bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine-Grained Metro-Trip Detection from Cellular Trajectory Data Using Local and Global Spatial–Temporal Characteristics
Authors: Li Guanyao , Xu Ruyu , Shi Tingyan , Deng Xingdong , Liu Yang , Di Deshi , Zhao Chuanbao , Liu Guochao
Published: August 2024

A fine-grained metro trip contains complete information on user mobility, including the original station, destination station, departure time, arrival time, transfer station(s), and corresponding transfer time during the metro journey. Understanding such detailed trip information within a city is crucial for various smart city applications, such as effective urban planning and public transportation system optimization. In this work, we study the problem of detecting fine-grained metro trips from cellular trajectory data. Existing trip-detection approaches designed for GPS trajectories are often not applicable to cellular data due to the issues of location noise and irregular data sampling in cellular data. Moreover, most cellular data-based methods focus on identifying coarse-grained transportation modes, failing to detect fine-grained metro trips accurately. To address the limitations of existing works, we propose a novel and efficient fine-grained metro-trip detection (FGMTD) model in this work. By considering both the local and global spatial–temporal characteristics of a trajectory and the metro network, FGMTD can effectively mitigate the effects of location noise and irregular data sampling, ultimately improving the accuracy and reliability of the detection process. In particular, FGMTD employs a spatial–temporal hidden Markov model with efficient index strategies to capture local spatial–temporal characteristics from individual positions and metro stations, and a weighted trip-route similarity measure to consider global spatial–temporal characteristics from the entire trajectory and metro route. We conduct extensive experiments on two real datasets to evaluate the effectiveness and efficiency of our proposed approaches. The first dataset contains cellular data from 30 volunteers, including their actual trip details, while the second dataset consists of data from 4 million users. The experiments illustrate the significant accuracy of our approach (with a precision of 87.80% and a recall of 84.28%). Moreover, we demonstrate that FGMTD is efficient in detecting fine-grained trips from a large amount of cellular data, achieving this task within 90 min of processing a day’s data from 4 million users.
Quercetin Mitigates Lysophosphatidylcholine (LPC)-Induced Neutrophil Extracellular Traps (NETs) Formation through Inhibiting the P2X7R/P38MAPK/NOX2 Pathway
Authors: Liu Si , Wang Yan , Ying Linyao , Li Hao , Zhang Keyi , Liang Na , Luo Gang , Xiao Lin
Published: August 2024

Neutrophil extracellular traps (NETs) are three-dimensional reticular structures that release chromatin and cellular contents extracellularly upon neutrophil activation. As a novel effector mechanism of neutrophils, NETs possess the capacity to amplify localized inflammation and have been demonstrated to contribute to the exacerbation of various inflammatory diseases, including cardiovascular diseases and tumors. It is suggested that lysophosphatidylcholine (LPC), as the primary active component of oxidized low-density lipoprotein, represents a significant risk factor for various inflammatory diseases, such as cardiovascular diseases and neurodegenerative diseases. However, the specific mechanism of NETs formation induced by LPC remains unclear. Quercetin has garnered considerable attention due to its anti-inflammatory properties, serving as a prevalent flavonoid in daily diet. However, little is currently known about the underlying mechanisms by which quercetin inhibits NETs formation and alleviates associated diseases. In our study, we utilized LPC-treated primary rat neutrophils to establish an in vitro model of NETs formation, which was subsequently subjected to treatment with a combination of quercetin or relevant inhibitors/activators. Compared to the control group, the markers of NETs and the expression of P2X7R/P38MAPK/NOX2 pathway-associated proteins were significantly increased in cells treated with LPC alone. Quercetin intervention decreased the LPC-induced upregulation of the P2X7R/P38MAPK/NOX2 pathway and effectively reduced the expression of NETs markers. The results obtained using a P2X7R antagonist/activator and P38MAPK inhibitor/activator support these findings. In summary, quercetin reversed the upregulation of the LPC-induced P2X7R/P38MAPK/NOX2 pathway, further mitigating NETs formation. Our study investigated the potential mechanism of LPC-induced NETs formation, elucidated the inhibitory effect of quercetin on NETs formation, and offered new insights into the anti-inflammatory properties of quercetin.
Advancing 3Rs: The Mouse Estrus Detector (MED) as a Low-Stress, Painless, and Efficient Tool for Estrus Determination in Mice
Authors: Belozertseva Irina V. , Merkulovs Dmitrijs D. , Kaiser Helena , Rozhdestvensky Timofey S. , Skryabin Boris V.
Published: August 2024

