bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially-resolved analyses of muscle invasive bladder cancer microenvironment unveil a distinct fibroblast cluster associated with prognosis
Authors: Feng Chao , Wang Yaobang , Song Wuyue , Liu Tao , Mo Han , Liu Hui , Wu Shulin , Qin Zezu , Wang Zhenxing , Tao Yuting , He Liangyu , Tang Shaomei , Xie Yuanliang , Wang Qiuyan , Li Tianyu 
Published: December 2024

BackgroundMuscle-invasive bladder cancer (MIBC) is a prevalent cancer characterized by molecular and clinical heterogeneity. Assessing the spatial heterogeneity of the MIBC microenvironment is crucial to understand its clinical significance.MethodsIn this study, we used imaging mass cytometry (IMC) to assess the spatial heterogeneity of MIBC microenvironment across 185 regions of interest in 40 tissue samples. We focused on three primary parameters: tumor (T), leading-edge (L), and nontumor (N). Cell gating was performed using the Cytobank platform. We calculated the Euclidean distances between cells to determine cellular interactions and performed single-cell RNA sequencing (scRNA-seq) to explore the molecular characteristics and mechanisms underlying specific fibroblast (FB) clusters. scRNA-seq combined with spatial transcriptomics (ST) facilitated the identification of ligand–receptor (L–R) pairs that mediate interactions between specific FB clusters and endothelial cells. Machine learning algorithms were used to construct a prognostic gene signature.ResultsThe microenvironments in the N, L, and T regions of MIBC exhibited spatial heterogeneity and regional diversity in their components. A distinct FB cluster located in the L region—identified as S3—is strongly associated with poor prognosis. IMC analyses demonstrated a close spatial association between S3 and endothelial cells, with S3-positive tumors exhibiting increased blood vessel density and altered vascular morphology. The expression of vascular endothelial growth factor receptor and active vascular sprouting were significant in S3-positive tumors. scRNA-seq and ST analyses indicated that the genes upregulated in S3 were associated with angiogenesis. NOTCH1–JAG2 signaling pathway was identified as a significant L–R pair specific to S3 and endothelial cell interactions. Further analysis indicated that YAP1 was a potential regulator of S3. Machine learning algorithms and Gene Set Variation Analysis were used to establish an S3-related gene signature that was associated with the poor prognosis of tumors including MIBC, mesothelioma, glioblastoma multiforme, lower-grade glioma, stomach adenocarcinoma, uveal melanoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, and lung squamous cell carcinoma.ConclusionsWe assessed the spatial landscape of the MIBC microenvironment and revealed a specific FB cluster with prognostic potential. These findings offer novel insights into the spatial heterogeneity of the MIBC microenvironment and highlight its clinical significance.
Association between GRIN2B polymorphism and Parkinson’s disease risk, age at onset, and progression in Southern China
Authors: Cui Can , Li Hongxia , Bao Yiwen , Han Yingying , Yu Hongxiang , Song Huan , Zhang Bei 
Published: December 2024

Background and objectivesThe role of N-methyl-D-aspartate receptor 2B (GRIN2B) single nucleotide polymorphisms (SNPs) in influencing the risk and progression of Parkinson’s disease (PD) is still unclear. This study aimed to assess the impact of GRIN2B genotype status on PD susceptibility and symptom progression.MethodsWe enrolled 165 individuals with sporadic PD and 154 healthy controls, all of whom had comprehensive clinical data available at the start and during follow-up. We used chi-squared (χ2) analysis to compare the allele and genotype frequency distributions between the patient and control groups. Linear mixed-effect models were employed to investigate the link between the GRIN2B genotype and the progression of motor and cognitive symptoms.ResultsThe prevalence of the GG + GT genotype and G allele was higher in patients compared to controls (p = 0.032 and p = 0.001, respectively). Subgroup analysis revealed that the GG + GT genotype and G allele were significantly more frequently observed in late-onset PD (LOPD) patients compared to early-onset PD (EOPD) patients (p = 0.014 and p = 0.035, respectively). Notably, individuals with the GG + GT genotype exhibited an estimated annual progression rate of 6.10 points on the Unified Parkinson’s Disease Rating Scale (UPDRS), which is significantly higher than that of the TT genotype carriers. Furthermore, the GG + GT carriers showed a markedly rapid progression in rigidity. In addition, the GG + GT carriers demonstrated significantly faster progression rates in rigidity (1.83 points/year) and axial impairment (1.2 points/year) compared to the TT carriers. Notably, the GG genotype carriers exhibited a more rapid decline in recall function.ConclusionThe GRIN2B rs219882 G allele is associated with increased PD susceptibility, particularly in LOPD. The carriers of the GG + GT genotype exhibited more rapid motor symptom progression, with a pronounced impact on rigidity and axial impairment.
Magnesium intake and serum magnesium concentration in children with type 1 diabetes mellitus: association with glycemic control and clinical symptoms
Authors: Dobrovolska Lesya , Boyarchuk Oksana 
Published: December 2024

