bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Super-Flexible Silica Aerogel and Its Application in Oil–Water Separation
Authors: Li Linghan , Xu Tianci , Zhang Faping , Du Chunhua , He Song
Published: September 2023

Using silica as the precursor, and methyltrimethoxysilane and dimethyldimethoxysilane as the silicon sources, a super-flexible hydrophobic lipophilic gel solid was prepared via hydrolysis, drying, solvent replacement, and atmospheric-pressure drying. The characterization test showed that the sample had good flexibility, hydrophobicity, an amorphous structure, and a hydrophobic contact angle of 137°. Through the adsorption separation experiment, it was concluded that the adsorption separation rate of aerogel to oil substances is related to the viscosity of the oil substances. The hydrophobic and oleophilic properties of flexible silicon aerogel materials can be applied to many aspects, such as crude oil leakage and kitchen waste oil recovery, with broad future development prospects and great research significance.
Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair
Authors: Zheng Jianuo , Wang Yunping , Wang Yuwen , Duan Ruiping , Liu Lingrong
Published: September 2023

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment.
Editorial for Special Issue: Gel Films and Coatings Applied in Active Food Packaging
Authors: Giannakas Aris E.
Published: September 2023

Nowadays, the global trends of bioeconomy and sustainability require the use of biobased raw materials in all scientific and application fields to reduce the global carbon dioxide fingerprint [...]
The Conserved Chromatin Remodeler SMARCAD1 Interacts with TFIIIC and Architectural Proteins in Human and Mouse
Authors: Sachs Parysatis , Bergmaier Philipp , Treutwein Katrin , Mermoud Jacqueline E.
Published: September 2023

In vertebrates, SMARCAD1 participates in transcriptional regulation, heterochromatin maintenance, DNA repair, and replication. The molecular basis underlying its involvement in these processes is not well understood. We identified the RNA polymerase III general transcription factor TFIIIC as an interaction partner of native SMARCAD1 in mouse and human models using endogenous co-immunoprecipitations. TFIIIC has dual functionality, acting as a general transcription factor and as a genome organizer separating chromatin domains. We found that its partnership with SMARCAD1 is conserved across different mammalian cell types, from somatic to pluripotent cells. Using purified proteins, we confirmed that their interaction is direct. A gene expression analysis suggested that SMARCAD1 is dispensable for TFIIIC function as an RNA polymerase III transcription factor in mouse ESCs. The distribution of TFIIIC and SMARCAD1 in the ESC genome is distinct, and unlike in yeast, SMARCAD1 is not enriched at active tRNA genes. Further analysis of SMARCAD1-binding partners in pluripotent and differentiated mammalian cells reveals that SMARCAD1 associates with several factors that have key regulatory roles in chromatin organization, such as cohesin, laminB, and DDX5. Together, our work suggests for the first time that the SMARCAD1 enzyme participates in genome organization in mammalian nuclei through interactions with architectural proteins.
Magnetic Fabric and Paleomagnetic Analyses of the Zaghar and Tafresh Areas, Central Urumieh-Dokhtar Magmatic Arc, Iran
Authors: Sheibi Maryam , Rahimi Nima , Rochette Pierre , Demory François , Mirnejad Hassan
Published: September 2023

Magnetic fabric, paleomagnetic, and petrophysical studies were conducted on rocks in the Tafresh area of the central Urumieh-Dokhtar magmatic arc in Iran. The samples included Late Triassic dark gray sandstone, a mafic dyke, diorites, and a felsic dyke in the Zaghar region. Hydrothermal alteration in the Spid intrusion was investigated to understand the effects of alteration on magnetic fabric patterns. The AMS measurements support the theory that the Nayband Formation was constructed under a crustal extension regime. Magnetic susceptibility anisotropy in a microdioritic dyke indicates compression from the NNE-SSW, likely due to tectonic activity. AMS results from diorites in Zaghar suggest intrusions were emplaced in extensional spaces between the Tafresh and Chaghar thrust faults. The Spid intrusion’s magnetite is the primary carrier of magnetic susceptibility, but hydrothermal alteration has partly converted it into hematite, resulting in lower susceptibility and higher porosity in altered diorites. This process leads to a bimodal distribution of magnetic lineation trends. The Spid and Zaghar massifs underwent a northward tilt of about 30 degrees around an east-west axis following the Early Miocene. Post-Eocene rotations in the area are typically within ±20 degrees. This study demonstrates how magnetic properties can provide new insights into the evolution of tectono-magmatic processes and structural controls within a magmatic arc.
Conservation and Education in Spanish Geoparks: Exploratory Analysis of Land Stewardship Experiences and Valuation Proposal through Outdoor Education
Authors: Iranzo-García Emilio , Hueso-Kortekaas Katia , Fansa-Saleh Ghaleb
Published: September 2023