Determining the estrous cycle stages in mice is essential for optimizing breeding strategies, synchronizing experimental timelines, and facilitating studies in behavior, drug testing, and genetics. It is critical for reducing the production of genetically unmodified offspring in the generation and investigation of genetically modified animal models. An accurate detection of the estrus cycle is particularly relevant in the context of the 3Rs—Replacement, Reduction, and Refinement. The estrous cycle, encompassing the reproductive phases of mice, is key to refining experimental designs and addressing ethical issues related to the use of animals in research. This study presents results from two independent laboratories on the efficacy of the Mouse Estrus Detector (MED) from ELMI Ltd. (Latvia) for the accurate determination of the estrus phase. The female mice of five strains/stocks (CD1, FVB/N, C57Bl6/J, B6D2F1, and Swiss) were used. The results showed that the MEDProTM is a low-traumatic, simple, rapid, and painless method of estrus detection that supports the principles of the 3Rs. The use of the MEDProTM for estrus detection in mice caused minimal stress, enhanced mating efficiency, facilitated an increase in the number of embryos for in vitro fertilization, and allowed the production of the desired number of foster animals.
Conjugation of CRAMP18–35 Peptide to Chitosan and Hydroxypropyl Chitosan via Copper-Catalyzed Azide–Alkyne Cycloaddition and Investigation of Antibacterial Activity
Authors: Rathinam Sankar , Sørensen Kasper K. , Hjálmarsdóttir Martha Á. , Thygesen Mikkel B. , Másson Már
Published: August 2024

We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP18–35) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP18–35 carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. The chitosan–peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP18–35 conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan–peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and two species of Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria.
Effect of High Glucose on Embryological Development of Zebrafish, Brachyodanio, Rerio through Wnt Pathway
Authors: Thompson Ebony , Hensley Justin , Taylor Renfang Song
Published: August 2024

Gestational diabetes mellitus (GDM) is a worldwide pregnancy complication. Gestational diabetes can significantly impact fetus development. However, the effects of high glucose on embryological development post-fertilization are yet to be researched. Danio rerio embryos are a great model for studying embryonic development. In this study, the effects on embryological (morphological and genetic) development were examined in the presence of a high-glucose environment that mimics the developing fetus in pregnant women with GDM. Fertilized zebrafish embryos were treated with normal media and high glucose for 5 days from 3 h post-fertilization (hpf) to 96 hpf, respectively, as control and experimental groups. Morphological changes are recorded with microscope images. Hatch rate and heart rate are compared between groups at set time points. RNA-Seq is performed to examine the gene changes in the experimental group. Glucose delayed the zebrafish embryo development by slowing the hatch rate by about 24 h. The brain, heart, and tail started showing smaller morphology in the glucose group compared to the control group at 24 hpf. Heart rate was faster in the glucose group compared to the control group on days 2 and 3 with a statistically significant difference. Among the zebrafish whole genome, the significantly changed genes were 556 upregulated genes and 1118 downregulated genes, respectively, in the high-glucose group. The metabolic and Wnt pathways are altered under high-glucose conditions. These conditions contribute to significant physiological differences that may provide insight into the functionality of post-embryological development.
Purinergic Signaling in Non-Parenchymal Liver Cells
Authors: Mata-Martínez Esperanza , Ramírez-Ledesma María Guadalupe , Vázquez-Victorio Genaro , Hernández-Muñoz Rolando , Díaz-Muñoz Mauricio , Vázquez-Cuevas Francisco G.
Published: August 2024

Purinergic signaling has emerged as an important paracrine–autocrine intercellular system that regulates physiological and pathological processes in practically all organs of the body. Although this system has been thoroughly defined since the nineties, recent research has made substantial advances regarding its role in aspects of liver physiology. However, most studies have mainly targeted the entire organ, 70% of which is made up of parenchymal cells or hepatocytes. Because of its physiological role, the liver is exposed to toxic metabolites, such as xenobiotics, drugs, and fatty acids, as well as to pathogens such as viruses and bacteria. Under injury conditions, all cell types within the liver undergo adaptive changes. In this context, the concentration of extracellular ATP has the potential to increase dramatically. Indeed, this purinergic response has not been studied in sufficient detail in non-parenchymal liver cells. In the present review, we systematize the physiopathological adaptations related to the purinergic system in chronic liver diseases of non-parenchymal liver cells, such as hepatic stellate cells, Kupffer cells, sinusoidal endothelial cells, and cholangiocytes. The role played by non-parenchymal liver cells in these circumstances will undoubtedly be strategic in understanding the regenerative activities that support the viability of this organ under stressful conditions.
Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling
Authors: Castorina Alessandro , Scheller Jurgen , Keay Kevin A. , Marzagalli Rubina , Rose-John Stefan , Campbell Iain L.
Published: August 2024

