bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saturation genome editing-based functional evaluation and clinical classification of BRCA2 single nucleotide variants
Authors: Couch Fergus , Huang Huaizhi , Hu Chunling , Na Jie , Hart Steven , Gnanaolivu Rohan , Abozaid Mohamed , Rao Tara , Tecleab Yohannes , Pesaran Tina , Lyra Paulo , Karam Rachid , Yadav Siddhartha , Domchek Susan , Hoya Miguel de la , Robson Mark , Mehine Miika , Bandlamudi Chaitanya , Mandelker Diana , Monteiro Alvaro , Boddicker Nicholas , Chen Wenan , Richardson Marcy 
Published: December 2023

Abstract

Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to breast, ovarian, prostate and pancreatic cancer. However, variants of uncertain significance (VUS) (n>4000) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants. Here we report on comprehensive saturation genome editing-based functional characterization of 97% of all possible single nucleotide variants (SNVs) in the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants that is encoded by exons 15 to 26. The assay was based on deep sequence analysis of surviving endogenously targeted haploid cells. A total of 7013 SNVs were characterized as functionally abnormal (n=955), intermediate/uncertain, or functionally normal (n=5224) based on 95% agreement with ClinVar known pathogenic and benign standards. Results were validated relative to batches of nonsense and synonymous variants and variants evaluated using a homology directed repair (HDR) functional assay. Breast cancer case-control association studies showed that pooled SNVs encoding functionally abnormal missense variants were associated with increased risks of breast and ovarian cancer (odds ratio (OR) 3.89, 95%CI: 2.77-5.51). In addition, 86% of tumors associated with abnormal missense SNVs displayed loss of heterozygosity (LOH), whereas 26% of tumors with normal variants had LOH. The functional data were added to other sources of information in a ClinGen/ACMG/AMP-like model and 700 functionally abnormal SNVs, including 220 missense SNVs, were classified as pathogenic or likely pathogenic, while 4862 functionally normal SNVs, including 3084 missense SNVs, were classified as benign or likely benign. These classified variants can now be used for risk assessment and clinical care of variant carriers and the remaining functional scores can be used directly for clinical classification and interpretation of many additional variants.
Dynamic Identification of Important Nodes in Complex Networks based on the KPDN-INCC Method
Authors: Zhang Jieyong , Zhao Liang , Sun Peng , Liang Wei 
Published: December 2023

Abstract
Dynamic identification of influential nodes in complex networks is of great significance for practical applications. In real-world scenarios, resources are often limited, making it necessary to evaluate nodes by iteratively assessing the remaining network after removing certain nodes. Therefore, a dynamic identification method for important nodes in complex networks is more suitable for real-world applications. This paper proposes a method that combines both local and global characteristics. For the global features, we introduce an improved k-shell method that integrates the fusion degree, enhancing the resolution of node rankings. For the local features, we introduce the Solton factor and the improved network constraint coefficient (INCC) to enhance the algorithm's understanding of the relationship between neighboring nodes. Through a comparison with existing methods, we find that the proposed KPDN-INCC method complements the KPDN method and accurately identifies important nodes, thus facilitating rapid network disintegration. The experiments on artificial networks further validate the effectiveness of the proposed method in identifying important nodes in small-world networks with a random parameter less than 0.4.
USP10 drives cancer stemness and enables super-competitor signalling in Colorectal Cancer
Authors: Reissland Michaela , Hartmann Oliver , Tauch Saskia , Bugter Jeroen , Prieto-Garcia Cristian , Schulte Clemens , Loebbert Sinah , Solvie Daniel , Bitman-Lotan Eliya , Narain Ashwin , Jacomin Anne-Claire , Schuelein-Voelk Christina , Fuss Carmina , Pahor Nikolett , Ade Carsten , Buck Victoria , Potente Michael , Li Vivian , Beliu Gerti , Wiegering Armin , Grossmann Tom , Eilers Martin , Wolf Elmar , Maric Hans , Rosenfeldt Mathias , Maurice Madelon , Dikic Ivan , Gallant Peter , Oryan Amir , Diefenbacher Markus 
Published: December 2023

