bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of Lipopeptides and Their Applications in Food and Human Health: A Review
Authors: Chen Shuyi , Chen Sumin , Yu Xin , Wan Caijing , Wang Ying , Peng Lianxin , Li Qiang
Published: January 2025

Lipopeptides (LPs) are widely sourced surface-active natural products with a wide range of functions and low toxicity, high potency, and good biodegradability. In this paper, we summarize, for the first time, the plant, animal, microbial, and synthetic sources of LPs. We also introduce the applications of LPs in food and human health, including (1) LPs can inhibit the growth of food microorganisms during production and preservation. They can also be added to food packaging materials for preservation and freshness during transportation, and can be used as additives to improve the taste of food. (2) LPs can provide amino acids and promote protein synthesis and cellular repair. Due to their broad-spectrum antimicrobial properties, they exhibit good anticancer effects and biological activities. This review summarizes, for the first time, the sources of LPs and their applications in food and human health, laying the foundation for the development and application of LPs.
Microstructural Analysis and Radiological Characterization of Alkali-Activated Materials Based on Aluminosilicate Waste and Metakaolin
Authors: Mladenović Nikolić Nataša , Kandić Aleksandar , Potočnik Jelena , Latas Nemanja , Ivanović Marija , Nenadović Snežana , Kljajević Ljiljana
Published: January 2025

The formation of an aluminosilicate gel structure made of alkali-activated materials (AAMs) was conducted through an alkali-activation reaction of the solid precursors (fly ash, metakaolin, and wood ash). Fly and wood ash are by-products of the burning process of coal and wood, respectively. Alkali-activated materials of aluminosilicate origin, made from the different ashes, fly and wood, are very attractive research targets and can be applied in various technological fields due to their thermal stability, resistance to thermal shock, high porosity, high sustainability, and finally, low energy loss during production. In this paper, we evaluate physico-chemical properties, microstructure, and radiological environmental impacts when wastes that contain elevated levels of naturally occurring radionuclides (NORs) such as fly ash and wood ash are made into “green cements” such as AAMs. The determination of radionuclide content was performed by means of gamma-ray spectrometry. Results showed that the AAMs have a lower value in the activity concentration of radionuclides than raw materials. The external absorbed gamma dose rate was 74.7–107.3 nGy/h, and the external radiation hazard index values were in range of 0.445–0.628 Bq/kg. The results of the activity concentration measurements for alkali-activated materials indicate the potential of their safe application in building construction. In terms of the structural characterizations, the obtained alkali-activated materials were examined using XRD, DRIFT, FESEM, and TEM analyses.
Regularities of Plastic Deformation Zone Formation Around Unsupported Shafts in Tectonically Disturbed Massive Rock
Authors: Demenkov Petr A. , Romanova Ekaterina L.
Published: January 2025

In the presented paper, an approach to assessing the size of the plastic deformation zone around a circular cavity intersecting a crushed disintegrated layer in tectonically stressed massive rock is suggested. Fractured rock zones of different quality and spatial configurations are investigated in order to predict the size of dangerous plastic deformation zones or zones of potential rock collapses. The analysis is performed by means of numerical modeling after preliminary verification of the model by in situ and monitoring data. The paper explores the impact of such parameters of the fractured rock zone as the GSI index, the true thickness of the zone, and its inclination angle relative to the plane perpendicular to the axis of the excavation. It was found that with the increase in the thickness and angle of inclination of the fractured rock zone, the size of the hazardous zone in the vicinity of the excavation increases, while with the increase in its strength characteristics, the size of the potential failure zone decreases. According to the results of the study, qualitative dependencies are established, which localize and predict the size of the danger zone, or the potential failure zone in the vicinity of an unfixed excavation.
SPING Block Analgesia in Non-Operative Management of Proximal Femur Fractures in Older Adults Living with Frailty: A Retrospective Cohort Study
Authors: van der Velden Miriam W. A. , Kroes Thamar , Visschers Nick J. G. , de Loos Frank P. J. F. , Janssens Pleun , Spaetgens Bart , Faes Miriam C. , van den Beuken-van Everdingen Marieke H. J. , Suman Arnela
Published: January 2025

Background/Objectives: Spinal Phenol IN Glycerol (SPING) block is a novel palliative pain treatment for the non-operative management of proximal femur fractures (PFFs) in older adults living with frailty. Effective pain management that aligns with patient preferences and minimizes opioid use is critical in this setting. This study evaluated the patient, safety, and process outcomes of SPING block in this population. Methods: A retrospective cohort study was conducted in a suburban teaching hospital from March 2021 to June 2024, which included sixty-eight older adults living with frailty that suffered from a PFF and received SPING block. Data were collected from the Electronic Patient Records. The patient living situation was visualized with a Sankey diagram. Changes in pain scores and opioid use were assessed using the Wilcoxon Signed Rank test. Results: The median patient age was 89 years (Interquartile range (IQR) 83–92). Most were severely or terminally ill (American Society of Anesthesiologists (ASA) ≥ 4, 72%) and had cognitive impairment or dementia (68%). SPING block was effective in 93% of patients, significantly reducing median pain scores (4 [IQR 3–5] to 0 [IQR 0–1], p < 0.001) and opioid use (15 mg/day [IQR 4–30] to 0 mg/day [IQR 0–0], p < 0.001). Within 24 h, 84% could sit upright and 44% could transfer between their bed and chair. The median time to discharge was one day (IQR 0–3), with a median survival of 13 days (IQR 7–44). Conclusions: This study supports SPING block as a viable option for older adults living with frailty suffering from a PFF who opt for non-operative management in a palliative setting. SPING block for PFFs in a palliative setting offers effective pain relief, reduces opioid use, and enables mobility for older adults living with frailty. Follow-up is essential to monitor efficacy and safety. Prospective studies are needed to confirm these findings.
Physicians’ Intentions to Recommend Influenza Vaccine: A Multi-Centered Hospital-Based Study Using the Theory of Planned Behavior in Bangladesh
Authors: Biswas Md Abdullah Al Jubayer , Rahman Mahbubur , Khan Sazzad Hossain , Basher Ahamed Khairul , Islam Md Ariful , Pyash Ashrak Shad , Shoshi Homayra Rahman , Riaj Md Altaf Ahmed , Islam Md Nazrul , Rabbany Md Arif , Haque Md Azizul , Chakraborty Shishir Ranjan , Parvin Syeda Rukhshana , Rahman Mahmudur , Chowdhury Fahmida , Shirin Tahmina , Hassan Md. Zakiul
Published: January 2025