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown. In this study, PACAP/VIP levels were assessed in the brain of GFAP-IL6 mice. In addition, we utilised bi-genic GFAP-IL6 mice carrying the human sgp130-Fc transgene (termed GFAP-IL6/sgp130Fc mice) to determine whether trans-signalling inhibition rescued PACAP/VIP changes in the CNS. Transcripts and protein levels of PACAP and VIP, as well as their receptors PAC1, VPAC1 and VPAC2, were significantly increased in the cerebrum and cerebellum of GFAP-IL6 mice vs. wild type (WT) littermates. These results were paralleled by a robust activation of the JAK/STAT3, NF-κB and ERK1/2MAPK pathways in GFAP-IL6 mice. In contrast, co-expression of sgp130Fc in GFAP-IL6/sgp130Fc mice reduced VIP expression and activation of STAT3 and NF-κB pathways, but it failed to rescue PACAP, PACAP/VIP receptors and Erk1/2MAPK phosphorylation. We conclude that forced expression of IL-6 in astrocytes induces the activation of the PACAP/VIP neuropeptide system in the brain, which is only partly modulated upon IL-6 trans-signalling inhibition. Increased expression of PACAP/VIP neuropeptides and receptors may represent a homeostatic response of the CNS to an uncontrolled IL-6 synthesis and its neuroinflammatory consequences.
Genetic Diversity of Whiteflies Colonizing Crops and Their Associated Endosymbionts in Three Agroecological Zones of Cameroon
Authors: Kepngop Lanvin R. K. , Wosula Everlyne N. , Amour Massoud , Ghomsi Pierre G. T. , Wakam Louise N. , Kansci Germain , Legg James P.
Published: August 2024

Bemisia tabaci (Gennadius) is as a major pest of vegetable crops in Cameroon. These sap-sucking insects are the main vector of many viruses infecting plants, and several cryptic species have developed resistance against insecticides. Nevertheless, there is very little information about whitefly species on vegetable crops and the endosymbionts that infect them in Cameroon. Here, we investigated the genetic diversity of whiteflies and their frequency of infection by endosymbionts in Cameroon. Ninety-two whitefly samples were collected and characterized using mitochondrial cytochrome oxidase I (mtCOI) markers and Kompetitive Allele Specific PCR (KASP). The analysis of mtCOI sequences of whiteflies indicated the presence of six cryptic species (mitotypes) of Bemisia tabaci, and two distinct clades of Bemisia afer and Trialeurodes vaporariorum. Bemisia tabaci mitotypes identified included: MED on tomato, pepper, okra, and melon; and SSA1-SG1, SSA1-SG2, SSA1-SG5, SSA3, and SSA4 on cassava. The MED mitotype predominated in all regions on the solanaceous crops, suggesting that MED is probably the main phytovirus vector in Cameroonian vegetable cropping systems. The more diverse cassava-colonizing B. tabaci were split into three haplogroups (SNP-based grouping) including SSA-WA, SSA4, and SSA-ECA using KASP genotyping. This is the first time that SSA-ECA has been reported in Cameroon. This haplogroup is predominant in regions currently affected by the severe cassava mosaic virus disease (CMD) and cassava brown streak virus disease (CBSD) pandemics. Three endosymbionts including Arsenophonus, Rickettsia, and Wolbachia were present in female whiteflies tested in this study with varying frequency. Arsenophonus, which has been shown to influence the adaptability of whiteflies, was more frequent in the MED mitotype (75%). Cardinium and Hamiltonella were absent in all whitefly samples. These findings add to the knowledge on the diversity of whiteflies and their associated endosymbionts, which, when combined, influence virus epidemics and responses to whitefly control measures, especially insecticides.
Geographic Location, Population Dynamics, and Fruit Damage of an Invasive Citrus Mealybug: The Case of Delottococcus aberiae De Lotto in Eastern Spain
Authors: Gavara Aitor , Vacas Sandra , Navarro-Llopis Vicente
Published: August 2024

The invasive mealybug Delottococcus aberiae De Lotto (Hemiptera: Pseudococcidae) has rapidly spread in the Mediterranean basin since its detection in 2009 in the Valencia Community in eastern Spain. The use of sticky traps baited with its sex pheromone, (4,5,5-trimethyl-3-methylenecyclopent-1-en-1-yl)methyl acetate, has allowed to determine the geographical distribution of D. aberiae by means of the surveillance network described in the present work. The population monitoring of the pest over a five-year period (2019–2023) has revealed an increase from 31% to 70% of the affected citrus-growing area. The monitoring network has also allowed a better understanding of the pests’ biological cycle throughout the year. The populations start growing from March to June and reach their maximum in July–August. During autumn, there is a gradual decline in the population. Although the highest annual populations were detected in 2022 and 2023, the greatest crop losses were recorded in 2020 and 2021, with mean values near 18%. Data suggest that the damage responsible for fruit deformation, and thus the economic losses, are related to the population levels in spring (April–May) rather than those in summer (July–August). The findings of this study can be valuable for future research and development of effective pest control strategies.
Surgical Management and Its Impact on Adjuvant Treatment in Recurrent Ipsilateral Breast Cancer: A Retrospective Cohort Study
Authors: Torras Ines , Cebrecos Isaac , Castillo Helena , Rodríguez Laura , Zaragoza-Ballester Pablo , Sitges Carla , Loinaz Ignacio , Garcia Marta , Molla Meritxell , Vidal-Sicart Sergi , Mension Eduard
Published: August 2024

