophagia. Conclusions: The practise of geophagia was associated with various negative health outcomes. The reproductive health statuses of women of reproductive age were negatively impacted by the practise of geophagia affecting maternal and childhood mortalities and morbidities.
An Overview of Health-Promoting Programs and Healthy Lifestyles for Adolescents and Young People: A Scoping Review
Authors: Raimundo Marta , Cerqueira Ana , Gaspar Tania , Gaspar de Matos Margarida
Published: October 2024

The health of children, adolescents, and young adults is a primary global concern. In 2021, there were 2.1 million deaths among children and adolescents. Injuries, violence, communicable diseases, nutritional deficiencies, substance use, non-communicable diseases, and mental health disorders are among the leading causes of death in this age group. Background/objectives: This scoping review aims to identify and describe health promotion and healthy lifestyle programs developed worldwide targeting adolescents and young adults. Methods: A total of 106 programs were included, of which 8 were selected through scientific databases and 98 through other research methods (e.g., government websites and other online sources). Results: The results show that Europe, North America, New Zealand, and the United States of America are the continents and countries with the highest number of programs. Most programs originated before 2020 and are aimed at children, adolescents, and young adults. Mental health, substance and non-substance dependencies, and sexual and reproductive health were the most frequent areas among the available youth programs. Most programs do not mention evaluating or monitoring the services provided. Conclusions: This work allows for a deeper understanding of the programs available for adolescents and young adults, providing an overview of their characteristics. Moreover, it emphasizes the importance of increasing the number of available programs, especially in countries with higher morbidity and mortality rates among the young population. The programs must be based on population studies to better meet their needs. Lastly, programs should become sustainable and integrated into national public policies, accompanied by ongoing training, supervision, and intervision of professionals working in these contexts.
Relationship Between Oral Motor and Cognitive Function in Community-Dwelling Korean Older Adults: A Cross-Sectional, Observational Study
Authors: Jung Nam-Hae
Published: October 2024

Background: The present study analyzed the relationship between oral motor and cognitive functions in community-dwelling older Korean adults. Methods: Study participants included 113 community-dwelling older adults with a mean age of 73.84 years. Subjects’ cognition was assessed using the Korean version of the Montreal Cognitive Assessment, and tongue, cheek, and lip pressures were assessed using the Iowa Oral Performance Instrument. Tongue and masseter thicknesses were measured using an ultrasound device (Sonon, Healcerion, Roseville, CA, USA). The occlusal force was measured using a specialized device (Innobyte, Kube Innovation, Montreal, QC, Canada), and the number of lost teeth was directly verified by a dental hygienist. Results: Results of analysis of cognitive function according to demographic characteristics of older community-dwelling adults revealed a significant difference in cognitive function according to education level and employment status. Cognitive function demonstrated a positive correlation with oral motor function, including pressure on the cheek, lips, and tongue, thickness of the masseter and tongue, occlusal force, number of lost teeth, and age. Hierarchical regression analysis revealed that demographic characteristics and cheek, lip, tongue, and masseter functions did not affect cognition, whereas occlusal force and number of lost teeth significantly affected cognition. In this study, oral motor function, excluding occlusal force and number of lost teeth, did not affect cognition. Conclusions: Future studies, however, are required to analyze the relationship between oral motor function and cognition in older adults with a wider range of such functions.
Physical Ripening Indices Improve the Assessment of Mechanical Harvesting Time for Olive Cultivars Resistant to Xylella fastidiosa subsp. pauca
Authors: Garofalo Simone Pietro , Maldera Francesco , Nicolì Francesco , Vivaldi Gaetano Alessandro , Camposeo Salvatore
Published: October 2024

