bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug utilization and medication adherence for the treatment of psoriatic arthritis: an Italian study
Authors: Santoleri Fiorenzo , Abrate Paolo , Pestrin Laura , Pasut Enrico , Modesti Germana , Musicco Felice , Fulgenzio Chiara , Zuzolo Eva , Pieri Gabriella , Roperti Martina , Gazzola Pietro , Gambera Marco , Martignoni Isabella , Montresor Valentina , Guarino Francesca , Grossi Laura , Di Fabio Letizia , Roberti Cristina , Spoltore Concetta , Tinari Gabriella , De Rosa Stefania , Giannini Romina , Langella Roberto , Mingolla Grazia , Piccoli Mariantonietta , Costantini Alberto 
Published: October 2024

Introduction: This study aims to evaluate the persistence, treatment adherence and drug cost associated with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the management of psoriatic arthritis (PsA) in Italy, with a focus on biosimilar drugs.
Methods: This was a retrospective observational study involving eight hospital pharmacies, between January 2017 and December 2020, on naïve patients with at least one b/tsDMARD dispensation indicated for PsA. Patients were followed up for 12 months and persistence and adherence were evaluated by proportion of days covered (PDC). The originator and biosimilar for adalimumab and etanercept were compared. Furthermore, the real annual cost per patient based on adherence to therapy was calculated.
Results: Patients initiating b/tsDMARDs for PsA had a mean persistence of 263 days and 48.6% remained persistent for 1 year. Adherent patients (PDC ≥ 0.8) were 47.6% for the overall population. Similar persistence and adherence were observed between patients treated with the adalimumab originator and its biosimilar, while patients treated with the etanercept originator showed lower persistence and adherence compared to those treated with its biosimilar (mean persistence: 222 vs. 267 days, patient persistent at 1 year: 29.4% vs. 51.5%, mean PDC: 0.53 vs. 0.70, adherent patients: 23.5% vs. 51.5%). The average annual drug cost ranged from €8,724 (etanercept) to €14,783 (ustekinumab), with an annual saving of more than €2,500 by using biosimilars.
Conclusion: Poor adherence to medications contributes to suboptimal clinical outcomes. The comparison between biosimilar and originator offers further evidence in support of the biosimilar to optimizing resources in healthcare.
Characteristics of the vaginal microbiota and vaginal metabolites in women with cervical dysplasia
Authors: Yu Tiantian , Gao Shan , Jin Fen , Yan Bingbing , Wang Wendong , Wang Zhongmin 
Published: October 2024

IntroductionEmerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia.MethodsIn this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC–MS)-based metabolomics, and integrated analysis.ResultsThe results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC group-decreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer.DiscussionOur results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.
A Mendelian randomization study on the association between systemic inflammatory regulators and essential and secondary hypertension
Authors: Ji Xiang , Ren Jiao , Dong Feng , Peng Wei 
Published: October 2024

BackgroundInflammation is an important driver of hypertension with numerous components, and there is a paucity of research on the specific inflammatory factors that induce hypertension; therefore, we wanted to investigate the relationship between specific inflammatory factors and hypertension.PurposeA two-sample Mendelian randomization (MR) study was conducted to assess the causal relationship between systemic inflammatory regulators and hypertension (primary or secondary types).Methoda large-scale, published genome-wide association study (GWAS) meta-analysis encompassing 41 cytokines (involved 8,293 Finnish participants from three independent population cohorts: the Cardiovascular Risk in Young Finns Study (YFS), FINRISK1997, and FINRISK2002.)were utilized, a variety of analyses including MR-Egger, weighted median, simple mode and weighted mode were used as sensitive analyses, to corroborate the causal relationship between inflammatory regulators and hypertension. Additionally, we used MR-Egger intercept test and Mendelian Randomization Pleiotropy RE Sidual Sum and Outlier (MR-PRESSO global test) to further evaluate the presence of horizontal pleiotropy.Results3 inflammatory regulators were found related to secondary hypertension, TNFb was negatively associated with risk of secondary hypertension, with a OR of one SD increase in genetically predicted TNFb causing 16.6% (95% CI: 4.4%–27.1%) lower risk of secondary hypertension. Similar trend was also found in MIP1b (OR = 0.91; 95% CI 0.84–0.99, p = 0.024) and MIG (OR = 0.88; 95% CI 0.78–0.99, p = 0.040). Additionally, there was not any evidence of 41 inflammatory regulators associated with primary hypertension.ConclusionThis study supports a negative correlation between TNFb, MIP1b, MIG and secondary hypertension.
Standardizing CRISPR-Cas13 knockdown technique to investigate the role of cdh2 gene in pituitary development through growth hormone expression and transcription factors
Authors: Ventura Fernandes Bianca Helena , Junqueira Mara S. , MacRae Calum , Silveira de Carvalho Luciani R. 
Published: October 2024

