bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-target drugs against Leishmania donovani for potential novel therapeutics
Authors: Bora Kushal , Sarma Manash , Kanaujia Shankar Prasad , Dubey Vikash Kumar 
Published: October 2023

AbstractAntioxidant defense mechanisms are important for a parasite to overcome oxidative stress and survive within host macrophage cells. Mitochondrial iron superoxide dismutase A (FeSODA) and trypanothione reductase (TR) are critical enzymes in the antioxidant defense mechanism of Leishmania donovani. FeSODA is responsible for neutralizing reactive oxygen species in mitochondria, while TR is responsible for reducing trypanothione, the molecules that help the parasite fight oxidative stress in Leishmania. In this study, we used multitarget ligands to inhibit both the FeSODA and TR enzymes. We combined structure-based drug design using virtual screening approach to find inhibitors against both the targets. The ZINC15 database of biogenic compounds was utilized to extract drugs-like molecules against leishmaniasis. The compounds were screened by standard precision (SP) and extra precision (XP) docking methods. Two compounds, ZINC000008876351 and ZINC000253403245, were selected based on molecular docking based on the binding affinity for both the targets. The screened molecules ZINC000008876351 and ZINC000253403245 showed strong hydrogen bonding with the target proteins according to the Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) techniques. These two compounds were also experimentally investigated on promastigotes stage of L. donovani. Under in vitro condition, the compounds show inhibitory effects on L. donovani promastigotes with IC50 values of 24.82 ± 0.61 µM for ZINC000008876351 and 7.52 ± 0.17 µM for ZINC000253403245. Thus, the screened compounds seem to have good potential as therapeutic candidates for leishmaniasis.
Screening of genes interacting with high myopia and neuropsychiatric disorders
Authors: Liu Yang , Liu Yang , Zhang Wen , Xue Zhong-Qi , Zhang Fang-Xia , Xu Wei-Gang , Zhuang Wen-Juan 
Published: October 2023

AbstractClinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.
No transfer of arousal from other’s eyes in Williams syndrome
Authors: Kleberg Johan Lundin , Hallman Astrid E. Z. , Galazka Martyna A. , Riby Deborah M. , Bölte Sven , Willfors Charlotte , Fawcett Christine , Nordgren Ann 
Published: October 2023

AbstractTypically developing humans automatically synchronize their arousal levels, resulting in pupillary contagion, or spontaneous adaptation of pupil size to that of others. This phenomenon emerges in infancy and is believed to facilitate social interaction. Williams syndrome (WS) is a genetic condition characterized by a hyper-social personality and social interaction challenges. Pupillary contagion was examined in individuals with WS (n = 44), age-parallel-matched typically developing children and adults (n = 65), and infants (n = 79). Bayesian statistics were used. As a group, people with WS did not show pupillary contagion (Bayes factors supporting the null: 25–50) whereas control groups did. This suggests a very early emerging atypical developmental trajectory. In WS, higher pupillary contagion was associated with lower autistic symptoms of social communication. Diminished synchronization of arousal may explain why individuals with WS have social challenges, whereas synchronization of arousal is not a necessary correlate of high social motivation.
Effects of elevated temperatures on the mechanical properties of laterized concrete
Authors: Ukpata Joseph O. , Ewa Desmond E. , Liwhuliwhe Joseph U. , Alaneme George Uwadiegwu , Obeten Koyonor E. 
Published: October 2023

AbstractThis study explored the impact of elevated temperatures on the residual structural properties of concrete made with a non-conventional fine aggregate such as laterite and quarry dust. In regions prone to high temperatures, such as tropical climates, the structural integrity of concrete can be compromised when exposed to elevated temperatures. Concrete samples were subjected to high temperatures (250 °C) and compared with control samples tested under normal conditions. In this research, the concrete mix was altered by replacing fine aggregates with different combinations of laterite (Lat) and quarry dust (QD) at varying percentages: 10%Lat:90%QD, 25%Lat:75%QD, 90%Lat:10%QD, 75%Lat:25%QD, and 50%Lat:50%QD. The physical properties of the constituent aggregates, including sand, laterite, quarry dust, and granite, were assessed, and an experimental mix was designed. The concrete samples underwent curing for 3, 7, 14, and 28 days, and their mechanical properties, specifically compression and flexural strength, were analyzed. The results demonstrated that as the percentage of laterite in the concrete matrix increased, there was a linear improvement in performance in terms of density, sorptivity, and strength gain. The maximum compressive strength reached 32.80 N/mm2 at 90% laterite replacement. However, flexural strength showed a different response, with the highest strength of 5.99 N/mm2 observed at 50% laterite replacement, after which strength declined with further increases in the laterite ratio. For economic and engineering considerations, it is recommended to use 25% laterite replacement with sand to produce grade 30 concrete, while 50% laterite replacement is suitable for grade-25 concrete. Importantly, the study found that a temperature of 250 °C did not significantly affect concrete strength, with changes of no more than 5%, which is consistent with expectations for conventional concrete. Furthermore, this research suggests that an optimal laterite replacement range of 25–50% should be considered when using laterite in concrete production.
Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease
Authors: Wang Fei , Yang Boxin , Qiao Jiao , Bai Linlu , Li Zijing , Sun Wenyuan , Liu Qi , Yang Shuo , Cui Liyan 
Published: October 2023