IntroductionMagnesium is involved in numerous reactions that regulate the functioning of different organs and systems. Hypomagnesemia impacts on the development of various metabolic disorders, including insulin resistance and diabetes mellitus (DM). Studying magnesium levels in children with type 1 DM is crucial, as deficiencies are linked to many diabetes complications. The study aimed to determine dietary magnesium intake, serum magnesium concentration in children with type 1 DM, and their impact on the clinical course of DM.MethodsThis case-control study involved 50 children with type 1 DM (cases) and 67 healthy children (control) aged 6–17 years. We conducted a survey to gather basic characteristics, weekly consumption of specific food items, and clinical data for patients with DM and healthy children. Additionally, serum magnesium, calcium, and phosphorus concentration were measured.ResultsInsufficient magnesium dietary intake was observed in 46% of patients with DM and in 34.3% of healthy children (p &gt; 0.05). Serum magnesium concentration in healthy children was higher than in children with DM (0.94 ± 0.24 vs. 0.84 ± 0.14, p = 0.011), although the proportion of children with hypomagnesemia did not differ between the groups (11.9% and 14.0%, respectively). Hypomagnesemia was more frequently observed in children from rural areas in both groups: 85.7% in children with DM (p = 0.054) and 62.5% in healthy children (p = 0.010). All children with hypomagnesemia had poor DM control compared to 61.3% of patients with normal magnesium concentration (p = 0.047). The mean magnesium concentration in children with optimal glycemic control was significantly higher than in children with poor control (0.96 ± 0.09 vs. 0.78 ± 0.14 mmol/L, p = 0.001). In DM children and hypomagnesemia, significant decreases in serum calcium and phosphorus concentrations were observed (p = 0.008 and p = 0.017, respectively). Headache and attention disorders were significantly more frequent in DM patients with hypomagnesemia (71.4% vs. 20.9%, p = 0.006; 28.6% vs. 4.7%, p = 0.031, respectively).ConclusionThe study demonstrates lower serum magnesium levels in children with type 1 DM than in healthy children, with a higher prevalence of hypomagnesemia in rural areas and those with poor glycemic control. Hypomagnesemia in DM children was associated with lower serum calcium and phosphorus levels, as well as more frequent symptoms such as headaches and attention deficits. Monitoring of serum magnesium is essential in routine care of children with DM.
Nanoparticle trends and hotspots in lung cancer diagnosis from 2006-2023: a bibliometric analysis
Authors: Yilun Wang , Yaojing Zhang , Hongcan Shi 
Published: December 2024

BackgroundLung cancer possesses the highest incidence and mortality rates among malignancies globally. Despite substantial advancements in oncology, it is frequently diagnosed at an advanced stage, resulting in a poor prognosis. Over recent decades, the swift progress of nanotechnology has precipitated the extensive utilization of nanomaterials as carriers in cancer diagnosis and therapy. The deployment of nanoparticles as an innovative diagnostic strategy aspires to enable the earlier detection of lung cancer, thereby permitting earlier intervention and enhancing prognosis. This study endeavors to deepen our understanding of this domain through a comprehensive analysis employing bibliometric tools.MethodRelated articles were retrieved from the Web of Science Core Collection from January 1st, 2006, to December 14st, 2023. Thereaf CiteSpace, VOSviewer and the online platform of bibliometrics (http://bibliometric.com/) were utilized to visually analyze Author/Country/Institutions/Cited Journals/Keyword, et al.ResultsA total of 966 articles were retrieved for this study. The analysis unveils a progressive increase in annual publications within this field, with China at the forefront in publication volume, followed by the United States and India. Moreover, Chinese research institutions, notably the Chinese Academy of Sciences and Shanghai Jiao Tong University, prevail in publication output. Upon exclusion of irrelevant search terms, keywords clustering analysis highlights that “biomarkers”, “sensors”, “gold nanoparticles”, and “silver nanoparticles” are predominant research focuses.ConclusionThis bibliometric study furnishes a quantitative perspective on the extant literature, serving scholars in related fields. Furthermore, it anticipates future research trend concerning nanoparticles and lung cancer diagnosis, thereby aiding in the formulation of project planning and the design of experiments.
Multipool-CEST and CEST-based pH assessment as predictive tools for glioma grading, IDH mutation, 1p/19q codeletion, and MGMT promoter methylation in gliomas
Authors: Zhang Xinli , Lu Jue , Liu Xiaoming , Sun Peng , Qin Qian , Xiang Zhengdong , Cheng Lan , Zhang Xiaoxiao , Guo Xiaotong , Wang Jing 
Published: December 2024