Background: Influenza remains a significant public health challenge in low- and middle-income countries (LMICs) like Bangladesh, where vaccine uptake remains low despite the substantial disease burden. Physicians play a vital role in promoting vaccination, yet their intentions and influencing factors are not well understood. Methods: We conducted a cross-sectional study from June to October 2022 across four tertiary-level hospitals in Bangladesh using a questionnaire grounded in the Theory of Planned Behavior (TPB). Hierarchical logistic regression was employed to identify factors associated with vaccine recommendation intentions. Results: Among 972 physicians with an average age of 32.1 years, 40.1% intended to recommend and administer the influenza vaccine. Most (85.3%) agreed vaccination reduces risk, 65.5% desired vaccination for self-protection, 63.5% would vaccinate if available at work, and 85.3% anticipated Ministry of Health support. Male (OR = 1.9, 95% CI: 1.5–2.3) and married (OR = 1.5, 95% CI: 1.1–1.9) physicians were more likely to recommend vaccination. Each unit increase in attitude score doubled the likelihood of recommending the vaccine (OR = 2.0, 95% CI: 1.4–3.0). Conclusions: Physicians’ influenza vaccine recommendations in Bangladesh are suboptimal, influenced by gender, marital status, and attitudes. Targeted educational interventions addressing attitudinal barriers and leveraging institutional support could improve recommendation practices.
Assessing the Risks and Cultural Relativity of Diabetes in Black Individuals of African Caribbean Ancestry (ACB) Aged 18–39 Years in Toronto
Authors: Alamgir Akm , Raghunauth Rhea , Momoh Osezua , Ledwos Cliff
Published: January 2025

Context: Diabetes rates are high in Black and some other ethnic communities, often leading to more severe complications. We conducted a study to identify the prevalence and risk of diabetes among African Caribbean Black (ACB) individuals aged 18–39 and to assess the sensitivity of glycated hemoglobin (HbA1c) compared to an oral glucose tolerance test (OGTT) to diagnose diabetes. Methods: In this mixed-methods study, maximum variation sampling was used to recruit 272 ACB participants from fourteen African and five Caribbean countries from Toronto. Participants’ height, weight, waist circumference, HbA1c, OGTT, demographic, and behavioural data were collected. SPSS was used to analyze the quantitative data. This study used descriptive statistics for frequency distribution and cross-tabulation while inferential statistics (regression, ANOVA, factor analysis, etc.) were used for relational analysis. Because of the small sample size, qualitative data were analyzed manually using the charting technique. Results: This study found that 1.5% of participants had diabetes, 9.2% had prediabetes, and 44.9% were at risk of developing diabetes. The mean value of HbA1c, FBS, and 2hPG was 5.5%, 4.8 mmol/L, and 5.7 mmol/L, respectively. The mean BMI was 28.2 kg/m2, and the waist circumference was 85.8 cm. This study found a correlation between glucose intolerance and increasing body mass index (BMI) and waist circumference (WC). Dietary habits, physical inactivity, and mental health challenges were risk factors among the participants. HbA1c was found to be a more sensitive and culturally acceptable screening measure than OGTT in diagnosing diabetes. Conclusions: ACB individuals are at high risk of having diabetes, requiring culturally tailored peer-based health promotion strategies to reduce diabetes prevalence and risk. HbA1c is a culturally acceptable and statistically more capable measure than OGTT in identifying individuals with prediabetes. Further longitudinal research is needed.
Capacity Planning (Capital, Staff and Costs) of Inpatient Maternity Services: Pitfalls for the Unwary
Authors: Jones Rodney P.
Published: January 2025