AbstractAcute exacerbation chronic obstructive pulmonary disease (AECOPD) has a high mortality rate. However, there is no efficiency biomarker for diagnosing AECOPD. The purpose of this study was to find biomarkers that can quickly and accurately diagnose AECOPD.45 normal controls (NC), 42 patients with stable COPD (SCOPD), and 66 patients with AECOPD were enrolled in our study. Serum exosomes were isolated by ultracentrifuge and verified by morphology and specific biomarkers. Fluorescent quantitation polymerase chain reaction (qRT-PCR) was used to detect the expression of micro RNAs (miRNAs), including miR-660-5p, miR-1258, miR-182-3p, miR-148a-3p, miR-27a-5p and miR-497-5p in serum exosomes and serum. Logistic regression and machine learning methods were used to constructed the diagnostic models of AECOPD. The levels of miR-1258 in the patients with AECOPD were higher than other groups (p < 0.001). The ability of exosomal miR-1258 (AUC = 0.851) to identify AECOPD from SCOPD was superior to other biomarkers, and the combination of exosomal miR-1258 and NLR can increase the AUC to 0.944, with a sensitivity of 81.82%, and specificity of 97.62%. The cross-validation of the models displayed that the logistic regression model based on exosomal miR-1258, NLR and neutrophil count had the best accuracy (0.880) in diagnosing AECOPD from SCOPD. The three most correlated biomarkers with serum exosome miR-1258 were neutrophil count (r = 0.57, p < 0.001), WBC (r = 0.50, p < 0.001) and serum miR-1258 (r = 0.33, p < 0.001). In conclusion, serum exosomal miR-1258 is associated with inflammation, and can be used as a valuable and reliable biomarker for the diagnosis of AECOPD, and the establishment of diagnostic model based on miR-1258, NLR and neutrophils count can help to improving the accuracy of AECOPD diagnosis.
I-gel Plus acts as a superior conduit for fiberoptic intubation than standard i-gel
Authors: Chaki Tomohiro , Tachibana Shunsuke , Kumita Sho , Sato Satoshi , Hirahata Tomoki , Ikeshima Yuta , Ohsaki Yuki , Yamakage Michiaki 
Published: October 2023

AbstractThe supraglottic airway (SGA) is widely used. I-gel Plus is a next-generation i-gel with some improvements, including facilitation of fiberoptic tracheal intubation (FOI). To compare the performance of i-gel Plus and standard i-gel as conduits for FOI, a Thiel-embalmed cadaveric study was conducted. Twenty-two anesthesiologists were enrolled as operators in Experiment 1. The i-gel Plus and standard i-gel were inserted into one cadaver, and the FOI was performed through each SGA. The primary outcome was time required for FOI. The secondary outcomes were the number of attempts and visual analog scale (VAS) score for difficulty in FOI. Moreover, fiberoptic views of the vocal cords in each SGA were assessed by an attending anesthesiologist using nine cadavers in Experiment 2. The percentage of glottic opening (POGO) score without fiberscope tip upward flexion and upward angle of the fiberscope tip to obtain a 100% POGO score were evaluated as secondary outcomes. The time for FOI through i-gel Plus was significantly shorter than that through standard i-gel (median (IQR), i-gel Plus: 30.3 (25.4–39.0) s, vs standard i-gel: 54.7 (29.6–135.0) s; median of differences, 24.4 s; adjusted 95% confidence interval, 3.0–105.7; adjusted P = 0.040). Although the number of attempts for successful FOI was not significantly different, the VAS score for difficulty in the i-gel Plus group was significantly lower (easier) than that in the standard i-gel group. Moreover, i-gel Plus required a significantly smaller upward angle of the fiberscope tip to obtain a 100% POGO score. FOI can be performed more easily using i-gel Plus than using standard i-gel because of the improved fiberoptic visibility of vocal cords.
Factors influencing extrathyroidal extension of papillary thyroid cancer and evaluation of ultrasonography for its diagnosis: a retrospective analysis
Authors: Wang Hui , Zhao Shanshan , Yao Jincao , Yu Xiuhua , Xu Dong 
Published: October 2023

