bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet-related inflammation is positively associated with atherogenic indices
Authors: Heidarzadeh-Esfahani Neda , Hajahmadi Salimeh , Pasdar Yahya , Darbandi Mitra , Najafi Farid , Moradinazar Mehdi , Bonyani Mitra , Feyz-BashiPoor Roxana , Soltani Shahin
Published: June 2024

Current evidence suggests that non-traditional serum lipid ratios are more effective than traditional serum lipid parameters in predicting vascular diseases, and both of them are associated with dietary patterns. Therefore, this study aimed to investigate the relationship between the dietary inflammatory index (DII) and atherogenic indices using traditional serum lipid parameters (triglyceride (TG), total cholesterol (TC), LDL cholesterol (LDL–c), high-density lipoprotein cholesterol (HDL–c)) and non-traditional serum lipid ratios (atherogenic index of plasma (AIP), Castelli's index-I (CRI_I), Castelli's index-II (CRI_II), the lipoprotein combination index (LCI), and the atherogenic coefficient (AC)). Basic information from the Ravansar Non-Communicable Diseases cohort study was utilized in the present cross-sectional observational study. The study included 8870 adults aged 35–65 years. A validated food frequency questionnaire (FFQ) was used to measure DII. We compared the distributions of outcomes by DII score groups using multivariable linear regression. The difference between DII score groups was evaluated by the Bonferroni test. The mean ± SD DII was − 2.5 ± 1.43, and the prevalence of dyslipidemia was 44%. After adjusting for age, sex, smoking status, alcohol consumption status, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), body mass index (BMI) and socioeconomic status (SES), participants in the highest quartile of DII had a greater risk for CRI_I (β = 0.11, CI 0.05, 0.18), CRI_II (β = 0.06, CI 0.01, 0.11), LCI (β = 0.11, CI 288.12, 8373.11), AC (β = 0.11, CI 0.05, 0.17) and AIP (β = 0.06, CI 0.02, 0.10). Moreover, according to the adjusted logistic regression model, the risk of dyslipidemia significantly increased by 24% (OR: 1.24, 95% CI 1.08–1.41), 7% (OR: 1.07, 95% CI 0.94, 1.21) and 3% (OR: 1.03, 95% CI 0.91, 1.16) in Q4, Q3 and Q2 of the DII, respectively. Finally, diet-related inflammation, as estimated by the DII, is associated with a higher risk of CRI-I, CRI-II, LCI, AC, and AIP and increased odds of dyslipidemia.
Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods
Authors: Saif Minhaz Zabin , Esha Nusrat Jahan Ikbal , Quayum Syeda Tasnim , Rahman Shofiur , Al-Gawati Mahmoud A. , Alsowygh Ghadah , Albrithen Hamad , Alodhayb Abdullah N. , Poirier Raymond A. , Uddin Kabir M.
Published: June 2024

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1–16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO–LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of − 8.5 kcal mol−1. This result outperformed the affinity of the reference standard dapagliflozin (− 7.9 kcal mol−1) as well as two other compounds that target human IDE, namely vitexin (− 8.3 kcal mol−1) and myricetin (− 8.4 kcal mol−1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein–ligand complex at the active site.
Neural underpinnings of ethical decisions in life and death dilemmas in naïve and expert firefighters
Authors: Duarte Isabel C. , Dionísio Ana , Oliveira Joana , Simões Marco , Correia Rita , Dias Joana A. , Caldeira Salomé , Redondo João , Castelo-Branco Miguel
Published: June 2024

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.
Multimodal fusion for anticipating human decision performance
Authors: Tran Xuan-The , Do Thomas , Pal Nikhil R. , Jung Tzyy-Ping , Lin Chin-Teng
Published: June 2024

Anticipating human decisions while performing complex tasks remains a formidable challenge. This study proposes a multimodal machine-learning approach that leverages image features and electroencephalography (EEG) data to predict human response correctness in a demanding visual searching task. Notably, we extract a novel set of image features pertaining to object relationships using the Segment Anything Model (SAM), which enhances prediction accuracy compared to traditional features. Additionally, our approach effectively utilizes a combination of EEG signals and image features to streamline the feature set required for the Random Forest Classifier (RFC) while maintaining high accuracy. The findings of this research hold substantial potential for developing advanced fault alert systems, particularly in critical decision-making environments such as the medical and defence sectors.
Disparate nonlinear neural dynamics measured with different techniques in macaque and human V1
Authors: Zhou Jingyang , Whitmire Matt , Chen Yuzhi , Seidemann Eyal
Published: June 2024