This study investigates the process of planning for future inpatient resources (beds, staff and costs) for maternity (pregnancy and childbirth) services. The process of planning is approached from a patient-centered philosophy; hence, how do we discharge a suitably rested healthy mother who is fully capable of caring for the newborn baby back into the community? This demonstrates some of the difficulties in predicting future births and investigates trends in the average length of stay. While it is relatively easy to document longer-term (past) trends in births and the conditions relating to pregnancy and birth, it is exceedingly difficult to predict the future nature of such trends. The issue of optimum average bed occupancy is addressed via the Erlang B equation which links number of beds, average bed occupancy and turn-away. Turn-away is the proportion of times that there is not an immediately available bed for the next arriving inpatient. Data for maternity units show extreme and unexplained variation in turn-away. Economy of scale implied by queuing theory (and the implied role of population density) explains why many well intended community-based schemes fail to gain traction. The paper also addresses some of the erroneous ideas around the dogma that reducing length of stay ‘saves’ money. Maternity departments are encouraged to understand how their costs are calculated to avoid the trap where it is suggested by others that in reducing the length of stay, they will reduce costs and increase ‘efficiency’. Indeed, up to 60% of calculated maternity ‘costs’ are apportioned from (shared) hospital overheads from supporting departments such as finance, personnel, buildings and grounds, IT, information, etc., along with depreciation charges on the hospital-wide buildings and equipment. These costs, known as ‘the fixed costs dilemma’, are totally beyond the control of the maternity department and will vary by hospital depending on how these costs are apportioned to the maternity unit. Premature discharge, one of the unfortunate outcomes of turn-away, is demonstrated to shift maternity costs into the pediatric and neonatal departments as ‘boomerang babies’, and then require the cost of avoidable inpatient care. Examples are given from the English NHS of how misdirected government policy can create unforeseen problems.
Exploring the Efficacy of Aboriginal Men’s Socioemotional Healing Programs in Australia: A Scoping Review of Evaluated Programs
Authors: Horak Elizabeth , Thompson Sandra C.
Published: January 2025

Aboriginal and Torres Strait Islander (hereafter, respectfully, Indigenous) men’s health and social indicators reflect an ongoing legacy of social disruption with profound implications for broader family and community contexts. In response to recognized needs, healing programs have been implemented within Australia. The literature on relevant best practices for Indigenous men’s healing was explored to inform the planning and implementation of a local program. A scoping review of electronic databases was undertaken to retrieve information between 2012 and 2022 on social and emotional healing programs for Indigenous men that included a program evaluation. Of the 2123 identified articles, many lacked a program evaluation or were not specific to male participants, with nine meeting the inclusion criteria for the review. Six central elements that supported the programs’ reported efficacy were identified: kinship, cultural understanding, a view of healing as being holistic, a strengths-based approach, a male leadership team, and a consistent meeting space. These elements were important for the social and emotional healing of the Indigenous male participants. Based on these findings, there is an increased need for the identified elements to be incorporated into programs for Indigenous men to accompany ongoing efforts in improving the wellbeing of the Indigenous population overall.
Determinants of Debt Financing Behavior of Unlisted Moroccan Family SMEs: A Panel Data Analysis
Authors: Boumlik Zouhair , Oulhadj Badia , Colot Olivier
Published: January 2025

This paper investigates the firm-level determinants of debt policy in private family SMEs. It employs a comparative analysis of two sub-samples of family and non-family SMEs using panel data from 200 Moroccan SMEs over the period from 2018 to 2022. The findings reveal that family SMEs adopt a conservative financing strategy, maintaining lower debt levels compared to their non-family counterparts. This conservative approach appears to be driven by risk considerations related to bankruptcy costs associated with higher debt levels. Indeed, the results show that the financing behaviors of family SMEs align more closely with pecking order theory than trade-off theory. Furthermore, the study suggests that the financing behavior of family SMEs differs slightly from that of non-family SMEs, but this difference is not resistant to changes in debt measures. This study makes several contributions to the literature. First, it identifies the key determinants of debt policy among family SMEs, offering insights into the distinctive financing strategies employed by these firms. Second, it offers evidence supporting the relevance of capital structure theories in explaining the financing decisions of family firms within the context of developing economies. In addition, the study’s findings have practical implications insofar as they can guide policymakers and banking stakeholders, especially those in bank-based economies where debt is the primary financing option for SMEs, in conceiving adapted financing options that align with the characteristics of family firms, thereby fostering their growth and, consequently, the economy’s development.
DNA Methylation in Pituitary Adenomas: A Scoping Review
Authors: Møller Morten Winkler , Nortvig Mathias Just , Andersen Mikkel Schou , Poulsen Frantz Rom
Published: January 2025

Pituitary adenomas are a diverse group of neoplasms with variable clinical behavior. Despite advances in genetic analysis, understanding the role of epigenetic modifications, particularly DNA methylation, remains an area under investigation. This scoping review aimed to update and synthesize the current body of literature on DNA methylation in pituitary adenomas, focusing on methodological advancements and clinical correlations. A systematic search conducted across multiple databases, including Embase, Scopus, MEDLINE, and CENTRAL, identified 107 eligible studies. Early methods, such as methylation-restricted digestion and methylation-specific PCR (MSP), have evolved into more comprehensive approaches, such as chip-based DNA methylation analysis. Key findings suggest that genes like POMC, SOCS-1, and RASSF1A show a significant association between methylation and clinical behavior. However, methylation patterns alone are insufficient to fully explain tumorigenesis. Emerging data suggest that DNA methylation might serve as a prognostic marker for invasive growth and recurrence, but further longitudinal studies are needed. This review highlights the need for future research to explore the methylome more thoroughly and to better define the clinical impact of epigenetic modifications in pituitary adenomas.
The Ocular Surface and the Anterior Segment of the Eye in the Pseudoexfoliation Syndrome: A Comprehensive Review
Authors: Thomas Maya Natasha , Skopiński Piotr , Roberts Harry , Woronkowicz Małgorzata
Published: January 2025

