bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review on the Process of Greenhouse Gas Inventory Preparation and Proposed Mitigation Measures for Reducing Carbon Footprint
Authors: Yaman Cevat
Published: March 2024

Greenhouse gases trap heat in the atmosphere, causing the Earth’s surface temperature to rise. The main greenhouse gases are carbon dioxide, methane, nitrous oxide, perfluorocarbons, hydrofluorocarbons, and sulfur hexafluoride. Human activities are increasing greenhouse gas concentrations rapidly, which is causing global climate change. Global climate change is increasing environmental and public health problems. To reduce greenhouse gas emissions, it is necessary to identify where the emissions are coming from, develop a plan to reduce them, and then implement and monitor the plan to ensure that emissions are actually reduced. Anthropogenic global climate change has large and increasingly adverse economic effects. Cities emit the most greenhouse gas due to fossil fuel burning and power usage. The four major greenhouse gas emitters are energy, transportation, waste management, and urban land use sectors. Organizations should prepare action plans to lower their greenhouse gas emissions and stop the worst consequences of climate change. These action plans require companies and local authorities to submit their greenhouse gas emissions reports on a yearly basis. A greenhouse gas emissions management system includes several processes and tools created by organizations to understand, measure, monitor, report, and validate their greenhouse gas emissions. Two of the most widely adapted frameworks for greenhouse gases inventory reporting are ISO 14064 and the greenhouse gas protocol. This review paper aims to identify some of the key points of GHG inventory preparation and mitigation strategies.
Characterization and Functional Analysis of Fads Reveals Δ5 Desaturation Activity during Long-Chain Polyunsaturated Fatty Acid Biosynthesis in Dwarf Surf Clam Mulinia lateralis
Authors: Teng Tianhao , Zheng Zhenghua , Jiao Wenqian , Liu Na , Wang Ao , Liu Mengjiao , Xie Le , Yang Zujing , Hu Jingjie , Bao Zhenmin
Published: March 2024

Fatty acid desaturases (Fads), as key enzymes in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), catalyze the desaturation between defined carbons of fatty acyl chains and control the degree of unsaturation of fatty acids. In the present study, two Fads genes, designated MulFadsA and MulFadsB, were identified from the genome of the dwarf surf clam Mulinia lateralis (Mollusca, Mactridae), and their spatiotemporal expression was examined. MulFadsA and MulFadsB contained the corresponding conserved functional domains and clustered closely with their respective orthologs from other mollusks. Both genes were expressed in the developmental stages and all tested adult tissues of M. lateralis, with MulFadsA exhibiting significantly higher expression levels in adult tissues than MulFadsB. Subsequently, the effects of dietary microalgae on Fads expressions in the dwarf surf clam were investigated by feeding clams with two types of unialgal diets varying in fatty acid content, i.e., Chlorella pyrenoidosa (Cp) and Platymonas helgolandica (Ph). The results show that the expressions of MulFads were significantly upregulated among adult tissues in the Cp group compared with those in the Ph group. In addition, we observed the desaturation activity of MulFadsA via heterologous expression in yeasts, revealing Δ5 desaturation activity toward PUFA substrates. Taken together, these results provide a novel perspective on M. lateralis LC-PUFA biosynthesis, expanding our understanding of fatty acid synthesis in marine mollusks.
Sibling Rivalry, (Dis)Inheritance and Politics in Aphra Behn’s The Younger Brother and Susanna Centlivre’s The Artifice
Authors: Rubik Margarete
Published: March 2024

Behn and Centlivre used their comedies about the rivalry between an elder and a younger brother concerning an inheritance to make a political statement. Primogeniture was customary in early-modern England, and if an estate was entailed (rather than held in fee simple), it was difficult, though not impossible, to will it away to another person. The reasons meriting disinheritance were widely discussed, but in the two plays, the Tory fathers disinherit their Whig elder sons for political reasons. As The Younger Brother was staged posthumously and altered by Charles Gildon, it is arguable what Behn’s manuscript looked like, but there are indications that the elder brother was meant to be a downright republican and that Behn saw to it that the estate would go to the Tory younger brother, whose political stance she shared. In The Artifice, the father disinherits his upright elder son because he punished a Jacobite clergyman (whom the Whigs would have considered traitorous), but Centlivre—a zealous Whig herself—engineered an ending that reinstates the elder brother but also provides the younger with a comfortable income. Both dramatists also dealt with the inheritance prospects of women and the power of disposal they have over their portions.
Technical Efficiency of Mexico’s Public Health System in the Delivery of Obstetric Care, during 2012–2018
Authors: Aracena-Genao Belkis , Leyva-Flores René , Santos-Luna Rene , Lara-Diaz Saul , Mejía-Avilez Angel Argenis
Published: March 2024