Background: Breast cancer (BC) recurrence, defined as the reappearance of cancer in the ipsilateral breast after primary treatment, poses significant challenges in clinical management. Despite advances in treatment, recurrence rates persist, ranging from 0.6 to 1.5% annually, reaching 10–15% at 20 years. This study aims to analyze the surgical and oncological characteristics of patients with BC recurrence. Methods: This retrospective study includes 56 patients diagnosed with recurrent BC between October 2018 and April 2022. Data were collected from a prospectively maintained surgical database. A descriptive analysis was performed on the initial BC, and the recurrence, including surgical complications, was classified using the Clavien–Dindo system. The success rates of selective sentinel lymph node (SLN) biopsies and aberrant drainages were assessed based on previous surgeries. Results: The cohort included 55 females and 1 male, with a median age of 65.3 years. The mean time to BC recurrence was 11.5 years. Among them, 26.8% underwent breast-conserving surgery, 41.1% had a mastectomy, 21.4% had a mastectomy with reconstruction, and 10.7% had an excision over a previous mastectomy. An SLN biopsy was performed in 78.6% of cases, with higher success rates in those without a previous axillary lymph node dissection (85.7% vs. 63.2%). Aberrant drainage was more frequent in patients with a previous ALND (44.4% vs. 20%). The median follow-up was 41.3 months, with 10.7% experiencing a second recurrence. Conclusions: Repeat breast-conserving surgery with re-irradiation for ipsilateral recurrence is feasible and does not significantly increase complications. SLN biopsy is valuable for restaging and tailoring adjuvant therapies, with ALND not being necessary if re-SLN biopsy shows no drainage. The management of aberrant drainage remains controversial.
Improved Composite Hydrogel for Bioengineered Tracheal Graft Demonstrates Effective Early Angiogenesis
Authors: Martins Russell Seth , Weber Joanna , Drake Lauren , Latif M. Jawad , Poulikidis Kostantinos , Razi Syed Shahzad , Luo Jeffrey , Bhora Faiz Y.
Published: August 2024

Background/Objectives: Collagen–agarose hydrogel blends currently used in tracheal graft bioengineering contain relatively high concentrations of collagen to withstand mechanical stresses associated with native trachea function (e.g., breathing). Unfortunately, the high collagen content restricts effective cell infiltration into the hydrogel. In this study, we created an improved hydrogel blend with lower concentrations of collagen (<5 mg/mL) and characterized its capacity for fibroblast invasion and angiogenesis. Methods: Four collagen–agarose hydrogel blends were created: 1 mg/mL type 1 collagen (T1C) and 0.25% agarose, 1 mg/mL T1C and 0.125% agarose, 2 mg/mL T1C and 0.25% agarose, and 2 mg/mL T1C and 0.125% agarose. The hydrogel surface was seeded with fibroblasts, while both endothelial cells and fibroblasts (3:1 ratio) were mixed within the hydrogel matrix. We assessed early angiogenesis by observing fibroblast migration and endothelial cell morphology (elongation and branching) at 7 days. In addition, we performed immunostaining for alpha-smooth muscle actin (aSMA) and explored the gene expression of various angiogenic markers (including vascular endothelial growth factor; VEGF). Results: Gels with lower agarose concentrations (0.125%) with 1 or 2 mg/mL T1C were more effective in allowing early attachment and migration of surface-applied fibroblasts compared to gels with higher (0.25%) agarose concentrations. The low-agarose gels also allowed cells to quickly adopt a spread morphology and self-assemble into elongated structures indicative of early angiogenesis, while demonstrating positive immunostaining for aSMA and increased gene expression of VEGF by day 7. Conclusions: Hydrogel blends with collagen and low agarose concentrations may be effective in allowing early cellular infiltration and angiogenesis, making such gels a suitable cell substrate for use in the development of composite bioengineered tracheal grafts. The collagen–agarose hydrogel blend is meant to be cast around a three-dimensional (3D) printed polycaprolactone support structure and wrapped in porcine small intestine submucosa ECM to create an off-the-shelf bioengineered tracheal implant.
Symptom Persistence Relates to Volume and Asymmetry of the Limbic System after Mild Traumatic Brain Injury
Authors: Vanier Cheryl , Santhanam Priya , Rochester Nicholas , Carter Lauren , Lim Mike , Kilani Amir , Venkatesh Shivani , Azad Sherwin , Knoblauch Thomas , Surti Tapasya , Brown Colin , Sanchez Justin Roy , Ma Leon , Parikh Shaunaq , Germin Leo , Fazzini Enrico , Snyder Travis H.
Published: August 2024