Pseudoexfoliation syndrome (PXS) is an age-related fibrillopathy where fibrillar exfoliation material accumulates and deposits in ocular and extra-ocular tissue. Within the eye, this substance accumulates on the ocular surface and in the anterior segment of the eye, impacting ocular structures such as the conjunctiva, Tenon’s capsule, sclera, cornea, iris, ciliary body, trabecular meshwork, and lens. This review aims to collate the current literature on how each anatomical part of the eye is affected by PXS, with a strong focus on molecular changes. We also summarise the current understanding of the key genetic factors influencing the development of PXS.
Complete Chloroplast Genomes of 9 Impatiens Species: Genome Structure, Comparative Analysis, and Phylogenetic Relationships
Authors: Ma Hui , Liu Zhiqiang , Lan Wenxiang , Yang Mengqing , Mo Qing , Huang Xi , Wu Peiqing , Huang Haiquan , Huang Meijuan
Published: January 2025

Impatiens is a genus of functional herbaceous plants in the Balsaminaceae, which are not only of great ornamental value and one of the world’s top three flower bedding plants but also have a wide range of medicinal and edible uses. Currently, the taxonomy and phylogenetic relationships of Impatiens species are still controversial. In order to better understand their chloroplast properties and phylogenetic evolution, nine Impatiens plants (Impatiens repens, Impatiens rectirostrata, Impatiens baishaensis, Impatiens rostellata, Impatiens faberi, Impatiens oxyanthera, Impatiens tienchuanensis, Impatiens blepharosepala, Impatiens distracta) were sequenced, and their complete chloroplast genomes were analysed. Nine species of Impatiens chloroplast genomes ranged in length from 150,810 bp (I. rectirostrata) to 152,345 bp (I. blepharosepala). The chloroplast genomes were all typical circular DNA molecules, and the GC content in each region was consistent with the published chloroplast genomes of Impatiens plants. The results showed that the seven mutational hotspots (trnL-UAG, ndhG, ycf1, ccsA, rrn23, trnA-UGC, and ycf2) could be used as supporting data for further analyses of the phylogenetic tree and species identification. In addition, the results of the phylogenetic tree support that Balsaminaceae is a monophyletic taxon, and that Hydrocera triflora is at the base of the branch, is the original species of Balsaminaceae, and is in a sister group relationship with Impatiens species. The results of this paper enrich the data of Impatiens chloroplast genomes, and the availability of these chloroplast genomes will provide rich genetic information for species identification, thus enhancing the taxonomic accuracy and phylogenetic resolution of Impatiens, and further promoting the investigation and rational use of Impatiens plant resources.
Neuroprotective Effects of VEGF-B in a Murine Model of Aggressive Neuronal Loss with Childhood Onset
Authors: Pérez-Revuelta Laura , Pérez-Boyero David , Pérez-Martín Ester , Cabedo Valeria Lorena , Téllez de Meneses Pablo González , Weruaga Eduardo , Díaz David , Alonso José Ramón
Published: January 2025

In recent decades, the scientific community has faced a major challenge in the search for new therapies that can slow down or alleviate the process of neuronal death that accompanies neurodegenerative diseases. This study aimed to identify an effective therapy using neurotrophic factors to delay the rapid and aggressive cerebellar degeneration experienced by the Purkinje Cell Degeneration (PCD) mouse, a model of childhood-onset neurodegeneration with cerebellar atrophy (CONDCA). Initially, we analyzed the changes in the expression of several neurotrophic factors related to the degenerative process itself, identifying changes in insulin-like growth factor 1 (IGF-1) and Vascular Endothelial Growth Factor B (VEGF-B) in the affected animals. Then, we administered pharmacological treatments using human recombinant IGF-1 (rhIGF-1) or VEGF-B (rhVEGF-B) proteins, considering their temporal variations during the degenerative process. The effects of these treatments on motor, cognitive, and social behavior, as well as on cerebellar destructuration were analyzed. Whereas treatment with rhIGF-1 did not demonstrate any neuroprotective effect, rhVEGF-B administration at moderate dosages stopped the process of neuronal death and restored motor, cognitive, and social functions altered in PCD mice (and CONDCA patients). However, increasing the frequency of rhVEGF-B administration had a detrimental effect on Purkinje cell survival, suggesting an inverted U-shaped dose–response curve of this substance. Additionally, we demonstrate that this neuroprotective effect was achieved through a partial inhibition or delay of apoptosis. These findings provide strong evidence supporting the use of rhVEGF-B as a pharmacological agent to limit severe cerebellar neurodegenerative processes.
Pyrrolysine Aminoacyl-tRNA Synthetase as a Tool for Expanding the Genetic Code
Authors: Dakhnevich Anastasia , Kazakova Alisa , Iliushin Danila , Ivanov Roman A.
Published: January 2025