The objective of this study was to evaluate the technical efficiency of Mexico’s public health system in the delivery of obstetric care from 2012 to 2018. A multi-stage quantitative study of the public health institutions responsible for 95% of the system’s obstetric services was conducted using data envelopment analysis. The efficiency of state-level productive units (decision-making units, or DMUs) was calculated and juxtaposed with the DMUs’ maximum (0.82) and minimum (0.22) scores. Using the outcomes of the initial stage, the average technical efficiency of each institution at the national level was estimated and compared. The results were also utilized to estimate and compare the average efficiency of each state-level health system based on economic characteristics (state GDP per capita). Outputs included prenatal visits and deliveries, while inputs comprised gynecologists, exam rooms, and delivery rooms. Institutional efficiency ranged from 0.16 to 0.82, with an average of 0.417. The Ministry of Health (0.82) and the Mexican Social Security Institute (0.747) exhibited the highest efficiency scores, while the remaining institutions (Institute for Social Security and Services for State Workers [ISSSTE]; Mexican Petroleum [PEMEX]; the Secretary of National Defense [SEDENA]; and the Navy [SEMAR]) scored below the health system average. Of the 153 DMUs, 20% surpassed the maximum (0.82) and 40.6% fell below the minimum (0.22). These findings indicate that 80% of DMUs have unused operational capacity that could be utilized to enhance technical efficiency. No relationship was found between efficiency and the GDP of Mexico’s 32 politico-administrative divisions. The efficiency gap between institutions (0.66) shows that while some DMUs are saturated (exhibiting high efficiency scores), the majority have unused operational capacity. Leveraging this untapped capacity could address the needs of vulnerable populations facing restricted access due to health system fragmentation.
Association between Gingival Phenotype and Periodontal Disease Severity—A Comparative Longitudinal Study among Patients Undergoing Fixed Orthodontic Therapy and Invisalign Treatment
Authors: Alasiri Mansour M. , Almalki Abdullah , Alotaibi Saud , Alshehri Abdullah , Alkhuraiji Alhanouf A. , Thomas Julie Toby
Published: March 2024

This longitudinal study aimed to compare the association between gingival phenotype (thin vs. thick) and periodontal disease severity in patients undergoing fixed orthodontic therapy (FOT) and Invisalign treatment over a six-month follow-up period. Clinical periodontal parameters, including full mouth plaque score (FMPS), full mouth bleeding score (FMBS), gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), gingival recession (GR), keratinized tissue width (KTW), transgingival probing, and gingival biotype assessment, were recorded at baseline and 6 months into treatment for both orthodontic groups and a control group. Statistical analysis evaluated differences in parameters between groups and across time points. In the thick phenotype, both Invisalign and FOT groups showed a significant mean reduction in FMPS (baseline to 6 months) by −24.8707 and −12.3489, respectively (p < 0.05). The gingival index decreased significantly for both groups, with Invisalign and FOT showing reductions of −0.83355 and −1.10409, respectively (p < 0.05). FMBS (baseline to 6 months) decreased significantly for Invisalign and FOT, with mean differences of −9.10298 and −12.6579 (p < 0.05). Probing pocket depth (baseline to 6 months) was also significantly reduced for both Invisalign and FOT groups while CAL showed non-significant differences in both groups (p > 0.05). Similar changes were seen in the thin phenotype too. This study highlights the positive influence of both Invisalign and fixed orthodontic therapy on periodontal health, particularly in patients with thin and thick gingival biotypes. These findings, with significant reductions in key periodontal parameters, offer valuable insights to guide orthodontic treatment decisions and enhance patient outcomes.
Medication-Seeking Behaviors and Correlated Characteristics of Zolpidem Users in Taiwan—A Shared Patient Network Analysis
Authors: Pan Yi-Ju , Chang Sheng-Hsuan , Lee Wei-Chen , Chen Yu-Chun
Published: March 2024

