bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technological approaches to improve the bioavailability of the poor soluble substance Candesartan Cilexetil in mini-tablets
Authors: Tserkovnaya K. M. , Surbeeva E. S. , Gusev K. A. , Vishnyakov E. V. , Flisyuk E. V. , Narkevich I. A. 
Published: December 2024

Introduction. The polypill in the form of a hard gelatin capsule containing mini-tablets of the original antihypertensive combination is being developed at the Saint-Petersburg State Chemical and Pharmaceutical University. One of the components of the polypill is Candesartan, which has high antihypertensive activity and organoprotective properties. The active pharmaceutical ingredient (API) of Candesartan Cilexetil is characterized by low solubility in water and gastrointestinal tract media, therefore increasing the solubility of this substance can lead to a significant improving the bioavailability.Aim. Comparative analysis of technological approaches to increasing the bioavailability of the poor soluble API Сandesartan Сilexetil in a mini-tablet dosage form.Materials and methods. API Сandesartan Сilexetil, β-cyclodextrin (β-CD), copolymer of polyvinylpyrrolidone and vinyl acetate and excipients for the production of mini-tablets, such as diluents, binders, disintegrant, dusting components were used. The release profiles of Candesartan Cilexetil from the developed mini-tablets were assessed in comparison with the original drug Atacand®, 8 mg tablets. The complex of candesartan cilexetil with β-CD in a 1 : 1 ratio was prepared by three methods: dry mixing, paste method and lyophilization. A solid dispersion (SD) of candesartan was obtained by hot melt extrusion. The API complexes with β-CD and SD were characterized by FTIR-spectroscopy and differential scanning calorimetry. Tablet mixtures were produced by dry mixing and wet granulation technology. Mini-tablets were obtained on a laboratory automatic single-punch tablet press. Quality control of the mini-tablets was conducted by the methods of State Pharmacopoeia of the Russian Federation XV ed. and United State Pharmacopeia methods.Results and discussion. Comparative analysis of technological approaches to increasing the bioavailability of Candesartan Cilexetil showed, that preparation of a complex including API with β-CD in a 1 : 1 ratio using the paste method with further using of wet granulation technology allowed to obtain mini-tablets with improved release of poor soluble API compared to the original drug. On the contrary, the use of TDS in mini-tablet technology led to a slower release of API compared to the original drug. The developed mini-tablets of Candesartan composition № 7 met pharmacopoeial requirements by all acceptance criteria.Conclusion. The creation of complex of Candesartan Cilexetil with β-CD by the paste method with further using of wet granulation technology is the optimal technological approach to increasing the bioavailability of the poor soluble API Candesartan Cilexetil in mini-tablets.
Longitudinal ozone exposure and SARS-CoV-2 infection in late pregnancy: a retrospective cohort study
Authors: Zhang Lin , Tian Jiaqi , Duan Shuyin 
Published: December 2024

BackgroundAtmospheric ozone is a common air pollutant with known impacts on maternal and fetal health. However, the relationship between gestational ozone exposure and susceptibility to respirovirus infection remains unclear. This study aims to assess the association between longitudinal ozone exposure during pregnancy and COVID-19 risk in late gestation.MethodsThis retrospective cohort study included 600 pregnant women (300 infected with SARS-CoV-2 and 300 uninfected) who delivered at one hospital in Jinan, China from November 2022 to January 2023. Individual ozone exposure levels throughout gestation were estimated based on local ambient monitoring data. Logistic regression models were constructed to examine the association between gestational ozone exposure and COVID-19 status in late pregnancy, adjusting for demographic and clinical variables.ResultsIn Jinan, ozone levels increased by 1.85 ppb annually and peaked between April and October, corresponding to winds from the south and southwest. Higher ozone exposure over pregnancy was associated with lower odds of SARS-CoV-2 infection in late gestation (OR per IQR increase = 0.60, 95% CI: 0.40-0.90). Compared to the lowest quartile (reference), the highest ozone quartile corresponded to a 99% decreased infection risk (OR = 0.01, 95% CI: 0.00-0.03). Increased maternal age and pre-pregnancy BMI were associated with higher COVID-19 risk.ConclusionsLongitudinal ozone exposure during gestation may be protective against SARS-CoV-2 infection in late pregnancy. Further studies are needed to confirm this finding and elucidate underlying mechanisms. These results highlight the potential importance of environmental exposures in COVID-19 susceptibility.
Dyslipidemia and associated factors among adult type two diabetes mellitus patients in Felege Hiywot Refral, Hospital, Bahir Dar, Ethiopia, 2023
Authors: Addis Zemenu , Nega Ayenew Tega , Tebeje Robel Demelash , Asmare Engdaw , Tegegnie Alemu Bezabih , Tamir Workineh , Alene Tamiru 
Published: December 2024