Diverse neuro-imaging techniques measure different aspects of neural responses with distinct spatial and temporal resolutions. Relating measured neural responses across different methods has been challenging. Here, we take a step towards overcoming this challenge, by comparing the nonlinearity of neural dynamics measured across methods. We used widefield voltage-sensitive dye imaging (VSDI) to measure neural population responses in macaque V1 to visual stimuli with a wide range of temporal waveforms. We found that stimulus-evoked VSDI responses are surprisingly near-additive in time. These results are qualitatively different from the strong sub-additive dynamics previously measured using fMRI and electrocorticography (ECoG) in human visual cortex with a similar set of stimuli. To test whether this discrepancy is specific to VSDI—a signal dominated by subthreshold neural activity, we repeated our measurements using widefield imaging of a genetically encoded calcium indicator (GcaMP6f)—a signal dominated by spiking activity, and found that GCaMP signals in macaque V1 are also near-additive. Therefore, the discrepancies in the extent of sub-additivity between the macaque and the human measurements are unlikely due to differences between sub- and supra-threshold neural responses. Finally, we use a simple yet flexible delayed normalization model to capture these different dynamics across measurements (with different model parameters). The model can potentially generalize to a broader set of stimuli, which aligns with previous suggestion that dynamic gain-control is a canonical computation contributing to neural processing in the brain.
Selective and sensitive CQD-based sensing platform for Cu2+ detection in Wilson’s disease
Authors: Zarei Armin , Rezaei Aram , Shahlaei Mohsen , Asani Zhaleh , Ramazani Ali , Wang Chuanyi
Published: June 2024

Excessive Cu2+ intake can cause neurological disorders (e.g. Wilson’s disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting.
N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells
Authors: Satriyo Pamungkas Bagus , Mustofa Mustofa , Wahyuningsih Tutik Dwi , Damayanti Ema , Wiraswati Hesti Lina , Satria Denny , Bashari M. Hasan , Sholikhah Eti Nurwening
Published: June 2024

Protein kinase dysregulation induces cancer cell aggressiveness leading to rapid tumor progression and poor prognosis in TNBC patients. Many small-molecule kinase inhibitors have been tested in clinical trials to treat TNBC patients. In the previous study, we found that N-phenylpyrazoline small molecule acts as a protein kinase inhibitor in cervical cancer cells. However, there remains unknown about N-phenyl pyrazoline potency as a kinase inhibitor and its anti-cancer activity in TNBC cells. In this study, we investigated the activity of N-phenyl pyrazoline against TNBC cells via tyrosine kinase inhibition. Based on the MTT assay, the IC50 values for the N-phenyl pyrazoline 2, 5, A, B, C, and D against Hs578T were 12.63 µM, 3.95 µM, not available, 18.62 µM, 30.13 µM, and 26.79 µM, respectively. While only P5 exhibited the IC50 against MDA MB 231 (21.55 µM). Further, N-phenyl pyrazoline 5 treatment significantly inhibited the cell proliferation rate of Hs578T and MDA MB 231 cells. The migration assay showed that treatment with the compound N-phenyl pyrazoline 5 with 4 µM concentration significantly reduced cell migration of Hs578T cells. N-phenyl pyrazoline 5 treatment at 1 µM and 2 µM was able to reduce the tumorsphere size of Hs578t cells. A combination treatment of P5 and paclitaxel showed a synergistic effect with a combination index score > 1 in both TNBC cells. Further, the P5 predictively targeted the protein kinases that significantly correlated to breast cancer prognosis. The GSEA analysis result shows that receptor tyrosine kinase, Notch3, Notch4, and Ephrin signaling pathways were targeted by P5. The P5 treatment reduced the EGFR expression level and activation in TNBC cells.
Patient-centered radiology reports with generative artificial intelligence: adding value to radiology reporting
Authors: Park Jiwoo , Oh Kangrok , Han Kyunghwa , Lee Young Han
Published: June 2024