Background: Persistent symptoms have been reported in up to 50% of the 27 million people with mild traumatic brain injuries (mTBI) every year. MRI findings are currently limited by low diagnostic and prognostic sensitivities, constraining the value of imaging in the stratification of patients following mTBI. Limbic system structures are promising brain regions in offering prognostic factors for symptom persistence following mTBI. The objective of this study was to associate volume and symmetry of limbic system structures with the presence and persistence of common symptoms in patients with mTBI. Methods: This study focused on 524 adults (aged 18–82), 58% female, with 82% injured in motor vehicle accidents and 28% reporting loss of consciousness (LOC). Magnetic resonance imaging (MRI) data included a sagittal 3D T1-weighted sequence with 1.2 mm slice thickness, with voxel sizes of 0.93 mm × 0.93 mm × 1.2 mm, obtained a median of 156 days after injury. Symptom diagnosis and persistence were collected retrospectively from patient medical records. Intracranial volume-adjusted regional volumes per side utilizing automated volumetric analysis (NeuroQuant®) were used to calculate total volume, laterality index, and side-independent asymmetry. Covariates included age, sex, LOC, and days from injury. Limbic volumetrics did not relate to symptom presentation, except the (-) association between headache presence and thalamus volume (adjusted odds ratio = 0.51, 95% confidence interval = 0.32, 0.85). Headache, balance problems, anxiety, and depression persistence was (-) associated with thalamus volume (hazard ratio (HR) 1.25 to 1.94). Longer persistence of balance problems was associated with (-) lateral orbitofrontal cortex volume (HR = 1.33) and (+) asymmetry of the hippocampus (HR = 0.27). Persistence of cognitive deficits was associated with (+) asymmetry in the caudal anterior cingulate (HR = 0.67). Depression persistence was associated with (+) asymmetry in the isthmus of the cingulate gyrus (HR = 5.39). Persistence of anxiety was associated with (-) volume of the parahippocampal gyrus (HR = 1.67), orbitofrontal cortex (HR > 1.97), and right-biased laterality of the entorhinal cortex (HR = 0.52). Conclusions: Relative volume and asymmetry of the limbic system structures in patients with mTBI are associated with the persistence of symptoms, particularly anxiety. The conclusions of this study are limited by the absence of a reference group with no mTBI.
The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience
Authors: Eftimie Spitz Raphaël , Popa Stefan Lucian , Grad Simona , Dumitrascu Dan Lucian , Ismaiel Abdulrahman , Surdea-Blaga Teodora
Published: August 2024

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.
Two Members of Vitamin-K-Dependent Proteins, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), as Possible New Players in the Molecular Mechanism of Osteoarthritis
Authors: Kurtulus Burhan , Atilgan Numan , Yilmaz Mehmet , Dokuyucu Recep
Published: August 2024

Objectives: The pathophysiology of osteoarthritis is mainly unknown. Matrix Gla protein (MGP) and Gla-rich protein (GRP) are both vitamin-K-dependent mineralization inhibitors. In this study, we aimed to compare the levels of MGP and GRP in the synovial fluid of osteoarthritic (OA) and non-osteoarthritic (non-OA) knee joints. Materials and Methods: Two groups were formed, with one consisting of patients with OA and the other non-OA, serving as a control group. The non-OA group included individuals who had arthroscopic surgery for non-cartilage-related issues. In the OA group, all participants had undergone total knee arthroplasty because of grade 4 primary degenerative osteoarthritis. During the operation, at least 1 mL of knee synovial fluid was collected. The GRP and MGP levels in the synovial fluid were measured using an ELISA kit. Results: The mean age in the OA group (62.03 ± 11.53 years) was significantly higher than that in the non-OA group (47.70 ± 14.49 years; p = 0.0001). GRP levels were significantly higher in the OA group (419.61 ± 70.14 ng/mL) compared to the non-OA group (382.18 ± 62.34 ng/mL; p = 0.037). MGP levels were significantly higher in the OA group (67.76 ± 11.36 ng/mL) compared to the non-OA group (53.49 ± 18.28 ng/mL; p = 0.001). Calcium levels (Ca++) were also significantly higher in the OA group (12.89 ± 3.43 mg/dL) compared to the non-OA group (9.51 ± 2.15 mg/dL; p = 0.0001). There was a significantly positive correlation between MGP levels and age (p = 0.011, R = +0.335). Linear regression analysis was performed to determine the effect of age on MGP levels (p = 0.011, R-Square = 0.112). The dependent variable in this analysis was MGP (ng/mL), and age was the predictor. Conclusions: In conclusion, both GRP and MGP are potentially usable biomarkers in osteoarthritis. However, GRP seems to be more valuable because it is not associated with age. In the future, both proteins could provide important contributions to the diagnosis and treatment of osteoarthritis.
Probiotics in the Management of Vulvovaginal Candidosis
Authors: Akinosoglou Karolina , Schinas Georgios , Polyzou Eleni , Tsiakalos Aristotelis , Donders Gilbert G. G.
Published: August 2024

Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics.
Active Biomedical Materials and Their Applications
Authors: Lung Christie Ying Kei
Published: August 2024

Active biomedical materials are designed to heal and restore the functions of people recovering after injuries or diseases [...]
Changing the Mandibular Position in Rowing: A Brief Report of a World-Class Rower
Authors: Cardoso Filipa , Cardoso Ricardo , Fonseca Pedro , Rios Manoel , Vilas-Boas João Paulo , Pinho João C. , Pyne David B. , Fernandes Ricardo J.
Published: August 2024

We investigated the acute biophysical responses of changing the mandibular position during a rowing incremental protocol. A World-class 37-year-old male rower performed two 7 × 3 min ergometer rowing trials, once with no intraoral splint (control) and the other with a mandibular forward repositioning splint (splint condition). Ventilatory, kinematics and body electromyography were evaluated and compared between trials (paired samples t-test, p ≤ 0.05). Under the splint condition, oxygen uptake was lower, particularly at higher exercise intensities (67.3 ± 2.3 vs. 70.9 ± 1.5 mL·kg−1·min−1), and ventilation increased during specific rowing protocol steps (1st–4th and 6th). Wearing the splint condition led to changes in rowing technique, including a slower rowing frequency ([18–30] vs. [19–32] cycles·min−1) and a longer propulsive movement ([1.58–1.52] vs. [1.56–1.50] m) than the control condition. The splint condition also had a faster propulsive phase and a prolonged recovery period than the control condition. The splint reduced peak and mean upper body muscle activation, contrasting with an increase in lower body muscle activity, and generated an energetic benefit by reducing exercise cost and increasing rowing economy compared to the control condition. Changing the mandibular position benefited a World-class rower, supporting the potential of wearing an intraoral splint in high-level sports, particularly in rowing.
Increased Salivary BDNF and Improved Fundamental Motor Skills in Children Following a 3-Month Integrated Neuromuscular Training in Primary School
Authors: Vasileva Fidanka , Font-Lladó Raquel , Carreras-Badosa Gemma , López-Ros Víctor , Ferrusola-Pastrana Anna , López-Bermejo Abel , Prats-Puig Anna
Published: August 2024

Brain-derived neurotrophic factor (BDNF) is a protein involved in synaptic transmission and neuronal plasticity, which underlie the processes of learning and memory formation. Acute exercise and exercise training increase BDNF concentration. We aimed to evaluate the effects of a 3-month integrated neuromuscular training (INT) on salivary BDNF concentration and the mastery of fundamental motor skills in school-aged children. An additional goal was to explore the associations between potential changes in BDNF and fundamental motor skills. Sixty-seven primary school-aged children were randomly allocated to control (N = 32; 7.52 ± 0.31 y) or INT groups (N = 35; 7.56 ± 0.29 y). A 3-month INT was applied during the warm-up of physical education (PE) classes, twice weekly. Salivary BDNF was measured using a sandwich-enzyme-linked immunosorbent assay and the mastery of fundamental motor skills was assessed using the CAMSA test, at baseline and after 3 months. The children in the INT group, as compared to the children in the control group, exhibited higher salivary BDNF (F = 8.865; p = 0.004), higher scores for sidestep (F = 13.240, p = 0.001), 1-foot hop (F = 11.684, p = 0.001), kick (F = 4.010, p = 0.050), the sum of locomotor skills (F = 18.799, p < 0.0001), and the sum of control and manipulative skills (F = 8.151, p = 0.006), as well as the total sum of fundamental motor skills (F = 11.266, p = 0.001) after the 3 months. Interestingly, the increase in salivary BDNF concentration after the 3-month INT was associated with an improvement in locomotor skills (beta = 0.385; p = 0.039; adjusted R2 = 0.088) and the total improvement in fundamental motor skills (beta = 0.428; p = 0.020; adjusted R2 = 0.124). A school-based 3-month INT increased salivary BDNF and improved the mastery of fundamental motor skills in children, highlighting the positive impact of this intervention for a pediatric population.
Artificial Intelligence in Multilingual Interpretation and Radiology Assessment for Clinical Language Evaluation (AI-MIRACLE)
Authors: Khanna Praneet , Dhillon Gagandeep , Buddhavarapu Venkata , Verma Ram , Kashyap Rahul , Grewal Harpreet
Published: August 2024