BackgroundDyslipidemia is a common condition in type two diabetic patients, and it is thought to have a significant role in moderating the cardiovascular risk associated with diabetes. Data on serum lipid profiles in type 2 diabetes patients from Bahir Dar, Ethiopia is limited. This study aimed to evaluate the prevalence of dyslipidemia among adult type 2 diabetes patients and to explore potential contributing factors.Method and materialsA facility-based cross-sectional study was conducted with 354 type 2 diabetes mellitus patients from April 3 to June 4, 2023. Data were collected through the use of structured questionnaires and checklists. The data were entered into EpiData version 4.6 and analyzed using SPSS version 26. Logistic regression was employed to identify variables significantly associated with the outcomes, with a p-value ≤ 0.05 and a 95% confidence interval.ResultsA total of 369 individuals with diabetes were approached in this study, resulting in a response rate of 96%. The overall prevalence of dyslipidemia was 61.3% (95% CI: 56.2–66.7). Of those with dyslipidemia, 11% had a single serum lipid abnormality, while 50.3% had a combined serum lipid abnormality. Significant factors associated with dyslipidemia included being over 60 years old (AOR: 2.4, 95% CI: 1.2–5.0), poor fasting blood glucose control (AOR: 2.5, 95% CI: 1.2–5.1), being overweight (AOR: 5.8, 95% CI: 3.2–11), physical inactivity (AOR: 3.4, 95% CI: 1.7–7.0), and being a past alcohol drinker (AOR: 3.1, 95% CI: 1.3–7.4).ConclusionIn the study area, a high prevalence of dyslipidemia was found among diabetic patients. Independent factors associated with dyslipidemia included older age, poor fasting blood glucose control, physical inactivity, a history of alcohol consumption, and being overweight. To address this issue, it is essential to implement preventive measures such as early detection, patient education, dietary monitoring, regular clinical visits, physical exercise, and weight management. These strategies represent the most effective approach to combating dyslipidemia.
Referential gaps between Arabic and English
Authors: Alhendi Noor , Baniamer Asem 
Published: December 2024

IntroductionThe study addresses the phenomenon of referential gaps between Arabic and English, highlighting the distinct referential behaviors each language employs during communication. These differences pose challenges to both language recipients and educators, creating obstacles for Arabic and English teachers and learners alike. Understanding these gaps is crucial for improving language learning and teaching processes.MethodsThe study investigates referential gaps by analyzing their manifestations across four linguistic levels: phonetic, lexical, morphological, and syntactic systems in both Arabic and English.ResultsThe findings demonstrate that the distinct referential behaviors in Arabic and English differ significantly across the analyzed linguistic levels. These differences contribute to the challenges faced by language learners and educators.DiscussionThe study underscores the importance of understanding referential gaps to address the challenges they present. By highlighting these differences, it provides insights into improving teaching strategies and fostering better communication between Arabic and English speakers.
Novel MKRN3 gene mutation associated with central precocious puberty in a Chinese child: a case report
Authors: Wang Jingna , Li Rongmin , Wang Jieying , Wu Di , Lei Shuqin , Sang Yanmei , Chang Jie 
Published: December 2024