Advances in research on environmental problems and public awareness of them have led to renewed concern about the need to establish mechanisms and figures to protect and manage sites so that geoecological processes remain outside the dynamics of anthropic occupation. This research has been approached from an inductive and qualitative perspective based on case studies to examine the articulation of the Spanish geoparks, their dynamics, and the experiences of private valorization in them. Geological heritage is seen as a lever for the promotion of the territory. In all cases, although the geological–geomorphological–paleontological–environmental resources must be significant, this designation aims to enhance the value of all assets, both natural and cultural, conceiving the geopark not as a figure of environmental protection but as a “figure to promote local development”. A total of 48 land stewardship initiatives were identified in 11 of the 15 Spanish geoparks. The most significant presence of initiatives was found in the geoparks of Catalonia, followed by the Lanzarote Geopark. No nature-based schools are located within geoparks, except for Wild Me in Central Catalonia. However, the presence of nature-based schools in biosphere reserves (BRs) seems to be more common. Framing alternative proposals, such as nature-based schools in these areas and using land stewardship in their operation, can become an opportunity to protect a region’s geological and cultural heritage and improve local communities’ quality of life through sustainable and responsible economic and tourism activities. Early-years education in the natural environment facilitates the acquisition of long-term pro-environmental skills, competencies, and behaviors that last into adulthood and act as multipliers for others.
Promoting Respectful Maternity Care by Reducing Unnecessary Episiotomies: Experiences from Centers of Excellence for Breastfeeding in Vietnam
Authors: Vu Duong Hoang , Ta Binh T. T. , Aasen Ina Landau , Le Dai Q. T. , Mathisen Roger , Becker Genevieve E. , Phan Hang Thi , Bui Cuong Minh , Nguyen Trinh Thi Kieu , Hoang Suong Thi Thu , Cashin Jennifer
Published: September 2023

(1) Background: Routine episiotomy is not recommended by international guidelines; however, it occurs at a high rate in Vietnam. (2) Methods: A process to reduce unnecessary episiotomies was developed and implemented as part of the Centers of Excellence for Breastfeeding initiative, which aims to deliver high-quality breastfeeding and early essential newborn care services within a supportive policy environment. The aim of this project report is to outline the steps undertaken to reduce episiotomies, the experience in pilot hospitals, and the process towards changing policy. (3) Results: During the 14 months following the change in episiotomy policy, pilot hospital records showed no infant death or injury. Monthly monitoring data from four pilot hospitals showed that the prevalence of episiotomy was substantially lower than the average in national hospitals in Vietnam. Facilitators to reducing the episiotomy rate include the incentive of Centers of Excellence for Breastfeeding designation and supportive hospital leadership. Challenges include the ambiguity of Vietnam’s national guideline on episiotomy and lack of routine monitoring on the episiotomy rate and indications. (4) Discussion: Our experience suggests that through training and routine monitoring hospitals can apply a policy of selective episiotomy and reduce the practice, particularly among multiparous women, and improve breastfeeding rates.(5) Conclusions: Sharing our experience of implementing this process and offering four areas for action will hopefully contribute to expanded use of mother-friendly, evidence-based care as policy and routine practice in Vietnam and similar settings.
Describing Trends in Maternal Mortality in the State of São Paulo, Brazil, from 2009 to 2019
Authors: da Silva Bueno Luciane Amorim , Ribeiro Mariane Albuquerque Lima , Martins Camila Bertini , de Abreu Luiz Carlos , de Almeida Alvaro Dantas , Correa João Antonio
Published: September 2023

Background: Maternal mortality is a significant public health concern, with varying impacts across different regions in Brazil, particularly affecting women from lower-income social classes with limited access to social resources. The aim of this study is to describe the trends in maternal mortality in São Paulo, Brazil, from 2009 to 2019. Materials and Methods: This study employed an ecological approach utilizing a time-series design to examine maternal deaths. Secondary data from the Mortality Information System (SIM) and the Live Births Information System (SINASC) from 2009 to 2019 were utilized. The analysis included all maternal deaths among women aged 10 to 49 years residing in the state of São Paulo. Time-series data for maternal mortality ratios were constructed for the seven regions within São Paulo State. Joinpoint regression analysis was applied to characterize the maternal mortality ratio. The study estimated the annual percentage variation, the average annual percentage variation, and their respective 95% confidence intervals. Results: In São Paulo, a total of 3075 maternal deaths were reported, resulting in a mortality ratio of 45.9 deaths per 100,000 live births. The leading causes of maternal death were eclampsia (7.13%), gestational hypertension (6.09%), and postpartum hemorrhage (5.89%). The analysis of the annual percentage change in the maternal mortality ratio for São Paulo State and its six clusters showed stationarity. Conclusions: The assessment of the maternal mortality ratio in the state of São Paulo, Greater São Paulo, and Baixada Santista revealed an increase in the maternal death ratio over the studied period.
Exploring Acute Pancreatitis Clinical Pathways Using a Novel Process Mining Method
Authors: Yang Xue , Huang Wei , Zhao Weiling , Zhou Xiaobo , Shi Na , Xia Qing
Published: September 2023

