bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention and management of dental erosion and decay
Authors: Campus Guglielmo , Niu John Yun , Sezer Berkant , Yu Ollie Yiru 
Published: April 2024

AbstractThe 2017 Global Disease Study revealed 2.3 billion untreated cavities and 139 million other oral conditions like dental erosion. Modern treatments prioritise controlling etiological factors and preventing related diseases. This Editorial invites researchers to contribute to the collection, ‘Prevention and management of dental erosion and decay’.
Patients’ experiences with shared decision-making in home-based palliative care – navigation through major life decisions
Authors: Svendsen Sandra Jahr , Grov Ellen Karine , Staats Katrine 
Published: April 2024

Abstract
Background
This study addresses the issue of shared decision-making (SDM) in a Norwegian home-based palliative care setting. The significance of patient involvement in SDM is widely acknowledged, and many patients want to participate in decisions about care and treatment. Yet, it remains a need for more knowledge regarding the initiators and approaches of SDM in the context of home-based palliative care, particularly from the patients’ perspective. The aim of this study is to understand patients' experiences and preferences for SDM in home-based palliative care, seeking to enhance the quality of care and direct the planning of healthcare services.

Methods
We used a qualitative explorative design. A hermeneutic approach was employed, and data was collected through in-dept interviews with 13 patients.

Results
The study uncovered an overarching theme of "Navigating to reach own decisions," comprising three sub-themes: “To be trapped in life without decisions to act on”; “To surrender to others and let others deal with decisions”; “To continue to be oneself without focusing on disease and decision-making”.

Conclusions
The findings underscore the need for flexible, person-centered approaches in SDM, tailored to the fluctuating health literacy and changing preferences of patients in palliative care settings. Our study contributes to the understanding of SDM in palliative care by highlighting how patients navigate the balance between autonomy and reliance on HCPs. Future research should explore how healthcare systems, including HCPs’ roles in the system, can adapt to the patients’ dynamic needs, to ensuring that SDM will remain a supportive and empowering process for patients at all stages of their disease.
Text mining and portal development for gene-specific publications on Alzheimer’s disease and other neurodegenerative diseases
Authors: Liu Jiannan , Wu Huanmei , Robertson Daniel H. , Zhang Jie 
Published: April 2024

Abstract
Background
Tremendous research efforts have been made in the Alzheimer’s disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers.

Methods
In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database. The collected publication information was filtered and cleaned to construct AD-related gene-specific publication profiles. Six categories of AD-related information are extracted from the processed publication data: publication trend by year, dementia type occurrence, brain region occurrence, mouse model information, keywords occurrence, and co-occurring genes. A user-friendly web portal is then developed using Django framework to provide gene query functions and data visualizations for the generalized and summarized publication information.

Results
By implementing the NLP pipeline, we extracted gene-specific ND-related publication information from the abstracts of the publications in the PubMed database. The results are summarized and visualized through an interactive web query portal. Multiple visualization windows display the ND publication trends, mouse models used, dementia types, involved brain regions, keywords to major AD-related biological processes, and co-occurring genes. Direct links to PubMed sites are provided for all recorded publications on the query result page of the web portal.

Conclusion
The resulting portal is a valuable tool and data source for quick querying and displaying AD publications tailored to users’ interested research areas and gene targets, which is especially convenient for users without informatic mining skills. Our study will not only keep AD field researchers updated with the progress of AD research, assist them in conducting preliminary examinations efficiently, but also offers additional support for hypothesis generation and validation which will contribute significantly to the communication, dissemination, and progress of AD research.
Analysis of REST binding sites with canonical and non-canonical motifs in human cell lines
Authors: Choi Jaejoon , Lee Eunjung Alice 
Published: April 2024

Abstract
Background
Repressor element 1 (RE1) silencing transcription factor (REST) is a transcriptional repressor abundantly expressed in aging human brains. It is known to regulate genes associated with oxidative stress, inflammation, and neurological disorders by binding to a canonical form of sequence motif and its non-canonical variations. Although analysis of genomic sequence motifs is crucial to understand transcriptional regulation by transcription factors (TFs), a comprehensive characterization of various forms of RE1 motifs in human cell lines has not been performed.

