bluuebunny/crossref_metadata_2025_split huggingface dataset:
A de novo pathogenic variant in MICAL‐1 causes epilepsy with auditory features
Authors: Bonanni Paolo , Giorda Roberto , Michelucci Roberto , Nobile Carlo , Dazzo Emanuela 
Published: April 2024

AbstractFamilial epilepsy with auditory features (FEAF), previously known as autosomal‐dominant lateral temporal lobe epilepsy (ADLTE) is a genetically heterogeneous syndrome, clinically characterized by focal seizures with prominent auditory symptoms. It is inherited with autosomal‐dominant pattern with reduced penetrance (about 70%). Sporadic epilepsy with auditory features cases are more frequent and clinically indistinguishable from familial cases. One causal gene, MICAL‐1, encodes MICAL‐1, an intracellular multi‐domain enzyme that is an important regulator of filamentous actin (F‐actin) structures. Pathogenic variants in MICAL‐1 account for approximately 7% of FEAF families. Here, we describe a de novo MICAL‐1 pathogenic variant, p.Arg915Cys, in a sporadic case, an affected 21‐year‐old Italian man with no family history of epilepsy. Genetic testing was performed in the patient and his parents, using a next‐generation sequencing panel. In cell‐based assay, this variant significantly increased MICAL‐1 oxidoreductase activity, which likely resulted in dysregulation of F‐actin organization. This finding provides further support for a gain‐of‐function effect underlying MICAL‐1‐mediated epilepsy pathogenesis, as previously seen with other pathogenic variants. Furthermore, the case study provides evidence that de novo MICAL‐1 pathogenic variants can occur in sporadic cases with epilepsy with auditory feature (EAF).Plain Language SummaryIn this study, we report a new MICAL‐1 pathogenic variant in a patient without family history for epilepsy, not inherited from his parents. MICAL‐1 is a protein with enzymatic activity that reorganizes the structure of the cell. We proved the pathological effect of this variant by testing its enzymatic activity and found an increase of this activity. This result suggests that non‐familial cases should be tested to find novel pathogenic variants in this gene.
Seismic intensity measures and predictive equations for the evaluation of earthquake—induced crest settlements of earth dams
Authors: Nardo Andrea , Biondi Giovanni , Casablanca Orazio , Di Filippo Giuseppe , Cascone Ernesto 
Published: April 2024

AbstractIn this paper the results of 2D dynamic finite element analyses of a zoned earth dam are presented and discussed with the aim of detecting proper intensity measures able to describe the variation of the crest permanent settlement with the characteristics of the input ground motion. A large set of horizontal components of earthquake records has been selected and used as input motion considering both upstream and downstream directions. This allowed to explore the activation of plastic mechanisms in the dam embankment and the amplification of the horizontal accelerations. Starting from the analysis results, two original intensity measures, related to the amplitude, energy and frequency content of the input motion, have been detected and original empirical predictive formulas have also been derived to estimate the permanent crest settlement of the dam. The effectiveness of the proposed intensity measures and the reliability of the novel relationships between these intensity measures and earthquake‐induced permanent crest settlements have been checked against (i) numerical results of further dynamic analyses carried out for the same dam using additional sets of input motions, (ii) numerical results available in the literature for two other earth dams and (iii) field data relative to the crest settlements induced in four earth dams by two recent large earthquakes. The whole set of analysis results allowed defining an empirical equation that appears as a promising general predictive tool for the earthquake‐induced crest settlement of earth dams.
Credit card loss forecasting: Some lessons from COVID
Authors: Sengupta Partha , Wheeler Christopher H. 
Published: April 2024

AbstractModels developed by banks to forecast losses in their credit card portfolios have generally performed poorly during the COVID‐19 pandemic, particularly in 2020, when large forecast errors were observed at many banks. In this study, we attempt to understand the source of this error and explore ways to improve model fit. We use account‐level monthly performance data from the largest credit card banks in the U.S. between 2008 and 2018 to build models that mimic the typical model design employed by large banks to forecast credit card losses. We then fit these on data from 2019 to 2021. We find that COVID‐period model errors can be reduced significantly through two simple modifications: (1) including measures of the macroeconomic environment beyond indicators of the labor market, which served as the primary macro drivers used in many pre‐pandemic models and (2) adjusting macro drivers to capture persistent/sustained changes, as opposed to temporary volatility in these variables. These model improvements, we find, can be achieved without a significant reduction in model performance for the pre‐COVID period, including the Great Recession. Moreover, in broadening the set of macro influences and capturing sustained changes, we believe models can be made more robust to future downturns, which may bear little resemblance to past recessions.
Submarine geohazards on the northwestern continental margin of the South China Sea and their mechanism
Authors: Du Wenbo , Zhu Rongwei , Hu Xiaosan , Gao Hongfang 
Published: April 2024