Increasing insomnia signals a public health problem, alongside rising zolpidem use. This study investigates the factors behind the disproportionate rise in zolpidem prescriptions in Taiwan. It aims to identify the determinants of high-dose zolpidem users in Taiwan’s Yilan County and employ an innovative approach to outline their medication-seeking patterns, using Taiwan’s healthcare database. The associations between sociodemographic and clinical factors and low-dose and high-dose users were analyzed using multiple logistic regression. Social network analysis was employed to explore medication-seeking behavior among these user groups across different healthcare institutions. Of our 5290 participants, 22.82% are high-dose users. This study found that males face a 1.33-fold higher risk and that having chronic diseases is a major risk factor, contributing to a more than four-times higher risk (adjusted OR = 4.27, 95% CI 1.55–11.70) of being a high-dose user of zolpidem. A social network analysis showed a higher density (0.52) for high-dose users, revealing their frequent visits, for zolpidem, to different healthcare institutions. Psychiatrists have a central role in both low-dose and high-dose user networks, with a greater influence on low-dose users (64.4) than high-dose users (32.2). In sum, patients seeking high doses of zolpidem are driven by personal factors. Future efforts should include regulated dispensing, public health education, and specialized training for healthcare professionals on drug addiction.
Food Security and Diet Quality Improvements among At-Risk, Low-Income, Older Adults following a Free Meal Pilot Program
Authors: Barr-Porter Makenzie , OoNorasak Kendra , Stephenson Tammy , Goodson Ryan , Bonilla Sofia , Alhamdani Abraham
Published: March 2024

Older adults are at a greater risk for food insecurity compared to the general population. This study aimed to describe changes in diet quality and food insecurity following a free meal program at low-income, older adult housing complexes. Study participants were recruited from two low-income older adult public housing complexes in Kentucky. Fifty participants were enrolled and received 1–4 free weekly meals across 3 months as part of the Meals on Wings pilot program. Surveys and a 24 h dietary recall were completed at baseline and 3 months. Participants were predominately female, 69 years of age, and Black or African American race. Food security status (FSS) and dietary quality through the Healthy Eating Index (HEI) were assessed as primary measures. Participants were placed in “at-risk” categories of the (1a) lower quartile of the HEI and (1b) lower than 51% HEI, or (2) “low” or “very low” food security status based on the USDA Household Food Security Screener (FSS). Multiple linear regression (MLR) models were conducted for HEI and FSS scores to include time, group, time*group interaction, and control of meal utilization percentage (i.e., dose). The MLR for the HEI quartile had a significant time by quartile interaction that was present for an increase in the HEI in Q1 (n = 12; 32.42 ± 5.95% to n = 6; 46.10 ± 10.62%; p < 0.0001) and a decrease in the HEI for Q4 (n = 12; 70.68 ± 7.13% to n = 9; 52.36 ± 11.57%; p < 0.0001). For those low food security participants (n = 24; 48.0%), the average food insecurity score from the 6-item USDA screener improved from 4.09 ± 1.62 at baseline to 2.63 ± 2.41 at 3 months (p = 0.0064). The MLR for the FSS had a significant group*time interaction (p = 0.0071). In our population, particularly those vulnerable with lowest dietary quality and food insecurity status, we did see improvements across the free meal pilot program. However, a small sample, limited generalizability, and limited data collection measures urge caution when using these results to extrapolate for the general population. However, the current results are promising and should encourage further investigation of the effects of meal assistance programs on the health and well-being of older adults.
Flourishing or Frightening? Feelings about Natural and Built Green Spaces in Singapore
Authors: Dillon Denise , Lee Sean T. H. , Tai Eunice W. L.
Published: March 2024

