bluuebunny/crossref_metadata_2025 huggingface dataset:
U.S. college students’ perspectives on contraception and abortion post-Dobbs: the influence of socioeconomic privilege and gender inequity
Authors: Mann Emily S. , McLennan Jessica A. , Broussard Kathleen
Published: January 2024

This study examined college students’ perspectives about contraception and abortion in the context of the United States Supreme Court’s decision to eliminate the constitutional right to abortion in June 2022. Individual, semi-structured interviews were conducted between October 2022 and February 2023 with a convenience sample of 20 college students, ages 18–22, attending a public university in the southeastern United States. Qualitative data analysis revealed three main themes. First, most participants conveyed fear, dismay, and anger about the decision in Dobbs v. Jackson Women’s Health Organization to overturn Roe v. Wade and a few expressed concerns about potential restrictions on contraception. Second, women participants felt heightened pressure to continue or initiate use of a highly effective contraceptive method, with some lamenting inequitable experiences of the gendered contraceptive burden in their relationships with men. Third, when asked what they would do if they or their partner became pregnant while in college, most asserted they would seek abortion. Notably, participants assumed their socioeconomic advantages would ensure their or their partner’s access to abortion, regardless of growing restrictions. The findings illustrate that among a group of relatively privileged young adults, the Dobbs decision simultaneously compelled their increased vigilance regarding contraceptive use and conferred the perception that they would not be personally impacted should they need an abortion.
Prejudice and determinants regarding tuberculosis patients among medical students in Dalian, Northeast China: a cross-sectional study
Authors: Yi Yaohui , Sun Meng , Chen Xu , Pan Yuanping , Lu Jiachen , Yu Yingying , Dou Xiaofeng , Zhou Ling
Published: January 2024

Background

Health workers play a central role in global tuberculosis (TB) elimination efforts. If medical students have prejudiced attitudes toward TB patients, this may make it difficult for them to provide effective health care to TB patients in their future roles as health workers. There is currently no research on prejudice toward TB patients among medical students in China. This study aimed to explore the current status of medical students’ prejudice against patients with TB and its associated predictors.

Methods

We conducted a cross-sectional questionnaire survey among medical students at a medical university in Dalian, Liaoning Province, Northeast China. Multiple logistic regression analysis was employed to determine the predictive factors of medical students’ prejudice against patients with TB.

Results

More than half (57.23%) of the medical students held prejudices against individuals with TB. Multivariate logistic regression analysis revealed that not receiving TB health education (OR: 2.12, 95% CI: 1.35–3.32), not knowing a person with TB (OR: 2.52, 95% CI: 1.39–4.56), and fear of TB/TB patients (OR: 6.79, 95% CI: 4.36–10.56) were identified as risk factors for medical students’ prejudice against TB patients. Conversely, residing in rural areas (OR: 0.60, 95% CI: 0.38–0.95), agreeableness (OR: 0.82, 95% CI: 0.73–0.92) and emotional stability (OR: 0.90, 95% CI: 0.81–1.00) in the Big Five personality traits, and a better understanding of TB knowledge (OR: 0.58, 95% CI: 0.38–0.89) were identified as protective factors.

Conclusion

In China, a considerable number of medical students still exhibit prejudice against patients with TB. Targeted interventions, such as incorporating TB health education into the core curriculum of medical students, and enhance their agreeableness and emotional stability, are still needed. Furthermore, greater focus should be placed on medical students from urban backgrounds or those who harbor fear or do not know a person with TB.
Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration
Authors: Mariscal-Aguilar Pablo , Gómez-Carrera Luis , Bonilla Gema , Díaz-Almirón Mariana , Gayá Francisco , Carpio Carlos , Zamarrón Ester , Fernández-Velilla María , Torres Isabel , Esteban Isabel , Regojo Rita , Villamañán Elena , Prados Concepción , Álvarez-Sala Rodolfo
Published: January 2024

Introduction

Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF).

Aim

This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF.

Methods

This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 μM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment.

Results

There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01–1.33] and OR and 95% CI = 1.80 [1.07–3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01–2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33–3.44], OR and 95% CI = 1.76 [1.15–2.66] and OR and 95% CI = 1.16 [1.03–1.3], respectively).