Mining process models of medical behavior from electronic medical records is an effective way to optimize clinical pathways. However, clinical medical behavior is an extremely complex field with high nonlinearity and variability, and thus we need to adopt a more effective method. In this study, we developed a fuzzy process mining method for complex clinical pathways. Firstly, we designed a multi-level expert classification system with fuzzy values to preserve finer details. Secondly, we categorized medical events into long-term and temporary events for more specific data processing. Subsequently, we utilized electronic medical record (EMR) data of acute pancreatitis spanning 9 years, collected from a large general hospital in China, to evaluate the effectiveness of our method. The results demonstrated that our modeling process was simple and understandable, allowing for a more comprehensive representation of medical intricacies. Moreover, our method exhibited high patient coverage (>0.94) and discrimination (>0.838). These findings were corroborated by clinicians, affirming the accuracy and effectiveness of our approach.
Diffuse Large B-Cell Lymphoma of the Frontal Sinus: A Case Report
Authors: Urbanelli Anastasia , Testi Francesca , Riva Giuseppe , Pecorari Giancarlo
Published: September 2023

Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin Lymphoma (NHL). It often involves the gastrointestinal tract, head and neck, and skin, but virtually any tissue or organ can be affected. The primary NHL of the nasal cavity and paranasal sinuses are extremely rare, causing diagnostic and therapeutic difficulties. We present the case of a 49-year-old woman with a 4-week history of diplopia and right superior eyelid swelling. Clinical, radiological, and histological examination led to the diagnosis of DLBCL of the right frontal sinus with anterior invasion of subcutaneous soft tissues and posterior intracranial involvement of the frontal region. She underwent three cycles of MATRIX chemotherapy, three cycles of R-DA-EPOCH, and CAR-T therapy. Unfortunately, treatments were unsuccessful and the patient died 11 months after diagnosis. In conclusion, an early diagnosis of DLBCL of the frontal sinus is difficult as it is often confused with other nasal pathologies. This causes a delay in treatment.
Effects of 1–MCP Treatment on Postharvest Fruit of Five Pomegranate Varieties during Low-Temperature Storage
Authors: Wan Ran , Song Jinhui , Lv Zhenyang , Qi Xingcheng , Feng Zhiliang , Yang Zhenfeng , Cao Xinyue , Shi Jiangli , Jian Zaihai , Tong Ruiran , Hu Qingxia , Chen Yanhui
Published: September 2023

Pomegranate fruit production and consumption are restricted by appropriate postharvest handling practices. 1–MCP (1–methylcyclopropene) is a natural preservative of fruits and vegetables; however, its effects on the storage of different pomegranate varieties have not been extensively investigated. Herein, the effects of 1.0 μL L−1 1–MCP on postharvest pomegranate fruit of three soft-seed ‘Mollar’, ‘Malisi’, and ‘Tunisan soft seed’ and two semi-soft-seed ‘Moyuruanzi’ and ‘Dongyan’ were investigated over 90 d (days) under low-temperature storage at 4 ± 0.5 °C with a relative humidity of 85–90%. Several indexes of exterior and interior quality were recorded, the sensory quality was evaluated, and the respiration and ethylene production were also determined. The results showed that peel browning was generally more severe in the soft-seed varieties than in the semi-soft-seed varieties. Significantly lighter peel browning presented in the three soft-seed fruits from 45 d after the 1–MCP treatment, with 35%, 19%, and 28% less than those controls at 90 d, correspondingly. However, 1–MCP only significantly decreased peel browning in the semi soft-seed fruits at 60 days. A prominent decrease in weight loss was recorded in all five varieties, with ‘Malisi’ showing the largest and ‘Dongyan’ the smallest difference between the 1–MCP and control treatments. Through the results of color, physiological, and chemical changes, as well as sensory properties, better color and total acceptance were found with higher titratable acids and vitamin C but with decreased anthocyanins in most fruits treated with 1–MCP. In contrast to the control, remarkable suppression of ethylene production peaks in all whole fruits and periodical increase in respiration rates in the soft-seed whole fruits were activated at 30–60 d after storage by the 1–MCP treatment, roughly when peel browning occurred and began increasing. Overall, our findings provided a crucial foundation for extending the application of 1–MCP in postharvest preservation of pomegranates.
The Dynamic Return and Volatility Spillovers among Size-Based Stock Portfolios in the Saudi Market and Their Portfolio Management Implications during Different Crises
Authors: Al-Nassar Nassar S.
Published: September 2023

