bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells
Authors: Lin Huan-Ting , Takagi Masatoshi , Kubara Kenji , Yamazaki Kazuto , Michikawa Fumiko , Okumura Takashi , Naruto Takuya , Morio Tomohiro , Miyazaki Koji , Taniguchi Hideki , Otsu Makoto 
Published: April 2024

Abstract
Background
Although oncogenic RAS mutants are thought to exert mutagenic effects upon blood cells, it remains uncertain how a single oncogenic RAS impacts non-transformed multipotent hematopoietic stem or progenitor cells (HPCs). Such potential pre-malignant status may characterize HPCs in patients with RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD). This study sought to elucidate the biological and molecular alterations in human HPCs carrying monoallelic mutant KRAS (G13C) with no other oncogene mutations.

Methods
We utilized induced pluripotent stem cells (iPSCs) derived from two unrelated RALD patients. Isogenic HPC pairs harboring either wild-type KRAS or monoallelic KRAS (G13C) alone obtained following differentiation enabled reliable comparative analyses. The compound screening was conducted with an established platform using KRAS (G13C) iPSCs and differentiated HPCs.

Results
Cell culture assays revealed that monoallelic KRAS (G13C) impacted both myeloid differentiation and expansion characteristics of iPSC-derived HPCs. Comprehensive RNA-sequencing analysis depicted close clustering of HPC samples within the isogenic group, warranting that comparative studies should be performed within the same genetic background. When compared with no stimulation, iPSC-derived KRAS (G13C)-HPCs showed marked similarity with the wild-type isogenic control in transcriptomic profiles. After stimulation with cytokines, however, KRAS (G13C)-HPCs exhibited obvious aberrant cell-cycle and apoptosis responses, compatible with "dysregulated expansion," demonstrated by molecular and biological assessment. Increased BCL-xL expression was identified amongst other molecular changes unique to mutant HPCs. With screening platforms established for therapeutic intervention, we observed selective activity against KRAS (G13C)-HPC expansion in several candidate compounds, most notably in a MEK- and a BCL-2/BCL-xL-inhibitor. These two compounds demonstrated selective inhibitory effects on KRAS (G13C)-HPCs even with primary patient samples when combined.

Conclusions
Our findings indicate that a monoallelic oncogenic KRAS can confer dysregulated expansion characteristics to non-transformed HPCs, which may constitute a pathological condition in RALD hematopoiesis. The use of iPSC-based screening platforms will lead to discovering treatments that enable selective inhibition of RAS-mutated HPC clones.
Classification of substances by health hazard using deep neural networks and molecular electron densities
Authors: Singh Satnam , Zeh Gina , Freiherr Jessica , Bauer Thilo , Türkmen Isik , Grasskamp Andreas T. 
Published: April 2024

Abstract
In this paper we present a method that allows leveraging 3D electron density information to train a deep neural network pipeline to segment regions of high, medium and low electronegativity and classify substances as health hazardous or non-hazardous. We show that this can be used for use-cases such as cosmetics and food products. For this purpose, we first generate 3D electron density cubes using semiempirical molecular calculations for a custom European Chemicals Agency (ECHA) subset consisting of substances labelled as hazardous and non-hazardous for cosmetic usage. Together with their 3-class electronegativity maps we train a modified 3D-UNet with electron density cubes to segment reactive sites in molecules and classify substances with an accuracy of 78.1%. We perform the same process on a custom food dataset (CompFood) consisting of hazardous and non-hazardous substances compiled from European Food Safety Authority (EFSA) OpenFoodTox, Food and Drug Administration (FDA) Generally Recognized as Safe (GRAS) and FooDB datasets to achieve a classification accuracy of 64.1%. Our results show that 3D electron densities and particularly masked electron densities, calculated by taking a product of original electron densities and regions of high and low electronegativity can be used to classify molecules for different use-cases and thus serve not only to guide safe-by-design product development but also aid in regulatory decisions.

Scientific contribution
We aim to contribute to the diverse 3D molecular representations used for training machine learning algorithms by showing that a deep learning network can be trained on 3D electron density representation of molecules. This approach has previously not been used to train machine learning models and it allows utilization of the true spatial domain of the molecule for prediction of properties such as their suitability for usage in cosmetics and food products and in future, to other molecular properties. The data and code used for training is accessible at https://github.com/s-singh-ivv/eDen-Substances.
Protocol for a systematic review and meta-analysis of the prevalence of mental illness among nursing home residents
Authors: Holt Jared , Bhar Sunil , Schofield Penelope , Koder Deborah , Owen Patrick , Seitz Dallas , Bhowmik Jahar 
Published: April 2024

Abstract
Background
There is a high prevalence of mental illness in nursing home residents compared to older adults living in the community. This was highlighted in the most recent comprehensive systematic review on the topic, published in 2010. In the context of a rapidly aging population and increased numbers of older adults requiring residential care, this study aims to provide a contemporary account of the prevalence of mental illness among nursing home residents.

