bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of good practices and false hits for QSAR-driven virtual screening real application: a SARS-CoV-2 main protease (Mpro) case study
Authors: Serafim Mateus Sá Magalhães , Pantaleão Simone Queiroz , da Silva Elany Barbosa , McKerrow James H. , O’Donoghue Anthony J. , Mota Bruno Eduardo Fernandes , Honorio Kathia Maria , Maltarollo Vinícius Gonçalves 
Published: July 2023

Computer-Aided Drug Design (CADD) approaches, such as those employing quantitative structure-activity relationship (QSAR) methods, are known for their ability to uncover novel data from large databases. These approaches can help alleviate the lack of biological and chemical data, but some predictions do not generate sufficient positive information to be useful for biological screenings. QSAR models are often employed to explain biological data of chemicals and to design new chemicals based on their predictions. In this review, we discuss the importance of data set size with a focus on false hits for QSAR approaches. We assess the challenges and reliability of an initial in silico strategy for the virtual screening of bioactive molecules. Lastly, we present a case study reporting a combination approach of hologram-based quantitative structure-activity relationship (HQSAR) models and random forest-based QSAR (RF-QSAR), based on the 3D structures of 25 synthetic SARS-CoV-2 Mpro inhibitors, to virtually screen new compounds for potential inhibitors of enzyme activity. In this study, optimal models were selected and employed to predict Mpro inhibitors from the database Brazilian Compound Library (BraCoLi). Twenty-four compounds were then assessed against SARS-CoV-2 Mpro at 10 µM. At the time of this study (March 2021), the availability of varied and different Mpro inhibitors that were reported definitely affected the reliability of our work. Since no hits were obtained, the data set size, parameters employed, external validations, as well as the applicability domain (AD) could be considered regarding false hits data contribution, aiming to enhance the design and discovery of new bioactive molecules.
Organochlorine pesticides and epigenetic alterations in thyroid tumors
Authors: Salimi Fouzieh , Asadikaram Gholamreza , Ashrafi Mohammad Reza , Zeynali Nejad Hamid , Abolhassani Moslem , Abbasi-Jorjandi Mojtaba , Sanjari Mojgan 
Published: July 2023

PurposeCancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients.MethodsOCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis.ResultsFurther TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P&lt;0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P&lt;0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P&lt;0.001) and H4K16 (OR=6.03, P&lt;0.001) acetylation.ConclusionThe current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.
Chronic-binge ethanol feeding aggravates systemic dyslipidemia in Ldlr-/- mice, thereby accelerating hepatic fibrosis
Authors: Hoebinger Constanze , Rajcic Dragana , Silva Beatriz , Hendrikx Tim 
Published: July 2023

ObjectiveChronic ethanol consumption is known to cause alcohol-associated liver disease, which poses a global health concern as almost a quarter of heavy drinkers develop severe liver damage. Alcohol-induced liver disease ranges from a mild, reversible steatotic liver to alcoholic steatohepatitis and irreversible liver fibrosis and cirrhosis, ultimately requiring liver transplantation. While ethanol consumption is associated with dysregulated lipid metabolism and altered cholesterol homeostasis, the impact of dyslipidemia and pre-existing hypercholesterolemia on the development of alcohol-associated liver disease remains to be elucidated.DesignTo address the influence of systemic dyslipidemia on ethanol-induced liver disease, chronic-binge ethanol feeding was applied to female C57BL/6J (wild type) mice and mice deficient for the low-density lipoprotein receptor (Ldlr-/-), which display a human-like lipoprotein profile with elevated cholesterol and triglyceride levels in circulation. Respective control groups were pair-fed an isocaloric diet.ResultsChronic-binge ethanol feeding did not alter systemic lipid levels in wild type mice. While increased systemic cholesterol levels in Ldlr-/- mice were not affected by ethanol feeding, chronic-binge ethanol diet aggravated elevated plasma triglyceride levels in Ldlr-/- mice. Despite higher circulatory triglyceride levels in Ldlr-/- mice, hepatic lipid levels and the development of hepatic steatosis were not different from wild type mice after ethanol diet, while hepatic expression of genes related to lipid metabolism (Lpl) and transport (Cd36) showed minor changes. Immunohistochemical assessment indicated a lower induction of infiltrating neutrophils in the livers of ethanol-fed Ldlr-/- mice compared to wild type mice. In line, hepatic mRNA levels of the pro-inflammatory genes Ly6g, Cd11b, Ccr2, Cxcl1 and F4/80 were reduced, indicating less inflammation in the livers of Ldlr-/- mice which was associated with reduced Tlr9 induction. While systemic ALT and hepatic MDA levels were not different, Ldlr-deficient mice showed accelerated liver fibrosis development after chronic-binge ethanol diet than wild type mice, as indicated by increased levels of Sirius Red staining and higher expression of pro-fibrotic genes Tgfb, Col1a1 and Col3a1. Ldlr-/- and wild type mice had similar plasma ethanol levels and did not show differences in the hepatic mRNA levels of Adh1 and Cyp2e1, important for ethanol metabolism.ConclusionOur results highlight that chronic-binge ethanol feeding enhances systemic dyslipidemia in Ldlr-/- mice which might accelerate the development of hepatic fibrosis, independent of hepatic lipid levels.
Clonal composition and differentiation stage of human CD30+ B cells in reactive lymph nodes
Authors: Küppers Ralf , Budeus Bettina , Hartmann Sylvia , Hansmann Martin-Leo 
Published: July 2023