Xylella fastidiosa subsp. pauca (Xfp) is a significant threat to Mediterranean agriculture, particularly impacting olive trees in southern Italy, causing Olive Quick Decline Syndrome. Resistant olive cultivars, such as ‘Leccino’ and ‘Fs-17’, have been identified as alternatives to restore the oliviculture within the infected areas. ‘Frantoio’ and ‘Cipressino’ are included in ongoing studies on genetic resistance to Xfp. The mechanization of olive harvesting is essential for reducing production costs in the olive oil sector. Two systems, trunk shakers and over-the-row machines, are used depending on the tree density and canopy structure, with super-high-density systems offering advantages in terms of cost and efficiency. This study investigates the feasibility of using simple and non-destructive indices to assess the optimal mechanical harvesting time. Different physical ripening indices, including detachment force, fresh weight, pigmentation, and firmness, were measured on four olive cultivars (‘Fs-17’, ‘Leccino’, ‘Frantoio’, ‘Cipressino’) in southern Italy over two years. The study found that the pigmentation index had a strong relationship with the detachment index, particularly for ‘Fs-17’, and ‘Leccino’, providing a reliable non-destructive measure for optimal harvesting time. The results indicate that the optimal harvesting times for mechanical harvesting are early September for ‘Cipressino’, early October for ‘Fs-17’, and mid-October for ‘Frantoio’ and ‘Leccino’.
Technical and Economic Assessment of Tomato Cultivation Through a Macro-Tunnel Production System with the Application of Gluconacetobacter diazotrophicus
Authors: Ceballos-Aguirre Nelson , Hurtado-Salazar Alejandro , Restrepo Gloria M. , Sánchez Óscar J. , Hernández María C. , Montoya Mauricio
Published: October 2024

Bacterial inoculants hold promise for enhancing the sustainability and profitability of tomato cultivation in macro-tunnel systems. This study aimed to evaluate the technical and economic viability of applying Gluconacetobacter diazotrophicus to tomato production. The separate addition of native G. diazotrophicus GIBI025 and GIBI029 isolates and a commercial inoculant containing Azotobacter chrococcum and Azospirillium sp. was evaluated at a rate of 1 × 108 CFU·mL−1 without nitrogen addition. Conventional fertilization treatment with no bacteria added and 100%-nitrogen fertilization relative to crop requirements (added as MAP and urea) was also assessed. The treatments were evaluated within the macro-tunnel production system. The experiment utilized a completely randomized block design with four replications per treatment, and each experimental unit consisted of 20 plants. The yield (kg·ha−1) was calculated and economic assessment was performed. The results show that native G. diazotrophicus isolates in tomato cultivation under the macro-tunnel production system improved its economic viability, achieving yields up to 95,501 kg·ha−1 without the addition of nitrogenous fertilizers. This research reveals benefit–cost ratios achieving 1.57 and net incomes reaching 16,707 US dollars per hectare. This work demonstrated that the native isolates assessed may be used in the pursuit of more integrated, sustainable, and competitive cultural practices.
Microbial Fertilizing Products Impact on Productivity and Profitability of Organic Strawberry Cultivars
Authors: Nakielska Małgorzata , Berbeć Adam Kleofas , Madej Andrzej , Feledyn-Szewczyk Beata
Published: October 2024

