bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on the Role of β2AR and TRPV1 in Respiratory Diseases
Authors: Manti Sara , Gambadauro Antonella , Galletta Francesca , Ruggeri Paolo , Piedimonte Giovanni
Published: September 2024

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. β2-adrenergic receptor (β2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. β2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of β2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of β2AR during viral infections or prolonged therapy with β2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies.
Utility of an Archival Dried Blood Spot (DBS) Collection from HIV-Infected Individuals with and without Cancer in a Resource-Limited Setting
Authors: Zhang Rongzhen , Bracci Paige M. , Leong Alan , Rapp Cassandra , McGrath Michael S.
Published: September 2024

The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings.
Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients
Authors: Yagüe-Serrano Roberto , Palomar Andrea , Quiñonero Alicia , Gómez Víctor Hugo , de los Santos Maria José , Vidal Carmen , Dominguez Francisco
Published: September 2024

Poor ovarian response (POR) patients often face the risk of not having enough competent oocytes. Then, aspirating small follicles could serve as a strategy to increase their number. Many efforts have been addressed to associate follicular size with oocyte competence, but results are controversial. Therefore, our study aimed to evaluate oocyte maturation and developmental competence, along with a non-invasive oocyte-maturation-related miRNA signature in oocytes retrieved from both large and small follicles. A total of 178 follicles, from 31 POR patients, were aspirated and measured on the day of ovarian puncture. Follicular diameters, oocyte collection, oocyte maturation, fertilization, blastocysts, and good-quality blastocyst rates were recorded. Simultaneously, follicular fluids were collected to quantify their miRNA expression. The efficacy of oocyte retrieval along with oocyte maturation, fertilization, and blastulation rates tended to increase with follicular size, but few significant differences were found. Despite there being significantly more collected oocytes from follicles > 11.5 mm compared to follicles ≤ 11.5 mm (p < 0.05), oocytes from the latter were also mature, with no significant differences in the miRNA signature, but only those > 13.5 mm demonstrated developmental competence. In conclusion, 11.5 mm follicles can produce mature oocytes, but only those larger than 13.5 mm yielded transferable embryos.
Antibacterial Activity and Mechanism of Taxillμs chinensis (DC.) Danser and Its Active Ingredients
Authors: Feng Yanjing , Huang Silu , Zhu Shengying , Gao Bo
Published: September 2024

Taxillμs chinensis (DC.) Danser is a traditional Chinese herbal medicine. It has not been reported regarding antibacterial active ingredients and mechanisms of action. However, the Chinese patent medicine Yinhua Miyanling Tablets containing Taxillμs chinensis has an obvious anti-infective effect in our patent. Therefore, we speculate that Taxillμs chinensis may have antibacterial activity. The purpose of this paper is to study the antibacterial effect and mechanism of Taxillμs chinensis and find active compounds with antibacterial activity and a mechanism. We studied the antibacterial effect and mechanism of Taxillμs chinensis extract. The compounds in the ethyl acetate extract of Taxillμs chinensis were preliminarily identified by UPLC-Q-Orbitrap and analyzed by mass spectrometry. Above all, the antibacterial effect and antibacterial mechanism of the active components of Taxillμs chinensis were determined. Finally, we found, for the first time, that Taxillμs chinensis has a good antibacterial effect and ethyl acetate extract has the best effect. In addition, we found, for the first time, that it has an active component, 4-indolecarbaldehyde, and the component has a good broad-spectrum antibacterial effect. Above all, the active chemical 4-indolecarbaldehyde of Taxillμs chinensis can destroy the bacterial structure, make it unable to maintain normal morphology, and significantly increase the number of deaths. In short, Taxillμs chinensis has an antibacterial effect, and one of its main antibacterial components is 4-indolecarbaldehyde. The antibacterial mechanism of Taxillμs chinensis and 4-indolecarbaldehyde is related to the change in bacterial membrane permeability.
Diarrheagenic Escherichia coli in Stool Specimens Collected from Patients Attending Primary Healthcare Facilities in Ethiopia: Whole-Genome Sequencing-Based Molecular Characterization
Authors: Wolde Deneke , Eguale Tadesse , Medhin Girmay , Haile Aklilu Feleke , Alemayehu Haile , Mihret Adane , Pirs Mateja , Strašek Smrdel Katja , Avberšek Jana , Kušar Darja , Cerar Kišek Tjaša , Janko Tea , Steyer Andrej , Starčič Erjavec Marjanca
Published: September 2024