ObjectivesTo comprehensively and noninvasively predict glioma grade, IDH mutation status, 1p/19q codeletion status, and MGMT promoter methylation status using chemical exchange saturation transfer (CEST)-based tumor pH assessment and metabolic profiling.MethodsWe analyzed 128 patients with pathologically confirmed adult diffuse glioma. CEST-derived metrics based on tumor regions were obtained using five-pool Lorentzian analysis and pH_weighted analysis. Histogram features of these metrics were computed to characterize tumor heterogeneity. These features were subsequently employed for glioma grading and molecular genotyping of IDH, 1p/19q and MGMT. Logistic regression analysis was used to predict the grade and IDH genotypes. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis.ResultsThe DS, MT and pH_weighted differed significantly between grade II and III, as well as grade III and IV. The amide, NOE, pH_weighted and MTR3.5 showed significantly differences within IDH genotypes. Regression models achieved the highest AUC for differentiating grade II from III (0.80, 95% CI: 0.64-0.91), grade III from IV (0.83, 95% CI: 0.74-0.90), and IDH mutant from wild status (0.84, 95% CI: 0.77-0.90). MT and pH_weighted metrics were the only indicators for identifying 1p/19q codeletion in grade II and grade III gliomas, respectively. MT 90th percentile (0.87, 95% CI: 0.65-0.98) and pH_weighted 25th percentile (0.83, 95% CI: 0.56-0.97) showed the best performance, respectively. The MTR3.5 was the only indicator which can distinguish MGMT promoter methylation and unmethylation gliomas, within MTR3.5 90th percentile performed best (AUC = 0.79, 95% CI: 0.61- 0.91).ConclusionCEST-based tumor pH assessment and metabolic profiling demonstrated promising potential for predicting glioma grade, IDH mutation status, 1p/19q codeletion, and MGMT genotype.
Integration of pharmacogenetic data in epic genomic module drives clinical decision support alerts
Authors: Newsom Kimberly J. , Hall Bradley , Martinez Katherine A. , Nelson Scott , Starostik Petr , Nguyen Khoa 
Published: December 2024

IntroductionThe Precision Medicine Program (PMP) at the University of Florida (UF) focuses on advancing pharmacogenomics (PGx) to improve patient care.MethodsThe UF PMP, in collaboration with the UF Health Pathology Laboratory (UFHPL), utilized Health Level Seven (HL7) standards to integrate PGx data into Epic’s Genomic Module to enhance the management and utilization of PGx data in clinical practice.ResultsA key feature of the Genomic Module is the introduction of genomic indicators—innovative tools that flag actionable genetic information directly within the electronic health record (EHR). These indicators enable the effective presentation of phenotypic information and, when leveraged with existing clinical decision support (CDS) alerts, help provide timely and informed therapeutic decisions based on genomic data.DiscussionThis advancement represents a significant shift in the utilization of genetic data, moving beyond traditional PDF reports to provide a comprehensive understanding of PGx data. Ultimately, this integration empowers healthcare providers with genomics-guided recommendations, enhancing precision and personalization in patient care, contributing significantly to the advancement of personalized medicine.
Clinical pharmacist recommendations in daily interdisciplinary ward rounds at a psychiatric hospital: a retrospective pre-post study on drug-related problems focused in somatic comorbidities
Authors: Stuhec Matej , Gazdag Anteja Gorjan , Cuk Zala , Oravecz Robert , Batinic Borjanka 
Published: December 2024