The current study’s aim was to better understand people’s feelings towards different types of natural and built green space environments in the highly urbanized “garden city” of Singapore. We examined which types of green spaces elicited positive (eudemonic) or negative (apprehensive) affective responses. A total of 288 adult residents of Singapore completed a survey that asked them to report their affective states in response to images of 10 locally different environment types and to complete measures of childhood location, frequency of visiting natural/built environments, nature connectedness, and dispositional anxiety, as well as demographic items on age and gender. The 10 green space environment types were mapped onto an experiential state space representing feelings of apprehension and eudemonia in response to specific types of urban green spaces. In terms of a biophilic response, feelings of eudemonia were no different in natural green spaces compared to built green spaces. A higher frequency of experience in specific environments is associated with enhanced feelings of eudemonia in these environments. The findings indicate that people in Singapore can be apprehensive as much in natural green spaces as in built green spaces, and they can also find eudemonic experiences in built green spaces such as roof-top gardens or town parks.
The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study
Authors: Morita Emi , Kadotani Hiroshi , Yamada Naoto , Sasakabe Tae , Kawai Sayo , Naito Mariko , Tamura Takashi , Wakai Kenji
Published: March 2024

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29–3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.
Content Analysis of Official Public Health Communications in Ontario, Canada during the COVID-19 Pandemic
Authors: Fields Maya , Spence Kelsey L.
Published: March 2024

Effective communication by governmental organizations is essential to keep the public informed during a public health emergency. Examining the content of these communications can provide insight into their alignment with best practices for risk communication. We used content analysis to determine whether news releases by the Ontario government contained key elements of effective risk communication, as outlined by the Health Canada and Public Health Agency of Canada Strategic Risk Communication Framework. News releases between 25 January 2020 and 31 December 2022 were coded following the five elements of the framework: situational transparency, stakeholder-centered content; evidence-based rationales for decisions; continuous improvements in updating information; and descriptions of risk management. All 322 news releases contained at least one element of the framework, and all five elements were identified at least once across the dataset. Risk management, transparency, and stakeholder-centered content were the most frequently identified elements. News releases near the beginning of the pandemic contained most elements of the framework; however, over time, there was an increase in the use of vague language and lack of evidence-based rationales. Increasing transparency regarding evidence-based decisions, as well as changes in decisions, is recommended to improve risk communication and increase compliance with public health measures.
The Commercial Determinants of Violence: Identifying Opportunities for Violence Prevention through a Public Health-Based Framework Analysis
Authors: Bellis Mark A. , McManus Sally , Hughes Karen , Adisa Olumide , Ford Kat
Published: March 2024

Violence has immediate and long-term repercussions for the health of individuals and communities. Recent increases in the understanding of public health approaches to violence prevention have focused on the policies and practices of government, health, and other public sector agencies. However, the roles of commercial bodies in fostering and preventing violence remain largely unaddressed. The wealth and influence of some companies now exceeds that of many countries. Consequently, it is timely to explore the roles of commercial processes in violence. Using a conceptual framework for the commercial determinants of health, we examine seven practices: political; scientific; marketing; supply chain and waste; labor and employment; financial; and reputational management. We include areas directly linked with violence (e.g., firearms) and those that indirectly impact violence through the following: design and promotion of products; employment practices; and impacts on environment, poverty, and local resources. A range of avoidable commercial behaviors are found to increase levels of violence including the following: lobbying practices; distortion of scientific processes; polluting manufacture and supply lines; poor employee protections; financial investment in organizations and regimes associated with violence; and misleading communications and marketing. We conclude commercial actors can take action to ensure their workers, clients, suppliers, and distributors help prevent, not promote, violence. New technologies such as artificial intelligence are transforming corporate processes and products and offer opportunities to implement violence prevention through commercial developments (e.g., monitoring online content). International regulation of commercial behaviors is needed to prevent interpersonal and interstate conflict and harms to health and trade.
Beyond Quiescent and Active: Intermediate Microglial Transcriptomic States in a Mouse Model of Down Syndrome
Authors: Fernández-Blanco Álvaro , Sierra Cèsar , Tejido Clara , Dierssen Mara
Published: March 2024

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. Indeed, recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a fully activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.
Microbiome Dysbiosis Is Associated with Castration Resistance and Cancer Stemness in Metastatic Prostate Cancer
Authors: Uzelac Matthew , Xin Ruomin , Ongkeko Weg M.
Published: March 2024