IntroductionNormal CD30+ B cells represent a distinct B-cell differentiation stage with features of strong activation. We lack an in depth understanding of these cells, because they are not present in peripheral blood and are typically very rare in reactive lymphoid organs. CD30+ B cells have been discussed as a potential precursor population for the malignant CD30+ Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma. As CD30+ B cells can be more numerous in some cases of reactive lymphadenitis, we aimed to characterize these CD30+ B cells in terms of their differentiation stage and clonal composition, also as a means to clarify whether such CD30+ B-cell populations may represent potential precursor lesions of Hodgkin lymphoma.MethodsWe microdissected single CD30+ B cells from tissue sections of eight reactive lymph nodes with substantial numbers of such cells and sequenced their rearranged immunoglobulin (Ig) heavy chain V region (IGHV) genes.ResultsThe CD30+ B cells were polyclonal B cells in all instances, and they not only encompass post-germinal center (GC) B cells with mutated IGHV genes, but also include a substantial fraction of pre-germinal center B cells with unmutated IGHV genes. In five of the lymph nodes, mostly small clonal expansions were detected among the CD30+ B cells. Most of the expanded clones carried somatically mutated IGHV genes and about half of the mutated clones showed intraclonal diversity.DiscussionWe conclude that in human reactive lymph nodes with relatively many CD30+ B cells, these cells are a heterogenous population of polyclonal B cells encompassing activated pre-GC B cells as well as GC and post-GC B cells, with some clonal expansions. Because of their polyclonality and frequent pre-GC differentiation stage, there is no indication that such cell-rich CD30+ B-cell populations represent precursor lesions of Hodgkin lymphoma.
The cold-water coral province of the eastern Ligurian Sea (NW Mediterranean Sea): historical and novel evidences
Authors: Bo Marzia , Enrichetti Francesco , Betti Federico , Gay Guido , Quarta Gianluca , Calcagnile Lucio , Bavestrello Giorgio 
Published: July 2023