Abstract

The contribution of deubiquitylating enzymes (DUBs) to b-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes b-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to b-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring b-catenin degradation. However, in APC-truncated cancer cells USP10 binds to b-catenin, increasing its stability which is critical for maintaining an undifferentiated tumour identity. Elimination of USP10 reduces the expression of WNT and stem cell signatures and induces the expression of differentiation genes. Remarkably, silencing of USP10 in murine and patient-derived CRC organoids established that it is essential for NOTUM signalling and the APC super competitor-phenotype, reducing tumorigenic properties of APC-truncated CRC. These findings are clinically relevant as patient-derived organoids are highly dependent on USP10, and abundance of USP10 correlates with poorer prognosis of CRC patients. Our findings reveal, therefore, a role for USP10 in CRC cell identity, stemness, and tumorigenic growth by stabilising b-Catenin, leading to aberrant WNT signalling and degradation resistant tumours. Thus, USP10 emerges as a unique therapeutic target in APC truncated CRC.
A Distributed Feature Selection Pipeline for Survival Analysis using Radiomics in Non-Small Cell Lung Cancer Patients
Authors: Gottardelli Benedetta , Gouthamchand Varsha , Masciocchi Carlotta , Boldrini Luca , Martino Antonella , Mazzarella Ciro , Massaccesi Mariangela , Monshouwer René , Findhammer Jeroen , Wee Leonard , Dekker Andre , Gambacorta Maria Antonietta , Damiani Andrea 
Published: December 2023

Abstract
Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients. The pipeline was run across datasets from three institutions without patient-level data exchange. It includes two FS techniques, Correlation-based Feature Selection and LASSO regularization, and Cox Proportional-Hazard regression with Overall Survival as endpoint. Trained and validated on 828 patients overall, our pipeline yielded a radiomic signature comprising "intensity-based energy" and "mean discretised intensity". Validation resulted in a mean Harrell C-index of 0.59, showcasing fair efficacy in risk stratification. In conclusion, we propose an approach for distributed radiomics involving preliminary FS to reduce the available feature set to the most important on a data-driven basis and reduce dimensionality problems other than those related to data limitations and interpretability.
Extraction Rates of Algorithmically Random Continuous Functionals
Authors: Cenzer Douglas , Fraize Cameron , Porter Christopher 
Published: December 2023

Abstract

In this article, we study the extraction rate, or output/input rate, of continuous functionals on the Cantor space 2ω, in particular for algorithmically random functionals. It is shown that random functionals have an average extraction rate over all inputs corresponding to the rate of producing a single bit of output, and that this average rate is attained for any sufficiently random input. We also examine functions computed by discrete distribution generating trees, where we calculate the expected extraction rate and show that this rate is attained for any sufficiently random input.
Do we need a ban on firecrackers? Explosion injuries to hands caused by pyrotechnic objects during the turn of the year in Berlin/Brandenburg
Authors: Eichenauer Frank , Pandura Stefan , Kim Simon , Ekkernkamp Axel , Eisenschenk Andreas , Weber Stefan 
Published: December 2023

Abstract
Introduction: Fireworks carry a high risk for hand injuries.
Methods: The study presents data of 146 patients hospitalized with hand injuries caused by fireworks during the turn of the years 2005 to 2023. Statistical data presented include number, age and sex, injury patterns and concomitant injuries.
Results: The number of injured increased over the years with a significant increase in 2016 and incision during the COVID pandemic. Those affected were predominantly male. The age group between 19 and 36 years was the most represented, followed by elders between 37 and 65 years. Children and adolescents under 18 were affected in one-third of cases. Injury patterns included combinations of soft tissue lesions, open fractures and finger amputations. Concomitant injuries predominantly involved the head. One quarter of the patients showed post-traumatic stress disorder.
Discussion: Hand injuries from fireworks often result in permanent physical integrity disorders. Posttraumatic stress disorder is often. The increasing number of cases may be due to structural changes in the rescue service and the level of awareness of a specialized facility, in addition to a fundamental increase in injuries. Most striking was the decline in numbers during the COVID pandemic. The immediate rebound after the end of the restrictions supports the consideration of a permanent ban.
The Relationship Between Leisure Time Physical Activity and Cognitive Function in Older Americans: NHANES 2011-2014
Authors: Yang Juxiang , Wang Yi , Zheng Xi , Wang Hongchu , Song Gang 
Published: December 2023