ObjectiveThe objective of this study is to investigate the clinical presentation and underlying genetic etiology of a Chinese child diagnosed with idiopathic central precocious puberty (ICPP).MethodsClinical data from a pediatric patient with ICPP, including medical history, physical examination findings, laboratory results, and imaging studies, were collected and analyzed. Whole exome sequencing (WES) was performed to identify potential pathogenic genetic variants underlying the patient’s ICPP.ResultsA 4 ¾-year-old female patient presented with precocious puberty, characterized by accelerated growth, Tanner stage II breast development, and Tanner stage I pubic hair. A café-au-lait macule was observed on the patient’s right flank. WES revealed a novel makorin RING finger protein 3 (MKRN3) gene heterozygous frameshift pathogenic variant c.1219delA (p.R407Gfs*75), which was inherited from the patient’s asymptomatic father, and leading to a truncated protein 73 amino acids downstream from the mutation site.ConclusionThis case underscores the genetic heterogeneity of ICPP and further implicates MKRN3 gene mutations in its pathogenesis. The identification of this novel pathogenic variant expands the known mutational spectrum associated with ICPP, particularly within the Chinese pediatric population. Comprehensive genetic testing should be considered in pediatric patients presenting with early-onset ICPP to facilitate accurate diagnosis, inform genetic counseling, and guide personalized management strategies.
Association of the immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination with computed tomography muscle images in patients with muscular disorders
Authors: Naka Tomoaki , Funato Michinori , Yasuda Kunihiko , Nakayama Takahiro , Kuru Satoshi 
Published: December 2024

BackgroundsIntramuscular mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a low intensity and latency of antibody response in patients with muscular disorders (MDs). However, the mechanisms involved in this phenomenon remain unknown. This study aimed to clarify the mechanism of the low immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination in patients with MDs.MethodsWe evaluated 44 individuals, including 23 patients with MDs and 21 patients without MDs. The median age of the patients was 39 years (range 20–63 years). The anti-SARS-CoV-2 spike protein receptor-binding domain (S-RBD) IgG levels from a previous study were reused. Mean computed tomography (CT) values and areas of the deltoid muscle from CT images were measured, and they were compared with the anti-SARS-CoV-2 S-RBD IgG levels.ResultsOne month following the second vaccination, the antibody response among patients with MDs showed a low tendency compared with that among patients without MDs. Surprisingly, a similar pattern was observed when comparing mean CT values. Patients with mean CT values of zero HU and lower had a lower tendency of antibody response after the intramuscular administration of SARS-CoV-2 mRNA vaccines.ConclusionThe low immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination against MDs may be mainly affected by disease type and MD pathogenesis. However, SARS-CoV-2 immunization in patients with MDs warrants further investigation.
Development of a two-component recombinant vaccine for COVID-19
Authors: Sun Yi-Sheng , Xu Fang , Zhu Han-Ping , Xia Yong , Li Qiao-Min , Luo Yuan-Yuan , Lu Hang-Jing , Wu Bei-Bei , Wang Zhen , Yao Ping-Ping , Zhou Zhan 
Published: December 2024