In addition to the 20 canonical amino acids encoded in the genetic code, there are two non-canonical ones: selenocysteine and pyrrolysine. The discovery of pyrrolysine synthetases (PylRSs) was a key event in the field of genetic code expansion research. The importance of this discovery is mainly due to the fact that the translation systems involving PylRS, pyrrolysine tRNA (tRNAPyl) and pyrrolysine are orthogonal to the endogenous translation systems of organisms that do not use this amino acid in protein synthesis. In addition, pyrrolysine synthetases belonging to different groups are also mutually orthogonal. This orthogonality is based on the structural features of PylRS and tRNAPyl, which include identical elements, such as a condensed core, certain base pairs and the structural motifs of tRNAPyl. This suggests that targeted structural changes in these molecules enable changes in their specificity for the amino acid and the codon. Such modifications were successfully used to obtain different aaRS/tRNA pairs that allow the incorporation of unnatural amino acids into peptides. This review presents the results of recent studies related to the correlation between the structure and activity of PylRS and tRNAPyl and the use of pyrrolysine synthetases to extend the genetic code.
In Vitro, In Vivo, Ex Vivo Characterisation of Dihydroimidazotriazinones and Their Thermal Decomposition Course Studied by Coupled and Simultaneous Thermal Analysis Methods
Authors: Worzakowska Marta , Sztanke Małgorzata , Rzymowska Jolanta , Sztanke Krzysztof
Published: January 2025

The biological and thermal properties of a class of synthetic dihydroimidazotriazinones were disclosed in this article for the first time. Molecules 1–6—as potential innovative antimetabolites mimicking bicyclic aza-analogues of isocytosine—were evaluated for their in vitro anticancer activity. Moreover, in vivo, in vitro, and ex vivo toxicity profiles of all the compounds were established in zebrafish, non-tumour cell, and erythrocyte models, respectively. Their antihaemolytic activity was also evaluated. Additionally, the thermal decomposition mechanism, path, and key thermal properties of heterocycles 1–6 were analysed. It was found that all the studied compounds revealed significant antiproliferative activities against tumour cells of the lung, cervix, ovary, and breast, as well as acute promyelocytic leukaemia cells, superior or comparable to that of an anticancer agent gemcitabine. Most of them were less toxic to non-tumour cells than this standard drug, and none had a haemolytic effect on red blood cells. All the tested heterocycles proved to be safer for zebrafish than a standard drug pemetrexed. Some exhibited the ability to inhibit oxidative haemolysis, suggesting their protective action on erythrocytes. The differential scanning calorimetry (DSC) analyses confirmed that all molecules melted within one narrow temperature range, proving their purity. The melting points depended solely on the type of substituent and increased as follows: 4 (R = 3-ClPh) < 2 (R = 4-CH3Ph) = 3 (R = 4-OCH3Ph) < 5 (R = 4-ClPh) = 1 (R = Ph) < 6 (R = 3,4-Cl2Ph). The thermogravimetry/differential thermogravimetry (TG/DTG) studies confirmed high thermal stability of all the investigated heterocycles in inert (>230 °C) and oxidising (>260 °C) atmospheres, which depended directly on the R. The pyrolysis process included one main decomposition stage and was connected with the emission of NH3, HCN, CH3CN, HNCO, alkane, alkene, aromatic fragments, CO2 (for all the compounds), and HCl (for the molecule with 3,4-Cl2Ph), which was confirmed by FTIR and QMS analyses. In turn, the oxidative decomposition process of the tested polyazaheterocycles took place in two main stages connected with the formation of the same volatiles as those observed in an inert atmosphere and additionally with the release of N2, NO, CO, and H2O. These results proved that the pyrolysis and oxidative decomposition run through the radical mechanism connected with the additional reactions between radicals and oxygen in synthetic air. The favourable biological and thermal properties of this class of dihydroimidazotriazinones imply their usefulness as potential pharmaceutics.
Hypothyroidism Alters Uterine Kisspeptin System and Activity Modulators in Cyclic Rats
Authors: da Silva Thayná Queiroz Menezes , Barbosa Erikles Macêdo , Santos Luciano Cardoso , Oliveira Luciana Santos de , Cunha Maria Clara da Silva Galrão , de Macedo Isabella Oliveira , Martins Brenda Geovana Campos , Oliveira Cibele Luz , Rodrigues Natalia Panhoca , Araújo-Lopes Roberta , Szawka Raphael Escorsim , Silva Juneo Freitas
Published: January 2025

Hypothyroidism causes ovarian dysfunction and infertility in women and animals and impairs the hypothalamic expression of kisspeptin (Kp). However, kisspeptin is also expressed in the genital system, and the lack of the Kp receptor (Kiss1r) in the uterus is linked to reduced implantation rates. This study investigated the impact of hypothyroidism on the uterine expression of Kp and Kiss1r in female rats throughout the estrous cycle and the associated changes in uterine activity modulators. Hypothyroidism was induced through daily administration of propylthiouracil (PTU) over a period of 14 days. Plasma levels of LH, E2, and P4, cyclicity, body and uterine weight, uterine histomorphometry, and the gene and/or protein expression of Kiss1, Kiss1r, estrogen receptor α (ERα), progesterone receptor (PR), and thyroid hormone receptor α (TRα) were assessed. Additionally, proliferative activity (CDC-47) and the gene expression of uterine receptivity mediators (SMO, WNT4, BMP2, HAND2, MUC1, and LIF) were evaluated. Hypothyroidism prolonged the diestrus and increased progesterone levels during this phase, while decreasing luteinizing hormone and estradiol on proestrus. In the uterus, hypothyroidism reduced Kp immunostaining on diestrus and KISS1R mRNA levels on proestrus. These changes were accompanied by reduced endometrial glands, reduced uterine proliferative activity, and reduced ERα gene and protein expression. Additionally, hypothyroidism led to reduced uterine gene expression of LIF, BMP2, WNT4, and HAND2. On the other hand, thyroid hypofunction increased uterine PR and TRα immunostaining, while it reduced PGR gene expression on diestrus. These findings demonstrate that hypothyroidism reduces the expression of Kiss1/Kiss1r system in the uterus, which is associated with disrupted uterine estrogen and progesterone signaling and reduced expression of uterine receptivity mediators across the rat estrous cycle.
Diverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment
Authors: Volynsky Pavel E. , Urban Anatoly S. , Pavlov Konstantin V. , Bershatsky Yaroslav V. , Bocharova Olga V. , Kryuchkova Anastasia K. , Zlobina Veronika V. , Gavrilenkova Alina A. , Dolotova Sofya M. , Kamynina Anna V. , Zangieva Olga T. , Taldaev Amir , Batishchev Oleg V. , Okhrimenko Ivan S. , Rakitina Tatiana V. , Efremov Roman G. , Bocharov Eduard V.
Published: January 2025