Abstract
Objective
This study aims to investigate the correlation between leisure-time physical activity (LTPA) and cognitive function in older adults.
Methods
We conducted an analysis of 2,662 participants (aged ≥ 60 years) from the cross-sectional National Health and Nutrition Examination Survey (NHANES) spanning 2011–2014. Physical activity was assessed using self-reported questionnaires, while cognitive function was evaluated through three measurement modalities and self-reported assessments of cognitive difficulties. Multiple logistic regression and multiple linear regression analyses were employed to explore the associations between the duration and frequency of leisure-time physical activity and cognitive function.
Results
Neither the duration nor frequency of leisure-time physical activity (LTPA) showed statistically significant associations with CERAD-WL and CERAD-DR. However, significant correlations were observed between LTPA duration and frequency with AF and DSST scores. Individuals adhering to recommended physical activity guidelines demonstrated higher AF scores [1.38 (0.93 to 1.83)] and DSST scores [3.32 (2.12 to 4.52)] compared to those with no leisure-time physical activity. Participants engaging in physical activity 1–4 times and 5 or more times per week showed increased AF scores [0.89 (0.43 to 1.36)] and [1.40 (0.91 to 1.90)], as well as DSST scores [2.61 (1.36 to 3.86)] and [3.50 (2.17 to 4.83)], respectively, compared to non-active individuals. Engaging in leisure-time physical activity 1–4 times per week was associated with a 33% reduced risk of memory decline compared to non-active individuals (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.48–0.92). An inverted U-shaped relationship was observed between LTPA duration and AF and a U-shaped relationship between LTPA frequency and the risk of memory decline.
Conclusion
Compliance with recommended leisure-time physical activity is associated with better cognitive function in older adults, although greater duration does not necessarily equate to greater benefits. For older adults, the frequency of leisure-time physical activity appears more critical than duration, with the most beneficial cognitive effects observed at 3–4 times per week. Therefore, clinical interventions utilizing physical activity should prioritize considerations of exercise frequency.
KRAS inhibition impacts chromatin organization and transcriptional performance in colorectal cancer cells
Authors: Martins Flávia , Machado Ana Luísa , Ribeiro Andreia , Oliveira Susana Mendonça , Carvalho Joana , Matthiesen Rune , Velho Sérgia 
Published: December 2023

Abstract
Background
Preclinical and clinical data revealed that targeting KRAS mutant tumors is more challenging than expected. While initially sensitive to treatment, cancer cells can rapidly bypass dependence on this oncogene to acquire a drug-tolerant phenotype. Gaining a comprehensive understanding of the mechanisms underlying the transition from a drug-sensitive to a drug-tolerant state is key to obtaining invaluable insights. Such insights will inform the development of therapeutic strategies aimed at disrupting intrinsic or adaptive resistance, ultimately enhancing therapeutic outcomes.
Methods
Building upon this rationale, we established 3D culture models of mutant-KRAS CRC cell lines with distinct KRAS-dependencies to investigate the response to KRAS silencing. siRNA was used to silence KRAS expression. Cells were grown in 3D, characterized, and analyzed using proteomics. Chromatin states were explored via transmission electron microscopy, and transcriptional performance was assessed through longitudinal RNA-Seq.
Results
Our approach revealed a unique response in KRAS-dependent cells characterized by G0/G1 cell cycle arrest and entry into a quiescent-like state. Proteomic analysis revealed nucleosome assembly, regulation of gene expression, mRNA splicing, and mRNA processing as the top biological processes that were upregulated in KRAS-dependent CRC cell lines upon KRAS silencing. Additionally, alterations in histone 3 posttranslational modifications and chromatin compaction were also observed, alongside enhanced transcriptional performance, as revealed by longitudinal RNA-Seq analysis.
Conclusion
Our discoveries substantiate the existence of an epigenetic mechanism responsible for inducing tolerance to KRAS loss. This mechanism involves chromatin reorganization and transcription upregulation, highlighting the remarkable ability of cancer cells to adapt and sustain malignancy without oncogenic KRAS.
Determination of birth prevalence of sickle cell disease using point of care test HemoTypeSC TM at Rundu hospital, Namibia
Authors: Mano Runyararo Mashingaidze , Kuona Patience , Misihairabgwi Jane Masiiwa 
Published: December 2023

Abstract

Background: Sickle cell disease (SCD), a non-communicable disease has its highest burden in Sub Saharan Africa. The majority of children (50-90%), with SCD die before their 5thbirthday with approximately 150,000–300,000 annual SCD child deaths in Africa. In developed countries, newborn screening (NBS) has been shown to improve survival of children with sickle cell disease with under 5 childhood mortality reduced 10 fold due to interventions done before development of complications. Point of care tests have been developed for resource limited settings to expand newborn screening. The aim of the study was to determine the birth prevalence of sickle cell disease using the point of care test HemoTypeSC in Namibia.Methods: A cross sectional descriptive study was carried out at Rundu Intermediate hospital in Kavango East Region. Two hundred and two (202) well newborns within 72 hours of birth were recruited in the study from 22 of February to the 28thof March 2023. Descriptive statistics was used to compute the hemoglobin types of the study participants.Results: The majority of the participants (n=105) (52%) were females and (n= 97) ,(48%) males. The median age of the participants was 23 hours interquartile range (IQR), (11-33 hours) with the age range of 2-98 hours. One hundred and eight three (183) ( 90.6%) had normal haemoglobin HbAA; 19 (9.4%) sickle cell trait (HbAS) and no participant was found to have sickle cell disease (HbSS).Conclusions: The study is the first to carry out birth prevalence for SCD and sickle cell trait as well as the first application of HemotypeSC as screening method in Namibia. There was a high prevalence of sickle cell trait but no SCD. This is a baseline study that can inform policy on the possible adoption of sickle cell disease newborn screening in Namibia.
Carbon balance in the silvopastoral systems of Caldén forest: sources or sinks of greenhouse gases?
Authors: Utello Marco Jesús , Tarico Juan Carlos , Plevich José Omar 
Published: December 2023