Several bathyal cold-water coral provinces, characterized by a lush growth of habitat-forming scleractinians, have been recognized in the Mediterranean Sea. However, the search for this biogenic habitat only marginally targeted the Italian coast of the Ligurian Sea (NW Mediterranean basin) despite historical and a few recent local studies in the region reporting the presence of corals. This study used bathymetry maps, side-scan sonar profiles, historical charts, and trawling routes to identify sites that could potentially host coral habitats in the eastern sector of the Ligurian Sea. Remotely operated vehicle video footage from various projects (2015-2021, 20 dives) was then used to characterize four sub-areas (Genoa Plateau, Portofino, Deiva Marina, and Monterosso) where corals were detected between 450 m and 750 m depth. Radiocarbon dating was used to trace back the geological history of the coral structures. A small coral mound, impacted by trawling activities, was found on the Genoa Plateau, while four massive coral structures were found in the other sub-areas, mainly located in a morphologically complex and highly energetic canyon region. High levels of megafaunal biodiversity, including rarely reported alcyonaceans as Placogorgia coronata, were observed together with moderate fishing impact. Overall, the identified coral areas potentially account for 9 km2 of both subfossil mounds (as old as 13300 years BP), dominated by Desmophyllum pertusum, and living reefs, dominated by Madrepora oculata, the latter representing up to 23% of the substrate coverage. The few living colonies of D. pertusum in the area represent the first documented records for the Ligurian Sea. These data support the presence of a distinct eastern Ligurian cold-water coral province.
Correlation analysis between body composition, serological indices and the risk of falls, and the receiver operating characteristic curve of different indexes for the risk of falls in older individuals
Authors: Zhang Kexin , Ju Yanmin , Yang Di , Cao Mengyu , Liang Hong , Leng Jiyan 
Published: July 2023

ObjectiveThis study assessed the risk factors for falls and evaluated the correlation between body composition, serological indices, and the risk of falls in older individuals.MethodThis cross-sectional study included 387 individuals ≥60 years of age in the cadre ward of the First Hospital of Jilin University. The information used in this study was obtained from the comprehensive geriatric assessment database of the cadre ward. The body composition of the individuals was measured by bioelectrical impedance analysis using an InBody S10 device. We assessed fall risk using the fall risk assessment tool. Individuals with ≤2 points were placed in the low-risk group, those with 3–9 points were placed in the medium-risk group, and those with ≥10 points were placed in the high-risk group.ResultsDifferences in age, educational background, height, cognitive impairment, malnutrition, ability of daily living, depression, diastolic blood pressure, heart rate, intracellular water, total body moisture, water ratio, limb moisture (right and left, upper and lower), trunk moisture, fat-free weight, arm girth, body cell mass, skeletal muscle mass, limb muscle (right and left, upper and lower), appendicular skeletal muscle mass index (ASMI), sarcopenia, hemoglobin level, hematocrit level, aspartate aminotransferase level, albumin level, anemia, and hypoproteinemia were observed among the three groups (p &lt; 0.001, p = 0.002, p = 0.006, p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, p = 0.008, p = 0.010). Ordinal logistic regression analysis showed that the probability of the fall risk increasing by one level was 1.902 times higher for each unit of decrease in educational background, respectively. In addition, the probability of the fall risk increasing by one level was 2.971, 3.732, 3.804, 1.690 and 2.155 times higher for each additional unit of age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia, respectively.ConclusionOur findings suggest that educational background, age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia were associated with falls in older individuals. Body composition and serological indices can assist in the early identification of falls in the older people.
Ssa1-targeted antibody prevents host invasion by Candida albicans
Authors: Qiu Xi-Ran , Shen Chen-Rui , Jiang Li-Wen , Ji Peng , Zhang Yu , Hou Wei-Tong , Zhang Wen , Shen Hui , An Mao-Mao 
Published: July 2023

IntroductionCandida albicans is a commensal fungus that colonizes most healthy individuals’ skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease.ResultHere we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus.DiscussionThese results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections.
Dispersive biofilm from membrane bioreactor strains: effects of diffusible signal factor addition and characterization by dispersion index
Authors: Song Wonjung , Ryu Junhee , Jung Jaehyun , Yu Youngjae , Choi Suyoung , Kweon Jihyang 
Published: July 2023