This study contributes to the ongoing debate on the size effect and size-based investment styles by investigating the return and volatility spillovers and time-varying conditional correlations among Saudi large-, mid-, and small-cap indices. To this end, we utilize the weekly returns on the MSCI Saudi large-, mid-, and small-cap indices over a long sample period, spanning several crises. The econometric approach that we use is a VAR-asymmetric BEKK-GARCH model which accounts for structural breaks. On the basis of the VAR-asymmetric BEKK-GARCH model estimation results, we calculate portfolio weights and hedge ratios, and discuss their risk management implications. The empirical results confirm the presence of unilateral return spillovers running from mid- to small-cap stocks, while multilateral volatility spillovers are documented, albeit substantially weakened when accounting for structural breaks. The time-varying conditional correlations display clear spikes around crises, which translate to higher hedge ratios, increasing the cost of hedging during turbulent times. The optimal portfolio weights suggest that investors generally overweight large caps in their portfolios during uncertain times to minimize risk without lowering expected returns. The main takeaway from our results is that passively confining fund managers to a particular size category regardless of the prevailing market conditions may lead to suboptimal performance.
Application of Kombucha Fermentation Broth for Antibacterial, Antioxidant, and Anti-Inflammatory Processes
Authors: Su Jingqian , Tan Qingqing , Wu Shun , Abbas Bilal , Yang Minhe
Published: September 2023

Treatment for sepsis and its complications in the clinic is primarily in the forms of antibiotics, anti-inflammatory agents, and antioxidant drugs. Kombucha, a traditional fermented beverage rich in tea polyphenols and organic acids, offers several benefits including bacteriostasis, anti-inflammation ability, and boosting the immune system. Currently, research on kombucha is primarily focused on its antibacterial and antioxidant properties; however, in-depth exploration of the involved mechanisms is lacking. Herein, turmeric, Paeoniae alba, and black tea were used as fermentation substrates to detect the bacteriostatic and antioxidant activities of the fermentation broth and evaluate its anti-inflammatory effects on RAW264.7 cells stimulated by lipopolysaccharides (LPSs). The results showed that fermentation enhanced the antibacterial activity of turmeric against E. coli and S. aureus and that of Paeoniae alba against S. aureus. Turmeric black tea exhibited the highest antioxidant activity. The fermentation broth of turmeric and turmeric black tea significantly reduced the expression of inflammatory cytokines induced by LPSs. Our results showed that using turmeric and Paeoniae alba culture media as substrates can enhance the anti-inflammatory effects of fermentation broth and provide a new strategy for developing anti-inflammatory substances.
Peculiarities of the Spatial and Electronic Structure of 2-Aryl-1,2,3-Triazol-5-Carboxylic Acids and Their Salts on the Basis of Spectral Studies and DFT Calculations
Authors: Alcolea Palafox Mauricio , Belskaya Nataliya P. , Kostova Irena P.
Published: September 2023

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. For two of them, the optimized geometry was determined in the monomer, cyclic dimer and stacking forms using the B3LYP, M06-2X and MP2 methods implemented in the GAUSSIAN-16 program package. The effect of the para-substitution on the aryl ring was evaluated based on changes in the molecular structure and atomic charge distribution of the triazole ring. An increment in the positive N4 charge was linearly related to a decrease in both the aryl ring and the carboxylic group rotation, with respect to the triazole ring, and by contrast, to an increment in the pyrrolidine ring rotation. Anionic formation had a larger effect on the triazole ring structure than the electronic nature of the different substituents on the aryl ring. Several relationships were obtained that could facilitate the selection of substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to monomer and dimer form calculations, together with the polynomic scaling equation procedure (PSE). The large red-shift of the C=O stretching mode indicates that strong H-bonds in the dimer form appear in the solid state through this group.
CuReSim-LoRM: A Tool to Simulate Metabarcoding Long Reads
Authors: Mesloub Yasmina , Beury Delphine , Vandermeeren Félix , Caboche Ségolène
Published: September 2023