The diarrheagenic Escherichia coli (DEC) is the major cause of diarrheal diseases in Africa, including Ethiopia. However, the genetic diversity of E. coli pathotypes found in Ethiopia has not been studied well. This study aimed to characterize potential DEC belonging to enteropathogenic (EPEC), Shiga toxin-producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), and enteroinvasive (EIEC) E. coli pathotypes from stool specimens of patients attending primary healthcare units (n = 260) in Addis Ababa and Hossana using whole-genome sequencing. Real-time PCR assays were used to identify DEC isolates belonging to EPEC, STEC, EAEC, ETEC, and EIEC pathotypes, which were then subjected to whole-genome sequencing on the Illumina platform. Twenty-four whole-genome nucleotide sequences of DEC strains with good enough quality were analyzed for virulence-associated genes (VAGs), antibiotic resistance genes (ARGs), phylogenetic groups, serogroups, and sequence types. The majority (62.5%) of DEC isolates belonged to the phylogenetic group B1. The identified DEC isolates belonged to 21 different serogroups and 17 different sequence types. All tested DEC isolates carried multiple VAGs and ARGs. The findings highlight the high diversity in the population structure of the studied DEC isolates, which is important for designing targeted interventions to reduce the diarrheal burden in Ethiopia.
X-ray Fluorescence Microscopy to Develop Elemental Classifiers and Investigate Elemental Signatures in BALB/c Mouse Intestine a Week after Exposure to 8 Gy of Gamma Rays
Authors: Smith Anthony , Dobinda Katrina , Chen Si , Zieba Peter , Paunesku Tatjana , Sun Zequn , Woloschak Gayle E.
Published: September 2024

Iron redistribution in the intestine after total body irradiation is an established phenomenon. However, in the literature, there are no reports about the use of X-ray fluorescence microscopy or equivalent techniques to generate semi-quantitative 2D maps of iron in sectioned intestine samples from irradiated mice. In this work, we used X-ray fluorescence microscopy (XFM) to map the elemental content of iron as well as phosphorus, sulfur, calcium, copper and zinc in tissue sections of the small intestine from eight-week-old BALB/c male mice that developed gastrointestinal acute radiation syndrome (GI-ARS) in response to exposure to 8 Gray of gamma rays. Seven days after irradiation, we found that the majority of the iron is localized as hot spots in the intercellular regions of the area surrounding crypts and stretching between the outer perimeter of the intestine and the surface cell layer of villi. In addition, this study represents our current efforts to develop elemental cell classifiers that could be used for the automated generation of regions of interest for analyses of X-ray fluorescence maps. Once developed, such a tool will be instrumental for studies of effects of radiation and other toxicants on the elemental content in cells and tissues. While XFM studies cannot be conducted on living organisms, it is possible to envision future scenarios where XFM imaging of single cells sloughed from the human (or rodent) intestine could be used to follow up on the progression of GI-ARS.
Using Spectral Flow Cytometry for CAR T-Cell Clinical Trials: Game Changing Technologies Enabling Novel Therapies
Authors: Beadnell Thomas C. , Jasti Susmita , Wang Ruqi , Davis Bruce H. , Litwin Virginia
Published: September 2024

Monitoring chimeric antigen redirected (CAR) T-cells post-infusion in clinical trials is a specialized application of flow cytometry. Unlike the CAR T-cell monitoring for individual patients conducted in clinical laboratories, the data generated during a clinical trial will be used not only to monitor the therapeutic response of a single patient, but determine the success of the therapy itself, or even of an entire class of therapeutic compounds. The data, typically acquired at multiple testing laboratories, will be compiled into a single database. The data may also be used for mathematical modeling of cellular kinetics or to identify predictive biomarkers. With the expanded context of use, a robust, standardized assay is mandatory in order to generate a valuable and reliable data set. Hence, the requirements for assay validation, traceable calibration, technology transfer, cross-instrument standardization and regulatory compliance are high.
Molecular Characteristics and Expression Patterns of Carotenoid Cleavage Oxygenase Family Genes in Rice (Oryza sativa L.)
Authors: Dai Hanjing , Ai Hao , Wang Yingrun , Shi Jia , Ren Lantian , Li Jieqin , Tao Yulu , Xu Zhaoshi , Zheng Jiacheng
Published: September 2024