IntroductionBiofilm occurs ubiquitously in water system. Excessive biofilm formation deteriorates severely system performance in several water and wastewater treatment processes. Quorum sensing systems were controlled in this study with a signal compound cis-2-Decenoic acid (CDA) to regulate various functions of microbial communities, including motility, enzyme production, and extracellular polymeric substance (EPS) production in biofilm.MethodsThe addition of CDA to six strains extracted from membrane bioreactor sludge and the Pseudomonas aeruginosa PAO1 strain was examined for modulating biofilm development by regulating DSF expression.Results and discussionAs the CDA doses increased, optical density of the biofilm dispersion assay increased, and the decrease in EPS of the biofilm was obvious on membrane surfaces. The three-dimensional visual images and quantitative analyses of biofilm formation with CDA proved thinner, less massive, and more dispersive than those without; to evaluate its dispersive intensity, a dispersion index was proposed. This could compare the dispersive effects of CDA dosing to other biofilms or efficiencies of biofouling control practices such as backwashing or new cleaning methods.
UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3
Authors: Hu Xiaole , Wu Jiahao , Xu Jianwei 
Published: July 2023

BackgroundAs a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis.MethodsUCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments.ResultsISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1.ConclusionUCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.
An in vitro model to study suction events by a ventricular assist device: validation with clinical data
Authors: Rocchi Maria , Gross Christoph , Moscato Francesco , Schlöglhofer Thomas , Meyns Bart , Fresiello Libera 
Published: July 2023

Introduction: Ventricular assist devices (LVADs) are a valuable therapy for end-stage heart failure patients. However, some adverse events still persist, such as suction that can trigger thrombus formation and cardiac rhythm disorders. The aim of this study is to validate a suction module (SM) as a test bench for LVAD suction detection and speed control algorithms.Methods: The SM consists of a latex tube, mimicking the ventricular apex, connected to a LVAD. The SM was implemented into a hybrid in vitro-in silico cardiovascular simulator. Suction was induced simulating hypovolemia in a profile of a dilated cardiomyopathy and of a restrictive cardiomyopathy for pump speeds ranging between 2,500 and 3,200 rpm. Clinical data collected in 38 LVAD patients were used for the validation. Clinical and simulated LVAD flow waveforms were visually compared. For a more quantitative validation, a binary classifier was used to classify simulated suction and non-suction beats. The obtained classification was then compared to that generated by the simulator to evaluate the specificity and sensitivity of the simulator. Finally, a statistical analysis was run on specific suction features (e.g., minimum impeller speed pulsatility, minimum slope of the estimated flow, and timing of the maximum slope of the estimated flow).Results: The simulator could reproduce most of the pump waveforms observed in vivo. The simulator showed a sensitivity and specificity and of 90.0% and 97.5%, respectively. Simulated suction features were in the interquartile range of clinical ones.Conclusions: The SM can be used to investigate suction in different pathophysiological conditions and to support the development of LVAD physiological controllers.
Intelligence Quotient (IQ) in school-aged preterm infants: A systematic review
Authors: Lacalle Laura , Martínez-Shaw Melissa Liher , Marín Yolanda , Sánchez-Sandoval Yolanda 
Published: July 2023

Preterm birth (before 37 weeks of gestational age) is associated with certain risks to child development. The aim of this systematic review was to summarize available and updated empirical evidence on prematurity as a risk factor for cognitive development in school age. Thus, we attempted to identify similarities and differences with the full-term population and to point out possible risk or protective factors among the biological, psychosocial and family variables. The conceptualization and methodology of this review followed the PRISMA recommendations. The search was carried out in Web of Science, Scopus, PsycInfo, and Dialnet databases, in May 2022. The search was limited to journal articles, published between 2012 and 2022, in English and Spanish. Research articles selected were those focused on the intelligence quotient (IQ) of preterm children aged 6–12 years. The review included studies with cross-sectional or longitudinal cohorts, compared to a control group of children born at term or to standardized scales. The quality of evidence of the selected studies was verified with the Mixed Methods Appraisal Tool (MMAT). The initial search identified 1,040 articles. Forty articles met the inclusion criteria and were finally included in this review. These studies involved 5,396 preterm children from 37 different cohorts. Despite the diversity found among the results, in general, total IQ scores were within the normative mean for premature children; however, compared to their full-term peers, these scores were lower. The most studied variables in relation to IQ are perinatal (e.g., gestational age and birth weight) and family (e.g., socioeconomic level and education level of the mother). Recent studies corroborate that premature birth affects cognitive development in school age, and identify associated perinatal and family variables.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337371; identifier: CRD42022337371.