Results
Here, we analyzed 23 ENCODE REST ChIP-seq datasets from diverse human cell lines and identified a non-redundant set of 68,975 loci with ChIP-seq peaks. Our systematic characterization of these binding sites revealed that the canonical form of REST binding motif was found primarily in ChIP-seq peaks shared across multiple cell lines, while non-canonical forms of motifs were identified in both cell-line-specific binding sites and those shared across cell lines. Remarkably, we observed a notable prevalence of non-canonical motifs that corresponded to half segments of the canonical motif. Furthermore, our analysis unveiled the presence of cell-line-specific REST binding patterns, as evidenced by the clustering of ChIP-seq experiments according to their respective cell lines. This observation underscores the cell-line specificity of REST binding at certain genomic loci, implying intricate cell-line-specific regulatory mechanisms.

Conclusions
Overall, our study provides a comprehensive characterization of REST binding motifs in human cell lines and genome-wide RE1 motif profiles. These findings contribute to a deeper understanding of REST-mediated transcriptional regulation and highlight the importance of considering cell-line-specific effects in future investigations.
Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice
Authors: Wang Vicki , Tseng Kuan-Yin , Kuo Tung-Tai , Huang Eagle Yi-Kung , Lan Kuo-Lun , Chen Zi-Rong , Ma Kuo-Hsing , Greig Nigel H. , Jung Jin , Choi Ho-II , Olson Lars , Hoffer Barry J. , Chen Yuan-Hao 
Published: April 2024

Abstract
Background
Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood.

Methods
In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse.

Results
Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae.

Conclusion
Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

Graphical Abstract
Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer
Authors: Li Chia-Jung , Tzeng Yen-Dun Tony , Hsiao Jui-Hu , Tseng Ling-Ming , Hsu Tzu-Sheng , Chu Pei-Yi 
Published: April 2024

AbstractThe mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU’s potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.
Widespread pfhrp2/3 deletions and HRP2-based false-negative results in southern Ethiopia
Authors: Mekonen Bacha , Dugassa Sisay , Feleke Sindew Mekasha , Dufera Boja , Gidisa Bedasa , Adamu Aderaw , Mandefro Aynalem , Tasew Geremew , Golassa Lemu 
Published: April 2024

Abstract
Background
Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia.

Methods
A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections.

Results
Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test.

Conclusion
This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country’s attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.
Health inequalities in childhood diseases: temporal trends in the inter-crisis period
Authors: Carrilero Neus , García-Altés Anna 
Published: April 2024

Abstract
Background
Since 2008, children in Catalonia (Spain) have suffered a period of great economic deprivation. This situation has generated broad-ranging health inequalities in a variety of diseases. It is not known how these inequalities have changed over time. The aim of the present study is to determine trends in inequalities over this period in ten relevant diseases in children according to sex and age.

Methods
A retrospective cross-sectional population-based study of all children under 15 years old resident in Catalonia during the 2014–2021 period (over 1.2 million children/year) and of their diagnoses registered by the Catalan Health System. Health inequalities were estimated by calculating the relative index of inequality and time trends using logistic regression models. Interaction terms were added to test for the effects of sex on time trends.

Results
Increasing significant temporal trends in inequalities were shown for both sexes in almost all the diseases or adverse events studied (asthma, injuries, poisoning, congenital anomalies, overweight and obesity), in mood disorders in boys, and in adverse birth outcomes in girls. Adjustment and anxiety and mood disorders in girls showed a decreasing temporal trend in inequalities. More than half of the diseases and adverse events studied experienced significant annual increases in inequality. Poisoning stood out with an average annual increase of 8.65% [4.30, 13.00], p ≤ 0.001 in boys and 8.64% [5.76, 11.52], p ≤ 0.001) in girls, followed by obesity with increases of 5.52% [4.15, 6.90], p =  < 0.001 in boys and 4.89% [4.26, 5.51], p ≤ 0.001) in girls.