Conclusion

This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.
Feasibility and accuracy of targeted axillary dissection in breast cancer patients; single center experience
Authors: Kaya Cemal , Burcu Büşra , Çetinoğlu Işık , Uçak Ramazan , Çerekçi Esma , Şahin Cennet , Demircioğlu Zeynep Gül , Şener Aziz , Halil Süleyman
Published: January 2024

Introduction

Axillary complete response (pCR) was observed in approximately half of breast cancer patients who received neoadjuvant chemotherapy (NAC) due to axillary positivity. Preventing axillary morbidity due to unnecessary axillary lymph node dissection (ALND) is extremely important for patients' quality of life. Targeted axillary dissection (TAD) is a technique developed to improve axillary staging and reduce the false negative rate in sentinel lymph node biopsy.

Methods

Patients with cN1-N2 (clinically node) breast cancer whose axillary lymph node metastasis was confirmed by biopsy and who received NAC marked with a clip were included in the study. Patients who achieved clinical response after systemic treatment underwent sentinel lymph node biopsy (SLNB) with additional methods such as methylene blue guided dissection, skin marking for clip on lymph node (CLN) localization, and wire guided with imaging excision of the CLN. TAD and ALND pathology results were evaluated and analyzed with patient and tumor characteristics.

Results

83 patients who met the eligibility criterias for the study were examined retrospectively. 21 of the patients underwent TAD alone, and 62 patients underwent ALND after TAD. CLN rate was 98.8% in patients underwent only TAD and this rate was increased to 100% in patients underwent ALND after TAD. FNR in SLN, CLN, and TAD were 28.6%, 10.7%, and 3.6%, respectively.

Conclusion

TAD is a feasible and reliable surgical approach to detect axillary residual disease with a high success rate.
Brain-derived neurotrophic factor (BDNF): an effect biomarker of neurodevelopment in human biomonitoring programs
Authors: Rodríguez-Carrillo Andrea , Verheyen Veerle J. , Van Nuijs Alexander L. N. , Fernández Mariana F. , Remy Sylvie
Published: January 2024

The present narrative review summarizes recent findings focusing on the role of brain-derived neurotrophic factor (BDNF) as a biomarker of effect for neurodevelopmental alterations during adolescence, based on health effects of exposure to environmental chemical pollutants. To this end, information was gathered from the PubMed database and the results obtained in the European project Human Biomonitoring for Europe (HBM4EU), in which BDNF was measured at two levels of biological organization: total BDNF protein (serum) and BDNF gene DNA methylation (whole blood) levels. The obtained information is organized as follows. First, human biomonitoring, biomarkers of effect and the current state of the art on neurodevelopmental alterations in the population are presented. Second, BDNF secretion and mechanisms of action are briefly explained. Third, previous studies using BDNF as an effect biomarker were consulted in PubMed database and summarized. Finally, the impact of bisphenol A (BPA), metals, and non-persistent pesticide metabolites on BDNF secretion patterns and its mediation role with behavioral outcomes are addressed and discussed. These findings were obtained from three pilot studies conducted in HBM4EU project. Published findings suggested that exposure to some chemical pollutants such as fine particle matter (PM), PFAS, heavy metals, bisphenols, and non-persistent pesticides may alter circulating BDNF levels in healthy population. Therefore, BDNF could be used as a valuable effect biomarker to investigate developmental neurotoxicity of some chemical pollutants.
Influence of repeated estrus synchronization treatment on hormone secretion, growth, and development of dairy goats
Authors: Sun Shuang , Lv Ming , Niu Huimin , Luo Jun
Published: January 2024

