bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis and bioactivity study on oxygen-heterocyclic-based pyran analogues as effective P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell
Authors: Abd El-Wahab Ashraf H. F. , Borik Rita M. A. , Al-Dies Al-Anood M. , Fouda Ahmed M. , Mohamed Hany M. , El-Eisawy Raafat A. , Mora Ahmed , El-Nassag Mohammed A. A. , Abd elhady Ahmed M. , Elhenawy Ahmed A. , El-Agrody Ahmed M. 
Published: March 2024

AbstractP-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based pyran analogues (4a–l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a–l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a–c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO2, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a–c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC50 = 5.0–10.7 μM. The Rho123 accumulation assay showed that compounds 4a–c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a–c derivatives showed high oral bioavailability, but they did not cross the blood–brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.
A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC
Authors: Wang Changqian , Liu Xiang , Nov Pengkhun , Li Lilin , Li Chunhui , Liao Xuejiao , Li Luyao , Du Kunpeng , Li Jiqiang 
Published: March 2024

AbstractThe morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.
A quest for cytosolic sequons and their functions
Authors: Desai Manthan , Chowdhury Syed Rafid , Sun Bingyun 
Published: April 2024

AbstractEvolution shapes protein sequences for their functions. Here, we studied the moonlighting functions of the N-linked sequon NXS/T, where X is not P, in human nucleocytosolic proteins. By comparing membrane and secreted proteins in which sequons are well known for N-glycosylation, we discovered that cyto-sequons can participate in nucleic acid binding, particularly in zinc finger proteins. Our global studies further discovered that sequon occurrence is largely proportional to protein length. The contribution of sequons to protein functions, including both N-glycosylation and nucleic acid binding, can be regulated through their density as well as the biased usage between NXS and NXT. In proteins where other PTMs or structural features are rich, such as phosphorylation, transmembrane ɑ-helices, and disulfide bridges, sequon occurrence is scarce. The information acquired here should help understand the relationship between protein sequence and function and assist future protein design and engineering.
Dietary determinants of overnutrition among hypertensive patients in southwest Ethiopia: an ordinal regression model
Authors: Gebre Melaku , Alemayehu Beyene Girma , Muktar Ebrahim , Zewdie Amare , Asfaw Agize , Wasie Kasahun Abebaw , Kemal Abdurezak , Oumer Abdu 
Published: April 2024

AbstractOvernutrition is a recognized risk factor for hypertension, but evidence is lacking among hypertensive patients for tailored dietary interventions. This study assessed dietary factors in 331 hypertensive patients in southwest Ethiopia. The data was collected through a questionnaire and analyzed using factor analysis. Body mass index (BMI) was calculated, and a BMI above 25 kg m−2 was considered overnutrition. An ordinal logistic regression model was used to model the data and control confounders. Adjusted odds ratio and p-values were reported. Among the 331 respondents, consumption of cereals and grains (57.0%); roots and tubers (58.5); and legumes (50.0%), while 28.6% drink alcohol, was common. About 29.0% (24.1–34.2) had overnutrition (22%, 17.6–26.6%, overweight and 7.0%, 4.5–10.3%, obesity). While the predicted odds of overnutrition were higher among males (AOR = 2.85; 1.35–6.02), married (AOR = 1.47; 0.69–3.12), illiterates (AOR = 2.09; 1.18–3.72), advanced age (AOR = 1.65; 0.61–4.61), government employees (AOR = 6.83; 1.19–39.2), and urban dwellers (AOR = 4.06; 1.76–9.36), infrequent vegetable consumption (AOR = 1.47; 0.72–2.96) and lower and higher terciles of cereals and animal-source food consumption (AOR = 1.56; 0.72–3.34). Overnutrition among hypertensive patients was significantly high and associated with unhealthy dietary consumption, educational status, residence, and occupation, emphasizing the need for targeted dietary counseling.
European soybean to benefit people and the environment
Authors: Rotundo Jose L. , Marshall Rachel , McCormick Ryan , Truong Sandra K. , Styles David , Gerde Jose A. , Gonzalez-Escobar Emmanuel , Carmo-Silva Elizabete , Janes-Bassett Victoria , Logue Jennifer , Annicchiarico Paolo , de Visser Chris , Dind Alice , Dodd Ian C. , Dye Louise , Long Stephen P. , Lopes Marta S. , Pannecoucque Joke , Reckling Moritz , Rushton Jonathan , Schmid Nathaniel , Shield Ian , Signor Marco , Messina Carlos D. , Rufino Mariana C. 
Published: March 2024