Metabarcoding DNA sequencing has revolutionized the study of microbial communities. Third-generation sequencing producing long reads had opened up new perspectives. Obtaining the full-length ribosomal RNA gene would permit one to reach a better taxonomic resolution at the species or the strain level. However, Oxford Nanopore Technologies (ONT) sequencing produces reads with high error rates, which introduces biases in analysis. Understanding the biases introduced during the analysis allows one to better interpret the biological results and take care of conclusions drawn from metabarcoding experiments. To benchmark an analysis process, the ground truth, i.e., the real composition of the microbial community, has to be known. In addition to artificial mock communities, simulated data are often used to evaluate the biases and performances of the bioinformatics analysis step. Currently, no specific tool has been developed to simulate metabarcoding long reads, mimic the error rate and the length distribution, and allow one to benchmark the analysis process. Here, we introduce CuReSim-LoRM, for the customized read simulator to generate long reads for metabarcoding. We showed that CuReSim-LoRM is able to produce reads with varying error rates and length distributions by mimicking the real data very well.
α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades
Authors: Nagoor Meeran Mohamed Fizur , Arunachalam Seenipandi , Azimullah Sheikh , Saraswathiamma Dhanya , Albawardi Alia , Almarzooqi Saeeda , Jha Niraj Kumar , Subramanya Sandeep , Beiram Rami , Ojha Shreesh
Published: September 2023

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3β signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested.
Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis
Authors: Niculae Andrei , Gherghina Mihai-Emil , Peride Ileana , Tiglis Mirela , Nechita Ana-Maria , Checherita Ionel Alexandru
Published: September 2023

Acute kidney injury (AKI) is one of the main conditions responsible for chronic kidney disease (CKD), including end-stage renal disease (ESRD) as a long-term complication. Besides short-term complications, such as electrolyte and acid-base disorders, fluid overload, bleeding complications or immune dysfunctions, AKI can develop chronic injuries and subsequent CKD through renal fibrosis pathways. Kidney fibrosis is a pathological process defined by excessive extracellular matrix (ECM) deposition, evidenced in chronic kidney injuries with maladaptive architecture restoration. So far, cited maladaptive kidney processes responsible for AKI to CKD transition were epithelial, endothelial, pericyte, macrophage and fibroblast transition to myofibroblasts. These are responsible for smooth muscle actin (SMA) synthesis and abnormal renal architecture. Recently, AKI progress to CKD or ESRD gained a lot of interest, with impressive progression in discovering the mechanisms involved in renal fibrosis, including cellular and molecular pathways. Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender). To provide a better understanding of AKI transition to CKD, we have selected relevant and updated information regarding the risk factors responsible for AKIs unfavorable long-term evolution and mechanisms incriminated in the progression to a chronic state, along with possible therapeutic approaches in preventing or delaying CKD from AKI.
Dual-Target Mycobacterium tuberculosis Inhibition: Insights into the Molecular Mechanism of Antifolate Drugs
Authors: Ramharack Pritika , Salifu Elliasu Y. , Agoni Clement
Published: September 2023

The escalating prevalence of drug-resistant strains of Mycobacterium tuberculosis has posed a significant challenge to global efforts in combating tuberculosis. To address this issue, innovative therapeutic strategies are required that target essential biochemical pathways while minimizing the potential for resistance development. The concept of dual targeting has gained prominence in drug discovery against resistance bacteria. Dual targeting recognizes the complexity of cellular processes and disrupts more than one vital pathway, simultaneously. By inhibiting more than one essential process required for bacterial growth and survival, the chances of developing resistance are substantially reduced. A previously reported study investigated the dual-targeting potential of a series of novel compounds against the folate pathway in Mycobacterium tuberculosis. Expanding on this study, we investigated the predictive pharmacokinetic profiling and the structural mechanism of inhibition of UCP1172, UCP1175, and UCP1063 on key enzymes, dihydrofolate reductase (DHFR) and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5′-phosphate reductase (RV2671), involved in the folate pathway. Our findings indicate that the compounds demonstrate lipophilic physiochemical properties that promote gastrointestinal absorption, and may also inhibit the drug-metabolizing enzyme, cytochrome P450 3A4, thus enhancing their biological half-life. Furthermore, key catalytic residues (Serine, Threonine, and Aspartate), conserved in both enzymes, were found to participate in vital molecular interactions with UCP1172, which demonstrated the most favorable free binding energies to both DHFR and RV2671 (−41.63 kcal/mol, −48.04 kcal/mol, respectively). The presence of characteristic loop shifts, which are similar in both enzymes, also indicates a common inhibitory mechanism by UCP1172. This elucidation advances the understanding of UCP1172’s dual inhibition mechanism against Mycobacterium tuberculosis.
Adipocyte-Derived Small Extracellular Vesicles from Patients with Alzheimer Disease Carry miRNAs Predicted to Target the CREB Signaling Pathway in Neurons
Authors: Batabyal Rachael , Bansal Ankush , Cechinel Laura , Authelet Kayla , Goldberg Madeleine , Nadler Evan , Keene C. , Jayadev Suman , Domoto-Reilly Kimiko , Li Gail , Peskind Elaine , Hashimoto-Torii Kazue , Buchwald Dedra , Freishtat Robert
Published: September 2023