Carotenoid cleavage oxygenases (CCOs) cleave carotenoid molecules to produce bioactive products that influence the synthesis of hormones such as abscisic acid (ABA) and strigolactones (SL), which regulate plant growth, development, and stress adaptation. Here, to explore the molecular characteristics of all members of the OsCCO family in rice, fourteen OsCCO family genes were identified in the genome-wide study. The results revealed that the OsCCO family included one OsNCED and four OsCCD subfamilies. The OsCCO family was phylogenetically close to members of the maize ZmCCO family and the Sorghum SbCCO family. A collinearity relationship was observed between OsNCED3 and OsNCED5 in rice, as well as OsCCD7 and OsNCED5 between rice and Arabidopsis, Sorghum, and maize. OsCCD4a and OsCCD7 were the key members in the protein interaction network of the OsCCO family, which was involved in the catabolic processes of carotenoids and terpenoid compounds. miRNAs targeting OsCCO family members were mostly involved in the abiotic stress response, and RNA-seq data further confirmed the molecular properties of OsCCO family genes in response to abiotic stress and hormone induction. qRT-PCR analysis showed the differential expression patterns of OsCCO members across various rice organs. Notably, OsCCD1 showed relatively high expression levels in all organs except for ripening seeds and endosperm. OsNCED2a, OsNCED3, OsCCD1, OsCCD4a, OsCCD7, OsCCD8a, and OsCCD8e were potentially involved in plant growth and differentiation. Meanwhile, OsNCED2a, OsNCED2b, OsNCED5, OsCCD8b, and OsCCD8d were associated with reproductive organ development, flowering, and seed formation. OsNCED3, OsCCD4b, OsCCD4c, OsCCD8b, and OsCCD8c were related to assimilate transport and seed maturation. These findings provide a theoretical basis for further functional analysis of the OsCCO family.
Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa
Authors: Zorina Alla , Zorin Vadim , Isaev Artur , Kudlay Dmitry , Manturova Natalia , Ustugov Andrei , Kopnin Pavel
Published: September 2024

This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7) caused by defects in the COL7A1 gene. The use of allogenic mesenchymal stem/stromal cells, which can be injected intradermally and intravenously, appears to be the most promising approach in the field of RDEB cell therapy. Injections of genetically modified autologous dermal fibroblasts are also worth mentioning under this framework. The most common methods of RDEB gene therapy are gene replacement using viral vectors and gene editing using programmable nucleases. Ex vivo epidermal transplants (ETs) based on autologous keratinocytes (Ks) have been developed using gene therapy methods; one such ET successively passed phase III clinical trials. Products based on the use of two-layer transplants have also been developed with both types of skin cells producing C7. Gene products have also been developed for local use. To date, significant progress has been achieved in the development of efficient biomedical products to treat RDEB, one of the most severe hereditary diseases.
Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer
Authors: Watrowski Rafał , Schuster Eva , Van Gorp Toon , Hofstetter Gerda , Fischer Michael B. , Mahner Sven , Polterauer Stefan , Zeillinger Robert , Obermayr Eva
Published: September 2024

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84–4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06–2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women.
Comprehensive, Genome-Wide Identification and Expression Analyses of Phenylalanine Ammonia-Lyase Family under Abiotic Stresses in Brassica oleracea
Authors: Karamat Umer , Guo Juxian , Jiang Shizheng , Khan Imran , Lu Mengting , Fu Mei , Li Guihua
Published: September 2024

Phenylalanine ammonia-lyase (PAL) acts as the rate-limiting enzyme for anthocyanin biosynthesis through the phenylpropanoid pathway, a crucial component of plant secondary metabolism. The PAL gene family plays a crucial role in plants’ defense and stress responses, but its in silico identification and expression analyses in Brassica oleracea under different abiotic stresses remain unexplored. In this study, nine BolPAL, seven BrPAL, four AtPAL, and seventeen BnPAL genes were obtained from the genomes of B. oleracea, Brassica rapa, Arabidopsis thaliana, and Brassica napus, respectively. Segmental duplication and purifying selection are the causes of the BolPAL gene’s amplification and evolution. The BolPAL genes with comparable intron–exon architectures and motifs were grouped together in the same clade. Three categories comprised the cis-regulatory elements: abiotic stressors, phytohormones, and light. According to the results of the qRT-PCR experiments, the majority of the BolPAL genes were expressed highly under MeJA, a low temperature, and a high temperature, and they were downregulated under ABA. Under white light (100 µmol m−2 s−1) with 50, 100, or 150 µmol m−2 s−1 far-red (FR), only a small number of the PAL genes were expressed at 50 and 100 µmol m−2 s−1 FR, while the majority of the PAL genes were slightly elevated at 150 µmol m−2 s−1 FR. This work offers a theoretical foundation for molecular breeding research to investigate the role of BolPAL genes and their role in anthocyanin biosynthesis.
Comment on Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66
Authors: Bouva Marelle J. , Maase Rose E. , van Elburg Ruurd M.
Published: September 2024

The assessment of newborn screening (NBS) algorithms’ performance to ensure quality improvements is a continuous process: false-positive referrals can enable optimisations in the shorter term, but false-negative referrals are often only discovered many years after the screening has taken place [...]
Development and Design Validation of an Inflow-Settling Chamber for Turbomachinery Test-Benches
Authors: Henke Michael , Gärling Stefan , Junge Lena , Wein Lars , Fleige Hans-Ulrich
Published: September 2024