The purposes were to assess the efficacy of AI-generated radiology reports in terms of report summary, patient-friendliness, and recommendations and to evaluate the consistent performance of report quality and accuracy, contributing to the advancement of radiology workflow. Total 685 spine MRI reports were retrieved from our hospital database. AI-generated radiology reports were generated in three formats: (1) summary reports, (2) patient-friendly reports, and (3) recommendations. The occurrence of artificial hallucinations was evaluated in the AI-generated reports. Two radiologists conducted qualitative and quantitative assessments considering the original report as a standard reference. Two non-physician raters assessed their understanding of the content of original and patient-friendly reports using a 5-point Likert scale. The scoring of the AI-generated radiology reports were overall high average scores across all three formats. The average comprehension score for the original report was 2.71 ± 0.73, while the score for the patient-friendly reports significantly increased to 4.69 ± 0.48 (p < 0.001). There were 1.12% artificial hallucinations and 7.40% potentially harmful translations. In conclusion, the potential benefits of using generative AI assistants to generate these reports include improved report quality, greater efficiency in radiology workflow for producing summaries, patient-centered reports, and recommendations, and a move toward patient-centered radiology.
Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures
Authors: Liu Yang , Ma Yongsheng , Yang Wenming , Lin Qitai , Xing Yugang , Shao Huifeng , Li Pengcui , He Yong , Duan Wangping , Wei Xiaochun
Published: June 2024

Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.
Biologically meaningful genome interpretation models to address data underdetermination for the leaf and seed ionome prediction in Arabidopsis thaliana
Authors: Raimondi Daniele , Passemiers Antoine , Verplaetse Nora , Corso Massimiliano , Ferrero-Serrano Ángel , Nazzicari Nelson , Biscarini Filippo , Fariselli Piero , Moreau Yves
Published: June 2024

Genome interpretation (GI) encompasses the computational attempts to model the relationship between genotype and phenotype with the goal of understanding how the first leads to the second. While traditional approaches have focused on sub-problems such as predicting the effect of single nucleotide variants or finding genetic associations, recent advances in neural networks (NNs) have made it possible to develop end-to-end GI models that take genomic data as input and predict phenotypes as output. However, technical and modeling issues still need to be fixed for these models to be effective, including the widespread underdetermination of genomic datasets, making them unsuitable for training large, overfitting-prone, NNs. Here we propose novel GI models to address this issue, exploring the use of two types of transfer learning approaches and proposing a novel Biologically Meaningful Sparse NN layer specifically designed for end-to-end GI. Our models predict the leaf and seed ionome in A.thaliana, obtaining comparable results to our previous over-parameterized model while reducing the number of parameters by 8.8 folds. We also investigate how the effect of population stratification influences the evaluation of the performances, highlighting how it leads to (1) an instance of the Simpson’s Paradox, and (2) model generalization limitations.
Impact of COVID-19 pandemic on the dynamic of patients with oral and maxillofacial trauma: interrupted time-series analysis
Authors: Tatsumi Hiroto , Matsuda Yuhei , Okui Tatsuo , Karino Masaaki , Koike Takashi , Okuma Satoe , Toda Erina , Ishizuka Shinji , Sonoyama-Osako Rie , Morioka Reon , Kotani Tatsuhito , Shimamura Yukiho , Kanno Takahiro
Published: June 2024

Oral and maxillofacial trauma is influenced by various factors, including regional characteristics and social background. Due to the coronavirus disease 2019 (COVID-19) pandemic, a state of emergency was declared in Japan in March 2020. In this study, we aimed to examine the dynamics of patients with oral and maxillofacial trauma over a 12-years period using interrupted time-series (ITS) analysis. Patients were examined at the Shimane University Hospital, Maxillofacial Trauma Center from April 2012 to April 2023. In addition to general patient characteristics, data regarding the type of trauma and its treatment were obtained from 1203 patients (770 men and 433 women). Group comparisons showed significant differences in age, trauma status, method of treatment, referral source, route, and injury occasion. ITS analysis indicated significant changes in combined nasal fractures, non-invasive reduction, and sports injuries (P < 0.05), suggesting COVID-19 significantly impacted oral and maxillofacial trauma dynamics. A pandemic of an infectious disease may decrease the number of minor trauma cases but increase the number of injuries from outdoor activities, resulting in no overall change in the dynamics of the number of trauma patients. Medical systems for oral and maxillofacial trauma should be in place at all times, independent of infectious disease pandemics.
Three-dimensional finite element analysis of the optimal mechanical design for maximum inward movement of the anterior teeth with clear aligners
Authors: Chen Jingcheng , Zhu Daoyu , Zhao Mengli , Cheng Zhiheng , Pan Yan , Liu Xin
Published: June 2024