AbstractEurope imports large amounts of soybean that are predominantly used for livestock feed, mainly sourced from Brazil, USA and Argentina. In addition, the demand for GM-free soybean for human consumption is project to increase. Soybean has higher protein quality and digestibility than other legumes, along with high concentrations of isoflavones, phytosterols and minerals that enhance the nutritional value as a human food ingredient. Here, we examine the potential to increase soybean production across Europe for livestock feed and direct human consumption, and review possible effects on the environment and human health. Simulations and field data indicate rainfed soybean yields of 3.1 ± 1.2 t ha−1 from southern UK through to southern Europe (compared to a 3.5 t ha−1 average from North America). Drought-prone southern regions and cooler northern regions require breeding to incorporate stress-tolerance traits. Literature synthesized in this work evidenced soybean properties important to human nutrition, health, and traits related to food processing compared to alternative protein sources. While acknowledging the uncertainties inherent in any modelling exercise, our findings suggest that further integrating soybean into European agriculture could reduce GHG emissions by 37–291 Mt CO2e year−1 and fertiliser N use by 0.6–1.2 Mt year−1, concurrently improving human health and nutrition.
Utilizing geospatial artificial intelligence to map cancer disparities across health regions
Authors: Fadiel Ahmed , Eichenbaum Kenneth D. , Abbasi Mohammad , Lee Nita K. , Odunsi Kunle 
Published: April 2024

AbstractWe have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities.iCATallows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms. This project aims to promote best practices to bridge the gap in healthcare access, resources, education, and economic opportunities. The project aims to engage local and regional stakeholders in data collection and evaluation, including patients, providers, and organizations. Their active involvement helps refine the platform and guides targeted interventions for more effective outcomes. In this paper, we present two sample illustrations demonstrating howiCATidentifies healthcare disparities and analyzes the impact of social and environmental variables on outcomes. Over time, this platform can help communities make decisions to optimize resource allocation.
Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults
Authors: Reis Laise Rodrigues , Costa-Rocha Ismael Artur , Abdala-Torres Thais , Campi-Azevedo Ana Carolina , Peruhype-Magalhães Vanessa , Araújo Márcio Sobreira Silva , Spezialli Elaine , do Valle Antonelli Lis Ribeiro , da Silva-Pereira Rosiane Aparecida , Almeida Gregório Guilherme , Fernandes Eder Gatti , Fantinato Francieli Fontana Sutile Tardetti , Domingues Carla Magda Allan Santos , Lemos Maria Cristina Ferreira , Chieppe Alexandre , Lemos Jandira Aparecida Campos , Coelho-dos-Reis Jordana Grazziela , de Lima Sheila Maria Barbosa , de Souza Azevedo Adriana , Schwarcz Waleska Dias , Camacho Luiz Antônio Bastos , de Lourdes de Sousa Maia Maria , de Noronha Tatiana Guimarães , Duault Caroline , Rosenberg-Hasson Yael , Teixeira-Carvalho Andréa , Maecker Holden Terry , Martins-Filho Olindo Assis ,   Collaborative Group for Studies of Yellow Fever Vaccine, Otta Dayane Andriotti , Martins-Filho Olindo Assis 
Published: April 2024

AbstractThe present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30–45) [Primary Vaccinees, PV(D30–45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30–45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30–45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30–45) as compared to NV(D0) (532vs398). Moreover, PV(D30–45) exhibited increased levels of Terminal Effector (CD45RA+CCR7−) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30–45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.
Relationships of SIGLEC family-related lncRNAs with clinical prognosis and tumor immune microenvironment in ovarian cancer
Authors: Jin Xin , Chen Ying , Hu Qing 
Published: March 2024