At Leibniz University of Hannover, Germany, a new turbomachinery test facility has been built over the last few years. A major part of this facility is a new 6 MW compressor station, which is connected to a large piping system, both designed and built by AERZEN. This system provides air supply to several wind tunnel and turbomachinery test rigs, e.g., axial turbines and axial compressors. These test rigs are designed to conduct high-quality aerodynamic, aeroelastic, and aeroacoustic measurements to increase physical understanding of steady and unsteady effects in turbomachines. One primary purpose of these investigations is the validation of aerodynamic and aeroacoustic numerical methods. To provide precise boundary conditions for the validation process, extremely high homogeneity of the inflow to the investigated experimental setup is imminent. Thus, customized settling chambers have been developed using analytical and numerical design methods. The authors have chosen to follow basic aerodynamic design steps, using analytical assumptions for the inlet section, the “mixing” area of a settling chamber, and the outlet nozzle in combination with state-of-the-art numerical investigations. In early 2020, the first settling chamber was brought into operation for the acceptance tests. In order to collect high-resolution flow field data during the tests, Leibniz University and AERZEN have designed a unique measurement device for robust and fast in-line flow field measurements. For this measurement device, total pressure and total-temperature rake probes, as well as traversing multi-hole probes, have been used in combination to receive high-resolution flow field data at the outlet section of the settling chamber. The paper provides information about the design process of the settling chamber, the developed measurement device, and measurement data gained from the acceptance tests.
A Systematic Review of the Use and Effect of Virtual Reality, Augmented Reality and Mixed Reality in Physical Education
Authors: Pérez-Muñoz Salvador , Castaño Calle Raimundo , Morales Campo Paula Teresa , Rodríguez-Cayetano Alberto
Published: September 2024

New technologies are tools that are present in daily life on a regular basis. In order to improve the didactic process, education must take into account these new technologies. In the field of physical education, the significance of these technologies is reflected in the existence of applications that can be carried out within the field, both for educational purposes and for physical fitness and health. This is due to the potential presented by virtual reality, augmented reality and mixed reality. The objective of this study was to examine the utilisation and impact of AR, VR and MR technologies in physical education at the compulsory stage. In order to achieve this objective, a design based on the PRISMA methodology for conducting systematic reviews was employed. The databases of WOS, Scopus, PubMed and Google Scholar were subjected to analysis. The results indicate that there has been a notable increase in research activity in this field in recent years. The analysis yielded four principal areas of focus, namely the utilisation of pedagogical methodologies, the enhancement of motor and health-related competencies, and moreover, the facilitation of optimal integration of students in physical education. The utilisation and consequences of novel technologies represent a suitable instrument for enhancing the educational experience of students enrolled in physical education programmes.
Rearing of Black Soldier Fly Larvae with Corn Straw and the Assistance of Gut Microorganisms in Digesting Corn Straw
Authors: Wang Xifeng , Tian Xiangru , Liu Zhi , Liu Zhihua , Shang Shuying , Li Haifeng , Qu Jianhang , Chen Pengxiao
Published: September 2024

Corn straw is considered a renewable biomass energy source, and its unreasonable disposal leads to resource waste and environmental pollution. Black soldier fly (Hermetia illucens L.) larvae (BSFL) facilitate the bioconversion of various types of organic wastes. In this study, we found that 88% of BSFL survived, and 37.4% of corn straw was digested after 14 days of feeding with corn straw. Contrary to expectations, the pretreatment of corn straw with alkaline hydrogen peroxide did not promote its digestion but rather reduced the growth and survival rates of BSFL. Acinetobacter, Dysgonomonas, and unclassified Enterobacteriaceae were the abundant genera in the BSFL gut fed with corn straw. Compared with the standard diet, the relative abundances of carbohydrate metabolism genes, such as the gene abundances of β-glucosidase and α-glucosidase, were higher with corn straw as the substrate. These results suggested that the gut microbial community could regulate suitable and functional microorganisms in response to the substrates. Furthermore, four cellulase-producing strains, namely Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, and Providencia rettgeri, were isolated from the guts of corn straw BSFL. These four strains helped increase the conversion rates of corn straw, the weights of BSFL, and survival rates. In summary, we reared BSFL with corn straw and discovered the functions of gut microorganisms in adapting to the substrates. We also isolated four cellulase-producing strains from the BSFL guts and declared the benefits of BSFL digesting corn straw.
Can a Mixture of Farnesene Isomers Avert the Infestation of Aphids in Sugar Beet Crops?
Authors: Kuhn Denise , Nägele Nils , Tolasch Till , Petschenka Georg , Steidle Johannes L. M.
Published: September 2024