AbstractSubmarine geohazards significantly threaten human economic activities and essential infrastructure. Based on multi‐beam data and high‐resolution 2D seismic data, two types of submarine geohazards are identified: direct and indirect geohazards on the northwestern continental slope and the Xisha Uplift of the South China Sea (SCS). Direct geohazards include submarine landslides and active faults, while indirect geohazards include buried channels, submarine canyons, pockmarks, volcanoes and magma diapirs. This study comprehensively analyzes geomorphological features, including their characteristics, genesis and distribution. Statistical analysis reveals that the gradient of the Xisha Uplift slope is steeper than the shelf break, making it a more unstable region. However, assessing disaster potential indicates that submarine geohazards at the shelf break pose a greater threat than those at the Xisha Uplift. Many factors, including tectonic activity, sediment supply and relative sea‐level changes, influence submarine geohazards' formation. These hazards do not occur in isolation but often interact with one another. The research results provide a scientific basis for predicting deep‐sea geohazards near the northern continental margin and Xisha Island in the SCS.
Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short‐term and long‐term complications and functional outcomes
Authors: Kanyo Emese C. , Wu Shannon S. , Reddy Chandana A. , Silver Natalie L. , Lamarre Eric D. , Burkey Brian B. , Prendes Brandon L. , Scharpf Joseph , Lorenz Robert R. , Kmiecik Joann , Ku Jamie A. 
Published: April 2024

AbstractBackgroundPrimary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary‐fit TEP in the setting of salvage laryngectomy.MethodsA retrospective, single‐center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short‐term and long‐term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy.ResultsIn this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes.ConclusionPrimary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.
When DNA damage responses meet tumor immunity: From mechanism to therapeutic opportunity
Authors: Pan Dong , Wang Qi , Shen Aihua , Qi Zhihao , Zheng Chunfu , Hu Burong 
Published: April 2024

AbstractDNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects. This review explores the mechanisms behind DNA damage‐induced antitumor immune responses, the importance of DNA damage in antitumor immunity, and potential therapeutic approaches for cancer immunotherapy targeting DDR. Additionally, we discuss the challenges of combination therapy and strategies for integrating DNA damage‐targeting therapies with current cancer immunotherapy. In summary, this review highlights the critical role of DNA damage in tumor immunology, underscoring the potential of DDR inhibitors as promising therapeutic modalities for cancer treatment.
Prediction of physicochemical and pharmacokinetic properties of botanical constituents by computational models
Authors: Liu Yitong , Lawless Michael , Li Miao , Fairman Kiara , Embry Michelle R. , Mitchell Constance A. 
Published: April 2024

AbstractBotanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. This study sought to use computational (i.e., in silico) models, including quantitative structure–activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were investigated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half of these constituents fell into BCS classes I and II at dose levels no greater than 100 mg per day, indicating high permeability and absorption (%Fa > 75%) in the gastrointestinal tract. However, some constituents such as glycosides in ashwagandha and Asian ginseng showed low bioavailability after oral administration due to poor absorption (BCS classes III and IV, %Fa < 40%). These in silico results fill data gaps for botanical constituents and could guide future safety studies. For example, the predicted human plasma concentrations may help select concentrations for in vitro toxicity testing. Additionally, the in silico data could be used in tiered or batteries of assays to assess the safety of botanical products. For example, highly absorbed botanical constituents indicate potential high exposure in the body, which could lead to toxic effects.
Neural graph distance embedding for molecular geometry generation
Authors: Margraf Johannes T. 
Published: April 2024