Poland is a major producer of various fruits, including strawberries. As growing consumer awareness of food quality, health, and wellbeing is increasing, farmers are receiving a new market opportunity for organic products of good quality. The integration of microbial solutions into agricultural practices can foster the transition of agricultural farms towards more resilient and sustainable production of quality food. The objective of this study was to assess the influence of novel microbial biopreparations (microbial fertilizing products) containing Bacillus sp., humic acids, and other organic compounds on the economic viability of three strawberry cultivars (‘Honeoye’, ‘Vibrant’, and ‘Rumba’) under organic farming conditions. This study was conducted in 2021 as a field experiment. Irrigated and non-irrigated strawberries were treated with five microbial fertilizing products (K2–K6). The single plot area was 16 m2, with a total of 144 plots. The adopted planting density of strawberries was 30,052 per hectare. K3 treatment was found to be the most universal microbial treatment in terms of positive impact on yields, with significant yield increase on both the non-irrigated (yield increase of 3.76 t·ha−1) and irrigated experiments (yield increase of 5.78 t·ha−1). The K4 treatment on the non-irrigated strawberries resulted in a yield increase of 4.96 t·ha−1, which at the same time had no effect on the yield of the irrigated experiment. On average, application of the K2–K6 combinations on the non-irrigated strawberries resulted in a yield increase from 13.4% (K2) to 33.5% (K4). The irrigated strawberries showed a yield increase from 3.9% (K4—non-significant yield increase) to as much as 36.1% (K3). The highest direct surplus for the non-irrigated strawberries was recorded for the K4 treatment (38,603 PLN·ha−1) and for K3 for the irrigated experiment (42,945 PLN·ha−1). The direct surplus for ‘Rumba’ and ‘Vibrant’ was higher than for ‘Honeoye’ on both the irrigated (22% and 53%, respectively) and non-irrigated (19% and 18%, respectively) experiments. The average profitability index for all tested non-irrigated and irrigated varieties improved when treated with microbial fertilizer products, with profitability indexes of 143.3–168.8% on the non-irrigated plantation and 129.2–169.7% on the irrigated plantation. The tested microbial fertilizing products proved to be valuable products to improve the productivity and economic effectiveness of organic strawberry production. At the same time, their use needs to be adapted to local plantation conditions.
Organic Nitrogen Nutrition Does Not Increase Glucosinolate Concentrations in Broccoli (Brassica oleracea L. var. italica)
Authors: Willson Adam K. , Rose Mick T. , Reading Michael J. , Borpatragohain Priyakshee , Rose Terry J.
Published: October 2024

Concentrations of specific secondary metabolites can be higher in organically grown crops. This may be linked to organic nitrogen (N) nutrition that provides a gradual supply of N to crops over the growing season. This study examined whether organic N nutrition influenced the concentration of glucosinolates in broccoli crops. Nitrogen release patterns were determined from three synthetic (Rustica, 12% N; calcium nitrate, 15.5% N; urea, 46% N) and two organic fertilizers in an incubation experiment. Broccoli seedlings were then grown in two N dose response pot trials with different N source or application timing treatments to investigate growth and glucosinolate responses. Synthetic fertilizers released 84 to 89% of total N after 28 days, while chicken manure pellets and composted cow manure had only released 52% and 13% of total N, respectively, after 91 days. Broccoli yield and N content were generally higher in synthetic fertilizer treatments. Glucosinolate concentrations were generally higher in the synthetic fertilizer treatments, and only sinigrin and glucoiberin concentrations in the 800 kg ha−1 N application rate of organic fertilizer matched those in the corresponding synthetic fertilizer treatment. Broccoli head weight was reduced when N was applied fortnightly compared to basal and weekly N applications, but glucosinolate concentrations were not significantly different. Overall, there was no evidence that organic (chicken manure) N nutrition, or the rate of N supply to broccoli plants, affect glucosinolate concentrations.
Cost-Effectiveness Analysis of Telehealth and In-Person Primary Care Visits for People Living with Alzheimer’s Disease-Related Disorders in the State of Nevada
Authors: Kim Yonsu , Shen Jay J. , Choe Ian , Reeves Jerry , Byun David , Ioanitoaia-Chaudhry Iulia , Frimer Leora , Jin Pengfeng , Tabrizi Maryam , Kang Hee-Taik , Lee Jae-Woo , Lee Claire Sieun , Chung Tae-Ha , Hwang Yena , Park Ian , Leung Hayden , Park Jenna , Yoo Ji Won
Published: October 2024