The negative impact of pesticides on the environment and the potential of pest species to develop pesticide resistance make it necessary to explore new methods of pest control. Pheromones and other behavior-modifying semiochemicals are already important in integrated pest management (IPM). (E)-ß-farnesene (EBF) is a semiochemical that acts as an alarm pheromone in aphids. Upon perception of EBF, aphids stop feeding, move away, and sometimes even abandon the host plant. The aphids Myzus persicae and Aphis fabae are significant crop pests and vectors of many harmful phytopathogens affecting sugar beet (Beta vulgaris). Field trials were conducted at different locations in Germany to test whether dispensers containing a mixture of farnesene isomers (FIMs) including EBF were able to reduce the infestation of these species on sugar beet. Our results showed a reduction in aphid abundance in the FIM-treated patches in two out of three sites. Therefore, we hypothesize that FIM dispensers could prevent aphid infestation and could be used in combination with other IPM measures. However, more research is required to increase the effect and ensure the reliability of this method.
Shielded Pair Method for Beam Screen Surface Resistance Measurement at Cryogenic Temperature
Authors: Brunner Kristóf , Krkotić Patrick , Calatroni Sergio , Barna Dániel
Published: September 2024

The shielded pair resonator method is a useful tool in the measurement of accelerator components, such as the beam screens used in the Large Hadron Collider (LHC), the High-Luminosity (HL) LHC, or future accelerators. It can measure the resistive losses at several frequency points by separating the resistive losses on the sample from other sources of losses. We built a new resonator to be inserted into a superconducting dipole magnet (peak magnetic field of 9.5 T) and to measure the surface resistance of beam screens, such as LHC beam screens coated with amorphous carbon (a-C). The device can measure surface resistance at any temperature between 4.2 K and 300 K, in the frequency range of 400 MHz to 1600 MHz. We conducted the first surface resistance measurements of two a-C coated beam screens at 4.2 K and showed that the 200 nm to 400 nm titanium underlayer plus 50 nm a-C only has a limited effect on the surface resistance. This first result supports the choice of this coating as baseline for the HL-LHC triplets magnets upgrade. The resonator will have an important role in the characterization of next-generation beam screens, such as a beam screen with laser-engineered surface structure (LESS). Further measurements of the LHC beam screen in the presence of magnetic fields up to 9.5 T and throughout the full temperature range are going to be reported separately.
Longitudinal Analysis of Bone Metabolic Markers and Bone Mechanical Properties in STZ-Induced Diabetic Rats
Authors: Tomaszewska Ewa , Dobrowolski Piotr , Muszyński Siemowit , Donaldson Janine , Gołyński Marcin , Zwolska Jowita , Szadkowski Mateusz , Osęka Maciej , Mielnik-Błaszczak Maria , Balicki Ireneusz
Published: September 2024

Background: This longitudinal study examined the early effects of type 1 diabetes on bone mechanical properties and metabolic markers in mature rats, focusing on the natural progression of diabetes-induced changes without external treatments. Methods: Forty-eight 8-month-old male Wistar rats were divided into two groups, with one group receiving a single dose of streptozotocin (STZ, 60 mg/kg). Assessments were performed 2, 4, and 8 weeks post-administration, including serum biochemical analyses, bone marker assessments, and mechanical bone tests. The data were analyzed using two-way ANOVA to evaluate the impact of time and treatment. Results: At 2 weeks, diabetic rats showed increased fasting blood glucose (p < 0.001), decreased insulin levels (p = 0.03), and changes in HOMA markers (p < 0.001), liver enzymes (p < 0.001), inflammatory markers (p < 0.001), and bone metabolism markers (osteocalcin (p < 0.001), OPG (p = 0.006), RANKL (p < 0.001), and OPG/RANKL ratio (p < 0.001)), with initial alterations in bone geometry. By week 4, decreased body weight in the diabetic group (p < 0.001) led to further changes in bone geometry and initial differences in mechanical properties. At 8 weeks, significant declines in body (p < 0.001) and bone (p < 0.001) weights were observed, along with further deterioration in bone geometry and mechanical properties. Conclusions: The study highlights the significant impact of STZ-induced diabetes on bone health as early as two weeks post-STZ administration, with marked temporal changes in biochemical markers and mechanical properties.
The Interaction of Complement and Intrinsic Coagulation System: A Comparative Study between COVID-19 and Bacterial Sepsis Patients
Authors: Papadakis Dimitrios-Dorotheos , Politou Marianna , Pittaras Theodoros , Stergiou Ioanna E. , Koutsoukou Antonia , Kompoti Maria , Vasileiadis Ioannis
Published: September 2024