Alzheimer disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD.
Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer
Authors: Stojanovic Bojan , Gajovic Nevena , Jurisevic Milena , Stojanovic Milica Dimitrijevic , Jovanovic Marina , Jovanovic Ivan , Stojanovic Bojana S. , Milosevic Bojan
Published: September 2023

Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to cancer progression and metastasis, its influence on the tumor microenvironment and cancer metabolism, and its potential as a therapeutic target. The IL-33/ST2 axis has been shown to have extensive pro-tumorigenic features in breast cancer, starting from tumor tissue proliferation and differentiation to modulating both cancer cells and anti-tumor immune response. It has also been linked to the resistance of cancer cells to conventional therapeutics. However, the role of IL-33 in cancer therapy remains controversial due to the conflicting effects of IL-33 in tumorigenesis and anti-tumor response. The possibility of targeting the IL-33/ST2 axis in tumor immunotherapy, or as an adjuvant in immune checkpoint blockade therapy, is discussed.
A High Proportion of Malaria Vector Biting and Resting Indoors despite Extensive LLIN Coverage in Côte d’Ivoire
Authors: Tondossama Naminata , Virgillito Chiara , Coulibaly Zanakoungo Ibrahima , Pichler Verena , Dia Ibrahima , della Torre Alessandra , Touré Andre Offianan , Adja Akré Maurice , Caputo Beniamino
Published: September 2023

Malaria is still a leading cause mortality in Côte d’Ivoire despite extensive LLINs coverage. We present the results of an entomological survey conducted in a coastal and in an inland village with the aim to estimate Anopheles gambiae sensu lato (s.l.) female’s abundance indoor/outdoor and Plasmodium falciparum infection rate and analyze the occurrence of blood-feeding in relation to LLINs use. Pyrethrum spray (PSC) and window exit traps (WT) collections were carried out to target endophagic/endophilic and endophagic/exophilic females, respectively. Data on LLINs use in sampled houses were collected. (1) high levels of malaria transmission despite LLINs coverage >70% (~1 An. gambiae s.l. predicted mean/person/night and ~5% Plasmodium falciparum infection rate); (2) 46% of females in the PSC sample were blood-fed, suggesting that they fed on an unprotected host inside the house; (3) 81% of females in WT were unfed, suggesting that they were leaving the house to find an available host. Model estimates that if everyone sleeps under LLINs the probability for a mosquito to bite decreases of 48% and 95% in the coastal and inland village, respectively. The results show a high proportion of mosquito biting and resting indoors despite extensive LLINs. The biological/epidemiological determinants of accounting for these results merit deeper investigations.
The Impact of Protective Face Coverings on Acoustic Markers in Voice: A Systematic Review and Meta-Analysis
Authors: Barsties v. Latoszek Ben , Jansen Viktoria , Watts Christopher R. , Hetjens Svetlana
Published: September 2023

Background: Wearing respiratory protective masks (RPMs) has become common worldwide, especially in healthcare settings, since the onset of the COVID-19 pandemic. Hypotheses have suggested that sound transmission could be limited by RPMs, which possibly affects the characteristics of acoustic energy and speech intelligibility. The objective of this study was to investigate the effect of RPMs on acoustic measurements through a systematic review with meta-analysis. Methods: Five database searches were conducted, ranging from their inception to August 2023, as well as a manual search. Cross-sectional studies were included that provided data on widely used gender-independent clinical acoustic voice quality measures (jitter, shimmer, HNR, CPPS, and AVQI) and habitual sound pressure level (SPL). Results: We found nine eligible research studies with a total of 422 participants who were compared both without masks and with different types of masks. All included studies focused on individuals with vocally healthy voices, while two of the studies also included those with voice disorders. The results from the meta-analysis were related to medical/surgical and FFP2/(K)N95 masks. None of the acoustic measurements showed significant differences between the absence and presence of masks (p > 0.05). When indirectly comparing both mask types, statistical significance was identified for parameters of jitter, HNR, CPPS and SPL (p < 0.001). Conclusions: The present meta-analysis indicates that certain types of RPMs have no significant influence on common voice quality parameters and SPL compared to recordings without masks. Nevertheless, it is plausible that significant differences in acoustic parameters might exist between different mask types. Consequently, it is advisable for the clinical practice to always use the same mask type when using RPMs to ensure high comparability and accuracy of measurement results.
Outcomes in Patients with Acute Myocardial Infarction and Known Sleep Apnea: A Nationwide Analysis
Authors: Rabec Claudio , Sombrun Chan , Bentounes Sid Ahmed , Georges Marjolaine , Bisson Arnaud , Bichat Florence , Bodin Alexandre , Herbert Julien , Zeller Marianne , Cottin Yves , Fauchier Laurent
Published: September 2023