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration resistance often develops during the course of treatment, but its pathogenesis is poorly understood. This study explores the human microbiome for its implications in castration resistance and metastasis in prostate cancer. RNA sequencing data were downloaded for the bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These included both metastatic and adjacent normal biopsies. These sequences were mapped to bacterial sequences, yielding species-level counts. A vast majority of species were found to be significantly underabundant in the CRPC samples. Of these, numerous were found to correlate with the expression of known markers of castration resistance, including AR, PI3K, and AKT. Castration resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for a relation to these species. EGFR and SLC3A2 were widely downregulated, with a greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of castration-resistant prostate cancer, allowing for the needed improvements in the treatment of this disease.
Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers
Authors: Tarjányi Vera , Ménes Ákos , Hamid Leila , Kurucz Andrea , Priksz Dániel , Varga Balázs , Gesztelyi Rudolf , Kiss Rita , Horváth Ádám István , Szentes Nikolett , Helyes Zsuzsanna , Szilvássy Zoltán , Bombicz Mariann
Published: March 2024

Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund’s adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility. CFA was injected into the plantar surface of one hind paw and the root of the tail on day 0, and the tail root injection was repeated on day 1. Flu vaccination was performed on day 1 or 7. Paw volume was measured by plethysmometry, mechanonociceptive threshold by dynamic plantar aesthesiometry, neutrophil myeloperoxidase (MPO) activity, and vascular leakage using in vivo optical imaging throughout the 21-day experiment. Inflammatory markers were determined by Western blot and histopathology. CFA-induced swelling, an increase in MPO activity, plasma extravasation in the tibiotarsal joint. Mechanical hyperalgesia of the hind paw was observed 3 days after the injection, which gradually decreased. Co-administration of the flu vaccine on day 7 but not on day 1 resulted in significantly increased heme oxygenase 1 (HO-1) expression. The influenza vaccination appears to have a limited impact on the progression and severity of the inflammatory response and associated pain. Nevertheless, delayed vaccination could alter the disease activity, as indicated by the findings from assessments of edema and inflammatory biomarkers. HO-1 may serve as a potential marker for the severity of inflammation, particularly in the case of delayed vaccination. However, further investigation is needed to fully understand the regulation and role of HO-1, a task that falls outside the scope of the current study.
A Molecular Perspective on HIF-1α and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update
Authors: Magar Anuja Gajanan , Morya Vivek Kumar , Kwak Mi Kyung , Oh Ji Ung , Noh Kyu Cheol
Published: March 2024

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional factor, which plays an important role in cellular reprogramming processes under hypoxic conditions, which facilitate solid tumors’ progression. HIF-1α is directly involved in the regulation of the angiogenesis, metabolic reprogramming, and extracellular matrix remodeling of the tumor microenvironment. Therefore, an in-depth study on the role of HIF-1α in solid tumor malignancies is required to develop novel anti-cancer therapeutics. HIF-1α also plays a critical role in regulating growth factors, such as the vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, in a network manner. Additionally, it plays a significant role in tumor progression and chemotherapy resistance by regulating a variety of angiogenic factors, including angiopoietin 1 and angiopoietin 2, matrix metalloproteinase, and erythropoietin, along with energy pathways. Therefore, this review attempts to provide comprehensive insight into the role of HIF-1α in the energy and angiogenesis pathways of solid tumors.
Effect of HY7602 Fermented Deer Antler on Physical Fatigue and Antioxidant Activity in Mice
Authors: Jeon Hyejin , Lee Kippeum , Kim Yong-Tae , Kim Joo-Yun , Shim Jae-Jung , Lee Jae-Hwan
Published: March 2024

Lactobacillus curvatus HY7602 fermented antler (FA) ameliorates sarcopenia and improves exercise performance by increasing muscle mass, muscle fiber regeneration, and mitochondrial biogenesis; however, its anti-fatigue and antioxidant effects have not been studied. Therefore, this study aimed to investigate the anti-fatigue and antioxidant effects and mechanisms of FA. C2C12 and HepG2 cells were stimulated with 1 mM of hydrogen peroxide (H2O2) to induce oxidative stress, followed by treatment with FA. Additionally, 44-week-old C57BL/6J mice were orally administered FA for 4 weeks. FA treatment (5–100 μg/mL) significantly attenuated H2O2-induced cytotoxicity and reactive oxygen species (ROS) production in both cell lines in a dose-dependent manner. In vivo experiments showed that FA treatment significantly increased the mobility time of mice in the forced swimming test and significantly downregulated the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and lactate. Notably, FA treatment significantly upregulated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione ratio (GSH/GSSG) and increased the mRNA expression of antioxidant genes (SOD1, SOD2, CAT, GPx1, GPx2, and GSR) in the liver. Conclusively, FA is a potentially useful functional food ingredient for improving fatigue through its antioxidant effects.
Nile Tilapia (Oreochromis niloticus) Patched1 Mutations Disrupt Cardiovascular Development and Vascular Integrity through Smoothened Signaling
Authors: Liu Xiang , Zhao Changle , Liu Lei , Peng Xi , Li Jianeng , Tao Wenjing , Wang Deshou , Wei Jing
Published: March 2024