Alzheimer’s disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the APP and secretase location relative to ordered or disordered membrane microdomains. We used high-resolution NMR to probe the interactions of the cholesterol analog with APP transmembrane domain in two membrane-mimicking systems resembling ordered or perturbed lipid environments (bicelles/micelles). In bicelles, spin-labeled sterol interacted with the peptide near the amphiphilic juxtamembrane region and N-terminal part of APP transmembrane helix, as described earlier for cholesterol. Upon transition into micellar environment, another interaction site appeared where sterol polar head was buried in the hydrophobic core near the hinge region. In MD simulations, sterol moved between three interaction sites, sliding along the polar groove formed by glycine residues composing the dimerization interfaces and flexible hinge of the APP transmembrane domain. Because the lipid environment modulates interactions, the role of lipids in the AD pathogenesis is defined by the state of the entire lipid subsystem rather than the effects of individual lipid species. Cholesterol can interplay with other lipids (polyunsaturated, gangliosides, etc.), determining the outcome of amyloid-β production cascades.
The Modulatory Effect of Selol (Se IV) on Pro-Inflammatory Pathways in RAW 264.7 Macrophages
Authors: Lim Gwan Yong , Grosicka-Maciąg Emilia , Szumiło Maria , Graska Daniel , Rahden-Staroń Iwonna , Kurpios-Piec Dagmara
Published: January 2025

Selol is a semi-synthetic mixture of selenized triglycerides. The results of biological studies revealed that Selol exhibits several anticancer effects. However, studies on its potential anti-inflammatory activity are scarce, and underlying signaling pathways are unknown. The aim of our study was to investigate the ability of Selol to exert anti-inflammatory effects in a RAW 264.7 cell line model of LPS (lipopolysaccharide)-induced inflammation. Cells were treated either with Selol 5% (4 or 8 µg Se/mL) or LPS (1 µg/mL) alone or with Selol given concomitantly with LPS. The parameters studied were reactive oxygen species (ROS) production, glutathione and thioredoxin (Txn) levels, and nuclear factor kappa B (NF-κB) activation, as well as nitric oxide/prostaglandin E2 (NO/PGE2) production. The presented research also included the effect of Selol and/or LPS on glucose (Glc) catabolism; for this purpose, the levels of key enzymes of the glycolysis pathway were determined. The results showed that Selol exhibited pro-oxidative properties. It induced ROS generation with a significant increase in the level of Txn; however, it did not affect the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. Selol moderately activated NF-κB but failed to affect NO/PGE2 production. The effect of Selol on glucose catabolism was not significant. However, the simultaneous administration of Selol with LPS exerted a statistically significant anti-inflammatory effect via a decrease in the production of pro-inflammatory mediators and NF-κB activation. Our study also showed that as a result of LPS action in cells, the anaerobic glycolysis activity was increased, and incubation with Selol caused a partial reprogramming of Glc metabolism towards aerobic metabolism. This may indicate different pharmacological and molecular effects of Selol action in physiological and pathological conditions.
Submicron Dispersions of Phytosterols Reverse Liver Steatosis with Higher Efficacy than Phytosterol Esters in a Diet Induced-Fatty Liver Murine Model
Authors: Gillet Raimundo , Cerda-Drago Tomás G. , Brañes María C. , Valenzuela Rodrigo
Published: January 2025

Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, could improve these effects. We explored the therapeutic activity of phytosterols, either formulated as submicron dispersions of phytosterols (SDPs) or conventional phytosterol esters (PEs), in a mouse model of MAFLD. MAFLD was induced in mice by atherogenic diet (AD) feeding. The reversion of distorted serum and liver parameter values after a period of AD feeding was investigated after supplementation of the AD with SDPs, PEs, or a placebo (PT). Additionally, the metabolic parameters of fatty acid synthesis, fatty acid oxidation, and inflammation were studied to understand the mechanism of action of phytosterols. AD supplementation with SDPs was shown to reduce liver fat, along with showing a significant improvement in liver triglycerides (TGs), free fatty acids (FFAs), and liver cholesterol levels. These results were reinforced by the analyses of the liver steatosis scores, and liver histologies, where SDP intervention showed a consistent improvement. Treatment with PEs showed slighter effects in the same analyses, and no effects were observed with the PT treatment. Additionally, SDP intervention reversed, with a higher efficacy than PEs, the effect of AD on the serum levels of TGs, total- and LDL-cholesterol levels, and glucose levels. And, exceptionally, while SDP improved HDL-cholesterol serum levels, PEs did not show any effect on this parameter. We provide evidence for the therapeutical activity of phytosterols in MAFLD beyond the regulation of cholesterol levels, which is increased when the phytosterols are formulated as submicron dispersions compared to ester formulations.
Characterizing Stream Condition with Benthic Macroinvertebrates in Southeastern Minnesota, USA: Agriculture, Channelization, and Karst Geology Impact Lotic Habitats and Communities
Authors: Mundahl Neal D.
Published: January 2025

