bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of the initial manifestations and renal involvement of chinese patients with classical and late-onset Fabry disease at different sexes and ages
Authors: Guo Wenkai , Xie Yuansheng , Ji Pengcheng , Li Shuang , Cai Guangyan , Chen Xiangmei 
Published: April 2023

Abstract
Background
Fabry disease is a rare hereditary disease involving multiple organs, and there are few reports on how the initial manifestations and renal involvement of these patients with classical and late-onset phenotype evolve with sexes and ages. To improve clinicians’ understanding of Fabry disease and avoid misdiagnoses by discussing the initial manifestations, first medical specialties visited and renal involvement development in patients.

Methods
This study collected relevant data from 311 Chinese Fabry disease patients (200 males, 111 females) and descriptive statistical analysis was used to analyze the evolution of the initial manifestations and renal involvement of patients with classical and late-onset phenotype at different sexes and ages.

Results
Regarding the age at manifestation onset, age at the first medical specialty visited and age at the diagnosis of Fabry disease, males were earlier than females, and males with classical phenotype were earlier than males with late-onset and females with classical phenotype. In both male and female patients, the initial manifestations of classical patients were mainly acroparesthesia, and the first medical specialty visited were mainly pediatrics and neurology. The initial manifestations of late-onset patients were mainly renal and cardiovascular involvement, and the first medical specialty visited were mainly nephrology and cardiology. In classical patients, both male and female, the initial manifestations of the preschool and the juvenile groups were mainly acroparesthesia, and the frequency of renal and cardiovascular involvement in the young group was higher than that in the preschool and juvenile groups. There was no obvious renal involvement in the preschool group, renal involvement was most common in the young group and the middle-aged and elderly group. Proteinuria can appear in classical male patients as early as approximately 20 years, and renal insufficiency can occur at approximately 25 years. With age, over 50% of classical male patients can develop varying degrees of proteinuria at the age of 25 and renal insufficiency at the age of 40. 15.94% of the patients progressed to dialysis or kidney transplantation, mainly classical males.

Conclusions
The initial manifestation of Fabry disease is affected by sex, age and classical/late-onset phenotype. The initial manifestations were mainly acroparesthesia and the frequency and degree of renal involvement increased gradually with aging in classical male patients.
A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia
Authors: Cañas Alejandro E. , Troutt Hayden R. , Jiang Luohua , Tonthat Sam , Darwish Omar , Ferrey Antoney , Lotfipour Shahram , Kalantar-Zadeh Kamyar , Hanna Ramy , Lau Wei Ling 
Published: April 2023

Abstract
Background
The KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy.

Methods
Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics).

Discussion
The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.

Trial registration
ClinicalTrials.gov Identifier: NCT04585542. Registered 14 October 2020.
Amygdala signal abnormality and cognitive impairment in drug-naïve schizophrenia
Authors: Guo Huagui , Ye Haibiao , Li Zhijian , Li Xuesong , Huang Wei , Yang Yu , Xie Guojun , Xu Caixia , Li Xiaoling , Liang Wenting , Jing Huan , Zhang Chunguo , Tang Chaohua , Liang Jiaquan 
Published: April 2023

Abstract
Background
Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study.

Methods
We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People’s Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC’s amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS.

Results
(1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p < 0.001), and the Fractional amplitude of low-frequency fluctuations (FALFF) values of bilateral amygdala increased (tL=3.916, p < 0.001; tR=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p < 0.001; rR=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively.

Conclusion
The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.
Six Spain Thymus essential oils composition analysis and their in vitro and in silico study against Streptococcus mutans
Authors: Park Su-Yeon , Raka Rifat Nowshin , Hui Xiu-Li , Song Yang , Sun Jin-Long , Xiang Jie , Wang Juan , Jin Jian-Ming , Li Xu-Kai , Xiao Jun-Song , Wu Hua 
Published: April 2023

Abstract
Background
Streptococcus mutans is a well-known oral pathogen that plays a critical role in the development of dental caries. Many studies have been directed to discover the chemical compounds present in natural products to inhibit the growth and biofilm formation activity of S. mutans. Thymus essential oils exhibit good inhibition on the growth and pathogenesis of S. mutans. However, details about the active compounds in Thymus essential oil and the inhibition mechanism still remain unclear. The aim of this study was to investigate the antimicrobial activity of 6 Thymus species (Three samples of Thymus vulgaris, two samples of Thymus zygis, and one sample of Thymus satureioides essential oils) on S. mutans, to identify the potential active components, and to reveal the underlying mechanism.