AbstractLong non-coding RNAs (lncRNAs) and Sialic acid-binding immunoglobulin-type lectin (SIGLEC) family members play an important role in proliferation, apoptosis, immune-cell activation and tumor development. However, the relationships of SIGLEC family-related lncRNAs with clinical prognosis and tumor immune microenvironment in ovarian cancer (OC) are still unclear. 426 SIGLEC family-related lncRNAs were obtained according to the screening criteria R > 0.4 and p < 0.05 using Pearson correlation analysis. A risk model contained AL133279.1, AL021878.2, AC078788.1, AC039056.2, AC008750.1 and AC007608.3 was conducted based on the univariate Cox regression analysis, a least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses. OC patient were divided into high-and low-risk group based on the median riskscore. K–M curve and ROC curve revealed that risk model has an abuset prognostic potential for OC patients. Moreover, we successfully validated the prognostic value of the model in the internal datasets, external datasets and clinical sample dataset. Finally, we found that the riskscore was positively correlated with the vast majority of immune cell infiltration. In conclusion, our research identified that a novel SIGLEC family-related lncRNAs risk model to predict the prognosis of OC patients. SIGLEC family-related lncRNAs risk model also has a positive relationship with the tumor immune microenvironment of OC, which may provide a new direction for immunotherapy of OC.
Efficacy and safety of mechanical thrombectomy in the posterior cerebral circulation—a single center study
Authors: Borończyk Michał , Kuźniak Mikołaj , Borończyk Agnieszka , Żak Amadeusz , Binek Łukasz , Wagner-Kusz Anna , Lasek-Bal Anetta 
Published: April 2024

AbstractMechanical thrombectomy (MT) is the current standard treatment for strokes in the anterior cerebral circulation (AMT) and has recently been proven to be beneficial in the posterior circulation strokes (PMT). Our study aims to evaluate parameters for favorable outcomes in PMT-patients and to compare the clinical characteristics of individuals who received AMT and PMT. For this purpose, we confronted AMT and PMT-receipients and performed a multivariate regression analysis to assess the influence of factors on favorable outcomes in the study group and in the AMT and PMT subgroups. When analysing 623 MT-patients, those who received PMT had significantly lower admission National Institutes of Health Stroke Scale (NIHSS) scores (9 vs. 13; p < 0.001) and 24 h post-MT (7 vs. 12; p = 0.006). Key parameters influencing the favorable outcomes of PMT at discharge and at 90th day include: NIHSS scores (OR: 0.865, 95% CI: 0.813–0.893, and OR: 0.900, 95% CI: 0.861–0.925), MT time (OR: 0.993, 95% CI: 0.987–0.998 and OR: 0.993, 95% CI: 0.990–0.997), and leukocytosis (OR: 0.961, 95% CI: 0.928–0.988 and OR: 0.974, 95% CI: 0.957–0.998). Different clinical profiles exist between AMT and PMT-recipients, with the neurological status post-MT being decisive for the prognosis. Several factors play an important role in predicting outcome, especially in the PMT group.
Bioengineering of vascularized porcine flaps using perfusion-recellularization
Authors: Xu Michael S. , D’Elia Andrew , Hadzimustafic Nina , Adil Aisha , Karoubi Golnaz , Waddell Thomas K. , Haykal Siba 
Published: March 2024

AbstractLarge volume soft tissue defects greatly impact patient quality of life and function while suitable repair options remain a challenge in reconstructive surgery. Engineered flaps could represent a clinically translatable option that may circumvent issues related to donor site morbidity and tissue availability. Herein, we describe the regeneration of vascularized porcine flaps, specifically of the omentum and tensor fascia lata (TFL) flaps, using a tissue engineering perfusion-decellularization and recellularization approach. Flaps were decellularized using a low concentration sodium dodecyl sulfate (SDS) detergent perfusion to generate an acellular scaffold with retained extracellular matrix (ECM) components while removing underlying cellular and nuclear contents. A perfusion-recellularization strategy allowed for seeding of acellular flaps with a co-culture of human umbilical vein endothelial cell (HUVEC) and mesenchymal stromal cells (MSC) onto the decellularized omentum and TFL flaps. Our recellularization technique demonstrated evidence of intravascular cell attachment, as well as markers of endothelial and mesenchymal phenotype. Altogether, our findings support the potential of using bioengineered porcine flaps as a novel, clinically-translatable strategy for future application in reconstructive surgery.
Detection of SARS-COV-2 variants and their proportions in wastewater samples using next-generation sequencing in Finland
Authors: Lipponen Anssi , Kolehmainen Aleksi , Oikarinen Sami , Hokajärvi Anna-Maria , Lehto Kirsi-Maarit , Heikinheimo Annamari , Halkilahti Jani , Juutinen Aapo , Luomala Oskari , Smura Teemu , Liitsola Kirsi , Blomqvist Soile , Savolainen-Kopra Carita , Pitkänen Tarja ,   WastPan Study Group, Länsivaara Annika , Hyder Rafiqul , Janhonen Erja , Heikinheimo Annamari , Heljanko Viivi , Johansson Venla , Kurittu Paula , Tiwari Ananda , Al-Mustapha Ahmad , Sarekoski Anniina , Möttönen Teemu , Räisänen Kati , Savolainen-Kopra Carita 
Published: April 2024

