bluuebunny/crossref_metadata_2025_split huggingface dataset:
A biobehavioral observational study to understand the multilevel determinants of cardiovascular health in Black women: the BLOOM Study protocol
Authors: Liao Yue , Brothers R. Matthew , Brown Kyrah K. , Lee Rebecca E. 
Published: July 2024

Abstract
Background
The racial/ethnic and gender disparities in cardiovascular disease (CVD) morbidity and mortality in the United States are evident. Across nearly every metric, non-Hispanic Black women have poorer overall cardiovascular health. Emerging evidence shows a disproportionately high burden of increased CVD risk factors in Black women of childbearing age, which has a far-reaching impact on both maternal and child outcomes, resulting in premature onset of CVD and further widens the racial disparities in CVD. There is growing recognition that the fundamental driver of persistent racial/ethnic disparities in CVD, as well as disparities in behavioral risk factors such as physical activity and sleep, is structural racism. Further, the lived personal experience of racial discrimination not only has a negative impact on health behaviors, but also links to various physiological pathways to CVD risks, such as internalized stress resulting in a pro-inflammatory state. Limited research, however, has examined the interaction between daily experience and health behaviors, which are influenced by upstream social determinants of health, and the downstream effect on biological/physiological indicators of cardiovascular health in non-pregnant Black women of childbearing age.

Methods/Design
The BLOOM Study is an observational study that combines real-time ambulatory assessments over a 10-day monitoring period with in-depth cross-sectional lab-based physiological and biological assessments. We will use a wrist-worn actigraphy device to capture 24-h movement behaviors and electronic ecological momentary assessment to capture perceived discrimination, microaggression, and stress. Blood pressure will be captured continuously through a wristband. Saliva samples will be self-collected to assess cortisol level as a biomarker of psychological stress. Lab assessments include a fasting venous blood sample, and assessment of various indices of peripheral and cerebral vascular function/health. Participants’ address or primary residence will be used to obtain neighborhood-level built environmental and social environmental characteristics. We plan to enroll 80 healthy Black women who are between 18 and 49 years old for this study.

Discussion
Results from this study will inform the development of multilevel (i.e., individual, interpersonal, and social-environmental levels) lifestyle interventions tailored to Black women based on their lived experiences with the goal of reducing CVD risk.

ClinicalTrials.gov Identifier
NCT06150989.
CALU promotes lung adenocarcinoma progression by enhancing cell proliferation, migration and invasion
Authors: Li Yan , Sun Shengnan , Zhang Hui , Jing Yongjian , Ji Xingzhao , Wan Qiang , Liu Yi 
Published: July 2024

Abstract
Background
Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms.

Methods
5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells.

Results
The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells.

Conclusions
The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients
Authors: Hovorkova Lenka , Winkowska Lucie , Skorepova Justina , Krumbholz Manuela , Benesova Adela , Polivkova Vaclava , Alten Julia , Bardini Michela , Meyer Claus , Kim Rathana , Trahair Toby N. , Clappier Emmanuelle , Chiaretti Sabina , Henderson Michelle , Sutton Rosemary , Sramkova Lucie , Stary Jan , Polakova Katerina Machova , Marschalek Rolf , Metzler Markus , Cazzaniga Giovanni , Cario Gunnar , Trka Jan , Zaliova Marketa , Zuna Jan 
Published: July 2024

Abstract
Background
The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively.

Methods
By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses.

Results
Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications.

Conclusions
Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.
Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway
Authors: Zhou Chunhao , Cai Zhihai , Guo Jialiang , Li Chengfu , Qin Chenghe , Yan Juanwen , Yang Dehong 
Published: July 2024

AbstractFailed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1–34), we previously designed a novel PTH analog, PTH(3–34)(29–34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA–MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.
Population-Specific gene expression profiles in prostate cancer: insights from Weighted Gene Co-expression Network Analysis (WGCNA)
Authors: Manouchehri Laleh , Zinati Zahra , Nazari Leyla 
Published: July 2024