Abstract
The objective of the following work was to address, through modeling and field data, a carbon balance as a function of forest cover for a silvopastoral breeding system in native Neltuma caldenia forest. For this, the herbaceous stratum in different forest covers was measured through sampling. Forage production for each tree density was affected by a use factor and was compared with the feed demand of a herd of breeding cows. The load values were affected by the estimated emissions in cattle breeding in the region (1,427 and 2,407 kg eq-CO2 animal− 1 year− 1). The evolution of the parameters of the forest mass was modeled using growth data obtained from 19 dendrometers distributed in 7 permanent plots in different tree densities. The results show that the herbaceous biomass was maximum in the condition of minimum woody cover and that from 8.5 m2 ha− 1 of basal area (BA) the forage yield decreases significantly (P < 0.05). The projected values of the forest flight show that from 2.4 m2 ha− 1 of BA, the eq-CO2 captures in the total tree biomass exceed the emissions of livestock supported by forage availability. If the capture of emissions that are trapped in the stem biomass is considered, the capture exceeds the emissions from 17.5 m2 ha− 1 of BA. It is concluded that managing the Caldén forest with appropriate silvicultural management would allow the production of "carbon neutral meat". The balance did not contemplate the capture of C by the soil.
Interpretable Mortality Prediction Model for ICU Patients with Pneumonia: Using Shapley Additive Explanation Method
Authors: li jiaxi , zhang yu , he shenyang , tang yan 
Published: December 2023

Abstract

Background
Pneumonia, a leading cause of morbidity and mortality worldwide, often necessitates Intensive Care Unit (ICU) admission. Accurate prediction of pneumonia mortality is crucial for tailored prevention and treatment plans. However, existing mortality prediction models face limited adoption in clinical practice due to their lack of interpretability.
Objective
This study aimed to develop an interpretable model for predicting pneumonia mortality in ICUs. Leveraging the Shapley Additive Explanation (SHAP) method, we sought to elucidate the Extreme Gradient Boosting (XGBoost) model and identify prognostic factors for pneumonia.
Methods
Conducted as a retrospective cohort study, we utilized electronic health records from the eICU-CRD (2014–2015) for all adult pneumonia patients. The first 24 hours of each ICU admission records were considered, with 70% of the dataset allocated for model training and 30% for validation. The XGBoost model was employed, and performance was assessed using the area under the receiver operating characteristic curve (AUC). The SHAP method provided insights into the XGBoost model.
Results
Among 10,962 pneumonia patients, in-hospital mortality was 16.33%. The XGBoost model demonstrated superior predictive performance (AUC: 0.732 ± 0.0065) compared to traditional scoring systems and other machine learning method, which achieved an improvement of 8% points. SHAP analysis identified Aspartate Aminotransferase (AST) as the most crucial predictor.
Conclusions
Interpretable predictive models enhance mortality risk assessment for pneumonia patients in the ICU, fostering transparency. AST emerged as the foremost predictor, followed by patient age, albumin, BMI et al. These insights, rooted in strong correlations with mortality, facilitate improved clinical decision-making and resource allocation.
Optimizing DC Microgrid: Fuzzy PI Controller with Metaheuristic Energy Storage Management
Authors: Kavousighahfarokhi Arash , Radzi Mohd Amran Mohd , Noorbakhsh S. Mohammad , Khorshidi Elahe , Dastgerdi Pedram Hematzadeh , Harchegani Amir Torki 
Published: December 2023

Abstract
One of the main issues with power systems that has a direct impact on voltage stability is the balance between power generation and load demand. On the other hand, due to the unpredictable nature of output power generation and the low inertia of these sources in comparison to other conventional sources, raising the penetration ratio of solar and wind power in the Microgrid (MG) may result in a lack of frequency control. The frequency stability performance can also be greatly improved by adjusting the gain of the inertia and drop control loops. However, it seems difficult to modify the aforementioned control coefficients with ordinary PI controllers in order to expect the greatest performance in all circumstances due to variations in wind speed, solar radiation, and load. Therefore, this work, by modelling load fluctuations and generation variations with the cooperation of battery and supercapacitor energy storage in the MG, suggests a control scheme based on a fuzzy gain scheduling PI (FGS-PI) model and improved grey wolf optimization (GWO) algorithm for faster performance and more robustness. Further, the effectiveness of the proposed technique is confirmed by simulation results in MATLAB/Simulink 2021b.