This study aims to refine clinical designs within clear aligner therapy, exploring the appropriate ratio of anterior tooth retraction to intrusion under maximum anchorage. Using a three-dimensional finite element model and evaluating 19 load scenarios with first premolar extraction, the research identifies the optimal force angle for anterior tooth retraction as 45 to 55°. For clinical planning, it is recommended to design a retraction of 0.19 mm combined with an intrusion of 0.16 mm to achieve anterior tooth retraction. This investigation is crucial for enhancing understanding of biomechanical principles in clear aligner orthodontics, offering significant insights for effective treatments.
Effect of the COVID-19 pandemic on Vogt–Koyanagi–Harada disease
Authors: Muto Tetsuya , Sakamoto Masaaki , Kusuda Shoichiro , Haruyama Yasuo , Machida Shigeki , Imaizumi Shinichiro , Sekiryu Tetsuju
Published: June 2024

To determine the disease prevalence rate and clinical characteristics of Vogt–Koyanagi–Harada (VKH) disease among new patients before and after the declaration of a state of emergency (April 7, 2020) in Japan. New patients and patients with newly diagnosed VKH disease were categorized into “Before” and “After” groups based on the initial visit. The prevalence rate, sex ratio, and age of patients newly diagnosed with VKH were compared between the groups. Best-corrected visual acuity (BCVA) and recurrence rates were compared among 59 patients observed for > 12 months after receiving pulse steroid therapy. For reference, we also examined the prevalence rate of patients newly diagnosed with acute angle closure (AAC) in the Before and After groups. The prevalence rates of VKH disease among newly diagnosed patients (P < 0.05) or patients with AAC (P < 0.001) were significantly higher in the After group. No significant differences in sex ratio or age of VKH disease were observed in both groups. BCVA and recurrence rates showed no significant differences. The COVID-19 pandemic increased the prevalence of VKH disease among new patients compared with that of AAC. However, the clinical features of VKH disease were unlikely affected by the COVID-19 pandemic.
Association between the cardiometabolic index and NAFLD and fibrosis
Authors: Yan Laisha , Hu Xiaoyan , Wu Shanshan , Cui Can , Zhao Shunying
Published: June 2024

Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44–1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84–1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis.
L-shaped association of systemic immune-inflammation index (SII) with serum soluble α-Klotho in the prospective cohort study from the NHANES database
Authors: Wen Zujun , Liu Xiang , Zhang Tingting
Published: June 2024

The systemic immune-inflammation index (SII), an integrated and ground-breaking inflammatory measure, has been widely used in various fields. We aimed to assess the association between the systemic immune-inflammation index (SII) and α-Klotho (a new anti-aging biomarker). In this cross-sectional investigation, people with complete information on SII and α-Klotho from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 were the study's subject population. SII was calculated by platelet count × neutrophil count/lymphocyte count. The association between SII and α-Klotho was investigated using multivariable linear regression and a generalized additive model. In order to explore the non-linear connection, we employed smoothed curve fitting. Subgroup analysis were also performed. A total of 13,701 participants with an average age of 57.73 ± 10.86 years were enrolled, of whom 51.53% were female. After fully adjustment, SII was negatively associated with serum soluble α-Klotho [β(95% CI) =  − 0.07 (− 0.08, − 0.05)]. Furthermore, we found L-shaped association between SII and klotho protein level, with the inflection point at 255 pg/ml. Subgroup analysis and interaction test revealed that there was no discernible dependence on gender, age, race, smoking, alcohol, diabetes and hypertension (all p for interaction > 0.05). SII level was negatively associated with serum klotho protein concentration in American adults. To verify our findings, more large-scale prospective investigations are still required.
Returners and explorers dichotomy in the face of natural hazards
Authors: He Zeyu , Hu Yujie , Duan Leo L. , Michailidis George
Published: June 2024