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants may have different characteristics, e.g., in transmission, mortality, and the effectiveness of vaccines, indicating the importance of variant detection at the population level. Wastewater-based surveillance of SARS-CoV-2 RNA fragments has been shown to be an effective way to monitor the COVID-19 pandemic at the population level. Wastewater is a complex sample matrix affected by environmental factors and PCR inhibitors, causing insufficient coverage in sequencing, for example. Subsequently, results where part of the genome does not have sufficient coverage are not uncommon. To identify variants and their proportions in wastewater over time, we utilized next-generation sequencing with the ARTIC Network's primer set and bioinformatics pipeline to evaluate the presence of variants in partial genome data. Based on the wastewater data from November 2021 to February 2022, the Delta variant was dominant until mid-December in Helsinki, Finland’s capital, and thereafter in late December 2022 Omicron became the most common variant. At the same time, the Omicron variant of SARS-CoV-2 outcompeted the previous Delta variant in Finland in new COVID-19 cases. The SARS-CoV-2 variant findings from wastewater are in agreement with the variant information obtained from the patient samples when visually comparing trends in the sewerage network area. This indicates that the sequencing of wastewater is an effective way to monitor temporal and spatial trends of SARS-CoV-2 variants at the population level.
Quercetin prophylaxis protects the kidneys by modulating the renin–angiotensin–aldosterone axis under acute hypobaric hypoxic stress
Authors: Rathi Vaishnavi , Sagi Sarada S. K. , Yadav Amit Kumar , Kumar Manoj , Varshney Rajeev 
Published: March 2024

AbstractThe study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.
Association between sociodemographic factors and health beliefs related to breast cancer screening behavior among Northern Thai women: a hospital-based study
Authors: Jiraniramai Surin , Pinyopornpanish Kanokporn , Wongpakaran Nahathai , Angkurawaranon Chaisiri , Champion Victoria L. , Chitapanarux Imjai , Jiraporncharoen Wichuda , Wongpakaran Tinakon 
Published: March 2024

AbstractEarly diagnosis of breast cancer is crucial for reducing mortality rates. The purpose of this study is to determine the impact of demographics/social determinants of health on beliefs about the practice of self-breast examination, using mammogram and ultrasound in the context of breast cancer screening among Thai women in a hospital-based setting for implying program planning and future research. A cross-sectional study was conducted in two health centers in Chiang Mai Province from August 2021 to December 2021, involving 130 Thai women ages 40 to 70 years. Data were collected by a survey using a questionnaire to gather sociodemographic information, and health beliefs about breast cancer and screening behavior utilizing the modified Thai version of Champion's Health Belief Model Scale (MT-CHBMS). Descriptive statistics, t-tests, ANOVA, and linear regression models were employed for examining association between sociodemographic factors and health beliefs about the practice of self-breast examination (BSE), using mammogram (MG) and ultrasound (UTS). Health insurance schemes were associated with Benefit-MG, Barrier-BSE, Barrier-MG and Barrier-UTS subscales. Additionally, monthly income was associated with Barrier-MG and Barrier-UTS subscales. The most common barriers reported were “embarrassment”, “worry”, and “takes too much time”. To enhance breast cancer screening in Thailand, program planning and future research should focus on health insurance schemes, especially women with social security schemes, as they may be the most appropriate target group for intervention.