To people living with Alzheimer’s Disease-Related Disorders (ADRD), timely and coordinated communication is essential between their informal caregivers and healthcare providers. In provider shortage areas, for example, the state of Nevada, telehealth can be an effective primary care delivery alternative to in-person visits. To evaluate the cost-effectiveness of telehealth visits for people living with ADRD in the state of Nevada, a decision-analytic Markov model was developed from healthcare system perspectives with a 10-year horizon/1-year cycle. To estimate the effects of demographic and geographic parameters on the Markov model, race parameters were divided into non-Hispanic White individuals vs. others and location parameters were divided into urban vs. rural. A 12-item short-version Zarit Burden Interview (ZBI-12) was applied to measure the informal caregiver burdens of non-institutionalized people living with ADRD. The values of mortality rate and healthcare utilization were obtained from healthcare systems’ publicly available payor administrative data and Nevada State Inpatient/Emergency Department datasets. Among urban-residing non-Hispanic White individuals, the Incremental Cost-Effectiveness Ratio (ICER) per modified ZBI-12 indicated a cost saving of USD 9.44 with telehealth visits; among urban-residing racial minorities, the ICER per modified ZBI-12 indicated a cost saving of USD 29.26 with in-person visits; and among rural residents, the ICER per modified ZBI-12 indicated a cost-saving of USD 320.93 with telehealth visits. Distributional differences in the cost-saving effects of telehealth primary care were noted in line with racial and geographic parameters. Workforce and caregiver training is necessary for reducing distributional differences, especially among urban-residing racial monitories living with ADRD in the provider shortage area of the state of Nevada.
Role of Magnesium in Skeletal Muscle Health and Neuromuscular Diseases: A Scoping Review
Authors: Liguori Sara , Moretti Antimo , Paoletta Marco , Gimigliano Francesca , Iolascon Giovanni
Published: October 2024

Magnesium (Mg) is a vital element for various metabolic and physiological functions in the human body, including its crucial role in skeletal muscle health. Hypomagnesaemia is frequently reported in many muscle diseases, and it also seems to contribute to the pathogenesis of skeletal muscle impairment in patients with neuromuscular diseases. The aim of this scoping review is to analyze the role of Mg in skeletal muscle, particularly its biological effects on muscle tissue in neuromuscular diseases (NMDs) in terms of biological effects and clinical implications. This scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. From the 305 studies identified, 20 studies were included: 4 preclinical and 16 clinical studies. Preclinical research has demonstrated that Mg plays a critical role in modulating pathways affecting skeletal muscle homeostasis and oxidative stress in muscles. Clinical studies have shown that Mg supplementation can improve muscle mass, respiratory muscle strength, and exercise recovery and reduce muscle soreness and inflammation in athletes and patients with various conditions. Despite the significant role of Mg in muscle health, there is a lack of research on Mg supplementation in NMDs. Given the potential similarities in pathogenic mechanisms between NMDs and Mg deficiency, further studies on the effects of Mg supplementation in NMDs are warranted. Overall, maintaining optimal Mg levels through dietary intake or supplementation may have important implications for improving muscle health and function, particularly in conditions associated with muscle weakness and atrophy.
Adipose-Derived Stem Cells as Carrier of Pro-Apoptotic Oncolytic Myxoma Virus: To Cross the Blood–Brain Barrier and Treat Murine Glioma
Authors: Jazowiecka-Rakus Joanna , Pogoda-Mieszczak Kinga , Rahman Masmudur M. , McFadden Grant , Sochanik Aleksander
Published: October 2024