IntroductionCongenital hypopituitarism (CH) is characterized by the deficiency of pituitary hormones. Among CH patients, 85% lack a molecular diagnosis. Whole Exome Sequencing (WES) identified a homozygous variant (c.865G&gt;A, p.Val289Ile) in the CDH2 gene, responsible for N-Cadherin production, crucial for cell-cell adhesion. Predicted to be likely pathogenic, the variant was found in a patient deficient in GH, TSH, ACTH, and LH/FSH. Its impact on cell adhesion was confirmed in L1 fibroblast cell lines.ObjectiveCreate a cdh2 knockdown in zebrafish for investigating its role in pituitary development through growth hormone and transcription factors expression.MethodsUtilized pET28B-RfxCas13d-His plasmid for Cas13 mRNA production via in vitro transcription, guiding Cas13 to cdh2 with three RNAs. Injected the complex into single-cell embryos for analysis up to 96 hpf. Assessed gene expression of cdh2, prop1, pit1, and gh1 using RT-qPCR. Evaluated cdh2 protein expression through the western blot technique.ResultsKnockdown animals displayed developmental delay. The cdh2 expression decreased by 75% within 24 hours, rebounded by 48 hours, and reached wild-type levels by 96 hpf. gh1 expression decreased at 48h but increased by 96 hpf, aligning with WT. No significant differences in prop1 and pit1 expression were observed.ConclusionOur findings underscore cdh2’s role in pituitary development and hormonal regulation, offering insights for developmental biology research.
Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention
Authors: Cameron Cheryl M. , Raghu Vineet , Richardson Brian , Zagore Leah L. , Tamilselvan Banumathi , Golden Jackelyn , Cartwright Michael , Schoen Robert E. , Finn Olivera J. , Benos Panayiotis V. , Cameron Mark J. 
Published: October 2024

IntroductionSelf-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine.MethodsHere we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses.ResultsMUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-κB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy.DiscussionThese findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness.
Quality-controlled characterization of a monoclonal antibody specific to an EC5-domain of human desmoglein 3 for pemphigus research
Authors: Eming Rüdiger , Riaz Shafaq , Müller Eliane J. , Zakrzewicz Anna , Linne Uwe , Tikkanen Ritva , Zimmer Christine Lea , Hudemann Christoph 
Published: October 2024

BackgroundPemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 auto-abs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community.MethodsPreviously, we have introduced a novel Dsg3 EC5-binding antibody termed 2G4 that may potentially serve as a superior tool for numerous PV related analysis. The purpose of this study was to develop a quality-controlled production and verification process that allows I) a continuous quality improvement, and II) a verified and comprehensible overall quality with regard to pathogenic antigen-specific binding in a variety of pemphigus assays for each batch production.ResultsThus, a workflow based on a standardized operating procedure was established. This includes the verification of purity and in-vitro binding capacity (SDS-page, direct and indirect immunofluorescence) as primary parameters, and size analysis by mass-spectrometry and ex-vivo pathogenicity by monolayer dissociation assay.ConclusionWe here present an extensive point-by-point quality controlled IgG production protocol, which will serve as a basis for a standardized antibody assessment in PV research.
Sentiment analysis of subcutaneous and intravenous immunoglobulin therapy: public healthcare perception through social media discourse
Authors: Tarango-García Alejandro , Rodríguez-Narciso Silvia , Castañeda-Leyva Netzahualcóyotl , Prieto-Nevárez Hannia M. , Lugo Reyes Saul O. , Espinosa-Rosales Francisco J. , Espinosa-Padilla Sara Elva , Staines-Boone Aidé T. , Torres-Bernal Luis F. , Álvarez-Cardona Aristóteles 
Published: October 2024

