bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐inflammatory mechanisms in cancer research: Characterization of a distinctM2‐like macrophage model derived from theTHP‐1 cell line
Authors: Scheurlen Katharina M. , Snook Dylan L. , Littlefield Andrew B. , George Joan B. , Parks Mary A. , Beal Robert J. , MacLeod Anne , Riggs Daniel W. , Gaskins Jeremy T. , Chariker Julia , Rouchka Eric C. , Galandiuk Susan 
Published: December 2023

AbstractAimsMacrophages play an essential role in cancer development. Tumor‐associated macrophages (TAMs) have predominantly M2‐like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell line‐derived TAM‐like M2 subtype is required to investigate the mechanisms mediated by anti‐inflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THP‐1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAM‐like M2 subtype macrophage created based on our protocol to introduce them as a standardized model for cancer research.Methods and resultsUsing qRT‐PCR and ELISA, we demonstrated that proinflammatory, anti‐inflammatory, and tumor‐associated marker expression changed during THP‐1‐derived marcrophage development in vitro, mimicking a TAM‐related profile (e.g., TNFα, IL‐1β). The anti‐inflammatory marker IL‐8/CXCL8, however, is most highly expressed in young M0 macrophages. Flow cytometry showed increased expression of CD206 in the final TAM‐like M2 macrophage. Single‐cell RNA‐sequencing analysis of primary human monocytes and colon cancer tissue macrophages demonstrated that cell line‐derived M2 macrophages resembled a TAM‐related gene profile.ConclusionsThe THP‐1‐derived M2 macrophage based on a standardized cell line model represents a distinct anti‐inflammatory TAM‐like phenotype with an M2a subtype profile. This model may provide a basis for in vitro investigation of functional mechanisms in a variety of anti‐inflammatory settings, particularly colon cancer development.
Design, Characterization and SAR Studies of Novel Bioactive Benzylideneacetophenone Derivatives as Insecticidal Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Abd El‐Lateef Hany M. , Elkanzi Nadia A. A. , Adel Thabet Marwa , Gad Mohamed A. , Omran Omran A. , Ali Ali M. 
Published: December 2023

AbstractUnintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4‐acetylphenyl 4‐methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1H‐NMR, 13C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4‐[3‐(4‐Methylphenyl)prop‐2‐enoyl]phenyl‐4‐methyl benzenesulfonate (4) was the most active with an LC50=3.46 mg/L of 2nd instar larvae and LC50=9.45 mg/L of 4th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions.
Recurrent abdominal wall mass in a hepatitis B‐positive male: An unusual case of lumbar mycetoma
Authors: Abdallah Alaa Tajeldeen Habeeb , Abdelkhalig Rami Elsiddig , Hamid Elwasila , Ahmed Ayman , Siddig Emmanuel Edwar 
Published: December 2023

Key Clinical MessageAtypical presentations of eumycetoma can pose a challenge in the diagnosis and treatment of the disease. Healthcare providers thorough in their differential diagnosis and investigations, even in the absence of classic symptoms, in order to improve early detection and the case management for such a neglected tropical disease.AbstractIn this communication, we present a case study of an unusual presentation of eumycetoma; a fungal infection that is considered a neglected tropical disease. The patient, a 28‐year‐old male from Sudan, presented with a recurrent mass in the abdominal wall. Despite two surgeries to remove the mass, it continued to recur. Unlike typical cases of eumycetoma, this patient did not exhibit common symptoms such as painless swelling, sinuses, or grain‐containing discharge. The diagnosis was made incidentally after surgical excision of the mass. The abstract highlights the importance of recognizing uncommon presentations and maintaining a high suspicion for rare diagnoses, even in the absence of classic symptoms. Further research is needed to better understand atypical presentations of eumycetoma and improve early detection.
Rational Design and Biological Application of Hybrid Fluorophores
Authors: Zhang Shiji , Qu Yunwei , Zhang Duoteng , Li Shuai , Tang Fang , Ding Aixiang , Hu Lei , Zhang Jin , Wang Hui , Huang Kai , Li Lin 
Published: December 2023