In large-scale intensive farms, dairy goats often undergo frequent estrus synchronization (ES) treatment, which may result in a decline in reproductive performance; however, the underlying mechanism remains unclear. The present study aimed to investigate the effect of pregnant mare serum gonadotropin (PMSG) and progesterone (P4)-mediated ES treatment on fertility in dairy goats, while also identifying key metabolic and endocrine mechanisms that influence reproductive performance in does subjected to repeated ES treatment. Forty-eight Saanen does were randomly assigned to two groups (24 goats each) that received ES treatments either thrice fortnightly (3-PMSG) or once (1-PMSG) simultaneously with the third ES treatment of the 3-PMSG group during the breeding season. ES treatment was performed via the intravaginal insertion of a controlled internal drug release (CIDR) device impregnated with 300 mg P4, followed by 300 IU PMSG injections 48 h before CIDR withdrawal. Blood was collected to detect the level of hormones and blood biochemical indices. Additionally, estrus rate, fecundity rate, body weight, size, and lactation performance were measured. The results showed that repeated ES treatment markedly decreased the estrus rate and fecundity rate of goats. Among the does in all groups, there was no substantial difference in follicle stimulating hormone, luteinising hormone, gonadotropin-releasing hormone, melatonin, growth hormone, PMSG, total cholesterol, total protein, and glucose levels, as well as the body weight, body size, and lactation performance. Repeated ES treatment elevated estrogen (E2) levels 36, 48, and 72 h post-CIDR removal; increased P4 upon CIDR insertion; and raised PMSG antibody levels 24, 48, and 72 h post-CIDR removal. The results suggest that elevated anti-PMSG levels are the primary reason for the decline in ES efficiency, and that high E2 and P4 levels at some time points also impair reproductive performance. These findings provide novel insights into the metabolic effects of repeated PMSG stimulation in goats, guiding future reproductive hormone use in breeding practices.
Plastinate Library: A Tool to Support Veterinary Anatomy Learning
Authors: Senos Rafael
Published: January 2024

The shortage of both time for anatomy courses in the new veterinary medicine curriculum and instructors prepared to teach biomedical sciences has raised a crisis in anatomical education. Often, students spend time out of their classes trying to learn not only concepts but also laboratory-wise content from 2D materials such as books and videos. In addition, since the global COVID-19 pandemic lockdown, studying and habits have been reviewed, with many people adopting an at-home style. The purpose of this study was to evaluate students’ acceptance of taking plastinate anatomical specimens to study at home. Thirty-three students were divided into three groups. G1 took home a set of kidneys composed of equine, bovine, and swine materials; G2 took home a pig kidney; and G3 (control) did not take any plastinate specimen home. Acceptance was assessed using an anonymous survey and interview. The method had high acceptance by the students, who believed that having the plastinate library was advantageous from different perspectives, including aiding with learning the differences between kidneys from different species, time flexibility, no commute to study after hours of laboratory classes, and time redistribution to prioritize the laboratory topics. The plastinate library has the potential to be a supportive tool for anatomy students in the contemporaneous veterinary curriculum paradigm, considering that the G1 and G2 groups used the plastinate specimens at home to complement the time they spent in the laboratory.
The Screening and Mechanism of Influenza-Virus Sensitive MDCK Cell Lines for Influenza Vaccine Production
Authors: Yang Zhaona , Yu Shouzhi , Xu Ying , Zhao Yuxiu , Li Lili , Sun Jingjie , Wang Xin , Guo Yancen , Zhang Yuntao
Published: January 2024

Influenza is a potentially fatal acute respiratory viral disease caused by the influenza virus. Influenza viruses vary in antigenicity and spread rapidly, resulting in seasonal epidemics. Vaccination is the most effective strategy for lowering the incidence and fatality rates of influenza-related disorders, and it is also an important method for reducing seasonal influenza infections. Mammalian Madin–Darby canine kidney (MDCK) cell lines are recommended for influenza virus growth, and such cell lines have been utilized in several commercial influenza vaccine productions. The limit dilution approach was used to screen ATCC-MDCK cell line subcellular strains that are especially sensitive to H1N1, H3N2, BV, and BY influenza viruses to increase virus production, and research on influenza virus culture media was performed to support influenza virus vaccine development. We also used RNA sequencing to identify differentially expressed genes and a GSEA analysis to determine the biological mechanisms underlying the various levels of susceptibility of cells to influenza viruses. MDCK cell subline 2B6 can be cultured to increase titer and the production of the H1N1, H3N2, BV, and BY influenza viruses. MDCK-2B6 has a significantly enriched and activated in ECM receptor interaction, JAK-STAT signaling, and cytokine receptor interaction signaling pathways, which may result in increased cellular susceptibility and cell proliferation activity to influenza viruses, promote viral adsorption and replication, and elevate viral production, ultimately. The study revealed that MDCK-2B6 can increase the influenza virus titer and yield in vaccine production by increasing cell sensitivity and enhancing proliferative activity.
The Green Mirage: The EU’s Complex Relationship with Palm Oil Biodiesel in the Context of Environmental Narratives and Global Trade Dynamics
Authors: Waters Keith , Altiparmak Suleyman O. , Shutters Shade T. , Thies Cameron
Published: January 2024