Background. Sleep apnea (SA) is a common breathing disorder characterized by repetitive upper airway narrowing and closure. Although SA has been demonstrated to be an independent risk factor for all-cause mortality, the direct contribution of SA to worse cardiovascular prognosis may be difficult to evaluate, and its independent association with the different types of cardiovascular outcomes may be debated, particularly in the context of patients with acute myocardial infarction (AMI). The aim of this study was to assess the impact of known SA on the outcomes of hospitalized patients who have had an AMI by analyzing 10-year data collected from a national registry. Methods. This longitudinal cohort study was based on the national hospitalization database that covers hospital care for the entire French population, including all patients admitted with AMI from January 2010 to June 2019. The clinical outcomes for the analysis were as follows: all-cause death, cardiovascular death, ischemic stroke, new-onset atrial fibrillation (FA), and re-hospitalization for heart failure (HF). Results. Among the 797,212 patients who presented with an AMI (528,351 men and 268,861 women), 37,075 (4.7%) had documented SA. During follow-up (mean [SD] 1.8 [2.4] years, median [interquartile range] 0.7 [0.1–3.1] years), 163,845 deaths (of which 85,649 were cardiovascular deaths), 20,168 ischemic strokes, 58,498 new-onset AF, and 92,381 rehospitalizations due to HF were recorded. Patients with known SA had a worse prognosis in the short and medium term, but after adjusting for all covariables, SA was only independently associated with a higher risk of rehospitalization for HF and new-onset AF in men and women. Conclusion. Data from our large nationwide analysis confirm that known SA is associated with poor cardiovascular outcomes in patients who have had an AMI. However, this impact is tem-pered when the model is adjusted for age, cardiovascular risk, or other covariables. Further studies need to be conducted to assess the independent impact of SA on the prognosis of patients with AMI.
Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU)
Authors: Matlac Dieter M. , Tonguc Tolga , Mutschler Nikola , Recker Florian , Ramig Olga , Strunk Holger M. , Dell Tatjana , Pieper Claus C. , Coenen Martin , Fuhrmann Christine , Vautey Oregan , Egger Eva-Katharina , Küppers Jim , Conrad Rupert , Essler Markus , Mustea Alexander , Marinova Milka
Published: September 2023

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20–50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.
A Novel Frailty Score Based on Laboratory Parameters (FIMS Score) for the Management of Older Patients with Severe Aortic Stenosis
Authors: Esposito Augusto , Foffa Ilenia , Bastiani Luca , Vecoli Cecilia , Rizza Antonio , Storti Simona , De Caterina Alberto Ranieri , Mazzone Annamaria , Berti Sergio
Published: September 2023

This study aimed to develop a novel score based on common laboratory parameters able to identify frail and sarcopenic patients as well as predict mortality in elderly patients with severe aortic stenosis (AS) for tailored clinical decision-making. A total of 109 patients (83 ± 5 years; females, 68%) with AS underwent a multidisciplinary pre-operative assessment and finalized a “frailty-based management” for the AS interventional treatment. Laboratory parameters of statistically significant differences between sarcopenic and non-sarcopenic individuals were tested in the structural equation model (SEM) to build a Frailty Inflammation Malnutrition and Sarcopenia score (FIMS score). Mortality at 20 months of follow-up was considered an outcome. FIMS score, in particular, the cut-off value ≥ 1.28 was able to identify “frail” and “early frail” patients and predict mortality with a sensitivity of 83.3% and 82.6%, respectively (p = 0.001) and was an independent determinant associated with a higher risk of mortality (HR 5.382; p-value = 0.002). The FIMS score, easily achievable and usable in clinical practice, was able to identify frail and sarcopenic patients as well as predict their adverse clinical outcomes. This score could provide appropriate guidance during decision-making regarding elderly patients with severe AS.
MCP1 Inverts the Correlation between FGF23 and Omega 6/3 Ratio: Is It Also True in Renal Transplantation?
Authors: Mattinzoli Deborah , Turolo Stefano , Ikehata Masami , Vettoretti Simone , Montini Giovanni , Agostoni Carlo , Conti Costanza , Benedetti Matteo , Messa Piergiorgio , Alfieri Carlo Maria , Castellano Giuseppe
Published: September 2023