Background/Objectives: Through the past several years, a constant interaction has been implicated between complement and coagulation cascades. SARS-CoV-2 infection and bacterial sepsis are potent activators of both cascades. This study aims to compare the extent of complement and intrinsic coagulation pathway activation (and the interplay between them) among patients with COVID-19 and bacterial sepsis. Methods: Serum and plasma samples were collected from 25 ICU patients (11 patients with COVID-19 and 14 patients with bacterial sepsis) at two time points (on admission and either on improvement or deterioration). The activities of coagulation factors XI and XII and complement factors C3a and C5a were measured at both time points. Results: The activities of factors XI and XII were increased in both groups of patients and at both time points. However, there were no statistically significant differences between SARS-CoV-2 and bacterial sepsis patients. On the other hand, both C3a and C5a were significantly higher in the COVID-19 group on admission. This correlation was preserved on reassessment. Conclusions: Complement activation seems to be more enhanced in COVID-19 than bacterial sepsis. However, the lack of statistical significance in factors XI and XII indicates t the presence of additional pathways for complement activation in SARS-CoV-2 infection.
Prevalence of Unwanted Loneliness and Associated Factors in People over 65 Years of Age in a Health Area of the Region of Murcia, Spain: HELPeN Project
Authors: Hernández-López María Jesús , Hernández-Méndez Solanger , Leal-Costa César , Ramos-Morcillo Antonio Jesús , Díaz-García Isidora , López-Pérez María Verónica , García-González Jessica , Ruzafa-Martínez María
Published: September 2024

Background/Objectives: Population aging poses many challenges to public health, highlighting loneliness and social isolation as severe problems that affect the physical and mental health of older adults. During the COVID-19 pandemic, these became aggravated. The objective of the present study was to assess the prevalence of loneliness and its relationship with social isolation, depression, cognitive deterioration, sleep quality, and the level of physical mobility and functioning of older adults in Health Area 3 of the Region of Murcia. Methods: A descriptive, observational, and cross-sectional study was performed. The inclusion criteria were age ≥ 65, living in Health Area 3 of the Region of Murcia, and not being institutionalized. The following variables were evaluated: sociodemographic variables, loneliness (UCLA scale), social isolation (DUFSS), depression (GDS), cognitive deterioration (Pfeiffer), sleep quality (PSQI), and mobility (Barthel index). A univariate and multivariate regression model was created to examine how the dependent variable was related to the independent variables. Results: A total of 102 older adults participated in the study. Of these, 31.4% perceived unwanted loneliness and 14.7% low social support. The multivariate regression analysis showed that social isolation, geriatric depression, and cognitive deterioration were significant predictors of loneliness. Conclusions: The findings highlight the importance of developing multifaceted interventions that address not only social isolation but also other interrelated factors such as depression, cognitive deterioration, and sleep quality. The strategies should be centered on community programs and support networks. It is fundamental to perform longitudinal studies to better understand the causal relationships between these variables.
Characterizing Unique Clinical and Virological Profiles in Concurrent Chronic Hepatitis B and Metabolic Dysfunction-Associated Liver Disease: Insights from a Population-Based Cohort Study
Authors: Abu Baker Fadi , Zeina Abdel-Rauf , Taher Randa , Abu Mouch Saif , Israel Ariel
Published: September 2024

Background: The concurrent presence of chronic hepatitis B virus (CHB) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) presents a unique clinical scenario with implications that are not yet fully understood. This study aims to characterize the distinct clinical and virological features of CHB in the context of MASLD and evaluate its impact on disease progression and outcomes. Methods: Utilizing a comprehensive health maintenance organization database, this study included 1186 patients with CHB from 2000–2020. Patients were categorized into two groups: CHB-MASLD (n = 188) and CHB alone (n = 998). CHB diagnosis was confirmed by serological markers, while MASLD was diagnosed based on imaging and cardiometabolic risk factors. Comparative analysis and multiple regression models were applied to assess variables related to viral parameters and clinical outcomes. Results: The CHB-MASLD group was older (mean age of 45.2 vs. 39.1, p < 0.001) with higher rates of obesity (46.8% vs. 23.8%, p < 0.001), diabetes (36.2% vs. 17.3%, p < 0.001), and dyslipidemia. Distinct viral profiles included higher HBeAg negativity (96.2%), a higher rate of HBeAg-negative infection (70.4% vs. 63.8%; p < 0.001), and increased HBeAg seroconversion under treatment. Cirrhosis was more prevalent in the CHB-MASLD group (9.6% vs. 4.4%, p = 0.007), while HCC rates were comparable. Multivariate analysis identified age, male gender, chronic active hepatitis, and diabetes as predictors of cirrhosis. Conclusions: CHB-MASLD patients were distinguished by a higher prevalence of metabolic features, along with a distinct viral profile marked by increased chronic HBeAg infection, higher rates of HBeAg seroconversion, and a potential association with worse disease outcomes.
Preclinical Evaluation of Electronic Health Records (EHRs) to Predict Poor Control of Chronic Respiratory Diseases in Primary Care: A Novel Approach to Focus Our Efforts
Authors: Navarro Ros Fernando M. , Maya Viejo José David
Published: September 2024