Treatment of glioblastoma is ineffective. Myx-M011L-KO/EGFP, a myxoma virus actively inducing apoptosis in BTICs linked to recurrence, offers innovative treatment. We loaded this construct into adipose-derived stem cells (ADSCs) to mitigate antiviral host responses and enable systemic delivery. The apoptotic and cytotoxic effects of the construct were studied using murine and human glioblastoma cell lines. Before implementing systemic delivery, we delivered the construct locally using ADSC to verify elimination of orthotopic murine glioma lesions. vMyx-M011L-KO/EGFP was cytotoxic to a murine cell line, preventing effective virus multiplication. In three human glioma cell lines, viral replication did occur, coupled with cell killing. The knock-out construct induced apoptotic cell death in these cultures. ADSCs infected ex vivo were shown to be sufficiently migratory to assure transfer of the therapeutic cargo to murine glioma lesions. Virus-loaded ADSCs applied to the artificial blood–brain barrier (BBB) yielded viral infection of glioma cells grown distally in the wells. Two rounds of local administration of this therapeutic platform starting 6 days post tumor implantation slowed down growth of orthotopic lesions and improved survival (total recovery < 20%). ADSCs infected ex vivo with vMyx-M011L-KO/EGFP show promise as a therapeutic tool in systemic elimination of glioma lesions.
Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model
Authors: Parab Sushant , Sarlo Valery , Capellero Sonia , Palmiotto Luca , Bartolini Alice , Cantarella Daniela , Turi Marcello , Gullà Annamaria , Grassi Elena , Lazzari Chiara , Rubatto Marco , Gregorc Vanesa , Carnevale-Schianca Fabrizio , Olivero Martina , Bussolino Federico , Comunanza Valentina
Published: October 2024

Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity and complex tumor microenvironment (TME). Single cell biology is an ideal and powerful tool to address these features at a molecular level. However, this approach requires enzymatic cell dissociation that can influence cellular coverage. By contrast, single nucleus RNA sequencing (snRNA-seq) has substantial advantages including compatibility with frozen samples and the elimination of a dissociation-induced, transcriptional stress response. To better profile and understand the functional diversity of different cellular components in melanoma progression, we performed snRNA-seq of 16,839 nuclei obtained from tumor samples along the growth of murine syngeneic melanoma model carrying a BRAFV600E mutation and collected 9 days or 23 days after subcutaneous cell injection. We defined 11 different subtypes of functional cell clusters among malignant cells and 5 different subsets of myeloid cells that display distinct global transcriptional program and different enrichment in early or advanced stage of tumor growth, confirming that this approach was useful to accurately identify intratumor heterogeneity and dynamics during tumor evolution. The current study offers a deep insight into the biology of melanoma highlighting TME reprogramming through tumor initiation and progression, underlying further discovery of new TME biomarkers which may be potentially druggable.
Enhancing the Growth of Chili Plants and Soil Health: Synergistic Effects of Coconut Shell Biochar and Bacillus sp. Strain Ya-1 on Rhizosphere Microecology and Plant Metabolism
Authors: Tan Shimeng , Wang Bao , Yun Qian , Yan Wanrong , Xiao Tongbin , Zhao Zhixiang
Published: October 2024

To mitigate soil degradation and decrease dependency on chemical inputs in agriculture, this study examined the joint effects of coconut shell biochar and Bacillus strain Ya-1 on soil fertility, rhizosphere bacterial communities, and the growth of chili (Capsicum annuum L.). A controlled pot experiment with four treatments was conducted: control (CK), biochar only (C), Bacillus strain Ya-1 only (B), and a combination of both (BC). The BC treatment significantly enhanced the soil carbon and available phosphorus contents by approximately 20% and the soil nitrogen content and pH by 18% and 0.3 units, respectively, compared to the control. It also increased microbial biomass carbon and nitrogen by 25% and 30%, respectively, indicating improved soil microbial diversity as shown by the highest Pielou evenness index and Shannon index values. The combined application of biochar and the Ya-1 strain resulted in a 15% increase in chili plant height and a 40% improvement in root dehydrogenase activity, suggesting enhanced nutrient uptake and metabolism. Metabolic profiling showed shifts in stress response and nutrient assimilation under different treatments. Collectively, these results indicate the potential of biochar and microbial inoculants to significantly promote soil and plant health, providing a sustainable strategy to improve agricultural productivity and reduce reliance on chemical inputs.
BRAF Modulates the Interplay Between Cell–Cell and Cell–Extracellular Matrix Adhesions in PECAM-1-Mediated Mechanotransduction
Authors: Gráczer Éva , Pászty Katalin , Harsányi Laura , Lehoczky Csilla , Fülöp Antónia , Varga Andrea
Published: October 2024