During chronic kidney disease (CKD) progression, an increase in fibroblast growth factor (FGF23) is present. In stage 5, a positive correlation between FGF23 and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) emerges. Hypothesizing that the rising positive correlation between monocyte chemoattractant protein 1 (MCP1) and n-6 in stage 4 could be the cause, we previously explored FGF23 and MCP1’s roles in dyslipidemia and cardiovascular risk in CKD. In the present paper, we retraced the study evaluating 40 kidney transplant patients (KTx), a cohort where several factors might modify the previous relationships found. An ELISA and gas chromatography assessed the MCP1, FGF23, and PUFA levels. Despite the FGF23 increase (p < 0.0001), low MCP1 levels were found. A decrease in the n-6/n-3 ratio (p = 0.042 CKD stage 4 vs. 5) lowered by the increase in both n-3 αlinolenic (p = 0.012) and docosapentaenoic acid (p = 0.049) was observed. A negative correlation between FGF23 and the n-6/n-3 ratio in CKD stage 4 (r2 −0.3 p = 0.043) and none with MCP1 appeared. According to our findings, different mechanisms in the relationship between FGF23, PUFAs, and MCP1 in CKD and KTx patients might be present, which is possibly related to the immunosuppressive status of the last. Future research will further clarify our hypothesis.
Refractive Error and Axial Length and Their Related Factors in 8-Year-Old Japanese Children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)
Authors: Okabe Natsuki , Takahashi Airi , Shigemoto Yumi , Kogure Chio , Ooka Tadao , Shinohara Ryoji , Otawa Sanae , Kobayashi Anna , Horiuchi Sayaka , Kushima Megumi , Yamagata Zentaro , Kashiwagi Kenji ,   The Yamanashi Adjunct Study of the Japan Environment and Children's Study Group
Published: September 2023

Purpose: To investigate the distribution of visual acuity, refractive error, and axial length in 8-year-old children who participated in an additional survey in Yamanashi Prefecture of the Japan Environmental Children’s Study (hereafter referred to as JECS-Y) conducted from 2019 to 2021. Participants and Methods: Eight-year-old children who participated in the JECS-Y study were subjected to noncycloplegic measurements of refractive error and axial length. If the uncorrected visual acuity was less than 20/20, the best corrected visual acuity was evaluated in accordance with the autorefraction data. A questionnaire was administered regarding the parent’s history of eyeglass wear or contact lens use. Results: Among the 400 participating children, the rate of uncorrected visual acuity of 20/20 or better in both eyes was 70.4%. The mean equivalent spherical equivalent error for both eyes was −0.366 ± 1.016 D. The mean axial length was 23.08 ± 0.225 mm in all patients. The males showed significantly longer axial length than the females despite no differences in body height. There was a significant correlation between axial length, spherical refractive, and uncorrected visual acuity. The children of parents with a history of wearing eyeglasses or contact lenses showed a significantly more myopic equivalent refractive error than those without a history. Conclusions: This study clarified the current state of refractive error in 8-year-old children and the association of inheritance with refractive error. In addition, the axials were significantly longer in male patients.
Catestatin—A Potential New Therapeutic Target for Women with Preeclampsia? An Analysis of Maternal Serum Catestatin Levels in Preeclamptic Pregnancies
Authors: Palmrich Pilar , Schirwani-Hartl Nawa , Haberl Christina , Haslinger Peter , Heinzl Florian , Zeisler Harald , Binder Julia
Published: September 2023

Background: Catestatin has been identified as an important factor in blood pressure control in non-pregnant adults. A possible impact on the development of hypertensive disorders of pregnancy has been indicated. Data on catestatin levels in pregnancy are scarce. The aim of this study was to investigate a potential association of maternal serum catestatin levels to the pathogenesis of preeclampsia. Methods: We evaluated serum catestatin levels of 50 preeclamptic singleton pregnancies and 50 healthy gestational-age-matched pregnancies included in the obstetric biobank registry of the Medical University of Vienna. Receiver operating characteristic curves and logistic regression models were performed to investigate an association between catestatin levels and development of preeclampsia. Results: Catestatin levels were significantly decreased in women with preeclampsia compared to healthy controls (median CST: 3.03 ng/mL, IQR [1.24–7.21 ng/mL] vs. 4.82 ng/mL, IQR [1.82–10.02 ng/mL]; p = 0.010), indicating an association between decreased catestatin values and the development of preeclampsia. There was no significant difference in catestatin values between early-onset preeclampsia and late-onset preeclampsia. Modelling the occurrence of preeclampsia via logistic regression was improved when adding catestatin as a predictive factor. Conclusions: Decreased serum catestatin levels are associated with the presence of preeclampsia. Further investigations into the diagnostic value and possible therapeutic role of catestatin in preeclampsia are warranted.