In the early 2000s, biofuels like biodiesel and bioethanol were seen as renewable alternatives to petroleum, driven by rising crude oil prices and environmental concerns. Palm oil became a key biodiesel raw material, turning the European Union (EU) into a major importer. However, sustainable palm oil concerns emerged in the EU in 2014, leading to trade disputes and import restrictions, with a goal to phase out palm oil biodiesel by 2030. This research explores the EU’s palm oil biodiesel policy impact, focusing on key producers, EU imports (crude and refined palm oil, biodiesel), the EU’s role in the global biodiesel network, and alignment with a green narrative. Analyzing trade data, we find that, despite concerns, the EU has not significantly reduced palm oil-related imports, highlighting the market’s complex relationship to policy. This suggests that the EU’s commitment to environmentally sustainable economic development may not align with market stakeholders’ preferences, emphasizing the complex interdependencies between the global biodiesel market and policy areas like sustainability, economy, energy, and environment.
Managing BEV Charge to Obtain a Positive Impact on a National Power System
Authors: Barsali Stefano , Ceraolo Massimo , Pasini Gianluca , Poli Davide
Published: January 2024

This paper’s research question is to evaluate the potential impact of large numbers of battery electric vehicles (BEVs) on the future electric grid, and whether the flexibility of BEV charging can induce enough system benefits to remunerate BEV users for the change in their recharging pattern. The considered scenario refers to the Italian situation and what might occur through the year 2040, where a share of BEV stock of 40% can be foreseen, as well as significant increases in PV and wind generation. Although this study is focused on Italy, its results are applicable, with minor differences, to several EU countries. This paper first shows that the future impact of increasing penetration of BEVs appears to be compatible with the expected growth of generation from renewable energy sources (RES) and the corresponding reduction in fossil fuel-based generation. It also gives an estimate of the CO2 emission reduction resulting from these changes, considering an unmanaged BEV charge profile and two different managed profiles that shift the car’s charging period to hours of the day when they have no negative impact on the grid and maximize the utilization of RES. Finally, it shows an evaluation of the economic benefits of displacing private car charging ranging from 4 to 10 cEUR/kWh, which could be used as tariff incentives to stimulate this displacing in recharging time.
The Microbial Diversity on the Surface of Smear-Ripened Cheeses and Its Impact on Cheese Quality and Safety
Authors: Ritschard Jasmine S. , Schuppler Markus
Published: January 2024

Smear-ripened cheeses are characterized by a viscous, red-orange surface smear on their rind. It is the complex surface microbiota on the cheese rind that is responsible for the characteristic appearance of this cheese type, but also for the wide range of flavors and textures of the many varieties of smear-ripened cheeses. The surface smear microbiota also represents an important line of defense against the colonization with undesirable microorganisms through various types of interaction, such as competitive exclusion or production of antimicrobial substances. Predominant members of the surface smear microbiota are salt-tolerant yeast and bacteria of the phyla Actinobacteria, Firmicutes, and Proteobacteria. In the past, classical culture-based approaches already shed light on the composition and succession of microorganisms and their individual contribution to the typicity of this cheese type. However, during the last decade, the introduction and application of novel molecular approaches with high-resolution power provided further in-depth analysis and, thus, a much more detailed view of the composition, structure, and diversity of the cheese smear microbiota. This led to abundant novel knowledge, such as the identification of so far unknown community members. Hence, this review is summarizing the current knowledge of the diversity of the surface smear microbiota and its contribution to the quality and safety of smear-ripened cheese. If the succession or composition of the surface-smear microbiota is disturbed, cheese smear defects might occur, which may promote food safety issues. Hence, the discussion of cheese smear defects in the context of an increased understanding of the intricate surface smear ecosystem in this review may not only help in troubleshooting and quality control but also paves the way for innovations that can lead to safer, more consistent, and higher-quality smear-ripened cheeses.
An Epidemic Model with Infection Age and Vaccination Age Structure
Authors: Webb Glenn , Zhao Xinyue Evelyn
Published: January 2024