AbstractThis article introduces neural graph distance embedding (nGDE), a method for generating 3D molecular geometries. Leveraging a graph neural network trained on the OE62 dataset of molecular geometries, nGDE predicts interatomic distances based on molecular graphs. These distances are then used in multidimensional scaling to produce 3D geometries, subsequently refined with standard bioorganic forcefields. The machine learning‐based graph distance introduced herein is found to be an improvement over the conventional shortest path distances used in graph drawing. Comparative analysis with a state‐of‐the‐art distance geometry method demonstrates nGDE's competitive performance, particularly showcasing robustness in handling polycyclic molecules—a challenge for existing methods.
Study on the correlation between retrograde ductus arteriosus flow and right ventricular function evaluated by Z‐score of tricuspid annular plane systolic excursion in fetuses with Ebstein anomaly
Authors: Guo Xianfeng , Li Yilin , Zhao Bowen , He Yihua 
Published: April 2024

AbstractPurposeTo analyze the influence of RV dysfunction evaluated by Free‐angle M‐mode (FAM) TAPSE Z‐score on retrograde ductus arteriosus flow (RDAF) in fetuses with Ebstein anomaly (EA).MethodsA retrospective cohort study of 30 EA and 60 normal fetuses were enrolled. The EA group was divided into two groups: with RDAF (EA‐RDAF group) and without RDAF (EA‐NRDAF group). FAM was used to measure TAPSE of EA and normal fetuses, and Z‐scores were calculated. The differences of FAM‐TAPSE Z‐score, gestational week (GW), maternal age (MA), and mitral valve‐tricuspid valve distance (MTD) between three groups were compared. The correlation and binary logistic regression between FAM‐TAPSE Z‐score, GW, MA, MTD, and RDAF were analyzed.ResultsFAM‐TAPSE Z‐score was significantly lower in EA‐RDAF group compared to other groups (p < 0.05). FAM‐TAPSE Z‐score, GW, and MA were negatively correlated with RDAF (p < 0.05), but no correlation was found between TR, MDT, and RDAF (p > 0.05). Multivariate logistic regression showed that FAM‐TAPSE Z‐score was an independent influencing factor for RDAF (OR = 0.102, p < 0.05).ConclusionRV dysfunction is an independent factor leading to RDAF in EA fetus, which provides a feasible theoretical basis for further study on improvement of RV function through intrauterine treatment to delay and prevent the RDAF, to avoid death cycle and improve live‐birth rate.
Utility of the cerebro‐placental‐uterine ratio in predicting composite adverse perinatal outcomes in pregestational diabetes: A prospective cohort study
Authors: Agaoglu Zahid , Tanacan Atakan , Ipek Goksun , Peker Ayca , Ozturk Agaoglu Merve , Bastemur Ayse Gulcin , Kara Ozgur , Sahin Dilek 
Published: April 2024

AbstractPurposeTo examine the cerebro‐placental‐uterine ratio (CPUR) in pregnant women with pregestational diabetes and determine its role in predicting adverse prenatal outcomes.MethodsThis prospective, cohort study conducted at a tertiary hospital included 65 patients with pregestational diabetes (25 with type1 diabetes, 40 with type2 diabetes) and 130 low‐risk patients in the control group. The cerebroplacental (CPR) ratio and the CPUR were calculated. Composite adverse perinatal outcome (CAPO) is defined as the presence of any of the following: (1) Neonatal intensive care unit (NICU) admission, (2) Apgar at 5 min <7, and (3) umbilical cord arterial pH <7.10. The relationship of CPR and CPUR with CAPO was investigated.ResultsCPR and CPUR were significantly lower in the pregestational diabetes group than in the control group. The NICU admission was higher in the case group. In receiver operating characteristic analyses, the optimal cut‐off value of CPUR was 1.46 (AUC = 0.72, p = 0.003, 80% sensitivity, and 69% specificity) to predict CAPO and the optimal cut‐off value of CPUR was 1.50 for NICU admission (AUC = 0.70, p = 0.013, 77% sensitivity, and 66% specificity).ConclusionLow CPUR values were found to be associated with adverse perinatal outcomes in women with pregestational diabetes. With the increasing number of studies, CPUR is expected to be utilized more widely in routine obstetric practice.
On the value of meta‐research for early career researchers: A commentary
Authors: Fabiano Nicholas , Gupta Arnav , Fiedorowicz Jess G. , Solmi Marco 
Published: April 2024