Methods
The composition of Thymus essential oils was analyzed by gas chromatography-mass spectrometry. And its antibacterial effect was evaluated based on the bacterial growth, acid production, biofilm formation and genetic expression of virulence factors by S. mutans. Potential active components of the Thymus essential oil were identified using molecular docking and correlation analysis.

Results
GC–MS analysis showed that the major components in the 6 Spain Thymus essential oils were linalool, α-terpineol, p-cymene, thymol and carvacrol. MIC and MBC analysis showed that 3 Thymus essential oils showed very sensitive antimicrobial activity, and were chosen for further analysis. The 3 Thymus essential oil exhibited a significant inhibitory effect on acid production, adherence and biofilm formation of S. mutans and the expression of virulence genes, such as brpA, gbpB, gtfB, gtfC, gtfD, vicR, spaP and relA. Correlation analysis showed that phenolic components, such as carvacrol and thymol, were positively related to DIZ value, which suggests that they are the potential antimicrobial components. Molecular docking between the Thymus essential oil components and virulence proteins also found that carvacrol and thymol exhibited strong binding affinity with functional domains of virulence genes.

Conclusions
Thymus essential oil showed significant inhibition against the growth and pathogenesis of S. mutans depending on their composition and concentration. And phenolic compounds, such as carvacrol and thymol, are the major active components. Thymus essential oil could be used in oral healthcare products as a potential anti-caries ingredient.
Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
Authors: Vanarsa Kamala , Castillo Jessica , Wang Long , Lee Kyung Hyun , Pedroza Claudia , Lotan Yair , Mohan Chandra 
Published: April 2023

Abstract
Background
Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease.

Methods
An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity.

Results
Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC.

Conclusions
Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.
Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo–YAP1 pathway
Authors: Liu Duanrui , Liu Yunyun , Zhu Wenshuai , Lu Yi , Zhu Jingyu , Ma Xiaoli , Xing Yuanxin , Yuan Mingjie , Ning Bin , Wang Yunshan , Jia Yanfei 
Published: April 2023

Abstract
Background
Helicobacterpylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood.

Methods
The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms.

Results
GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models.

Conclusions
Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.
Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration
Authors: Yang Zhujun , Li Xuejian , Gan Xueqi , Wei Mengying , Wang Chunbao , Yang Guodong , Zhao Yimin , Zhu Zhuoli , Wang Zhongshan 
Published: April 2023

Abstract
Background
Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration.

Results
Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration.

Conclusions
Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.
The prognostic value of quality of life in atrial fibrillation on patient value
Authors: Theunissen Luc J.H.J. , van de Pol Jeroen A.A. , van Steenbergen Gijs J. , Cremers Henricus-Paul , van Veghel Dennis , van der Voort Pepijn H. , Polak Peter E. , de Jong Sylvie F.A.M.S. , Seelig Jaap , Smits Geert , Kemps Hareld M.C. , Dekker Lukas R.C. 
Published: April 2023

Abstract
Background
In this study, the prognostic value of AF-related quality of life (AFEQT) at baseline on Major Adverse Cardiovascular Events (MACE) and improvement of perceived symptoms (EHRA) was assessed. Furthermore, the relationship between QoL and AF-related hospitalizations was assessed.

Methods
A cohort of AF-patients diagnosed between November 2014 and October 2019 in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. MACE was defined as stroke, myocardial infarction, heart failure and/or mortality. Subsequently, MACE, EHRA score improvement and AF-related hospitalizations between baseline and 12 months of follow-up were recorded.

Results
In total, 970 AF-patients were available for analysis. In analyses with patients with complete information on the confounder subset 36/687 (5.2%) AF-patients developed MACE, 190/432 (44.0%) improved in EHRA score and 189/510(37.1%) were hospitalized during 12 months of follow-up. Patients with a low AFEQT score at baseline more often developed MACE (OR(95%CI): 2.42(1.16–5.06)), more often improved in EHRA score (OR(95%CI): 4.55(2.45–8.44) and were more often hospitalized (OR(95%CI): 4.04(2.22–7.01)) during 12 months post diagnosis, compared to patients with a high AFEQT score at baseline.