AbstractFluorophores are considered powerful tools for not only enabling the visualization of cell structures, substructures, and biological processes, but also making for the quantitative and qualitative measurement of various analytes in living systems. However, most fluorophores do not meet the diverse requirements for biological applications in terms of their photophysical and biological properties. Hybridization is an important strategy in molecular engineering that provides fluorophores with complementarity and multifunctionality. This review summarizes the basic strategies of hybridization with four classes of fluorophores, including xanthene, cyanine, coumarin, and BODIPY with a focus on their structure‐property relationship (SPR) and biological applications. This review aims to provide rational hybrid ideas for expanding the reservoir of knowledge regarding fluorophores and promoting the development of newly produced fluorophores for applications in the field of life sciences.
Evaluation of the microleakage of class V composite restoration after cavity treatment with Erbium, CO2 lasers, Papain, and Bromelain enzymes
Authors: Sharafeddin Farahnaz , Tabrizi Anahita Fadaei 
Published: December 2023

AbstractObjectvesDifferent surface preparation and treatment methods may have dissimilar effects on the microleakage of composite resin. This study was conducted to determine the deproteinizing effect of 10% bromelain enzyme, 10% papain enzyme, CO2, and erbium‐YAG laser in regard to decrease in the microleakage of composite restorations.Materials and MethodsThirty teeth were selected and 60 class V cavities were prepared on the lingual and buccal sides. They were divided into six groups (n = 10): Group 1, phosphoric acid gel; Group 2, bromelain enzyme 10%; Group 3, papain enzyme 10%; Group 4, mixed papain and bromelain enzymes 10%; Group 5, CO2 laser; and Group 6, erbium‐YAG laser. They were stored in basic fuchsine and dye penetration was evaluated. Kruskal–Wallis and Mann–Whitney tests were used for statistical analysis, p < 0.05ResultsIn both occlusal and gingival margins, comparison of microleakage between groups 1, 2, 3, 4, and 5 showed no significant differences (p = 1) and group 6 had a significant difference with other groups (p ˂ 0.001).ConclusionsMicroleakage of composite resin in the dentin surface was not affected significantly using either bromelain or papain 10% enzymes or erbium laser. However, CO2 laser had a negative effect on the enamel and dentin margins and increased the microleakage. Erbium laser showed a better effect than enzymes on microleakage.
Untargeted metabolomics identifies metabolic dysregulation of sphingolipids associated with aggressive chronic lymphocytic leukaemia and poor survival
Authors: Nguyen Van Long Flora , Valcourt‐Gendron Délya , Caron Patrick , Rouleau Michèle , Villeneuve Lyne , Simonyan David , Le Trang , Sergerie Roxanne , Laverdière Isabelle , Vanura Katrina , Guillemette Chantal 
Published: December 2023

AbstractBackgroundMetabolic dependencies of chronic lymphocytic leukaemia (CLL) cells may represent new personalized treatment approaches in patients harbouring unfavourable features.MethodsHere, we used untargeted metabolomics and lipidomics analyses to isolate metabolomic features associated with aggressive CLL and poor survival outcomes. We initially focused on profiles associated with overexpression of the adverse metabolic marker glycosyltransferase (UGT2B17) associated with poor survival and drug resistance.ResultsLeukaemic B‐cell metabolomes indicated a significant perturbation in lipids, predominantly bio‐active sphingolipids. Expression of numerous enzyme‐encoding genes of sphingolipid biosynthesis pathways was significantly associated with shorter patient survival. Targeted metabolomics further exposed higher circulating levels of glucosylceramides (C16:0 GluCer) in CLL patients relative to healthy donors and an aggressive cancer biology. In multivariate analyses, C16:0 GluCer and sphinganine were independent prognostic markers and were inversely linked to treatment‐free survival. These two sphingolipid species function as antagonistic mediators, with sphinganine being pro‐apoptotic and GluCer being pro‐proliferative, tested in leukemic B‐CLL cell models. Blocking GluCer synthesis using ceramide glucosyltransferase inhibitors induced cell death and reduced the proliferative phenotype, which further sensitized a leukaemic B‐cell model to the anti‐leukaemics fludarabine and ibrutinib in vitro.ConclusionsSpecific sphingolipids may serve as prognostic markers in CLL, and inhibiting enzymatic pathways involved in their biosynthesis has potential as a therapaeutic approach.
Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials
Authors: Ferreira João Pedro , Butler Javed , Anker Stefan D. , Januzzi James L. , Panova‐Noeva Marina , Reese‐Petersen Alexander L. , Sattar Naveed , Schueler Elke , Pocock Stuart J. , Filippatos Gerasimos , Packer Milton , Sumin Mikhail , Zannad Faiez ,   EMPEROR Committees and Investigators
Published: December 2023

AbstractAimsExtracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR‐Preserved and EMPEROR‐Reduced trials.Methods and resultsOverall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy‐terminal propeptide (PICP), a fragment of N‐terminal type III collagen (PRO‐C3), procollagen type I amino‐terminal peptide (PINP), a fragment of C‐terminal type VIa3 collagen (PRO‐C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO‐C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high‐sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO‐C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO‐C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91–0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88–0.97, p = 0.003).Additionally, empagliflozin reduced PRO‐C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95–1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89–0.98, p = 0.003), without impact on other collagen markers.ConclusionOur observations are consistent with experimental observations that empagliflozin down‐regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated.
Development of a 39 MM‐InDel multiplex assay for the forensic application
Authors: Yao Yining , Ji Qiqi , Li Zhimin , Zhou Zhihan , Qian Jinglei , Ji Lili , Sun Kuan , Xie Jianhui 
Published: December 2023

AbstractInsertion/deletion polymorphisms (InDels) are a category of highly prevalent markers in the human genome, characterized by their distinctive attributes, including short amplicon sizes and low mutation rates, which have shown great potential in forensic applications. Multi‐allelic InDel and multi‐InDel markers, collectively abbreviated as MM‐InDels, were developed to enhance polymorphism by the introduction of novel alleles. Nevertheless, the relatively low mutation rates of InDels, coupled with the founder effect, result in distinct allele frequency distributions among populations. The divergent characteristics of InDels in different populations also pose challenges to the establishment of universally efficient InDel multiplex assays. To enhance the system efficiency of the InDel assay and its applicability across diverse populations, 39 MM‐InDels with high polymorphism in five different ancestry superpopulations were selected from the 1000 Genomes Project dataset and combined with an amelogenin gender marker to construct a multiplex assay (named MMIDplex). The combined power of discrimination and the cumulative probability of exclusion of 39 MM‐InDels were 1 − 1.3 × 10−23 and 1 − 9.83 × 10−6 in the Chinese Han population, and larger than 1–10−19 and 1–10−4 in the reference populations, relatively. These results demonstrate that the MMIDplex assay has the potential to obtain sufficient power for individual identification and paternity test in global populations.
Uncertainty quantification of bank vegetation impacts on the flood flow field in the American River, California, using large‐eddy simulations
Authors: Flora Kevin , Khosronejad Ali 
Published: December 2023

AbstractBank vegetation plays a key role in both hydrodynamics and morphodynamics of natural rivers; however, these effects are often unaccounted for in the computational flow dynamics of natural waterways. Recent studies using the large‐eddy simulation (LES), however, have attempted to gain insights into the impacts of bank vegetation on the mean flow field of the natural rivers using a vegetation model, which applies a sink term to the momentum equations of motion. This approach accounts for the effects of the vegetation and provides a practical approach to account for the complex patches of bank vegetation in large‐scale rivers. To implement the vegetation model, a drag coefficient reflecting the overall resistance of vegetal structures to the flow is needed, but due to the lack of calibrated data and range of size, density and type of vegetation, this parameter can be a significant source of uncertainty in the model results. In this study, we use uncertainty quantification (UQ) to investigate the hydrodynamics and bed shear results when a bank vegetation is incorporated in an LES model. To this end, we used the polynomial chaos expansion and Monte Carlo sampling techniques to determine the uncertainties associated with the drag coefficient in the vegetation model and from uncertainties in the bed roughness and inflow discharge. The UQ analysis provided spatially varying confidence levels for the spanwise and vertical distribution of velocity magnitude and for the bed shear stress distributions. In addition, Sobol indices were computed to indicate the relative influence that each parameter had on the overall uncertainty. In general, it was found that uncertainty in flow discharge was the dominant source of uncertainty; however, the drag coefficient in the vegetation model and the bed roughness parameter also made significant contribution to the uncertainty near the banks and bed, respectively.
Effectiveness of a tablet‐based intervention for people living with dementia in primary care—A cluster randomized controlled trial
Authors: Lech Sonia , Gellert Paul , Spang Robert P. , Voigt‐Antons Jan‐Niklas , Huscher Dörte , O’Sullivan Julie L. , Schuster Johanna 
Published: December 2023