A model of epidemic dynamics is developed that incorporates continuous variables for infection age and vaccination age. The model analyzes pre-symptomatic and symptomatic periods of an infected individual in terms of infection age. This property is shown to be of major importance in the severity of the epidemic, when the infectious period of an infected individual precedes the symptomatic period. The model also analyzes the efficacy of vaccination in terms of vaccination age. The immunity to infection of vaccinated individuals varies with vaccination age and is also of major significance in the severity of the epidemic. Application of the model to the 2003 SARS epidemic in Taiwan and the COVID-19 epidemic in New York provides insights into the dynamics of these diseases. It is shown that the SARS outbreak was effectively contained due to the complete overlap of infectious and symptomatic periods, allowing for the timely isolation of affected individuals. In contrast, the pre-symptomatic spread of COVID-19 in New York led to a rapid, uncontrolled epidemic. These findings underscore the critical importance of the pre-symptomatic infectious period and the vaccination strategies in influencing the dynamics of an epidemic.
Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3R451C Mouse Model of Autism
Authors: Hosie Suzanne , Abo-Shaban Tanya , Mou Kevin , Balasuriya Gayathri K. , Mohsenipour Mitra , Alamoudi Mohammed U. , Filippone Rhiannon T. , Belz Gabrielle T. , Franks Ashley E. , Bornstein Joel C. , Nurgali Kulmira , Hill-Yardin Elisa L.
Published: January 2024

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABAA antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.
Rapid Detection of the Strawberry Foliar Nematode Aphelenchoides fragariae Using Recombinase Polymerase Amplification Assay with Lateral Flow Dipsticks
Authors: Subbotin Sergei A.
Published: January 2024

Rapid and reliable diagnostic methods for plant-parasitic nematodes are critical for facilitating the selection of effective control measures. A diagnostic recombinase polymerase amplification (RPA) assay for Aphelenchoides fragariae using a TwistAmp® Basic Kit (TwistDx, Cambridge, UK) and AmplifyRP® Acceler8® Discovery Kit (Agdia, Elkhart, IN, USA) combined with lateral flow dipsticks (LF) has been developed. In this study, a LF-RPA assay was designed that targets the ITS rRNA gene of A. fragariae. This assay enables the specific detection of A. fragariae from crude nematode extracts without a DNA extraction step, and from DNA extracts of plant tissues infected with this nematode species. The LF-RPA assay showed reliable detection within 18–25 min with a sensitivity of 0.03 nematode per reaction tube for crude nematode extracts or 0.3 nematode per reaction tube using plant DNA extracts from 0.1 g of fresh leaves. The LF-RPA assay was developed and validated with a wide range of nematode and plant samples. Aphelenchoides fragariae was identified from seed samples in California. The LF-RPA assay has great potential for nematode diagnostics in the laboratory with minimal available equipment.
Effect of a New Substance with Pyridoindole Structure on Adult Neurogenesis, Shape of Neurons, and Behavioral Outcomes in a Chronic Mild Stress Model in Rats
Authors: Zvozilova Alexandra , Reichova Alexandra , Mach Mojmir , Bakos Jan , Koprdova Romana
Published: January 2024