PurposeImmunoglobulin replacement therapy remains a cornerstone of treatment in antibody deficiencies and other inborn errors of immunity. While patient preferences between subcutaneous and intravenous immunoglobulin have been studied through questionnaires, no study has yet explored patient perspectives in a free environment. Therefore, we aimed to conduct a sentiment analysis as well as a temporal and geographical analysis on public opinions obtained from social media to better understand patient satisfaction and public perception on immunoglobulin therapy.MethodsA dataset of 43,700 tweets spanning from the 1st of January of 2012 to the 31st of December of 2022 was obtained. A Valence Aware Dictionary for Sentiment Reasoning sentiment analysis was performed, followed by statistical, geographical and temporal analyses.ResultsMean polarity of intravenous immunoglobulin related tweets was 0.1295 (positive), while mean polarity for subcutaneous immunoglobulin was 0.2117 (positive). Temporal analysis through a statistical model demonstrated that the volume of tweets increased over time for both subcutaneous and intravenous treatment. Geographical analysis revealed that the majority of texts originated from the United States. The highest mean polarity was observed in Romania with a mean value of 0.2966, while the lowest polarity was documented in Norway with a mean of -0.0211.ConclusionTweets linked to subcutaneous immunoglobulin treatment had a higher average polarity, indicating a more positive public perception. The amount of tweets relating to both therapies showed a tendency to increase as the years progressed, implying an increase in public discussion on immunoglobulin treatment.
Intranasal sensitization model of alopecia areata using pertussis toxin as adjuvant
Authors: Liu Yuying , Freeborn Jasmin , Okeugo Beanna , Armbrister Shabba A. , Saleh Zeina M. , Fadhel Alvarez Ana Beatriz , Hoang Thomas K. , Park Evelyn S. , Lindsey John William , Rapini Ronald P. , Glazer Steven , Rubin Keith , Rhoads Jon Marc 
Published: October 2024

BackgroundNasopharyngeal Bordetella pertussis (BP) colonization is common, with about 5% of individuals having PCR evidence of subclinical BP infection on nasal swab, even in countries with high vaccination rates. BP secretes pertussis toxin (PTx). PTx is an adjuvant commonly used to induce autoimmunity in multiple animal models of human disease. Colocalization of PTx and myelin from myelinated nerves in the nasopharynx may lead to host sensitization to myelin with subsequent autoimmune pathology.MethodsC57BL/6J female adult mice were given varied doses and schedules of intranasal PTx, MOG35-55 antigen, or controls to test whether intranasal administration of PTx and myelin oligodendrocyte peptide (MOG35-55) could induce experimental autoimmune encephalomyelitis (EAE) in mice. While we observed systemic cell-mediated immunity against MOG35-55, we did not observe EAE. Unexpectedly, many mice developed alopecia. We systematically investigated this finding.ResultsPatchy alopecia developed in 36.4% of mice with the optimized protocol. Pathology consistent with alopecia areata was confirmed histologically by documenting concomitant reduced anagen phase and increased telogen phase hair follicles (HFs) in biopsies from patches of hair loss in mice with alopecia. We also found reduced CD200 staining and increased CD3+T cells surrounding the HFs of mice with alopecia compared to the mice without alopecia, indicating HF Immune Privilege (HFIP) collapse. Systemic immune responses were also found, with increased proportions of activated T cells and B cells, as well as MHCII+ dendritic cells in peripheral blood and/or splenocytes. Finally, in mice initially exposed to intranasal MOG35-55 and PTx in combination, but not to either agent alone, splenocytes were shown to proliferate after in vitro stimulation by MOG35-55. Consistent with prior investigations, PTx exhibited a dose-response effect on immune cell induction and phenotype, with the lowest PTx dose failing to induce autoimmunity, the highest PTx dose suppressing autoimmunity, and intermediate doses optimizing autoimmunity.ConclusionsWe propose that this is the first report of an autoimmune disease in an animal model triggered by colocalization of intranasal PTx and autoantigen. This model parallels a natural exposure and potential intranasal sensitization-to-pathology paradigm and supports the plausibility that nasopharyngeal subclinical BP colonization is a cause of alopecia areata.
A bibliometric analysis of diabetic gastroparesis from 1979 to 2024
Authors: Xu Hui , Miao Furui , Fan Yushan 
Published: October 2024

ObjectiveGastroparesis is one of the complications of diabetes mellitus, which has a major impact on the quality of life of patients, and the limited therapeutic options currently available make it a public health problem. No bibliometric studies on diabetic gastroparesis have been published to date. Therefore, the aim of this paper is to summarize and analyze the research hotspots for researchers.MethodsResearch articles related to Diabetic gastroparesis were searched in Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A comprehensive bibliometric analysis of 699 publications was conducted using Microsoft Excel 2019, Citespace and VOSviewers.ResultA total of 699 papers from 738 institutions in 41 countries were retrieved. Publications in this field have increased rapidly since 1979. USA (n = 370) and Mayo Clinical (n = 69) were the most productive country and institution, respectively. Neurogastroenterology and Motility (n = 67) was the most published journal with Parkman, Henry P. (n = 40) having the highest number of articles; Gastroenterology and Mccallum, Richard W. were the most influential journals and authors.ConclusionsThe research hotspots of Diabetic gastroparesis are mainly focused on treatment modalities and pathological mechanisms. Future research in diabetic gastroparesis will focus on exploring the pathomechanisms, finding long-term effective treatments, and improving patients' quality of life.
Asthma and hypertension: the role of airway inflammation
Authors: Visca Dina , Ardesi Francesco , Zappa Martina , Pignatti Patrizia , Grossi Sarah , Vanetti Marco , Migliori Giovanni Battista , Centis Rosella , Angeli Fabio , Spanevello Antonio 
Published: October 2024