AbstractThis study investigates the genetic factors contributing to the disparity in prostate cancer incidence and progression among African American men (AAM) compared to European American men (EAM). The research focuses on employing Weighted Gene Co-expression Network Analysis (WGCNA) on public microarray data obtained from prostate cancer patients. The study employed WGCNA to identify clusters of genes with correlated expression patterns, which were then analyzed for their connection to population backgrounds. Additionally, pathway enrichment analysis was conducted to understand the significance of the identified gene modules in prostate cancer pathways. The Least Absolute Shrinkage and Selection Operator (LASSO) and Correlation-based Feature Selection (CFS) methods were utilized for selection of biomarker genes. The results revealed 353 differentially expressed genes (DEGs) between AAM and EAM. Six significant gene expression modules were identified through WGCNA, showing varying degrees of correlation with prostate cancer. LASSO and CFS methods pinpointed critical genes, as well as six common genes between both approaches, which are indicative of their vital role in the disease. The XGBoost classifier validated these findings, achieving satisfactory prediction accuracy. Genes such as APRT, CCL2, BEX2, MGC26963, and PLAU were identified as key genes significantly associated with cancer progression. In conclusion, the research underlines the importance of incorporating AAM and EAM population diversity in genomic studies, particularly in cancer research. In addition, the study highlights the effectiveness of integrating machine learning techniques with gene expression analysis as a robust methodology for identifying critical genes in cancer research.
Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer
Authors: Li Xiaoxi , Su Nan , Yu Haining , Li Xiaoyan , Sun Shu-lan 
Published: July 2024

Abstract
Background
In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism.

Methods
We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1.

Results
HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions.

Conclusions
Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.
Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study
Authors: Yu Jing , Liu Jian-Ming , Chen Hui-Yi , Xiong Wei-Ming 
Published: July 2024

AbstractOseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van’t Hoff equation were − 77.49 kJ/mol, -176.54 J/(mol∙K), and − 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.
Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid
Authors: Cornelli Lotte , Van Paemel Ruben , Ferro dos Santos Maísa R. , Roelandt Sofie , Willems Leen , Vandersteene Jelle , Baert Edward , Mus Liselot M. , Van Roy Nadine , De Wilde Bram , De Preter Katleen 
Published: July 2024

AbstractPediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.
Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer’s disease: a nationwide nested case-control study
Authors: Damsgaard Line , Janbek Janet , Laursen Thomas Munk , Vestergaard Karsten , Gottrup Hanne , Jensen-Dahm Christina , Waldemar Gunhild 
Published: July 2024

Abstract
Background
Patients with young onset Alzheimer’s disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis.

Methods
In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016–2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals.

Results
The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05–1.31), increasing to 1.57 (95% CI 1.39–1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users.

Conclusions
In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.
Advancements in hand-drawn chemical structure recognition through an enhanced DECIMER architecture
Authors: Rajan Kohulan , Brinkhaus Henning Otto , Zielesny Achim , Steinbeck Christoph 
Published: July 2024

AbstractAccurate recognition of hand-drawn chemical structures is crucial for digitising hand-written chemical information in traditional laboratory notebooks or facilitating stylus-based structure entry on tablets or smartphones. However, the inherent variability in hand-drawn structures poses challenges for existing Optical Chemical Structure Recognition (OCSR) software. To address this, we present an enhanced Deep lEarning for Chemical ImagE Recognition (DECIMER) architecture that leverages a combination of Convolutional Neural Networks (CNNs) and Transformers to improve the recognition of hand-drawn chemical structures. The model incorporates an EfficientNetV2 CNN encoder that extracts features from hand-drawn images, followed by a Transformer decoder that converts the extracted features into Simplified Molecular Input Line Entry System (SMILES) strings. Our models were trained using synthetic hand-drawn images generated by RanDepict, a tool for depicting chemical structures with different style elements. A benchmark was performed using a real-world dataset of hand-drawn chemical structures to evaluate the model's performance. The results indicate that our improved DECIMER architecture exhibits a significantly enhanced recognition accuracy compared to other approaches.Scientific contributionThe new DECIMER model presented here refines our previous research efforts and is currently the only open-source model tailored specifically for the recognition of hand-drawn chemical structures. The enhanced model performs better in handling variations in handwriting styles, line thicknesses, and background noise, making it suitable for real-world applications. The DECIMER hand-drawn structure recognition model and its source code have been made available as an open-source package under a permissive license.Graphical Abstract