AbstractPathologists usually explore extrathyroidal extensions (ETEs) in thyroid cancer; however, sonographers are often not concerned with ETEs. We investigated factors influencing ETEs and the efficacy of ultrasound evaluation of thyroid capsule invasion. We retrospectively analysed 1933 papillary thyroid carcinoma patients who underwent thyroidectomy during 2018–2021. Patients were divided into three groups: no ETE, minor ETE (mETE), and gross ETE. Clinical characteristic differences were assessed using binary logistic regression analysis to identify ETE predictors, and the kappa test was performed to analyse consistency between ultrasonographic and pathological diagnoses of ETE. The mETE group was more likely to have larger tumour diameters and more extensive lymph node metastasis (LNM) than the no ETE group and more likely to be diagnosed in the isthmus. In the multivariate logistic regression analysis, longest tumour diameter, lesion site, LNM extent, and thyroglobulin concentration were significant mETE predictors. Minimal consistency existed between pathological and ultrasonographic examinations for neighbouring tissue invasion. Many clinical differences were observed between the no ETE and mETE groups, suggesting the importance of considering mETE. Therefore, sonographers should pay more attention to relationships between nodules and capsule and indicate these on ultrasound reports to provide more accurate preoperative ETE information for surgeons.
Equivalent impacts of logging and beaver activities on aboveground carbon stock loss in the southernmost forest on Earth
Authors: Miranda Alejandro , Hoyos-Santillan Jorge , Lara Antonio , Mentler Rayén , Huertas-Herrera Alejandro , Toro-Manríquez Mónica D. R. , Sepulveda-Jauregui Armando 
Published: October 2023

AbstractThe conservation of forest landscapes is crucial for global climate strategies, and the forest in Tierra del Fuego, located in Patagonia, represents the southernmost example on Earth. These ecosystems are critical for Chile’s roadmap toward carbon neutrality. Unfortunately, these ecosystems have been impacted by logging and beaver activities. Currently, the precise contribution of each driver to forest cover and carbon stock loss remains insufficiently quantified, impeding effective policymaking and the implementation of strategies to safeguard and enhance carbon stocks in these ecosystems. In this study, we conducted an assessment of forest carbon stock loss resulting from both logging and beaver activities in Chilean Tierra del Fuego from 1986 to 2019. While beavers have received significant attention for their substantial contribution to forest cover loss (56.1% forest cover, ≈ 1.4 MtC), our findings suggest that logging has nearly equally contributed to carbon stock depletion (43.8% forest cover, ≈ 1.2 MtC). Consequently, the prevailing focus on beavers has obscured the ongoing logging-induced carbon stock loss. The implications of our study highlight the urgency for comprehensive consideration of both drivers in Chile’s climate strategy to fulfill the country’s mitigation commitments.
Association of TERT (rs2736098 and rs2736100) genetic variants with elevated risk of hepatocellular carcinoma: a retrospective case–control study
Authors: Seif Eldin Walaa R. , Saad Entsar A. , Monier Ahmed , Elshazli Rami M. 
Published: October 2023

AbstractHepatocellular carcinoma (HCC) is an inflammatory problematic issue with higher mortality among different ethnic populations. The telomerase reverse transcriptase (TERT) gene has an imperative role in the proliferation of various cancerous illnesses, particularly HCC. Moreover, the TERT (rs2736098 and rs2739100) variants were correlated with the HCC susceptibility and telomere shortening, but with unconvincing outcomes. The main purpose of this outward work is to assess the correlation between these significant variants within the TERT gene and the elevated risk of HCC with the aid of various computational bioinformatics tools. This study included 233 participants [125 cancer-free controls and 108 HCC patients] from the same locality. In addition, 81.5% of HCC patients were positive for HCV autoantibodies, while 73.1% of HCC patients were positive for cirrhotic liver. Genomic DNA of the TERT (rs2736098 and rs2736100) variants were characterized utilizing the PCR–RFLP method. Interestingly, the frequencies of TERT (rs2736098*A allele) and TERT (rs2736100*T allele) conferred a significant correlation with increased risk of HCC compared to healthy controls (p-value = 0.002, and 0.016, respectively). The TERT (rs2736098*A/A) genotype indicated a definite association with positive smoking and splenomegaly (p-value < 0.05), while the TERT (rs2736100*T/T) genotype observed a significant difference with higher levels of HCV autoantibodies (p-value = 0.009). In conclusion, this significant work confirmed the contribution of the TERT (rs2736098*A and rs2736100*T) alleles with elevated risk of HCC progression and telomere shortening among Egyptian subjects.
Impact of tropical SSTs on the late-winter signal over the North Atlantic-European region and contribution of midlatitude Atlantic
Authors: Herceg-Bulić Ivana , Ivasić Sara , Popović Margareta 
Published: October 2023