Prior to implementing watershed-wide projects to reduce the impacts of agriculture on regional streams and rivers, stream habitats and benthic aquatic macroinvertebrate communities were assessed at 15 sites on the South Branch Root River and its major tributaries in southeastern Minnesota, USA. Triplicate kick-net samples were collected from each site during three time periods (1998, 1999, 2006/2008) and stream habitats were inventoried within 150 m long sections at each site. In total, 26,760 invertebrates representing 84 taxa were collected and used to rate stream sites using a regional multi-metric benthic index of biotic integrity (BIBI). BIBI scores were significantly correlated with total invertebrate taxa richness. BIBI ratings improved from poor and very poor at headwater sites in channelized stream sections draining agricultural lands to fair to good to excellent in downstream sections flowing through natural channels in largely forested lands. Fifty percent of samples rated stream sites as poor or very poor. Over 85% of stream habitat assessments indicated the presence of fair to good habitats, although stream sites were relatively wide and shallow and dominated by fine sediments that also embedded coarser substrates. BIBI metrics and scores were strongly positively correlated with pool area, riffle spacing-to-stream width ratios, and silt-free substrate, and negatively correlated with width-to-depth ratios. Most stream sites had few Ephemeroptera, Plecoptera, Trichoptera, and Diptera taxa and too few intolerant taxa. It is expected that benthic invertebrate communities should improve as more riparian buffers are added along all streams. However, on-going channel maintenance activities in headwater stream sections, mandated to encourage drainage of adjacent agricultural fields, will continue to negatively impact headwater habitats and biotic communities.
Tyrosine Kinase Inhibitor Therapy Enhances Stem Cells Profile and May Contribute to Survival of Chronic Myeloid Leukemiastem Cells
Authors: Rocco Simone , Maglione Alessandro , Schiavo Valentina , Ferrando Alessandro , Fava Carmen , Cilloni Daniela , Pergolizzi Barbara , Panuzzo Cristina
Published: January 2025

Background/Objectives: Treatment with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has revolutionized disease management and has transformed CML from a life-threatening disease to a chronic condition for many patients. However, overcoming resistance, particularly related to leukemic stem cells (LSC) that can persist even when the bulk of the leukemic cells are eliminated, remains a significant challenge. Methods: K562 and KU812 cell lines were treated in vitro with the TKI Imatinib (IM). Gene expression, protein analysis, and metabolomic screening were conducted to investigate the ability of the drug to enhance stem cell (SC) features. Moreover, a gene ontology analysis was performed on different available datasets, to further consolidate our data. Results: 48 h of IM treatment can significantly increase the expression of genes related to SC self-renewal, particularly SOX2 and OCT 3/4. Interestingly, these modulations occur in cells that remain alive after drug treatment and that displayed features consistent with leukemia stem-like CML cells, suggesting that SC genes levels are crucial even in cell population survived upon TKI treatment. Moreover, after in silico analysis of available data, we observed an enrichment of SOX2/NANOG and OCT 3/4 signatures after TKI treatment, thus strengthening our results. Conclusions: Our results confirmed the relevance of LSC features after TKI treatment, highlighting the need for more effective and potentially curative strategies targeting LSCs to overcome resistance in CML.
Oral Health and Quality of Life in Type 2 Diabetic Patients: Key Findings from a Romanian Study
Authors: Dumitrescu Ramona , Bolchis Vanessa , Popescu Simona , Ivanescu Adriana , Bolos Adrian , Jumanca Daniela , Galuscan Atena
Published: January 2025

Background: Diabetes mellitus is associated with various oral health complications that can negatively impact quality of life. Despite evidence of the relationship between diabetes and oral health issues, limited research exists on the perceptions, behaviors, and oral health-related quality of life (OHRQoL) of diabetic patients in Romania. This study aims to evaluate self-reported oral health, knowledge, behaviors, and OHRQoL among diabetic patients in western Romania. Methods: A cross-sectional study was conducted in early 2024 at Pius Brinzeu County Emergency Hospital, Timisoara, involving 121 patients with type 2 diabetes. Data were collected using self-administered questionnaires that assessed oral health status, behaviors, and OHRQoL, with the OHIP-14 instrument employed for quality-of-life measurement. Statistical analyses included descriptive statistics, multiple linear regression, and correlation analyses to identify the predictors of oral health knowledge and OHRQoL. Results: Participants (mean age: 63.24 years; 52.1% female; 60.5% urban residents) reported significant oral health challenges. Over half (56.2%) did not visit a dentist regularly, with financial constraints identified as the primary barrier (23.5%). Oral hygiene practices were suboptimal: only 38.0% brushed twice daily, while 78.5% used fluoride toothpaste. Auxiliary hygiene tools, such as mouthwash and toothpicks, were rarely used (13.22% and 11.57%, respectively). Regression analyses identified the significant predictors of oral health knowledge, including tooth mobility (β = 0.33, p < 0.01) and brushing frequency (β = −0.18, p < 0.05). The mean OHIP-14 score (0.55) indicated a moderate impact on OHRQoL, with domains such as psychological discomfort and social disability revealing nuanced challenges. Conclusions: Diabetic patients in Romania face oral health challenges and care barriers, emphasizing the need for preventive strategies, oral health education, and integrated diabetes care. Addressing these gaps can improve oral health outcomes and overall quality of life in this vulnerable population.
The Systemic Immune-Inflammation Index and the Risk of Parkinson’s Disease in the U.S.: A Cross-Sectional Study
Authors: Liu Fujun , Ran Qibo , Zhang Huajin , Chen Jing
Published: January 2025