The AI-MIRACLE Study investigates the efficacy of using ChatGPT 4.0, a large language model (LLM), for translating and simplifying radiology reports into multiple languages, aimed at enhancing patient comprehension. The study assesses the model’s performance across the most spoken languages in the U.S., emphasizing the accuracy and clarity of translated and simplified radiology reports for non-medical readers. This study employed ChatGPT 4.0 to translate and simplify selected radiology reports into Vietnamese, Tagalog, Spanish, Mandarin, and Arabic. Hindi was used as a preliminary test language for validation of the questionnaire. Performance was assessed via Google form surveys distributed to bilingual physicians, which assessed the translation accuracy and clarity of simplified texts provided by ChatGPT 4. Responses from 24 participants showed mixed results. The study underscores the model’s varying success across different languages, emphasizing both potential applications and limitations. ChatGPT 4.0 shows promise in breaking down language barriers in healthcare settings, enhancing patient comprehension of complex medical information. However, the performance is inconsistent across languages, indicating a need for further refinement and more inclusive training of AI models to handle diverse medical contexts and languages. The study highlights the role of LLMs in improving healthcare communication and patient comprehension, while indicating the need for continued advancements in AI technology, particularly in the translation of low-resource languages.
A Comprehensive Literature Review on Diagnostic Strategies and Clinical Outcome of Intraoral Angiosarcoma and Kaposi Sarcoma
Authors: Jayasooriya Primali Rukmal , Weerasinghe Hiruni Ashcharya Wijerathna , Jayasinghe Liyanaarachchige Anushan Hiranya , Peiris Prasangi Madubhashini , Abeyasinghe Wijeyapala Abeyasinghe Mudiyanselage Udari Lakshika , Jayasinghe Ruwan Duminda
Published: August 2024

This review analyzes the clinicopathological features, diagnostic challenges, and clinical outcomes of 60 intraoral angiosarcoma (InO-AS) and 20 intraoral Kaposi sarcoma (InO-KS) cases. These malignancies primarily affect adults, with mean ages of 52.3 years for InO-AS and 44 years for InO-KS, and are rare in children. Both show a male predilection, with InO-KS strongly linked to HIV infection. Metastatic InO-AS typically appears smaller and is located in the mandibular or maxillary gingiva. Most InO-KS cases occur in HIV-positive individuals, often in nodular form. Histological differentiation of InO-AS from poorly differentiated carcinoma and spindle cell carcinoma requires a comprehensive panel of immunohistochemical markers such as CK, CD31, and CD34, while HHV-8 antibody and CD34 help diagnose InO-KS. Treatment for InO-AS involves surgery with radiotherapy and/or chemotherapy, while InO-KS management may include antiretroviral therapy for AIDS patients. InO-AS is aggressive, with over half of patients dying from the disease, whereas InO-KS generally has a less severe course. Despite their rarity, both InO-AS and InO-KS behave similarly to their extraoral counterparts. A key limitation noted in this review is the inconsistent histopathological reporting of AS, particularly regarding histopathological grade, which complicates the assessment and comparison of treatment outcomes.
‘No’ Dimo’ par de Botella’ y Ahora Etamo’ Al Garete’: Exploring the Intersections of Coda /s/, Place, and the Reggaetón Voice
Authors: Powell Derrek
Published: August 2024

The rebranding of reggaetón towards Latin urban has been criticized for tokenizing Afro-Caribbean linguistic and cultural practices as symbolic resources recruitable by non-Caribbean artists/executives in the interest of profit. Consumers are particularly critical of an audible phonological homogeneity in the performances of ethnonationally distinct mainstream performers, framed as a form of linguistic minstrelsy popularly termed a ‘Caribbean Blaccent’ that facilitates capitalization on the genre’s popularity by tapping into the covert prestige of distinctive phonological elements of Insular Caribbean Spanish otherwise stigmatized. This work pairs acoustic analysis with quantitative statistical modeling to compare the use of lenited coronal sibilant allophones popularly considered indexical of Hispano-Caribbean origins in the spoken and sung speech of four of the genre’s top-charting female performers. A general pattern of style-shifting from interview to sung speech wherein sibilance is favored in the former and phonetic zeros in the latter is revealed. Moreover, a statistically significant increased incidence of [-] across time shows the most recent records to uniformly deploy near-categorical reduction independent of artists’ sociocultural and linguistic backgrounds. The results support the enregisterment of practices popularized by the genre’s San Juan-based pioneers as a stylistic resource—a reggaetón voice—for engaging the images of vernacularity sustaining and driving the contemporary, mainstream popularity of música urbana.
Single Center Characterization of a Cohort of Salivary Gland Carcinomas
Authors: Winkelmann Ria , Weißgerber Maja , Wild Peter J. , Bein Julia , Fleischmann Maximilian , Demes Melanie , Balermpas Panagiotis , Loth Andreas , Bankov Katrin , von der Grün Jens
Published: August 2024