ObjectiveOne potential strategy to address inadequate screening for somatic comorbidities among patients with mental disorders is to integrate a clinical pharmacist into the inpatient team for daily interdisciplinary ward rounds. This approach remains under-researched in psychiatric hospitals. This study aimed to evaluate the impact of a clinical pharmacist on drug-related problems (DRPs) during daily ward rounds within an interdisciplinary team in a psychiatric hospital.MethodsA retrospective observational pre-post study was conducted at the Ormož Psychiatric Hospital in Slovenia, including patients treated between 2019 and 2020, during which clinical pharmacists offered recommendations during daily ward rounds. The primary outcomes assessed the difference in the total number of DRPs observed at the time of hospital discharge compared to previous stage, as well as the recommendations and their continuation rate after three months. The secondary outcomes evaluated adherence to treatment guidelines.ResultsThe study included 186 patients (mean age: 58.1 years, SD=17.0). During ward rounds, 280 recommendations related to DRPs were conducted (1.5 recommendations per patient). Regarding the nature of DRPs, 154 (55.0%) were identified as expressed DRPs, while 127 (45.0%) were deemed potential DRPs. Following pharmacist recommendations, 133 (86.4%) of the expressed DRPs were successfully resolved. The majority of DRPs pertained to treatment effectiveness (N=179, 63.9%), followed by unnecessary treatments (N=86, 30.7%) and patient safety (N=15, 5.4%). Initially, the acceptance rate of recommendations was 88.9% (N=249) at discharge, declining to 63.2% (N=177) three months after discharge. The acceptance rate for somatic conditions at discharge was 87.8% (N=122), declining to 59.0% (N=82) three months after discharge. Adherence to treatment guidelines for somatic comorbidities increased (p &lt; 0.05).ConclusionsThe results indicate that this approach led to fewer DRPs, a high rate of acceptance, and better adherence to treatment guidelines. This is the first retrospective pre-post study in the European Union to include this collaboration in daily rounds at psychiatric hospitals, focusing on somatic comorbidities. However, the study also has significant limitations, such as its non-randomized design and short monitoring period, which should be addressed in future research.
Is internet-based cognitive behavioral therapy for alcohol use disorder equally effective for men and women? Implications of a secondary analysis of a clinical trial
Authors: Schettini Greta , Johansson Magnus , Andersson Sam , Romero Danilo , Berman Anne H. , Lindner Philip 
Published: December 2024

IntroductionExcessive alcohol use is a major public health concern, for which internet interventions have shown to be effective. Group-average effects may however mask substantial inter-individual variations in changes; identifying predictors of this variation remains an important research question. Biological sex is associated with pharmacokinetic differences in alcohol tolerance, which is reflected in many national guidelines recommending sex-specific thresholds for excessive drinking. Whether effects of internet interventions are moderated by sex, and whether any moderation is due to confounders, remains largely unexplored.AimTo examine sex-differences in outcomes (both response and remission) after an internet intervention for alcohol use disorder, and to identify any confounders.MethodThe current study is a secondary analysis of a randomized controlled trial. After identifying factors in which men and women differed at baseline, mixed effects models were re-run using a subsampling matching strategy.ResultsMen and women differed in baseline sum of drinks and self-rated anxiety. Sex was found to moderate (absolute) response but not remission, neither when using sex-specific or common thresholds for risky drinking. However, after controlling for baseline drinking through subsampling, the difference in response was no longer significant.ConclusionOur findings suggest that the apparent sex-difference in treatment response was confounded by intercept-slope correlation – i.e. since men on average drank more at baseline, this offered larger room for decreasing. When conducting studies on internet interventions for addictive disorders, it is crucial to consider which outcomes to use, and how these are operationalized.
“Equity” in genomic health policies: a review of policies in the international arena
Authors: Basnayake Ralalage Prabhathi , Mitchell Tala , Zammit Claire , Baynam Gareth , Kowal Emma , Masey Libby , McGaughran Julie , Boughtwood Tiffany , Jenkins Misty , Pratt Gregory , Ferdinand Angeline 
Published: December 2024