Hedgehog (Hh) signaling is crucial in cardiovascular development and maintenance. However, the biological role of Patched1 (Ptch1), an inhibitory receptor of the Hh signaling pathway, remains elusive. In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. When one-cell embryos were injected with CRISPR/Cas9 targeting ptch1, the mutation efficiency exceeded 70%. During 0–3 days post fertilization (dpf), no significant differences were observed between the ptch1 mutant group and the control group; at 4 dpf (0 day after hatching), about 10% of the larvae showed an angiogenesis defect and absence of blood flow; from 5 dpf, most larvae exhibited an elongated heart, large pericardial cavity, and blood leakage and coagulation, ultimately dying during the 6–8 dpf period due to the lack of blood circulation. Consistently, multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.
Alpha-Synuclein and GM1 Ganglioside Co-Localize in Neuronal Cytosol Leading to Inverse Interaction—Relevance to Parkinson’s Disease
Authors: Kumar Ranjeet , Chowdhury Suman , Ledeen Robert
Published: March 2024

Research on GM1 ganglioside and its neuroprotective role in Parkinson’s disease (PD), particularly in mitigating the aggregation of α-Synuclein (aSyn), is well established across various model organisms. This essential molecule, GM1, is intimately linked to preventing aSyn aggregation, and its deficiency is believed to play a key role in the initiation of PD. In our current study, we attempted to shed light on the cytosolic interactions between GM1 and aSyn based on previous reports demonstrating gangliosides and monomeric aSyn to be present in neuronal cytosol. Native-PAGE and Western blot analysis of neuronal cytosol from mouse brains demonstrated the presence of both GM1 and monomeric aSyn in the neuronal cytosol of normal mouse brain. To demonstrate that an adequate level of GM1 prevents the aggregation of aSyn, we used NG108-15 and SH-SY5Y cells with and without treatment of 1-phenyl-2-palmitoyl-3-morpholino-1-propanol (PPMP), which inhibits the synthesis/expression of GM1. Cells treated with PPMP to reduce GM1 expression showed a significant increase in the formation of aggregated aSyn compared to untreated cells. We thus demonstrated that sufficient GM1 prevents the aggregation of aSyn. For this to occur, aSyn and GM1 must show proximity within the neuron. The present study provides evidence for such co-localization in neuronal cytosol, which also facilitates the inverse interaction revealed in studies with the two cell types above. This adds to the explanation of how GM1 prevents the aggregation of aSyn and onset of Parkinson’s disease.
The Effects of Bioactive Compounds on Human Brain Structures and Diseases
Authors: Kiskova Terezia , Smajda Benadik
Published: March 2024

The human brain is the most intricate organ in the body [...]
Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists
Authors: Sharif Najam A. , Millar J. Cameron , Zode Gulab , Ota Takashi
Published: March 2024

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.
An Insight into Fluorinated Imines and Hydrazones as Antibacterial Agents
Authors: Sztanke Małgorzata , Wilk Agata , Sztanke Krzysztof
Published: March 2024