Background/Objectives: Managing chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) within the Spanish Sistema Nacional de Salud (SNS) presents significant challenges, particularly due to their high prevalence and poor disease control rates—approximately 45.1% for asthma and 63.2% for COPD. This study aims to develop a novel predictive model using electronic health records (EHRs) to estimate the likelihood of poor disease control in these patients, thereby enabling more efficient management in primary care settings. Methods: The Seleida project employed a bioinformatics approach to identify significant clinical variables from EHR data in primary care centers in Seville and Valencia. Statistically significant variables were incorporated into a logistic regression model to predict poor disease control in patients with asthma and COPD patients. Key variables included the number of short-acting β-agonist (SABA) and short-acting muscarinic antagonist (SAMA) canisters, prednisone courses, and antibiotic courses over the past year. Results: The developed model demonstrated high accuracy, sensitivity, and specificity in predicting poorly controlled disease in both asthma and COPD patients. These findings suggest that the model could serve as a valuable tool for the early identification of at-risk patients, allowing healthcare providers to prioritize and optimize resource allocation in primary care settings. Conclusions: Integrating this predictive model into primary care practice could enhance the proactive management of asthma and COPD, potentially improving patient outcomes and reducing the burden on healthcare systems. Further validation in diverse clinical settings is warranted to confirm the model’s efficacy and generalizability.
Long-Term Outcomes of Primary Cemented Total Hip Arthroplasty with Acetabular Bone Graft for Protrusio Acetabuli: Minimum 10-Year Follow-Up
Authors: Yapp Liam Z. , Clement Nick D. , Scott Chloe E. H. , Ng Nathan , Breusch Hanna P. , MacDonald Deborah J. , Gaston Paul , Breusch Steffen J.
Published: September 2024

Background: This study reports the long-term survivorship of primary total hip arthroplasty (THA) for protrusio acetabuli. Methods: Patients undergoing THA utilising cement and bone graft acetabular reconstruction for protrusio acetabuli in a university teaching hospital during the period 2003 to 2014 were included. Kaplan–Meier survival estimates were calculated with 95% confidence intervals (CI) up to 15 years following surgery. PROMs were collected pre- and post-operatively for hip-specific function (Oxford Hip Score [OHS]) and health-related quality of life (HRQoL) using the EQ-5D-3L. Results: 129 consecutive THAs (96 patients) performed for protrusio acetabuli were identified (median age 69, IQR 61–75; female 115 [89.1%]; 38 [29.5%] inflammatory arthritis) with a mean follow-up of 15.7 years (range: 10.1–20.1 years). At the final follow-up, fifty-six (43.4%) patients had died and there were eleven (8.5%) reoperations, of which eight (6.2%) involved the revision of the acetabular component. The fifteen-year Kaplan–Meier any-reoperation survival estimate was 91.3% (95% CI 85.9–97.0). When considering all-cause acetabular revision only, the 15-year survival estimate was 93.1% (95% CI 88.2–98.3). The median pre-operative OHS improved significantly from baseline to 1 year post-THA, beyond the minimal important change (mean difference 28, 95% CI 25–30, p < 0.001). Similarly, there were clinically relevant improvements in HRQoL at 1 year post surgery (mean difference 0.10, 95% CI 0.06–0.15, p < 0.001). Conclusions: This study demonstrates that primary cemented THA utilising acetabular bone graft for reconstruction in patients with protrusio acetabuli was associated with 15-year survival rates of 93.1% and clinically relevant improvements in hip-specific function and HRQoL.
Gene Mutation in Patients with Familial Hypercholesterolemia and Response to Alirocumab Treatment—A Single-Centre Analysis
Authors: Rogozik Joanna , Rokicki Jakub Kosma , Grabowski Marcin , Główczyńska Renata
Published: September 2024