IntroductionThough COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.MethodsIn the two-dose immunization experiment, female BALB/c mice were intramuscularly immunized with different ratios of RBD-Fc and NTD-Fc proteins, with a total protein dose of 8 μg per mouse. Mice were immunized on day 0 and boosted on day 7. In the sequential immunization experiment, groups of female BALB/c mice were immunized with two doses of the inactivated SARS-CoV-2 vaccine (prototype strain) on day 0 and 7. On day 28, mice were boosted with RBD-Fc, NTD-Fc, RBD-Fc/NTD-Fc (9:1), RBD-Fc/NTD-Fc (3:1), inactivated SARS-CoV-2 vaccine (protoype strain), inactivated SARS-CoV-2 vaccine (omicron strain), individually. The IgG antibodies were detected using ELISA, while the neutralizing antibodies were measured through a microneutralization assay utilizing both the prototype and omicron strains. The ELISPOT assays were performed to measure the secretion of IL-4 and IFN-γ, and the concentrations of secreted IL-2 and IL-10 in the supernatants were measured by ELISA.ResultsWe have first developed a two-component recombinant vaccine for COVID-19 based on RBD-Fc and NTD-Fc proteins, with an optimal RBD-Fc/NTD-Fc ratio of 3:1. This novel two-component vaccine demonstrated the ability to induce durable and potent IgG antibodies, as well as the neutralizing antibodies in both the two-dose homologous and sequential vaccinations. Heterologous booster with this two-component vaccine could induce higher neutralizing antibody titers than the homologous group. Additionally, the vaccine elicited relatively balanced Th1- and Th2-cell immune responses.ConclusionThis novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.
Very low doses of rituximab in autoimmune hemolytic anemia—an open-label, phase II pilot trial
Authors: Moser Miriam M. , Thalhammer Renate , Sillaber Christian , Derhaschnig Ulla , Firbas Christa , Jäger Ulrich , Jilma Bernd , Schoergenhofer Christian 
Published: December 2024

IntroductionAlthough rituximab is approved for several autoimmune diseases, no formal dose finding studies have been conducted. The amount of CD20+ cells differs significantly between autoimmune diseases and B-cell malignancies. Hence, dose requirements of anti-CD20 therapies may differ accordingly.MethodsWe conducted a phase II pilot trial investigating the effects and safety of very low doses of rituximab, i.e., 5 mg/m2 every 3 weeks, 20 mg every 4 weeks, 50 mg every 3 months (n = 3 each) and 100 mg every 3 months (n = 1) in patients with autoimmune hemolytic anemia (AIHA) to effectively suppress CD20+ cell counts. Doses were increased if circulating CD20+ cell depletion was insufficient (i.e., &lt;95% reduction from baseline) in a dose group. Plasma rituximab concentrations were quantified by enzyme-linked immunosorbent assay, CD20+ cell counts were determined by flow cytometry.ResultsTen patients were included in the final analysis (7 with cold agglutinin disease, 2 with warm AIHA, 1 with mixed-type AIHA). The first infusion depleted ≥95% of CD20+ cells in all but one of the included patients. However, the dosing regimens were found ineffective, because a sustained CD20+ cell depletion was not achieved, and CD20+ cells recovered with a high interindividual variability. CD20+ lymphocytes were below the detection limit if rituximab plasma concentrations exceeded 0.4 μg/mL. One endokarditis occured.ConclusionRituximab doses as low as 5 mg/m2 transiently depleted CD20+ cells in almost all patients, but the tested low-dose regimens failed to permanently suppress CD20+ cells. The empirically identified EC95% of 0.4 μg/mL rituximab may guide future studies using low-doses of rituximab.Clinical trial registrationhttps://clinicaltrials.gov/, identifier [EudraCT 2016-002478-11].
Identification and treatment of Enterococcus avium-induced diabetic foot ulcer: a case report and microbiome analysis
Authors: Jin Yuanling , Zhu Tao , Cai Xiao , Fu Zheng , Pan QiangLong , Tu HaiXia , Wang ShouXing , Li Yan 
Published: December 2024