Fluorinated imines (Schiff bases) and fluorinated hydrazones are of particular interest in medicinal chemistry due to their potential usefulness in treating opportunistic strains of bacteria that are resistant to commonly used antibacterial agents. The present review paper is focused on these fluorinated molecules revealing strong, moderate or weak in vitro antibacterial activities, which have been reported in the scientific papers during the last fifteen years. Fluorinated building blocks and reaction conditions used for the synthesis of imines and hydrazones are mentioned. The structural modifications, which have an influence on the antibacterial activity in all the reported classes of fluorinated small molecules, are highlighted, focusing mainly on the importance of specific substitutions. Advanced research techniques and innovations for the synthesis, design and development of fluorinated imines and hydrazones are also summarized.
Cycloolivil Isolated from Nardostachys jatamansi Inhibits TNF-α/IFN-γ-Induced Chemokine Production by Blocking NF-κB and JAK/STAT Activation in HaCaT Keratinocytes
Authors: Yoon Chi-Su , Lee Hwan , Liu Zhiming , Dong Linsha , Lee Gyoyoung , Kim Nayeon , Oh Hyuncheol , Lee Dong-Sung
Published: March 2024

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3′-hydroxy-5′-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4β-hydroxy-8β-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.
The Effectiveness and Cost-Effectiveness of the ‘Walk with Me’ Peer-Led Walking Intervention to Increase Physical Activity in Inactive Older Adults: Study Protocol for a Randomised Controlled Trial
Authors: Cunningham Conor , O’Doherty Maeve , Neill Ruth D. , Adams Michael , Kee Frank , Cupples Margaret E. , Hardeman Wendy , Simpson Ellen Elizabeth Anne , Murphy Marie H. , Callaghan Chris , O’Sullivan Roger , Brolly Colette , Agus Ashley , McDowell Cliona , Laventure Bob , Casey Siobhan , McDonough Suzanne M. , Tully Mark A.
Published: March 2024

Background: The proportion of the population aged 65 years or older is increasing. Typically, physical activity and health decline with age, which is why action to promote active ageing is a major public health priority, particularly due to health inequalities in older adults. The aim of this study is to assess the effectiveness and cost-effectiveness of the Walk with Me peer-led walking intervention for older adults. Methods: This study is a two-arm, assessor-blind, randomised controlled trial. The intervention is a 12-week peer-led walking intervention based on social cognitive theory. Participants in the control group will receive information on active ageing and healthy nutrition. The study will target 348 community-dwelling older adults, aged 60 years or over living in areas of socio-economic disadvantage communities. Trained peer mentors will deliver the intervention. The primary outcome will be a mean between-group change in moderate-to-vigorous physical activity at 12 months from baseline, measured using an Actigraph accelerometer. Secondary outcomes will include quality of life, mental wellbeing, blood pressure, BMI and waist circumference. An embedded process evaluation will involve focus groups and participant diaries. Discussion: Evidence-based, cost-effective interventions to promote physical activity in older adults living in socio-economically disadvantaged communities are needed to address health inequalities.
Reply to Spiess, B.D.; Houdijk, W.P.M. Comment on “Saner et al. The Yin and the Yang of Hemostasis in End-Stage Liver Disease. J. Clin. Med. 2023, 12, 5759”
Authors: Saner Fuat H. , Scarlatescu Ecaterina , Breoring Dieter C. , Bezinover Dmitri
Published: March 2024

Thank you for your insightful comments on our article [...]
Intravenous Landiolol for Rate Control in Supraventricular Tachyarrhythmias in Patients with Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis
Authors: Nasoufidou Athina , Papazoglou Andreas S. , Stachteas Panagiotis , Karagiannidis Efstratios , Samaras Athanasios , Alexiou Sophia , Mourtzos Michail-Angelos , Kassimis George , Fragakis Nikolaos
Published: March 2024

Background: This systematic review explores the effects of landiolol administration in individuals presenting with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction, without being septic or in a peri-operative period. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus databases, retrieving a total of 15 eligible studies according to prespecified eligibility criteria. Results: Patients treated with landiolol experienced a substantial reduction in heart rate (HR) (mean HR reduction: 42 bpm, 95% confidence intervals (CIs): 37–47, I2 = 82%) and were more likely to achieve the target HR compared to those receiving alternative antiarrhythmic therapy (pooled odds ratio (OR): 5.37, 95% CIs: 2.87–10.05, I2 = 0%). Adverse events, primarily hypotension, occurred in 14.7% of patients receiving landiolol, but no significant difference was observed between the landiolol and alternative antiarrhythmic receiving groups (pooled OR: 1.02, 95% CI: 0.57–1.83, I2 = 0%). No significant difference was observed between the two groups concerning sinus rhythm restoration (pooled OR: 0.97, 95% CI: 0.25–3.78, I2 = 0%) and drug discontinuation due to adverse events (pooled OR: 5.09, 95% CI: 0.6–43.38, I2 = 0%). Conclusion: While further research is warranted, this systematic review highlights the potential benefits of landiolol administration in the management of SVTs in the context of left ventricular dysfunction.
Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management
Authors: Niemann Britney , Moise John , Sestito Michael , Malla Midhun , Train Kevin , Murken Douglas , Mayers Keri , Groves Emily , Garland-Kledzik Mary
Published: March 2024