Mechanotransduction, the process of how cells sense and convert mechanical stimuli into biochemical response, is crucial in the migration of leukocytes or cancer cells through the endothelium during inflammation or metastasis. Migrating cells exert forces on the endothelium through cell surface adhesion molecules, such as platelet endothelial adhesion molecule PECAM-1, and this is essential for a successful transmigration. To study PECAM-1-mediated mechanotransduction, we applied PECAM-1-antibody-coated magnetic beads and exerted about 40 pN force on the endothelial monolayer. We show that force increases cell–ECM adhesion in the cell center and is accompanied by the opening of cell–cell junctions. Upon depletion of the MEK/ERK kinase, BRAF force increases cell–ECM adhesion both at the cell periphery and in the cell center, but this does not result in the opening of cell–cell junctions. Decreasing cell–ECM adhesion in BRAF-depleted cells through FAK inhibition results in the remodeling of cell–cell junctions. Force-induced increase in cell–ECM adhesion in the cell center correlates with the activation of the transcriptional cofactor Yes-associated protein (YAP). Furthermore, the induced activation of YAP through LATS inhibition prevents junctional remodeling in control cells. Thus, the activation of YAP might determine the strength of cell–cell junctions during PECAM-1-mediated mechanotransduction.
Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes
Authors: Antelo-Cea Damián A. , Martínez-Rojas Laura , Cabrerizo-Ibáñez Izan , Roudi Rashtabady Ayda , Hernández-Alvarez María Isabel
Published: October 2024

Obesity and type 2 diabetes (T2D) are widespread metabolic disorders that significantly impact global health today, affecting approximately 17% of adults worldwide with obesity and 9.3% with T2D. Both conditions are closely linked to disruptions in lipid metabolism, where peroxisomes play a pivotal role. Mitochondria and peroxisomes are vital organelles responsible for lipid and energy regulation, including the β-oxidation and oxidation of very long-chain fatty acids (VLCFAs), cholesterol biosynthesis, and bile acid metabolism. These processes are significantly influenced by estrogens, highlighting the interplay between these organelles’ function and hormonal regulation in the development and progression of metabolic diseases, such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and T2D. Estrogens modulate lipid metabolism through interactions with nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), which are crucial for maintaining metabolic balance. Estrogen deficiency, such as in postmenopausal women, impairs PPAR regulation, leading to lipid accumulation and increased risk of metabolic disorders. The disruption of peroxisomal–mitochondrial function and estrogen regulation exacerbates lipid imbalances, contributing to insulin resistance and ROS accumulation. This review emphasizes the critical role of these organelles and estrogens in lipid metabolism and their implications for metabolic health, suggesting that therapeutic strategies, including hormone replacement therapy, may offer potential benefits in treating and preventing metabolic diseases.
Secondary Dengue Infection Elicits Earlier Elevations in IL-6 and IL-10 Levels
Authors: Espindola Sonia L. , Fay Jessica , Carballo Graciela M. , Pereson Matías J. , Aloisi Natalia , Badano María Noel , Ferreras Julián , Argüelles Carina , Pezzarini Simón , Chuit Roberto , Miretti Marcos , Di Lello Federico A. , Baré Patricia
Published: October 2024