Salivary gland cancer (SGC) is a rare cancer that can present a diagnostic challenge to pathologists, with emerging, but still limited options for the treatment of recurrent/metastatic disease. We aimed to characterize the cohort of salivary gland cancers in our institute and generate a tissue microarray (TMA) with clinical data available for immunohistochemical analysis. We extracted the cases of salivary gland cancers in our institute and generated a TMA with 72 patients between 2002 and 2017 with sufficient paraffin block material. Follow-up data were present for all cases. The TMA was stained with three p53 antibodies as well as MSH2, MSH6, PMS2 and MLH1 antibodies. Additionally, we applied fragment analysis based on the Bethesda panel, and the IdyllaTM MSI test to cases with expression loss of any of the mismatch repair proteins (MMR-P) according to our immunohistochemistry (IHC). The investigated cohort shows that pT and pN stage are the only factors independently associated with survival, according to our multivariate analysis (p = 0.037 and p = 0.014). In univariate analysis, risk factors identified in our cohort were also age (p = 0.015), (lympho-) vascular invasion (p = 0.002 and p = 0.003) and risk stratification (p = 0.037). The p53 protein investigated by three antibodies showed no statistically significant association with survival or other tumor characteristics in the investigated cohort. According to MMR-P IHC, six cases of SGC showed an aberrant IHC phenotype. Additional IdyllaTM MSI test and fragment length analysis failed to confirm microsatellite instability. The pT and pN stage are the most important factors for survival in our cohort. In our cohort, antibodies directed against the protein p53 did not contribute to clinical decision-making and were not correlated with any known clinical characteristics. MSI appears to be insignificant in SGCs. Larger cohorts are needed for verification.
Prostate Cancer: Emerging Modifiable Risk Factors and Therapeutic Strategies in the Management of Advanced Cancer
Authors: Bossio Sabrina , Urlandini Lidia , Perri Anna , Conforti Francesco , Aversa Antonio , Di Agostino Silvia , Rago Vittoria
Published: August 2024

Prostate cancer (PCa) is the third highest cause of cancer death in men. PCa is a very heterogeneous tumor form in terms of grade, phenotypes, and genetics, often accompanied by complex networks. PCa is characterized by slow growth that does not compromise the patient’s quality of life, unlike more aggressive forms showing rapid growth and progression. Early diagnosis, even for the most aggressive forms, increases the possibilities of cure with less aggressive treatments and fewer side effects. However, it is important to know how to decrease the exposure to modifiable risk factors, including diet, sedentary life, smoking and alcohol, can represent an effective tool to reduce the incidence of PCa. In addition, the chronic exposure to environmental factors, most of which act as endocrine disruptors, is the focus of recent studies for their potential role in promoting the onset and progression of PCa. Although molecular therapies and clinical trials for biomarker identification have been introduced into the management of PCa, these still lag behind research performed in other solid tumors. This review provides an overview of the modifiable factors of PCa, linked to lifestyle and environmental pollutants, which together with the development of new therapeutic targets, can reduce the incidence of PCa and improve the quality of life of patients.
Theoretical Study of Co-Doping Effects with Different Ions on the Multiferroic Properties of BiFeO3 Nanoparticles
Authors: Apostolov Angel T. , Apostolova Iliana N. , Wesselinowa Julia M.
Published: August 2024

Using a microscopic model and the Green’s function theory, the size and co-doping effects on the multiferroic and optical (band gap) properties of BiFeO3 (BFO) nanoparticles are investigated. The magnetization increases, whereas the band gap energy decreases with decreasing nanoparticle size. The substitution with Co/Mn, Nd/Sm, Ce/Ni, and Cd/Ni is discussed and explained on a microscopic level. By the ion co-doping appear different strains due to the difference between the doping and host ionic radii, which leads to changes in the exchange interaction constants for tuning all properties. It is observed that by co-doping with Nd/Sm at the Bi site or with Co/Mn at the Fe site, the multiferroic properties are larger than those by doping with one ion. Moreover, by doping with Ni, the multiferroic properties are reduced. But by adding another ion (for example Ce or Cd), an increase in these properties is obtained. This shows the advantages of the co-doping, its flexibility, and its greater possibility of tuning the multiferroic properties compared to single ion substitution. The band gap energy decreases for all co-dopants. The polarization increases with increasing magnetic field. This is evidence of magnetoelectric coupling, which is enhanced by co-doping with Co/Mn. The observed theoretical results are in good qualitative agreement with the existing experimental data.