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol, which plays a major role in the progression of atherosclerosis and leads to a heightened risk of premature atherosclerotic cardiovascular disease. Methods: We have carried out an observational study on a group of 17 patients treated at the Outpatient Lipid Clinic from 2019 to 2024. Result: The most frequent mutation observed was found in the LDL receptor (LDLR) gene, which was identified in ten patients (58.8%). Five patients were identified to have a mutation in the apolipoprotein B (APOB) gene, whereas two patients had two points mutations, one in the LDLR, and the other in the APOB gene. The average age of patients with LDLR mutation was 54.8 (12.3); for APOB mutation it was 61.4 (9.3) and for patients with two points mutation it was 61.5 (14.8). The study results showed that at Week 12, individuals with LDLR-defective heterozygotes who were given alirocumab 150 mg every two weeks experienced a 63.0% reduction in LDL cholesterol levels. On the other hand, individuals with APOB heterozygotes experienced a 59% reduction in LDL cholesterol levels. However, in patients with double heterozygous for mutations in LDLR and APOB genes, there was a hyporesponsiveness to alirocumab, and the reduction in LDL-C was only by 23% in two individuals. Conclusions: In patients with a single mutation, there was a greater response to treatment with alirocumab in contrast to patients with double heterozygous mutation, who did not respond to treatment with PCSK9 inhibitors.
Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future
Authors: Bakirtzis Christos , Evangelopoulos Maria Elephteria , Grigoriadis Nikolaos
Published: September 2024

In the past two decades, there has been a considerable increase of our knowledge with regards to the pathophysiology and management of various demyelinating diseases of the central nervous system [...]
Clinical and Biochemical Differences in Patients Having Non-Variceal Upper Gastrointestinal Bleeding on NSAIDs, Oral Anticoagulants, and Antiplatelet Therapy
Authors: Ardelean Melania , Buzas Roxana , Ardelean Ovidiu , Preda Marius , Morariu Stelian Ion , Levai Codrina Mihaela , Rosca Ciprian Ilie , Lighezan Daniel Florin , Kundnani Nilima Rajpal
Published: September 2024

Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA.
Thoracic Fluid Content as an Indicator of High Intravenous Diuretic Requirements in Hospitalized Patients with Decompensated Heart Failure
Authors: Galas Agata , Krzesiński Paweł , Banak Małgorzata , Gielerak Grzegorz
Published: September 2024

Background: The main cause of hospitalization in patients with heart failure is hypervolemia. Therefore, the primary treatment strategy involves diuretic therapy using intravenous loop diuretics to achieve decongestion and euvolemia. Some patients with acutely decompensated heart failure (ADHF) do not respond well to diuretic treatment, which may be due to diuretic resistance (DR). Such cases require high doses of diuretic medications and combination therapy with diuretics of different mechanisms of action. Although certain predisposing factors for diuretic resistance have been identified (such as hypotension, type 2 diabetes, impaired renal function, and hyponatremia), further research is needed to identify other pathophysiological markers of DR. Objective: This study aims to identify admission markers that can predict a high requirement for intravenous diuretics in hospitalized patients with decompensated heart failure. Methods: This study included 102 adult patients hospitalized for ADHF. At admission, patients underwent clinical assessment, laboratory parameter evaluation (including the N-terminal prohormone of brain natriuretic peptide [NT-proBNP] levels), and hemodynamic assessment using impedance cardiography (ICG). Hemodynamic profiles were based on the use of parameters such as heart rate (HR), blood pressure (BP), and thoracic fluid content (TFC) as markers of volume status. The analysis included 97 patients with documented doses of intravenous diuretic use. Patients were stratified into two groups based on median diuretic consumption (equivalent to 540 mg of intravenous furosemide): the high-loop diuretic utilization (LDU) group (n = 49) and the low-LDU group (n = 48). Results: Compared to low-LDU patients, high-LDU patients had greater thoracic fluid content at admission, both quantitatively (37.4 ± 8.1 vs. 34.1 ± 6.9 kOhm-1; p = 0.024) and qualitatively (TFC ≥ 35 kOhm-1: 59.2% vs. 33.3%; p = 0.011). Anemia was more common in the high-LDU group (67.4% vs. 43.8%; p = 0.019), as was elevated NT-proBNP (≥median of 3952 pg/mL: 60.4% vs. 37.5%; p = 0.024). High LDU was associated with a significantly longer hospitalization duration (12.9 ± 6.4 vs. 7.0 ± 2.6 days; p < 0.001). Logistic regression analysis identified anemia, elevated NT-proBNP, and high TFC as predictors of high LDU (HR: 2.65, 2.54, and 2.90, respectively). In a multifactorial model, only high TFC remained an independent predictor (HR: 2.60, 95% CI 1.04–6.49; p = 0.038). Conclusions: TFC was the sole independent admission marker of a high requirement for intravenous diuretics in patients hospitalized for decompensated heart failure. An objective assessment of volume status by impedance cardiography may support intensive personalized decongestion therapy.