This study investigates the kinetics of interleukine-6 (IL-6) and interleukine-10 (IL-10) levels in dengue virus (DENV) infections during the febrile stage. Viremic patients were categorized into two phases based on anti-DENV IgM presence. Among 259 patients, 71% were in Phase I and 29% in Phase II. Secondary infections, accounting for 38.2% of cases, exhibited earlier elevations of IL-6 and IL-10 than primary infections, suggesting that pre-existing immune memory primes faster cytokine release. Thrombocytopenia and elevated aspartate transaminase (AST) levels were associated with Phase II, secondary infections, and hospitalization. Elevated IL-6 and IL-10 levels correlated with low platelet counts, linking them to clinical manifestations. The key finding is that IL-6 and IL-10 levels rise earlier in secondary infections compared to primary infections, whereas elevated cytokine levels typically occur later in the febrile phase. This study highlights the importance of cytokine dynamics in DENV infections, particularly during the early stages. The observation of cytokine concentration changes, especially in viremic samples, provides insights into the progression of dengue disease. Further research with broader cytokine panels is warranted to validate and expand these findings.
The Role of Tumor Biomarkers in Tailoring the Approach to Advanced Ovarian Cancer
Authors: Tonti Noemi , Golia D’Augè Tullio , Cuccu Ilaria , De Angelis Emanuele , D’Oria Ottavia , Perniola Giorgia , Laganà Antonio Simone , Etrusco Andrea , Ferrari Federico , Saponara Stefania , Di Donato Violante , Bogani Giorgio , Giannini Andrea
Published: October 2024

Growing evidence has demonstrated the role of mutations of tumor biomarkers in diagnosing and treating epithelial ovarian cancer. This review aims to analyze recent literature on the correlation between tumor biomarkers and chemotherapy in nonmucinous ovarian cancer, providing suggestions for personalized treatment approaches. An extensive literature search was conducted to identify relevant studies and trials. BRCA1/2 mutations are central in homologous recombination repair deficiency (HRD) in ovarian cancer, but several other genetic mutations also contribute to varying cancer risks. While the role of MMR testing in ovarian cancer is debated, it is more commonly linked to non-serous ovarian cancer, often associated with Lynch syndrome. A significant proportion of ovarian cancer patients have HRD, affecting treatment decisions in both first-line (especially in advanced stages) and second-line therapy due to HRD’s connection with platinum-based therapy and PARP inhibitors’ response. However, validated genetic tests to identify HRD have not yet been universally implemented. There is no definitive therapeutic algorithm for advanced ovarian cancer, despite ongoing efforts and multiple proposed tools. Future research should focus on expanding the utility of biomarkers, reducing resistance, and increasing the actionable biomarker pool.
A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis
Authors: Yoon Hyeon-Jeong , Jiang Enying , Liu Jingting , Jin Hui , Yoon Hee Su , Choi Ji Suk , Moon Ja Young , Yoon Kyung Chul
Published: October 2024

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4+ IFN-γ+ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p < 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4+ IFN-γ+ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure.
Chronic Corticosterone Administration-Induced Mood Disorders in Laboratory Rodents: Features, Mechanisms, and Research Perspectives
Authors: Wang Hao , Wang Xingxing , Wang Huan , Shao Shuijin , Zhu Jing
Published: October 2024

Mood disorders mainly affect the patient’s daily life, lead to suffering and disability, increase the incidence rate of many medical illnesses, and even cause a trend of suicide. The glucocorticoid (GC)-mediated hypothalamus–pituitary–adrenal (HPA) negative feedback regulation plays a key role in neuropsychiatric disorders. The balance of the mineralocorticoid receptor (MR)/glucocorticoid receptor (GR) level contributes to maintaining the homeostasis of the neuroendocrine system. Consistently, a chronic excess of GC can also lead to HPA axis dysfunction, triggering anxiety, depression, memory loss, and cognitive impairment. The animal model induced by chronic corticosterone (CORT) administration has been widely adopted because of its simple replication and strong stability. This review summarizes the behavioral changes and underlying mechanisms of chronic CORT administration-induced animal models, including neuroinflammatory response, pyroptosis, oxidative stress, neuroplasticity, and apoptosis. Notably, CORT administration at different doses and cycles can destroy the balance of the MR/GR ratio to make dose-dependent effects of CORT on the central nervous system (CNS). This work aims to offer an overview of the topic and recommendations for future cognitive function research.