Understanding human mobility patterns amid natural hazards is crucial for enhancing urban emergency responses and rescue operations. Existing research on human mobility has delineated two primary types of individuals: returners, who exhibit a tendency to frequent a limited number of locations, and explorers, characterized by a more diverse range of movement across various places. Yet, whether this mobility dichotomy endures in the context of natural hazards remains underexplored. This study addresses this gap by examining anonymized high-resolution mobile phone location data from Lee County, Florida residents, aiming to unravel the dynamics of these distinct mobility groups throughout different phases of Hurricane Ian. The results indicate that returners and explorers maintained their distinct mobility characteristics even during the hurricane, showing increased separability. Before the hurricane, returners favored shorter trips, while explorers embarked on longer journeys, a trend that continued during the hurricane. However, the hurricane heightened people’s inclination to explore, leading to a notable increase in longer-distance travel for both groups, likely influenced by evacuation considerations. Spatially, both groups exhibited an uptick in trips towards the southern regions, away from the hurricane’s path, particularly converging on major destinations such as Miami, Fort Lauderdale, Naples, and West Palm Beach during the hurricane.
Ultrasonic-assisted extraction of total flavonoids from Zanthoxylum bungeanum residue and their allelopathic mechanism on Microcystis aeruginosa
Authors: Cheng Jie , Xu Chengshuai , Sun Yang , Yu Qiuhan , Ding Shuo , Wang Yucai , Wei Wenxue , Xu Wei , Zhang Chaobo , Gong Donghui
Published: June 2024

Water eutrophication has emerged as a pressing concern for massive algal blooms, and these harmful blooms can potentially generate harmful toxins, which can detrimentally impact the aquatic environment and human health. Consequently, it is imperative to identify a safe and efficient approach to combat algal blooms to safeguard the ecological safety of water. This study aimed to investigate the procedure for extracting total flavonoids from Z. bungeanum residue and assess its antioxidant properties. The most favorable parameters for extracting total flavonoids from Z. bungeanum residue were a liquid–solid ratio (LSR) of 20 mL/g, a solvent concentration of 60%, an extraction period of 55 min, and an ultrasonic temperature of 80 °C. Meanwhile, the photosynthetic inhibitory mechanism of Z. bungeanum residue extracts against M. aeruginosa was assessed with a particular focus on the concentration-dependent toxicity effect. Z. bungeanum residue extracts damaged the oxygen-evolving complex structure, influenced energy capture and distribution, and inhibited the electron transport of PSII in M. aeruginosa. Furthermore, the enhanced capacity for ROS detoxification enables treated cells to sustain their photosynthetic activity. The findings of this study hold considerable relevance for the ecological management community and offer potential avenues for the practical utilization of resources in controlling algal blooms.
Experimental and theoretical investigation of the influence of post-curing on mixed mode fracture properties of 3d-printed polymer samples
Authors: Bahrami Bahador , Talebi Hossein , Momeni M. M. , Ayatollahi M. R.
Published: June 2024

This study explores the mechanical properties and fracture characteristics of additively manufactured acrylonitrile butadiene styrene specimens, focusing on the impact of raster angle and post-process heat treatment. To this end, a large number of tensile and semi-circular bending samples with three distinct raster angles of 0/90°, 22/ − 68°, and 45/ − 45° were prepared and exposed to four types of heat treatments with different temperature and pressure conditions. Simultaneously, theoretical models of maximum tangential stress (MTS) and generalized MTS (GMTS) were developed to estimate the onset of specimen fracture under mixed-mode in-plane loading conditions. Recognizing the non-linear behavior within the stress–strain curve of tensile test samples, particularly in the annealed samples, an effort was undertaken to transform the original ductile material into a virtual brittle material through the application of the equivalent material concept (EMC). This approach serves the dual purpose of bypassing intricate and tedious elastoplastic analysis, while concurrently enhancing the precision of the GMTS criterion. The experimental findings have revealed that while the annealing process has a minimal effect on the yield strength, it considerably enhances energy absorption capacity, increases fracture toughness, and reduces the anisotropy. Additionally, the combined EMC-GMTS criterion has demonstrated its capability to predict the failure of the additively manufactured parts with an acceptable level of accuracy.
Simplifying informed consent as a universal precaution
Authors: Feinberg Iris Z. , Gajra Ajeet , Hetherington Lori , McCarthy Kathryn S.
Published: June 2024