Conclusions
Our results suggest that inequalities persist and have increased since 2014. Policy makers should turn their attention to how interventions to reduce Health inequalities are designed, and who benefits from them.
DB-1310, an ADC comprised of a novel anti-HER3 antibody conjugated to a DNA topoisomerase I inhibitor, is highly effective for the treatment of HER3-positive solid tumors
Authors: Li Xi , Yao Jun , Qu Chen , Luo Lan , Li Bing , Zhang Yu , Zhu Zhongyuan , Qiu Yang , Hua Haiqing 
Published: April 2024

AbstractBackgroundHER3 (ErbB3), a member of the human epidermal growth factor receptor family, is frequently overexpressed in various cancers. Multiple HER3-targeting antibodies and antibody–drug conjugates (ADCs) were developed for the solid tumor treatment, however none of HER3-targeting agent has been approved for tumor therapy yet. We developed DB-1310, a HER3 ADC composed of a novel humanized anti-HER3 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor payload (P1021), and evaluate the efficacy and safety of DB-1310 in preclinical models.MethodsThe binding of DB-1310 to Her3 and other HER families were measured by ELISA and SPR. The competition of binding epitope for DB-1310 and patritumab was tested by FACS. The sensitivity of breast, lung, prostate and colon cancer cell lines to DB-1310 was evaluated by in vitro cell killing assay. In vivo growth inhibition study evaluated the sensitivity of DB-1310 to Her3 + breast, lung, colon and prostate cancer xenograft models. The safety profile was also measured in cynomolgus monkey.ResultsDB-1310 binds HER3 via a novel epitope with high affinity and internalization capacity. In vitro, DB-1310 exhibited cytotoxicity in numerous HER3 + breast, lung, prostate and colon cancer cell lines. In vivo studies in HER3 + HCC1569 breast cancer, NCI-H441 lung cancer and Colo205 colon cancer xenograft models showed DB-1310 to have dose-dependent tumoricidal activity. Tumor suppression was also observed in HER3 + non-small cell lung cancer (NSCLC) and prostate cancer patient-derived xenograft (PDX) models. Moreover, DB-1310 showed stronger tumor growth-inhibitory activity than patritumab deruxtecan (HER3-DXd), which is another HER3 ADC in clinical development at the same dose. The tumor-suppressive activity of DB-1310 synergized with that of EGFR tyrosine kinase inhibitor, osimertinib, and exerted efficacy also in osimertinib-resistant PDX model. The preclinical assessment of safety in cynomolgus monkeys further revealed DB-1310 to have a good safety profile with a highest non severely toxic dose (HNSTD) of 45 mg/kg.ConclusionsThese finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.
Relationship between pan-immune- inflammation value and in major cardiovascular and cerebrovascular events in stable coronary artery disease patients undergoing on-pump coronary artery bypass graft surgery
Authors: Dolapoglu Ahmet , Avci Eyup 
Published: April 2024

Abstract
Background
In this study, we aimed to evaluate the association of pan-immune-inflammation value (PIV) with major cardiovascular and cerebrovascular events (MACCE) in stable coronary artery disease patients undergoing on-pump coronary artery bypass graft (CABG) surgery.

Methods
We retrospectively analyzed data from 527 patients who underwent on-pump CABG surgery for stable coronary artery disease between June 2015 and December 2020. Patients were categorized into two groups based on MACCE development. PIV levels were calculated from blood samples taken on admission. PIV was calculated as [neutrophil count (×103/µL)×platelet count (×103/µL))×monocyte count (×103/µL)]/lymphocyte count (×103/µL). The primary endpoint was long-term major cardiovascular and cerebrovascular events (MACCE) at a median follow-up of 4.6 years.

Results
Of the included patients, 103 (19.5%) developed MACCE. PIV was higher in patients with MACCE compared to those without (470.8 [295.3-606.8] vs. 269.8 [184.3-386.4], p < 0.001). Multivariate analysis showed a significant positive association between PIV and MACCE (HR: 1.326, 95%CI:1.212–1452, p < 0.001). The cut-off value for the PIV in the estimation of MACCE was 368.28 ( AUC: 0.726 with 69% sensitivity, 71% specificity, p < 0.001).

Conclusion
This study shows a significant link between high PIV levels and MACCE in stable coronary artery disease patients undergoing on-pump CABG surgery. Our findings suggest that PIV may be a valuable, routinely available, and inexpensive marker for identifying patients at increased risk of MACCE.