Despite an accumulating number of studies, treatments for depression are currently insufficient. Therefore, the search for new substances with antidepressant potential is very important. In this study, we hypothesized that treatment with a newly synthesized pyridoindole derivative compound SMe1EC2M3 would result in protective and antidepressant-like effects on behavioral outcomes and reverse the impaired adult hippocampal neurogenesis caused by chronic mild stress (CMS). We found that chronic administration of 5 mg/kg and 25 mg/kg SMe1EC2M3 to adult Sprague Dawley rats ameliorated the consequences of CMS on immobility and swimming time in a forced swim test. A slight sedative effect of the highest dose of SMe1EC2M3 in the nonstress group was observed in the open field. SMe1EC2M3 in the highest dose ameliorated CMS-induced decreases in the sucrose preference test. Administration of SMe1EC2M3 significantly increased SOX2-positive cells in the hippocampal dentate gyrus (DG) in CMS compared to control animals. A significant reduction in glial fibrillary acid protein (GFAP)-positive cells in the DG of CMS compared to control animals was observed. Administration of both 5 and 25 mg/kg SMe1EC2M3 significantly increased signal of GFAP-positive cells in the DG of CMS animals. No such effects of SMe1EC2M3 were observed in the cornu ammonis hippocampal area. Additionally, we found that incubation of primary hippocampal neurons in the presence of 1.50 µM SMe1EC2M3 significantly stimulated the length of neurites. Overall, we found that the negative effects of CMS on depression-like behavior are partially reduced by the administration of SMe1EC2M3 and are associated with changes in hippocampal neurogenesis and neuronal differentiation. SMe1EC2M3 represents a potential drug candidate with positive neuroplastic effects and neurogenesis-associated effects in therapeutic approaches to depression.
Shining a Spotlight on Methyl Groups: Photochemically Induced Dynamic Nuclear Polarization Spectroscopy of 5-Deazariboflavin and Its Nor Analogs
Authors: Panter Sabrina , Ayekoi Audrey , Tesche Jannis , Chen Jing , Illarionov Boris , Bacher Adelbert , Fischer Markus , Weber Stefan
Published: January 2024

5-Deazaflavins are analogs of naturally occurring flavin cofactors. They serve as substitutes for natural flavin cofactors to investigate and modify the reaction pathways of flavoproteins. Demethylated 5-deazaflavins are potential candidates for artificial cofactors, allowing us to fine-tune the reaction kinetics and absorption characteristics of flavoproteins. In this contribution, demethylated 5-deazariboflavin radicals are investigated (1) to assess the influence of the methyl groups on the electronic structure of the 5-deazaflavin radical and (2) to explore their photophysical properties with regard to their potential as artificial cofactors. We determined the proton hyperfine structure of demethylated 5-deazariboflavins using photochemically induced dynamic nuclear polarization (photo-CIDNP) spectroscopy, as well as density functional theory (DFT). To provide context, we compare our findings to a study of flavin mononucleotide (FMN) derivatives. We found a significant influence of the methylation pattern on the absorption properties, as well as on the proton hyperfine coupling ratios of the xylene moiety, which appears to be solvent-dependent. This effect is enhanced by the replacement of N5 by C5-H in 5-deazaflavin derivatives compared to their respective flavin counterparts.
Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds
Authors: Limido Ettore , Weinzierl Andrea , Ampofo Emmanuel , Harder Yves , Menger Michael D. , Laschke Matthias W.
Published: January 2024

The treatment of wounds using the body’s own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP− vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.
Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease
Authors: Ponce-de-León Candelaria , Lorite Pedro , López-Casado Miguel Ángel , Mora Pablo , Palomeque Teresa , Torres María Isabel
Published: January 2024

We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200–CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.
Therapeutic Potential of a Novel Lytic Phage, vB_EclM_ECLFM1, against Carbapenem-Resistant Enterobacter cloacae
Authors: Ali Saieeda Fabia , Teh Soon-Hian , Yang Hsueh-Hui , Tsai Yun-Chan , Chao Huei-Jen , Peng Si-Shiuan , Chen Shu-Chen , Lin Ling-Chun , Lin Nien-Tsung
Published: January 2024