IntroductionAsthma is a chronic inflammatory respiratory disease often associated with comorbidities. Among cardiovascular comorbidities, arterial hypertension seems to create an additional health burden in asthmatics. However, evidence on this relationship is lacking.ObjectiveOur study aims to evaluate the characteristics of hypertensive asthmatics, focusing on the role of inflammation as a possible link between these diseases.MethodsWe conducted a monocentric retrospective analysis consecutively including asthmatics who underwent induced sputum (IS) at our asthma referral center. Patients were divided in two groups according to presence or absence of history of hypertension. Clinical, functional, and inflammatory (airway and systemic) data were collected.ResultsData on two hundred and sixty asthmatic patients were analyzed. Seventy-nine (30.4%) of them had a diagnosis of hypertension requiring a specific pharmacological treatment. Asthmatics with hypertension were more frequently male (p = 0.047), older (p &lt; 0.001), and with higher body max index (BMI) (p &lt; 0.001) when compared to normotensive patients. No difference concerning asthma control, severity and pharmacological treatment was observed between the two groups (all p &gt; 0.05); distribution of comorbidities and lung function impairment (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC); all p &lt; 0.05) were statistically different between groups. Mixed granulocytic airway inflammation was prevalent in the hypertensive asthmatics (p = 0.014). Interestingly, a multivariable analysis revealed that age ≥ 65 years and an increased percentage of sputum neutrophils (≥61%) were independent predictors of hypertensive status (p &lt; 0.001).ConclusionOur data suggest that neutrophilic airway inflammation (as evaluated by induced sputum) is strictly associated with hypertension. In clinical practice, phenotyping asthmatic patients with comorbidities like hypertension could be useful also from a therapeutic point of view. Additional studies are mandatory to further elucidate the role of neutrophilic airway inflammation in asthma with cardiovascular diseases.
A comparison of the effects of lung protective ventilation and conventional ventilation on the occurrence of atelectasis during laparoscopic surgery in young infants: a randomized controlled trial
Authors: Yue Kun , Wang Jingru , Wu Huangxing , Sun Yingying , Xia Yin , Chen Qi 
Published: October 2024

ObjectiveThis study utilized lung ultrasound to investigate whether lung protective ventilation reduces pulmonary atelectasis and improves intraoperative oxygenation in infants undergoing laparoscopic surgery.MethodsEighty young infants (aged 1–6 months) who received general anesthesia for more than 2 h during laparoscopic surgery were randomized into the lung protective ventilation group (LPV group) and the conventional ventilation group (control group). The LPV group received mechanical ventilation starting at 6 mL/kg tidal volume, 5 cmH2O PEEP, 60% inspired oxygen fraction, and half-hourly alveolar recruitment maneuvers. Control group ventilation began with 8–10 mL/kg tidal volume, 0 cmH2O PEEP, and 60% inspired oxygen fraction. Lung ultrasound was conducted five times—T1 (5 min post-intubation), T2 (5 min post-pneumoperitoneum), T3 (at the end of surgery), T4 (post-extubation), and T5 (prior to discharge from the PACU)—for each infant. Simultaneous arterial blood gas analysis was performed at T1, T2, T3, and T4.ResultsStatistically significant differences were observed in pulmonary atelectasis incidence, lung ultrasound scores, and the PaO2, PaCO2, PaO2/FiO2 ratios at T2, T3, and T4. However, at T5, no statistically significant differences were noted in terms of lung ultrasound scores (4.30 ± 1.87 vs. 5.00 ± 2.43, 95% CI: −1.67 to 0.27, p = 0.153) or the incidence of pulmonary atelectasis (32.5% vs. 47.5%, p = 0.171).ConclusionIn infants aged 1–6 months, lung protective ventilation during laparoscopy under general anesthesia significantly reduced the incidence of pulmonary atelectasis and enhanced intraoperative oxygenation and dynamic lung compliance compared to conventional ventilation. However, these benefits did not persist; no differences were observed in lung ultrasound scores or the incidence of pulmonary atelectasis at PACU discharge.Clinical trial registrationhttp://www.chictr.org.cn/, identifier: ChiCTR2200058653.