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.
Calcium Hydroxylapatite (CaHA) and Aesthetic Outcomes: A Systematic Review of Controlled Clinical Trials
Authors: Amiri Mojgan , Meçani Renald , Llanaj Erand , Niehot Christa D. , Phillips Terri L. , Goldie Katherine , Kolb Janina , Muka Taulant , Daughtry Hua
Published: March 2024

Background: This study aimed to systematically review and summarize the available controlled clinical trials on the effectiveness of calcium hydroxylapatite (CaHA) in terms of aesthetic outcomes, skin-aging-related outcomes, and patient/investigator satisfaction. Methods: We included controlled clinical trials involving at least 10 human adults that examined the effects of CaHA on aesthetic and skin-aging-related outcomes and satisfaction. Due to the high heterogeneity among the included studies, only a qualitative analysis is provided. Results: Out of 2935 relevant references, 13 studies were included, of which 8 studies focused on facial areas and 5 on dorsum of hand. CaHA injection was associated with enhancements in global aesthetic improvement scale, whether applied in facial regions or on the dorsum of hands. The findings suggested high patients’ satisfaction following CaHA when applied to facial areas. Studies highlighted improvements in hand grading scales and a reduction in facial wrinkles. Conclusions: Current evidence suggests that CaHA injections improve aesthetic results, including facial areas, such as nasolabial folds and jawline, and hands, with high levels of satisfaction. Considering the methodological limitations and heterogeneous comparisons groups, additional controlled clinical trials would contribute to a better understanding of the applications and advantages offered by CaHA.
Cardiac Sarcoidosis—Diagnostic and Therapeutic Challenges
Authors: Korthals Dennis , Bietenbeck Michael , Könemann Hilke , Doldi Florian , Ventura David , Schäfers Michael , Mohr Michael , Wolfes Julian , Wegner Felix , Yilmaz Ali , Eckardt Lars
Published: March 2024

Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials.
The Sum of the Leg Length Discrepancy and the Difference in Global Femoral Offset Is Equal to That of the Contralateral Intact Side and Improves Postoperative Outcomes after Total Hip Arthroplasty: A Three-Dimensional Analysis
Authors: Imai Norio , Hirano Yuki , Endo Yuki , Horigome Yoji , Suzuki Hayato , Kawashima Hiroyuki
Published: March 2024

Background/Objectives: Global femoral offset (GFO) and leg length discrepancy (LLD) affect outcomes after total hip arthroplasty (THA). Moreover, the sum of the difference in GFO between the THA and non-surgical sides and LLD (SGL) reportedly affects the outcomes in a two-dimensional evaluation. We examined the association of the GFO, LLD, and SGL with the Harris Hip Score (HHS) using a three-dimensional (3D) evaluation. Methods: We retrospectively surveyed 172 patients with hemilateral hip osteoarthritis who underwent THA. The GFO, LLD, and SGL were measured using the 3D pelvis and femur models; these models were adjusted for the pelvis and femur, and the coordinate systems were parallelized. Furthermore, their relationship with the modified HHS (mHHS) 1 year after THA was determined. Results: Significant correlations were found among mHHS, GFO, and SGL in the binomial group, whereas LLD was not significantly correlated. The optimal values of GFO and SGL were 1.01 mm and 0.18 mm/100 cm body height, respectively, which were considered optimal when the SGL values were approximately equal to those of the non-operative side. The optimal ranges for GFO and SGL were −1.65 to 3.67 mm and −4.78 to 5.14 mm/100 cm, respectively. Conclusions: Our findings were obtained after adjusting the pelvis and femur to a unified coordinate system. Therefore, the results of this study can be directly applied to 3D planning.