AbstractDiabetic foot ulcer (DFU) is a severe complication of diabetes. Due to conservative or delayed treatment, the majority of DFU patients frequently miss the optimal treatment window, thereby leading to amputation. Despite being a rare pathogen with low virulence, Enterococcus avium (E. avium) exhibits some antibiotic resistance and can be fatal for immunocompromised patients. This report describes a DFU case, caused by E. avium infection due to exposure to poultry. Wound microbiota was dynamically monitored using bacterial culture followed by 16S rRNA gene sequencing throughout the illness. Combination of antibiotics was administered to control the secondary infection.Case reportA 56-year-old man presented with a two-week history of redness, swelling, heat, pain, and pus discharge from a ruptured wound on his left heel. The patient was diagnosed with osteomyelitis and a Wagner grade 3 diabetic foot ulcer infection, complicated by the soft tissue infection in the left heel. Strain identification and antibiotic susceptibility tests were immediately performed after admission. The patient underwent three debridement procedures at the DFU site. However, we observed recurrent bacterial infections, based on the clinical progression. Second-generation sequencing detected various pathogens. After targeted treatment with Vacuum sealing drainage (VSD) combined with antibiotic bone cement, the patient’s condition stabilised. A skin graft was subsequently performed. Antibiotics were used to control the infection and blood glucose level was controlled throughout the treatment.ConclusionThus, this report provides a comprehensive description of a DFU case, caused by E. avium. Antibiotics and surgical measures should be adjusted according to the pathogens responsible for wound infections in DFU patients. It is important to reduce the mortality and prevent irreversible amputations.
Mapping the current trends and hotspots of extracellular vesicles in Alzheimer's disease: a bibliometric analysis
Authors: Xing Xiaolian , Liu Hongwei , Zhang Minheng , Li Yang 
Published: December 2024

BackgroundExtracellular vesicles (EVs) have garnered significant attention in Alzheimer's disease (AD) research over the past decade, largely due to their potential in diagnostics and therapeutics. Although the investigation of EVs in AD is a relatively recent endeavor, a comprehensive bibliometric analysis of this rapidly growing field has yet to be conducted.MethodsThis study aims to elucidate and synthesize the relationship between EVs and AD, offering critical insights to guide future research and expand therapeutic possibilities. Over the past 10–15 years, substantial progress has been made in this domain. Through bibliometric techniques, this analysis assesses research performance by examining scientific publications and metrics, including productivity indicators, impact measurements, data mining, and visualization tools.ResultsA total of 602 publications were analyzed using various online platforms for bibliometric analysis. Notably, the number of publications began to increase rapidly in 2018, with China and the United States emerging as leaders in this research area. The National Institute on Aging produced the highest number of publications among institutions. The Journal of Molecular Sciences and the Journal of Biological Chemistry were the most prolific and most frequently cited journals, respectively. Among individual contributors, Dimitrios Kapogiannis was identified as the most productive author, while Edward J. Goetzl was the most co-cited. The most prevalent keywords included “neurodegenerative diseases,” “exosomes,” “blood biomarkers,” “amyloid beta,” “microglia,” and “tau protein.” Current research hotspots involve microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs, indicating key areas for future research.ConclusionResearch on microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs represents a critical frontier in the study of Alzheimer's disease. The role of EV-mediated neuroinflammation in AD is a focal point of ongoing investigation and will likely shape future developments in the field.
Association between metallic implants and stroke in US adults from NHANES 2015–2023 a cross-sectional study
Authors: Wu Kai , Pang Liang , Su Pingping , Lv Cunxian 
Published: December 2024

ObjectiveMetal implants play a vital role in orthopedic treatment and are widely used in fracture repair, joint replacement and spinal surgery. Although these implants often contain key elements such as chromium (Cr), their potential health effects, particularly their association with stroke risk, have not been fully elucidated. This study aimed to evaluate the association between metallic implants and stroke.MethodsUsing data from the 2015 to 2023 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional analysis of 12,337 US adults, in which 3,699 participants reported having metal implants and 8,638 without. Implant-like.ResultsThrough logistic regression analysis, we revealed a significant positive association between metallic implants and stroke risk (adjusted OR = 1.458, 95%CI (1.130, 1.881), p = 0.004). Further stratified analysis found that this positive association was more significant among older and less physically active participants.ConclusionFindings suggest that metallic implants may be associated with an increased risk of stroke, but given the inherent limitations of cross-sectional studies, this study cannot establish causality.