The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-β-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by scarce resources and insufficient genomic data. In this study, we isolated ECLFM1, a novel E. cloacae phage, from sewage water using a carbapenem-resistant clinical strain as the host. ECLFM1 exhibited rapid adsorption and a 15-min latent period, with a burst size of approximately 75 PFU/infected cell. Its genome, spanning 172,036 bp, was characterized and identified as a member of Karamvirus. In therapeutic applications, owing to a high multiplicity of infection, ECLFM1 showed increased survival in zebrafish infected with E. cloacae. This study highlights ECLFM1’s potential as a candidate for controlling clinical E. cloacae infections, which would help address challenges in treating multidrug-resistant strains and contribute to the development of alternative treatments.
Inhibition of Caspase 1 Reduces Blood Pressure, Cytotoxic NK Cells, and Inflammatory T-Helper 17 Cells in Placental Ischemic Rats
Authors: Shields Corbin A. , Tardo Geilda A. , Wang Xi , Peacock Gregory , Robbins Marcus , Glenn Hannah , Wilson Rachel , Williams Jan M. , Cornelius Denise C.
Published: January 2024

Preeclampsia (PE) is characterized by maternal hypertension, fetal growth restriction (FGR), and increased inflammation and populations of cytotoxic NK cells (cNKs) and inflammatory T-Helper 17 cells (TH17s). Both cytotoxic NK cells and TH17 cells are heavily influenced via IL-1β signaling. Caspase 1 activity leads to the release of the inflammatory cytokine IL-1β, which is increased in women with PE. Therefore, we tested the hypothesis that the inhibition of Caspase 1 with VX-765 in rats with reduced uterine perfusion pressure (RUPP) will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant Sprague–Dawley rats underwent the RUPP or Sham procedure and were separated into groups that received either vehicle or VX-765 (50 mg/kg/day i.p.). On GD19, MAP was measured via carotid catheter and blood and tissues were collected. Bio-Plex and flow cytometry analysis were performed on placental tissues. Placental IL-1β was increased in the RUPP rats vs. the Sham rats and treatment with VX-765 reduced IL-1β in the RUPP rats. Caspase 1 inhibition reduced placental cNKs and TH17s in RUPP rats compared to vehicle-treated RUPP rats. Increased MAP was observed in RUPP rats compared with Sham rats and was reduced in RUPP + VX-765 rats. Placental reactive oxygen species (ROS) were elevated in RUPP rats compared to Sham rats. VX-765 administration reduced ROS in treated RUPP rats. Caspase 1 inhibition increased the number of live pups, yet had no effect on fetal weight or placental efficiency in the treated groups. In conclusion, Caspase 1 inhibition reduces placental IL-1β, inflammatory TH17 and cNK populations, and reduces MAP in RUPP rats. These data suggest that Caspase 1 is a key contributor to PE pathophysiology. This warrants further investigation of Caspase 1 as a potential therapeutic target to improve maternal outcomes in PE.
Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening
Authors: Timofeeva Angelika V. , Fedorov Ivan S. , Suhova Yuliya V. , Tarasova Alla M. , Ezhova Larisa S. , Zabelina Tatyana M. , Vasilchenko Oksana N. , Ivanets Tatyana Y. , Sukhikh Gennady T.
Published: January 2024

Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial–myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening. miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profiles in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or pre-eclampsia, were obtained using deep sequencing. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p, quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset pre-eclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to data from the literature, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for first-trimester screening of pregnant women, subject to validation with independent test samples.
Involvement of Yes-Associated Protein 1 Activation in the Matrix Degradation of Human-Induced-Pluripotent-Stem-Cell-Derived Chondrocytes Induced by T-2 Toxin and Deoxynivalenol Alone and in Combination
Authors: Liu Li , Liu Huan , Meng Peilin , Zhang Yanan , Zhang Feng’e , Jia Yumeng , Cheng Bolun , Lammi Mikko J. , Zhang Feng , Guo Xiong
Published: January 2024