Conclusions
AF-patients with a lower quality of life at diagnosis more often develop MACE, more often improve on their symptoms and also were more often hospitalized, compared to AF-patients with a higher quality of life. This study highlights that the integration of patient-reported outcomes, such as quality of life, has the potential to be used as a prognostic indicator of the expected disease course for AF.
Child and adolescent mental health services in a devolved healthcare system: a qualitative exploration of sustainable practices
Authors: Banwell Emily , Humphrey Neil , Qualter Pamela 
Published: April 2023

Abstract
Background
The transference of research evidence into routine healthcare practice remains poorly understood. This includes understanding the prerequisites of longer-term viability. The present study investigated the sustainable practices of GM i-THRIVE, a programme which reconceptualizes mental health services for children and young people (CYP) in Greater Manchester, United Kingdom. We aimed to establish whether a sustainable future was likely, and to identify areas of focus to improve that likelihood.

Methods
The NHS Sustainability Model, typically completed as a questionnaire measure, was converted into interview questions. The responses of nine professionals, from a variety of roles across the CYP mental health workforce, were explored using inductive thematic framework analysis. Selected participants completed the original questionnaire.

Results
Five themes (communication; support; barriers to implementation; past, present, and future: the implementation journey; and the nuances of GM i-THRIVE) and 21 subthemes formed the final thematic framework. Relationships with senior leaders and with colleagues across the workforce were seen as important. Leaders’ roles in providing meaning and fit were emphasized. Whilst training delivered the programme’s aims well, monitoring its dissemination was challenging. Widespread issues with dedicating sufficient time to implementation were raised. The flexibility of the programme, which can be applied in multiple ways, was discussed positively. This flexibility links to the idea of GM i-THRIVE as a mindset change, and the uniqueness of this style of intervention was discussed. To varying degrees, themes were supported by responses to the quantitative measure, although several limitations to the use of the questionnaire were discovered. Consequently, they were used to infer conclusions to a lesser degree than originally intended.

Conclusions
Professionals involved with GM i-THRIVE reported many elements that indicate a positive future for the programme. However, they suggested that more attention should be given to embedding the core concepts of the model at the current stage of implementation. Limitations relating to its use within our study are discussed, but we conclude that the NHS Sustainability Model is a suitable way of guiding qualitative implementation research. It is especially valuable for localized interventions. The constraints of our small sample size on transferability are considered.
Evaluation of lateral and anterior center-edge angles according to sex and anterior pelvic plane tilt angle: a three-dimensional quantitative analysis
Authors: Hong Kee-Bum , Lee Woo-suk , Kang Kyutae , Kang Kyoung Tak , Cho Byung Woo 
Published: April 2023

Abstract
Background
This study aimed to quantitatively evaluate lateral center-edge angle (LCEA) and anterior center-edge angle (ACEA) according to sex and the anterior pelvic plane (APP) tilt angle and analyze the correlation between these measurements and acetabular coverage.

Methods
Computed tomography scans of 71 adults (38 men and 33 women) with normal hip joints were obtained. LCEA, anterior ACEA, and acetabular coverage were measured with APP tilt every 5° from − 30° to + 30° and were compared between the sexes. The correlation between acetabular coverage and LCEA/ACEA was also analyzed.

Results
(1) LCEA, ACEA, and acetabular coverage were statistically larger in men than in women at all APP tilt angles (with the exception of acetabular coverage ≥ 25°). (2) LCEA, ACEA, and acetabular coverage differed according to APP tilt angle. LCEA and acetabular coverage showed maximum values at 10°. ACEA showed a tendency to increase by an average of 3.6° for every 5° increase in the APP tilt angle. LCEA demonstrated strong and very strong associations across all APP tilting angles, whereas ACEA showed a moderate association at angles ≥ 15° in men and ≥ 30° in women.

Conclusions
The LCEA and ACEA are adequate measurement methods that reflect actual acetabular coverage unless the pelvis is tilted excessively anteriorly. While pelvic tilting does not need to be considered for LCEA within the physiologic range, it should always be taken into account for ACEA, as it increases by an average of 3.6° for every 5° increase in APP tilt angle.

Level of evidence
Level III: retrospective cohort study.