Methods
This protocol was prepared in line with the PRISMA-P 2015 Statement. Systematic searches will be undertaken across six electronic databases: PubMed, Embase, Web of Science, PsycNET, CINAHL, and Abstracts in Social Gerontology. Peer-reviewed studies published from 2009 onwards which report the prevalence of mental illness within nursing home populations will be included. Database searches will be supplemented by forward and backward citation searching. Titles and abstracts of records will be screened using a semi-automated process. The full text of selected records will be assessed to confirm inclusion criteria are met. Study selection will be recorded in a PRISMA flowchart. A pilot-tested form will be used to extract data from included studies, alongside the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. A study characteristics and results table will be prepared to present key details from each included study, supported by a narrative synthesis. Random-effects restricted maximum likelihood meta-analyses will be performed to compute pooled prevalence estimates for mental illnesses represented in the identified studies. Heterogeneity will be assessed using Cochran’s Q and Higgins’ I2 statistics. A Funnel plot and Egger’s test will be used to assess publication bias. The GRADE approach will be used to assess the quality of the body of evidence identified.

Discussion
The study will provide a comprehensive and contemporary account of the prevalence of mental illness among nursing home residents. Meta-analyses will provide robust prevalence estimates across a range of presentations. Key insights will be highlighted, including potential sources of heterogeneity. Implications for residents, researchers, care providers, and policymakers will be noted.

Systematic review registration
PROSPERO: CRD42023456226.
Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis
Authors: Ji Zhenhua , Jian Miaomiao , Su Xuan , Pan Yingyi , Duan Yi , Ma Weijie , Zhong Lei , Yang Jiaru , Song Jieqin , Wu Xinya , Gao Li , Ma Weijiang , Kong Jing , Li Bingxue , Chen Jinjing , Liu Meixiao , Fan Yuxin , Peng Li , Dong Yan , Bao Fukai , Liu Aihua 
Published: April 2024

Abstract
Background
Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published.

Methods
We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics.

Results
There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI =  − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI =  − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI =  − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI =  − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI =  − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI =  − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others).

Conclusions
Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases.

Systematic review registration
PROSPERO CRD42022354938.
Novel results for separate families of fuzzy-dominated mappings satisfying advanced locally contractions in b-multiplicative metric spaces with applications
Authors: Rasham Tahair , Qadir Romana , Hasan Fady , Agarwal R. P. , Shatanawi Wasfi 
Published: April 2024

AbstractThe objective of this research is to present new fixed point theorems for two separate families of fuzzy-dominated mappings. These mappings must satisfy a unique locally contraction in a complete b-multiplicative metric space. Also, we have obtained novel results for families of fuzzy-dominated mappings on a closed ball that meet the requirements of a generalized locally contraction. This research introduces new and challenging fixed-point problems for families of ordered fuzzy-dominated mappings in ordered complete b-multiplicative metric spaces. Moreover, we demonstrate a new concept for families of fuzzy graph-dominated mappings on a closed ball in these spaces. Additionally, we present novel findings for graphic contraction endowed with graphic structure. These findings are groundbreaking and provide a strong foundation for future research in this field. To demonstrate the uniqueness of our novel findings, we provide evidence of their applicability in obtaining the common solution of integral and fractional differential equations. Our findings have resulted in modifications to several contemporary and classical results in the research literature. This provides further evidence of the originality and impact of our work.
Dynamical behaviors of a stochastic SIRV epidemic model with the Ornstein–Uhlenbeck process
Authors: Shang Jiaxin , Li Wenhe 
Published: April 2024

AbstractVaccination is an important tool in disease control to suppress disease, and vaccine-influenced diseases no longer conform to the general pattern of transmission. In this paper, by assuming that the infection rate is affected by the Ornstein–Uhlenbeck process, we obtained a stochastic SIRV model. First, we prove the existence and uniqueness of the global positive solution. Sufficient conditions for the extinction and persistence of the disease are then obtained. Next, by creating an appropriate Lyapunov function, the existence of the stationary distribution for the model is proved. Further, the explicit expression for the probability density function of the model around the quasi-equilibrium point is obtained. Finally, the analytical outcomes are examined by numerical simulations.
FiTMuSiC: leveraging structural and (co)evolutionary data for protein fitness prediction
Authors: Tsishyn Matsvei , Cia Gabriel , Hermans Pauline , Kwasigroch Jean , Rooman Marianne , Pucci Fabrizio 
Published: April 2024