IntroductionThe field of genomics is rapidly evolving and has made significant impact on the diagnosis and understanding of rare and genetic diseases, in guiding precision medicine in cancer treatment, and in providing personalized risk assessment for disease development and treatment responses. However, according to the literature, there is widespread socio economic and racial inequities in the diagnosis, treatment, and in the use of genomic medicine services. This policy review sets out to explore the concept of equity in access to genomic care, the level of inclusion of equity and how it is addressed and what mechanisms are in place to achieve equity in genomic care in the international health policy.MethodsA systematic search for genomic policies was conducted using 3 databases. In addition, General and Specific Policy Repositories, Global Consortia in Genomic Medicine, WHO Collaborating Centers in Genomics, Australian Genomics, Public Policy Projects, Global Genomic Medicine Consortium (G2MC), G2MC conference Oct 2023 and National Human Genome Research Institute databases were searched using the inclusion and exclusion criteria. Seventeen policies were selected and analyzed using the EquiFrame.ResultsThe Core Concept of access is highly cited in most of the selected policies. The CCs that are covered to a lesser degree are participation, quality, coordination of services, cultural responsiveness and non-discrimination. The CCs of liberty and entitlement are not addressed in any of the selected policies. The coverage of vulnerable communities in the policies varies from country to country.DiscussionGenomic health science is rapidly evolving and presents a major challenge for policies to remain current and effectively address new discoveries in the field. There is a relative dearth of policies that focus on clinical genetic services which may reflect a gap in policy and policy research translation and implementation. Recommendations for countries, irrespective of their economic and social contexts, include conducting regular policy reviews to accommodate the advances in genomics field and inclusion of specific mechanisms to achieve equity in genomic health. Insights and experiences in achieving healthcare equity in HICs and LMICs can offer valuable lessons for each other.
High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
Authors: Gu Ruonan , Wang Jerry , Morin Julianne , Lu Aizhu , Liang Wenbin 
Published: December 2024

Wnt/β-catenin signaling has been shown to regulate gene expressions in cardiomyocytes. However, it is not known if this effect is dependent on the sex of cells or the glucose level in the culture medium. In the present study, ventricular myocytes were prepared from male and female neonatal rats and maintained in either a glucose-rich (25 mM) medium or a low-glucose (3 mM), lipid-rich medium. Real-time quantitative PCR was used to measure changes in target genes (Axin2, Scn5a, and Tbx3) after treatment with 1, 3, or 10 µM of CHIR-99021, an activator of Wnt/β-catenin signaling. CHIR induced similar changes in Axin2, Tbx3, and Scn5a transcripts in male and female NRVMs in both media, suggesting the absence of sex difference. However, cells in a high-glucose medium showed greater increases in Axin2 and Tbx3 transcripts than cells in a low-glucose medium. In addition, a low concentration of CHIR (1 µM) reduced the Scn5a transcript in cells in a high-glucose medium but not in a low-glucose medium, suggesting an increased sensitivity to Wnt signaling by high glucose. A non-linear relationship was identified between Axin2 transcript upregulation and Scn5a transcript downregulation in CIHR-treated NRVMs. These data suggest that high glucose sensitizes both male and female cardiomyocytes to Wnt/β-catenin signaling.
Anti-Inflammatory Activity of Gomphrenin-Rich Fraction from Basella alba L. f. rubra Fruits
Authors: Rusak Agnieszka , Mrozowska Monika , Kozłowska Weronika , Wiatrak Benita , Dzięgiel Piotr , Wybraniec Sławomir , Carev Ivana , Jama-Kmiecik Agnieszka , Matkowski Adam , Zielińska Sylwia 
Published: December 2024

Background/Objectives: Basella alba L. (Malabar spinach, Basellaceae), widely consumed as a leafy vegetable, produces dark-colored fruits rich in betacyanins, including rare 6-glycosylated derivatives called gomphrenins. Comprehensive studies on the anti-inflammatory potential of its gomphrenin fraction (A) and crude extract (B) employed various analytical and biological methods. Methods: Cytotoxicity and anti-inflammatory effects were tested on human and animal cell models using SRB, DCF-DA, Griess, MDA, and ELISA assays. Results: Both the crude extract and enriched gomphrenin fraction exhibited significant anti-inflammatory and antioxidant effects in vitro. They inhibited pro-inflammatory cytokines IL-1β and IL-6, reduced oxidative stress markers (ROS, NO), and decreased lipid peroxidation. The enriched gomphrenin fraction (A) showed stronger antioxidant and anti-inflammatory effects, particularly in reducing ROS and NO levels, though not always concentration-dependent. Both A and B inhibited NF-κB and COX activity. Conclusions: These findings highlight the therapeutic potential of B. alba f. rubra fruit extract and betalain fraction for inflammation-related conditions, encouraging further exploration of their mechanisms and application.