One barrier to participating in clinical research is that patients with low literacy skills (1 in 5 US adults) may struggle to understand the informed consent document (ICD). Writing consents using health literacy and plain language guidelines including simplified syntax and semantics can increase understandability and facilitate inclusivity of research populations with literacy challenges. Our study aim was to evaluate a simplified ICD for understandability while considering factors known to relate to comprehension (reading skills and working memory). We performed an on-line survey of 192 adults ages 18–77 in Georgia. Participants performed significantly better on the simplified ICD test. We built an additional model with all version x measure interactions (i.e., age, sex, race, urbanicity, GMVT, WM). This model did not significantly improve model fit, F < 1.00, suggesting that individual differences did not moderate the effect of simplification. Our findings suggest that using plain language and simplified syntax and semantics in ICD as a universal precaution may reduce cognitive reading burden for adults regardless of differences in reading skill or working memory. Increasing understandability in ICD may help improve targets for clinical trial enrollment.
An empirical analysis of the coupling and coordinated development of new urbanization and ecological welfare performance in China’s Chengdu–Chongqing economic circle
Authors: Yang Jie , Li Zhigang , Zhang Dong , Zhong Jialong
Published: June 2024

New urbanization (NU) and ecological welfare performance (EWP) play pivotal roles in achieving sustainable urban development, with both emphasizing social equity and environmental management. Exploring the coordinated relationship between EWP and NU is invaluable for understanding the symbiotic interplay between humans and nature. We constructed a framework to elucidate the coupling mechanism of EWP and NU from the perspective of systems theory. We quantified the levels of NU and EWP utilizing the entropy weighting method and the super-efficient SBM method, respectively. Furthermore, we assessed the degree of coupling coordination between the two using the coupling coordination degree model (CCDM). Spatial and temporal evolution analysis was conducted, and factors influencing the degree of coupling coordination between EWP and NU were explored through a spatial–temporal geographically-weighted regression model (GTWR). The results indicate: (1) During the study period, the average annual increase in EWP in the study area was 2.59%, with a narrowing relative gap between cities. Conversely, the average annual increase in the level of NU was 7.6%, with demographic and economic dimensions carrying the highest weights. (2) The type of coupling coordination between EWP and NU transitions from basic coordination to moderate coordination, with the development of EWP lagging behind that of NU. (3) City size demonstrates a positive yet diminishing trend on the coupling coordination level, with economic development exerting the greatest influence and exhibiting a "V" trend, while the impact of green technology innovation diminishes negatively. Additionally, regional disparities are significant, with city size exhibiting a negative impact in areas of high population density and low economic levels, and green technology innovation showing notable polarization characteristics in core cities. These findings serve as a foundation for fostering coordinated ecological development amid the rapid urbanization process of the Chengdu–Chongqing Economic Circle.
Identification of a new HIV-1 circulating recombinant form (CRF159_01103) derived from CRF103_01B and CRF01_AE in Hebei Province, China
Authors: Fan Weiguang , Zhang Zhen , Shi Haoxi , Jia Jianru , Shi Penghui , Chen Sisi , Lu Xinli
Published: June 2024

Recombinant HIV-1 genomes identified in three or more epidemiological unrelated individuals are defined as circulating recombinant forms (CRFs). CRFs can further recombine with other pure subtypes or recombinants to produce secondary recombinants. In this study, a new HIV-1 intersubtype CRF, designated CRF159_01103, isolated from three men who have sex with men with no epidemiological linkage, was identified in Baoding city, Hebei Province, China. CRF159_01103 was derived from CRF103_01B and CRF01_AE. Bayesian molecular clock analysis was performed on the CRF01-AE and CRF103_01B regions of CRF159_01103. The time of origin of CRF159_01103 was predicted to be 2018–2019, indicating that it is a recent recombinant virus. The emergence of CRF159_01103 has increased the complexity of the HIV-1 epidemic in Hebei Province.
Artificial intelligence-based epigenomic, transcriptomic and histologic signatures of tobacco use in oral squamous cell carcinoma
Authors: Viet Chi T. , Asam Kesava R. , Yu Gary , Dyer Emma C. , Kochanny Sara , Thomas Carissa M. , Callahan Nicholas F. , Morlandt Anthony B. , Cheng Allen C. , Patel Ashish A. , Roden Dylan F. , Young Simon , Melville James , Shum Jonathan , Walker Paul C. , Nguyen Khanh K. , Kidd Stephanie N. , Lee Steve C. , Folk Gretchen S. , Viet Dan T. , Grandhi Anupama , Deisch Jeremy , Ye Yi , Momen-Heravi Fatemeh , Pearson Alexander T. , Aouizerat Bradley E.
Published: June 2024