Background: Inflammation is reportedly related to Parkinson’s disease (PD). However, the relationship between the systemic immune-inflammation index (SII) and PD remains unexplored. This study aimed to explore the potential relationship between the SII and PD. Methods: This retrospective cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2003 to 2020. We analyzed patients over 40 years of age after excluding those with missing SII, PD and covariate data. Logistic regression, subgroup analysis, and restricted cubic spline models were subsequently conducted to evaluate the associations between the SII and PD. Results: Finally, 30,638 participants were included in this study, of whom 416 (1.36%) were identified as having PD. Weighted multivariate regression analysis, adjusted for all covariates, revealed that participants with elevated in-transform (SII) values had a higher likelihood of PD [OR 1.39; 95% CI (1.02, 1.91), p = 0.039] compared to those with lower SII values. The fully adjusted restricted cubic spline curve revealed that the SII/100 was positively and linearly associated with the incidence of PD (p for nonlinearity > 0.05). Additionally, subgroup analysis revealed a stronger correlation between the SII and PD in female participants [OR = 1.06, 95% CI (1.03, 1.08)] compared to male participants [OR = 1.02, 95% CI (1.00, 1.03)] (p for interaction = 0.01). Conclusions: The SII showed a positive correlation with the incidence of PD, particularly in females. Further large-scale prospective studies are necessary to confirm these findings and explore the causal factors that may contribute to the early prevention of PD.
Impact of Echocardiographic Cardiac Damage Staging on Mortality and Heart Failure Hospitalizations in Aortic Stenosis Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Parada-Barcia José A. , Barreiro-Pérez Manuel , Baz José Antonio , Estévez-Loureiro Rodrigo , Echarte Julio César , Jiménez-Díaz Victor , Íñiguez-Romo Andrés
Published: January 2025

Background: A significant proportion of elderly patients referred to transcatheter aortic valve replacement (TAVR) do not experience an improvement of their symptoms. New tools are needed to better select candidates and avoid futile procedures. The objective of this study was to evaluate the impact of a new echocardiographic classification which assesses the consequences of chronic elevation of afterload on mortality and hospitalizations for heart failure (HF) in patients with severe AS undergoing TAVR. Methods: This study included 130 high-risk, elderly patients with severe AS who underwent TAVR between January 2018 and December 2019. The patients were classified into three groups according to anatomical and functional features based on transthoracic echocardiography (TTE). The combined end point was death from all causes and HF admissions. Results: Echocardiographic staging was significantly associated with increased rates of death and HF hospitalizations. After multivariate adjustment, the patients with severe cardiac damage exhibited a significant increase in hospitalizations for HF and all-cause mortality (HR 4.79; 95% CI 2.00–11.05; p = 0.000), whereas the moderate cardiac damage group did not (HR 1.84; 95% CI 0.88–3.84; p = 0.104). Conclusions: Echocardiographic staging of severe AS could be a useful tool for predicting HF hospitalizations and all-cause mortality after TAVR in elderly, high-risk patients. Evaluating cardiac damage with this new score may be a promising strategy to better select patients and improve outcomes following TAVR.
Autoimmune Type 1 Diabetes: An Early Approach Appraisal for Spain by the AGORA Diabetes Collaborative Group
Authors: Gómez-Peralta Fernando , Pinés-Corrales Pedro J. , Santos Estefanía , Cuesta Martín , González-Albarrán Olga , Azriel Sharona , Castaño Luis , Mathieu Chantal ,   on behalf of the AGORA Diabetes Collaborative Group
Published: January 2025

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta-cells, leading to lifelong insulin dependence. This review explores the current understanding of T1D pathogenesis, clinical progression, and emerging therapeutic approaches. We examined the complex interplay between genetic predisposition and environmental factors that could trigger the autoimmune response as well as the immunological mechanisms involved in beta-cell destruction. The clinical phases of T1D are discussed from the preclinical stage through diagnosis and long-term management, highlighting the importance of early detection and intervention. Recent advancements in treatment strategies are presented, including immunomodulatory therapies and potential cell-based treatments aimed at preserving or restoring beta-cell function. Additionally, this review critically evaluates the feasibility and potential benefits of implementing a population-wide screening program for T1D in Spain. The epidemiological, economic, and ethical implications of such an initiative were considered by the national expert panel, focusing on the potential of early diagnosis to improve clinical outcomes in the face of the challenges of large-scale implementation. This comprehensive analysis aims to provide healthcare professionals, researchers, and policymakers with valuable insights into the current landscape of T1D management and prospects for enhanced prevention and treatment strategies in the Spanish context.