AbstractBackgroundPrimary care physicians (PCP) play a key role in the care of people living with dementia. However, the implementation and practicability of the German S3 Dementia Guideline in primary care remain unclear. The main objective of the present study was to evaluate an intervention for improving guideline‐based dementia care in primary care.DesignA two‐arm, 9‐month follow‐up cluster‐randomized controlled trial with two parallel groups.Setting28 primary care practices in Berlin and the surrounding area in Germany.ParticipantsA total of N = 28 PCP, N = 91 people living with dementia, and N = 88 informal caregivers participated in the trial.InterventionA tablet‐based intervention to improve adherence to the German S3 Dementia Guideline in primary care was compared to a control group (care as usual plus a handbook on dementia). MeasurementsAdherence to dementia guideline (primary outcome) was measured on PCP’ (23 items) and informal caregivers' level (19 items) with a self‐developed checklist. Secondary outcomes (quality of life, neuropsychiatric symptoms, activities of daily living, general health status, depression, and caregiver burden) were measured with standardized assessments. Also, post‐hoc per‐protocol analyses were conducted.ResultsNo differences in guideline adherence between the intervention and the control group were observed. Further, no significant impact of the intervention on secondary outcomes was detected.ConclusionThe DemTab Study did not improve self‐reported guideline adherence in PCP. However, important implementation barriers such as lack of interoperability and low applicability of existing German S3 Dementia Guideline in the primary care setting were identified and are being discussed.Trial registration: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413). Registered 01 April 2019, https://doi.org/10.1186/ISRCTN15854413.
P2RY13 is a prognostic biomarker and associated with immune infiltrates in renal clear cell carcinoma: A comprehensive bioinformatic study
Authors: Chu Jie , Liu Wei , Hu Xinyue , Zhang Huiling , Jiang Jiudong 
Published: December 2023

AbstractBackground and AimsClear cell renal cell carcinoma (ccRCC) is a common and aggressive form of cancer with a high incidence globally. This study aimed to investigate the role of P2RY13 in the progression of ccRCC and elucidate its mechanism of action.MethodsGene Expression Omnibus and The Cancer Genome Atlas databases were used to extract gene expression profiles of ccRCC. These profiles were annotated and visualized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, as well as Gene Set Enrichment Analysis (GSEA). The STRING database was used to establish a protein–protein interaction network and to analyze the functional similarity. The GEPIA2 database was used to predict survival associated with hub genes. Meanwhile, the TIMER2.0 database was used to assess immune cell infiltration and its link with the hub genes. Immunohistochemistry (IHC) was used to determine the difference between ccRCC and adjacent normal tissue.ResultsWe identified 272 differentially expressed genes (DEGs). GO and KEGG analyses suggested that DEGs were primarily involved in lymphocyte activation, inflammatory response, immunological effector mechanism pathways. By cytohubba, the 20 highest‐scoring hub genes were screened to identify critical genes in the protein–protein interaction network linked with ccRCC. Resting dendritic cells, CD8 T cells, and activated mast cells all showed a significant positive correlation with these hub genes. Moreover, a higher immune score was associated with increased prognostic risk scores, which in turn correlated with a poorer prognosis. IHC revealed that P2RY13 was expressed at higher levels in ccRCC compared to para‐cancer tissues.ConclusionIdentifying the DEGs will aid in the understanding of the causes and molecular mechanisms involved in ccRCC. P2RY13 may play a pivotal role in the progression and prognosis of ccRCC, potentially driving carcinogenesis though immune system mechanisms.
Exploring the relationship between SARS‐CoV‐2 variants, illness severity at presentation, in‐hospital mortality and COVID‐19 vaccination in a low middle‐income country: A retrospective cross‐sectional study
Authors: Mushtaq Muhammad Zain , Nasir Nosheen , Mahmood Syed Faisal , Khan Sara , Kanji Akbar , Nasir Asghar , Syed M. Asif , Aamir Uzma Bashir , Hasan Zahra 
Published: December 2023

AbstractBackground and AimsCOVID‐19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS‐CoV‐2 variants of concern (VOC) with COVID‐19 severity and mortality among hospitalized patients in Pakistan.MethodsA retrospective review of clinical, laboratory, and vaccination data of 197 COVID‐19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS‐CoV‐2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID‐19 outcomes.ResultsThe median age of cases was 55 years and 51.8% were males. Twenty‐four percent of females were pregnant. Of COVID‐19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS‐CoV‐2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID‐19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45–13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82–9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11–0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23–0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92–13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45–17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10–0.53]).ConclusionOur study describes the relationship between the severity of COVID‐19, in‐hospital mortality in relation to SARS‐CoV‐2 variants, and the impact of COVID‐19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID‐19.