AbstractMeta‐research, also known as “research on research” is a field of study that investigates the methods, reporting, reproducibility, evaluation, and incentives along the research continuum. Meta‐research literacy is imperative to ensure high quality, transparent and reproducible primary data or meta‐research products. In this commentary, we propose that early career researchers should be trained in meta‐research as a foundation to develop a deeper understanding of the research process and ability to appraise the research literature and design high‐quality original studies, irrespective of their chosen field of study. We discuss the importance of meta‐research and open science from the perspective of an early career trainee, highlighting essential areas for growth and obstacles one may encounter.
From molecules to visuals: Empowering drug discovery and development with mass spectrometry imaging
Authors: Chen Bingming , Vavrek Marissa , Cancilla Mark T. 
Published: April 2024

AbstractOver the past three decades, mass spectrometry imaging (MSI) has emerged as a valuable tool for the spatial localization of drugs and metabolites directly from tissue surfaces without the need for labels. MSI offers molecular specificity, making it increasingly popular in the pharmaceutical industry compared to conventional imaging techniques like quantitative whole‐body autoradiography (QWBA) and immunohistochemistry, which are unable to distinguish parent drugs from metabolites. Across the industry, there has been a consistent uptake in the utilization of MSI to investigate drug and metabolite distribution patterns, and the integration of MSI with omics technologies in preclinical investigations. To continue the further adoption of MSI in drug discovery and development, we believe there are two key areas that need to be addressed. First, there is a need for accurate quantification of analytes from MSI distribution studies. Second, there is a need for increased interactions with regulatory agencies for guidance on the utility and incorporation of MSI techniques in regulatory filings. Ongoing efforts are being made to address these areas, and it is hoped that MSI will gain broader utilization within the industry, thereby becoming a critical ingredient in driving drug discovery and development.
Effects of intermittent fasting on periodontal inflammation and subgingival microbiota
Authors: Lira‐Junior Ronaldo , Aogáin Micheál Mac , Crncalo Eva , Ekberg Neda Rajamand , Chotirmall Sanjay H. , Pettersson Sven , Gustafsson Anders , Brismar Kerstin , Bostanci Nagihan 
Published: April 2024

AbstractBackgroundStudies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long‐term intermittent fasting on periodontal health and the subgingival microbiota.MethodsThis pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n = 14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6 months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing.ResultsAfter 6 months of intermittent fasting, weight, body mass index, C‐reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p < 0.05). Moreover, significant reductions were observed in bleeding on probing (p = 0.01) and the presence of shallow periodontal pockets after fasting (p < 0.001), while no significant change was seen in plaque index (p = 0.14). While we did not observe significant changes in α‐ or β‐diversity of the subgingival microbiota related to dietary intervention (p > 0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4–5 mm compared to those with <60% reduction (bad responders).ConclusionIntermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.
Structural and functional properties of whey protein isolate–inulin conjugates prepared with ultrasound or wet heating method
Authors: Qin Yu‐Qing , Fan Yan‐Ge , Ren Jing‐Nan , Wang Liu‐Yan , Han Nan‐Feng , Fan Gang 
Published: April 2024

AbstractBACKGROUNDWhey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI–polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI–inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined.RESULTSIn conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), new C–N bonds were formed in Fourier‐transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h.CONCLUSIONThis study revealed that WPI–inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.
A 4.7‐inch 650 PPI AMQLED display prepared by direct photolithography
Authors: Zhang Di , Li Zhuo , Lu Shaoyong , Li Dong , Chen Zhuo , Li Yanzhao , Li Xinguo , Xu Xiaoguang 
Published: April 2024

AbstractIn this work, a highly efficient photosensitive quantum dot (QD) system was designed. The optimized photosensitive QD system had high photoluminescence quantum yield and colloidal stability. By direct photolithography, RGB pixel arrays with a single sub‐pixel size of 39 μm × 5 μm were successfully prepared. Further, the full‐color QLED device was realized. There were no residual QD emission peaks from neighboring sub‐pixels observed in the electroluminescence spectra. Experience on the full‐color QLED device guided the successful preparation of a 4.7‐inch 650 PPI active matrix QLED prototype. The active matrix QLED prototype could display clear and complete pictures. The color gamut reached 85% of the BT2020 standard. This is the first active matrix QLED prototype prepared with a record‐high resolution by direct photolithography, which promoted the development of QLED display technology.