AbstractThe impact of tropical sea surface temperatures (SSTs) on the signal of geopotential heights (GH200) over the North Atlantic-European (NAE) region is analysed from the aspects of seasonality, the contribution of individual tropical basins and midlatitude North Atlantic, El Niño-Southern Oscillation (ENSO) effect and spatial pattern of the atmospheric response. For this purpose, ensembles of targeted numerical simulations with SST forcing prescribed in various ocean basins are performed and examined. A clear atmospheric response is obtained in the late winter months. The strongest signal is linked to ENSO events during late winter. The competitive influences of individual tropical basins are indicated. At the same time, the superposition effect of the extratropical North Atlantic SSTs, which is established through the modulation of storm tracks, is demonstrated. Both, the modelled signal and the NOAA-CIRES-DOE 20th Century Reanalysis variance reveal the ENSO signature as a pattern in the North Atlantic projecting onto the East Atlantic pattern.
NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology
Authors: Mock Andreas , Teleanu Maria-Veronica , Kreutzfeldt Simon , Heilig Christoph E. , Hüllein Jennifer , Möhrmann Lino , Jahn Arne , Hanf Dorothea , Kerle Irina A. , Singh Hans Martin , Hutter Barbara , Uhrig Sebastian , Fröhlich Martina , Neumann Olaf , Hartig Andreas , Brückmann Sascha , Hirsch Steffen , Grund Kerstin , Dikow Nicola , Lipka Daniel B. , Renner Marcus , Bhatti Irfan Ahmed , Apostolidis Leonidas , Schlenk Richard F. , Schaaf Christian P. , Stenzinger Albrecht , Schröck Evelin , Hübschmann Daniel , Heining Christoph , Horak Peter , Glimm Hanno , Fröhling Stefan 
Published: October 2023

AbstractAnalysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities of individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive molecular characterization adds significant clinical value. However, the complexity and heterogeneity of the resulting data are major challenges for disciplines involved in interpretation and recommendations for individualized care, and limited information exists on how to approach multilayered tumor profiles in clinical routine. We report our experience with the practical use of data from whole-genome or exome and RNA sequencing and DNA methylation profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program of the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Research Center (DKFZ). We cover all relevant steps of an end-to-end precision oncology workflow, from sample collection, molecular analysis, and variant prioritization to assigning treatment recommendations and discussion in the molecular tumor board. To provide insight into our approach to multidimensional tumor profiles and guidance on interpreting their biological impact and diagnostic and therapeutic implications, we present case studies from the NCT/DKFZ molecular tumor board that illustrate our daily practice. This manual is intended to be useful for physicians, biologists, and bioinformaticians involved in the clinical interpretation of genome-wide molecular information.
Digital lifestyle treatment improves long-term metabolic control in type 2 diabetes with different effects in pathophysiological and genetic subgroups
Authors: Salunkhe Vishal A. , Sinha Neha , Ahlqvist Emma , Prasad Rashmi B. , Johansson Svetlana , Abrahamsson Birgitta , Rosengren Anders H. 
Published: October 2023

AbstractTo address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden (n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009). This is paralleled by reduced body weight, ameliorated insulin secretion, increased physical activity, and cognitive eating restraints. Participants with high BMI and insulin resistance have an even larger response, as have non-risk allele carriers for the FTO gene. The findings open a new avenue for scalable lifestyle management with sustained efficacy and highlight a previously unrecognized opportunity for digital precision treatment based on genetics and individual pathophysiology. ClinicalTrials.gov NCT04624321.
Prognosis Individualized: Survival predictions for WHO grade II and III gliomas with a machine learning-based web application
Authors: Karabacak Mert , Jagtiani Pemla , Carrasquilla Alejandro , Germano Isabelle M. , Margetis Konstantinos 
Published: October 2023

AbstractWHO grade II and III gliomas demonstrate diverse biological behaviors resulting in variable survival outcomes. In the context of glioma prognosis, machine learning (ML) approaches could facilitate the navigation through the maze of factors influencing survival, aiding clinicians in generating more precise and personalized survival predictions. Here we report the utilization of ML models in predicting survival at 12, 24, 36, and 60 months following grade II and III glioma diagnosis. From the National Cancer Database, we analyze 10,001 WHO grade II and 11,456 grade III cranial gliomas. Using the area under the receiver operating characteristic (AUROC) values, we deploy the top-performing models in a web application for individualized predictions. SHapley Additive exPlanations (SHAP) enhance the interpretability of the models. Top-performing predictive models are the ones built with LightGBM and Random Forest algorithms. For grade II gliomas, the models yield AUROC values ranging from 0.813 to 0.896 for predicting mortality across different timeframes, and for grade III gliomas, the models yield AUROCs ranging from 0.855 to 0.878. ML models provide individualized survival forecasts for grade II and III glioma patients across multiple clinically relevant time points. The user-friendly web application represents a pioneering digital tool to potentially integrate predictive analytics into neuro-oncology clinical practice, to empower prognostication and personalize clinical decision-making.