T-2 toxin and deoxynivalenol (DON) are two prevalent mycotoxins that cause cartilage damage in Kashin–Beck disease (KBD). Cartilage extracellular matrix (ECM) degradation in chondrocytes is a significant pathological feature of KBD. It has been shown that the Hippo pathway is involved in cartilage ECM degradation. This study aimed to examine the effect of YAP, a major regulator of the Hippo pathway, on the ECM degradation in the hiPS-derived chondrocytes (hiPS-Ch) model of KBD. The hiPS-Ch injury models were established via treatment with T-2 toxin/DON alone or in combination. We found that T-2 toxin and DON inhibited the proliferation of hiPS-Ch in a dose-dependent manner; significantly increased the levels of YAP, SOX9, and MMP13; and decreased the levels of COL2A1 and ACAN (all p values < 0.05). Immunofluorescence revealed that YAP was primarily located in the nuclei of hiPS-Ch, and its expression level increased with toxin concentrations. The inhibition of YAP resulted in the dysregulated expression of chondrogenic markers (all p values < 0.05). These findings suggest that T-2 toxin and DON may inhibit the proliferation of, and induce the ECM degradation, of hiPS-Ch mediated by YAP, providing further insight into the cellular and molecular mechanisms contributing to cartilage damage caused by toxins.
Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review
Authors: Serrano Quentin A. , Le Garf Sébastien , Martin Vincent , Colson Serge S. , Chevalier Nicolas
Published: January 2024

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs’ adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis, and gut microbiota dysbiosis, that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery, where weight loss promotes POPs’ blood release.
The Role of Intracellular Potassium in Cell Quiescence, Proliferation, and Death
Authors: Marakhova Irina I. , Yurinskaya Valentina E. , Domnina Alisa P.
Published: January 2024

This brief review explores the role of intracellular K+ during the transition of cells from quiescence to proliferation and the induction of apoptosis. We focus on the relationship between intracellular K+ and the growth and proliferation rates of different cells, including transformed cells in culture as well as human quiescent T cells and mesenchymal stem cells, and analyze the concomitant changes in K+ and water content in both proliferating and apoptotic cells. Evidence is discussed indicating that during the initiation of cell proliferation and apoptosis changes in the K+ content in cells occur in parallel with changes in water content and therefore do not lead to significant changes in the intracellular K+ concentration. We conclude that K+, as a dominant intracellular ion, is involved in the regulation of cell volume during the transit from quiescence, and the content of K+ and water in dividing cells is higher than in quiescent or differentiated cells, which can be considered to be a hallmark of cell proliferation and transformation.
Isolation and Characterization of Antimicrobial Metabolites from the Sophora tonkinensis-Associated Fungus Penicillium sp. GDGJ-N37
Authors: Huang Lili , Li Yongxia , Pang Jing , Lv Liuxia , Zhou Jiatong , Liang Liqi , He Xianhua , Li Jun , Xu Weifeng , Yang Ruiyun
Published: January 2024

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3–6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.
Minimizing Fuel Consumption for Surveillance Unmanned Aerial Vehicles Using Parallel Particle Swarm Optimization
Authors: Roberge Vincent , Labonté Gilles , Tarbouchi Mohammed
Published: January 2024

This paper presents a method based on particle swarm optimization (PSO) for optimizing the power settings of unmanned aerial vehicle (UAVs) along a given trajectory in order to minimize fuel consumption and maximize autonomy during surveillance missions. UAVs are widely used in surveillance missions and their autonomy is a key characteristic that contributes to their success. Providing a way to reduce fuel consumption and increase autonomy provides a significant advantage during the mission. The method proposed in this paper included path smoothing techniques in 3D for fixed-wing UAVs based on circular arcs that overfly the waypoints, an essential feature in a surveillance mission. It used the equations of motions and the decomposition of Newton’s equation to compute the fuel consumption based on a given power setting. The proposed method used PSO to compute optimized power settings while respecting the absolute physical constraints, such as the load factor, the lift coefficient, the maximum speed and the maximum amount of fuel onboard. Finally, the method was parallelized on a multicore processor to accelerate the computation and provide fast optimization of the power settings in case the trajectory was changed in flight by the operator. Our results showed that the proposed PSO was able to reduce fuel consumption by up to 25% in the trajectories tested and the parallel implementation provided a speedup of 21.67× compared to a sequential implementation on the CPU.