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.
Large-area phosphorene for stable carbon-based perovskite solar cells
Authors: Myagmarsereejid Purevlkham , Suragtkhuu Selengesuren , Trinh Quang Thang , Gould Tim , Nguyen Nam‐Trung , Bat-Erdene Munkhjargal , Campbell Eric , Hoang Minh Tam , Chiu Wei-Hsun , Li Qin , Wang Hongxia , Zhong Yu Lin , Batmunkh Munkhbayar
Published: June 2024

Carbon-based perovskite solar cells (c-PSCs) have attracted increasing attention due to their numerous advantages including ease of fabrication, the potential of assembling flexible devices, low manufacturing costs as well as large-scale production. However, c-PSCs suffer from the limited hole extraction and high charge carrier recombination due to the inadequate interface contact between the carbon electrode and perovskite film. Herein, we report the fabrication of planar c-PSCs with high efficiency and excellent stability by employing electrochemically produced large-area phosphorene flakes as a hole-transporting layer (HTL). Large-area phosphorene shows well-aligned band energy levels with the perovskite, and thus led to the efficient hole extraction and the reduced hysteresis behaviour. Consequently, while exhibiting excellent stability under various harsh testing conditions, the devices with phosphorene HTL delivered a power conversion efficiency of over 15% with an open-circuit voltage of 1.082 V, which is the highest reported value for c-PSCs without traditional hole transporting materials to date.
Environmental microbiome diversity and stability is a barrier to antimicrobial resistance gene accumulation
Authors: Klümper Uli , Gionchetta Giulia , Catão Elisa , Bellanger Xavier , Dielacher Irina , Elena Alan Xavier , Fang Peiju , Galazka Sonia , Goryluk-Salmonowicz Agata , Kneis David , Okoroafor Uchechi , Radu Elena , Szadziul Mateusz , Szekeres Edina , Teban-Man Adela , Coman Cristian , Kreuzinger Norbert , Popowska Magdalena , Vierheilig Julia , Walsh Fiona , Woegerbauer Markus , Bürgmann Helmut , Merlin Christophe , Berendonk Thomas Ulrich
Published: June 2024

When antimicrobial resistant bacteria (ARB) and genes (ARGs) reach novel habitats, they can become part of the habitat’s microbiome in the long term if they are able to overcome the habitat’s biotic resilience towards immigration. This process should become more difficult with increasing biodiversity, as exploitable niches in a given habitat are reduced for immigrants when more diverse competitors are present. Consequently, microbial diversity could provide a natural barrier towards antimicrobial resistance by reducing the persistence time of immigrating ARB and ARG. To test this hypothesis, a pan-European sampling campaign was performed for structured forest soil and dynamic riverbed environments of low anthropogenic impact. In soils, higher diversity, evenness and richness were significantly negatively correlated with relative abundance of >85% of ARGs. Furthermore, the number of detected ARGs per sample were inversely correlated with diversity. However, no such effects were present in the more dynamic riverbeds. Hence, microbiome diversity can serve as a barrier towards antimicrobial resistance dissemination in stationary, structured environments, where long-term, diversity-based resilience against immigration can evolve.
Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus
Authors: Wassano Natália S. , da Silva Gabriela B. , Reis Artur H. , A. Gerhardt Jaqueline , Antoniel Everton P. , Akiyama Daniel , Rezende Caroline P. , Neves Leandro X. , Vasconcelos Elton J. R. , de Figueiredo Fernanda L. , Almeida Fausto , de Castro Patrícia A. , Pinzan Camila F. , Goldman Gustavo H. , Paes Leme Adriana F. , Fill Taicia P. , Moretti Nilmar S. , Damasio André
Published: June 2024

Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD+-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins’ involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.
Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro
Authors: Schüller Simone S. , Barman Soumik , Mendez-Giraldez Raul , Soni Dheeraj , Daley John , Baden Lindsey R. , Levy Ofer , Dowling David J.
Published: June 2024

Vaccination reduces morbidity and mortality due to infections, but efficacy may be limited due to distinct immunogenicity at the extremes of age. This raises the possibility of employing adjuvants to enhance immunogenicity and protection. Early IFNγ production is a hallmark of effective vaccine immunogenicity in adults serving as a biomarker that may predict effective adjuvanticity. We utilized mass cytometry (CyTOF) to dissect the source of adjuvant-induced cytokine production in human blood mononuclear cells (BMCs) from newborns (~39-week-gestation), adults (~18-63 years old) and elders (>65 years of age) after stimulation with pattern recognition receptors agonist (PRRa) adjuvants. Dimensionality reduction analysis of CyTOF data mapped the BMC compartment, elucidated age-specific immune responses and profiled PRR-mediated activation of monocytes and DCs upon adjuvant stimulation. Furthermore, we demonstrated PRRa adjuvants mediated innate IFNγ induction and mapped NK cells as the key source of TLR7/8 agonist (TLR7/8a) specific innate IFNγ responses. Hierarchical clustering analysis revealed age and TLR7/8a-specific accumulation of innate IFNγ producing γδ T cells. Our study demonstrates the application of mass cytometry and cutting-edge computational approaches to characterize immune responses across immunologically distinct age groups and may inform identification of the bespoke adjuvantation systems tailored to enhance immunity in distinct vulnerable populations.
High-affinity tuning of single fluorescent protein-type indicators by flexible linker length optimization in topology mutant
Authors: Hara Yusuke , Ichiraku Aya , Matsuda Tomoki , Sakane Ayuko , Sasaki Takuya , Nagai Takeharu , Horikawa Kazuki
Published: June 2024

Genetically encoded Ca2+ indicators (GECIs) are versatile for live imaging of cellular activities. Besides the brightness and dynamic range of signal change of GECIs, Ca2+ affinity is another critical parameter for successful Ca2+ imaging, as the concentration range of Ca2+ dynamics differs from low nanomolar to sub-millimolar depending on the celltype and organism. However, ultrahigh-affinity GECIs, particularly the single fluorescent protein (1FP)-type, are lacking. Here, we report a simple strategy that increases Ca2+ affinity through the linker length optimization in topology mutants of existing 1FP-type GECIs. The resulting ultrahigh-affinity GECIs, CaMPARI-nano, BGECO-nano, and RCaMP-nano (Kd = 17–25 nM), enable unique biological applications, including the detection of low nanomolar Ca2+ dynamics, highlighting active signaling cells, and multi-functional imaging with other second messengers. The linker length optimization in topology mutants could be applied to other 1FP-type indicators of glutamate and potassium, rendering it a widely applicable technique for modulating indicator affinity.
Discovery of NSD2 non-histone substrates and design of a super-substrate
Authors: Weirich Sara , Kusevic Denis , Schnee Philipp , Reiter Jessica , Pleiss Jürgen , Jeltsch Albert
Published: June 2024

The human protein lysine methyltransferase NSD2 catalyzes dimethylation at H3K36. It has very important roles in development and disease but many mechanistic features and its full spectrum of substrate proteins are unclear. Using peptide SPOT array methylation assays, we investigate the substrate sequence specificity of NSD2 and discover strong readout of residues between G33 (-3) and P38 (+2) on H3K36. Unexpectedly, we observe that amino acid residues different from natural ones in H3K36 are preferred at some positions. Combining four preferred residues led to the development of a super-substrate which is methylated much faster by NSD2 at peptide and protein level. Molecular dynamics simulations demonstrate that this activity increase is caused by distinct hyperactive conformations of the enzyme-peptide complex. To investigate the substrate spectrum of NSD2, we conducted a proteome wide search for nuclear proteins matching the specificity profile and discovered 22 peptide substrates of NSD2. In protein methylation studies, we identify K1033 of ATRX and K819 of FANCM as NSD2 methylation sites and also demonstrate their methylation in human cells. Both these proteins have important roles in DNA repair strengthening the connection of NSD2 and H3K36 methylation to DNA repair.