AbstractSystematically predicting the effects of mutations on protein fitness is essential for the understanding of genetic diseases. Indeed, predictions complement experimental efforts in analyzing how variants lead to dysfunctional proteins that in turn can cause diseases. Here we present our new fitness predictor, FiTMuSiC, which leverages structural, evolutionary and coevolutionary information. We show that FiTMuSiC predicts fitness with high accuracy despite the simplicity of its underlying model: it was among the top predictors on the hydroxymethylbilane synthase (HMBS) target of the sixth round of the Critical Assessment of Genome Interpretation challenge (CAGI6) and performs as well as much more complex deep learning models such as AlphaMissense. To further demonstrate FiTMuSiC’s robustness, we compared its predictions with in vitro activity data on HMBS, variant fitness data on human glucokinase (GCK), and variant deleteriousness data on HMBS and GCK. These analyses further confirm FiTMuSiC’s qualities and accuracy, which compare favorably with those of other predictors. Additionally, FiTMuSiC returns two scores that separately describe the functional and structural effects of the variant, thus providing mechanistic insight into why the variant leads to fitness loss or gain. We also provide an easy-to-use webserver at https://babylone.ulb.ac.be/FiTMuSiC, which is freely available for academic use and does not require any bioinformatics expertise, which simplifies the accessibility of our tool for the entire scientific community.
Quantitative analysis methods for evaluating colour on architectural heritage: survey of colour restoration and perception of the Wen Yuan Ge in the Forbidden City
Authors: Shao Jie , Li Luke , Jiang Yutong , Liu Xin , Yang Hong 
Published: April 2024

Abstract
Three methods can be used to evaluate the colour used on architectural heritage: manual evaluation, instrumental measurement, and process restoration. Optical instruments that can obtain relatively accurate chromaticity data are ideal. As architectural heritage sites age, their colour fluctuates. Researchers must screen colour data and analyse the features based on experience with colour perception. This study combines quantitative colour analysis and a scaled perception survey to analyse the Wen Yuan Ge in the Forbidden City and provide a new reference for researching and designing colour in architectural heritage.
Performance assessment of activated carbon thermally modified with iron in the desulfurization of biogas in a static batch system supported by headspace gas chromatography
Authors: Montaño Mayerlin Edith Acuña , Effting Luciane , Guedes Carmen Luisa Barbosa , Arizaga Gregorio Guadalupe Carbajal , Giona Renata Mello , Cordeiro Patricia Hissae Yassue , Tarley César Ricardo Teixeira , Bail Alesandro 
Published: April 2024

AbstractA static batch arrangement composed of anti-leak vials coupled to gas chromatography is proposed as a complementary system for performance assessment of biogas desulfurization by adsorption. For testing, a modified commercial activated carbon produced by controlled thermal treatment in the presence of iron(III) species improved biogas desulfurization. The adsorbents showed a superior hydrogen sulfide removal compared to ordinary one. Pseudo-first-order, pseudo-second-order, and Bangham’s kinetic models were used to fit experimental data. All studied samples followed pseudo-first-order model, indicating the predominance of physisorption, and Bangham’s model, confirming that the micropores structure played an important role for gases diffusion and adsorbent capacity. Additionally, the materials were characterized by N2 adsorption–desorption, X-ray diffraction, infrared spectroscopy, scanning electron microscopy and energy-dispersive spectroscopy. The thermal treatment associated with iron impregnation caused significant modifications in the surface of the materials, and the iron species showed two main benefits: an expressive increase in the specific area and the formation of specific adsorption sites for hydrogen sulfide removal. The results reinforce the advantages of iron-modified adsorbents in relation to their non-modified counterparts. The analytical methodology based on the confinement of multiple gases contributes to improving the understanding of the hydrogen sulfide adsorption process using pressure swing adsorption technology.
Graphical Abstract
Direct and accurate miRNA detection based on CRISPR/Cas13a-triggered exonuclease-iii-assisted colorimetric assay
Authors: Li Yunxiao , Wang Qiuxia , Wang Yali 
Published: April 2024

AbstractThe abnormally expressed microRNAs (miRNAs) serve as crucial indicators for disease diagnosis and are strongly associated with the progression of various diseases. The quantification of miRNAs is highly significant for the clinical diagnosis and treatment of various types of cancers. This study utilizes the CRISPR/Cas13a system, which combines CRISPR RNA (crRNA) and CRISPR-associated Cas13a, to recognize the miRNA directly and specifically, thus activating the trans-cleavage activity of Cas13a. By integrating the CRISPR-Cas13a system with an exonuclease-iii (Exo-iii)-assisted chain cleavage of silver ions (Ag+)-aptamer and an Ag+ -based color reaction, a method for the detection of miRNA that is specific and sensitive is developed. This approach demonstrated exceptional sensitivity in detecting miRNA, with a low detection limit of 5.12 fM. Moreover, the suggested method was effectively utilized to precisely measure the amount of miRNA in intricate biological samples, demonstrating its practical applicability. Furthermore, due to its elevated sensitivity and simple probe design and fluorophore labeling, the suggested colorimetric technique holds great potential for use in clinical diagnostics.
The Night-Time Sleep and Autonomic Activity of Male and Female Professional Road Cyclists Competing in the Tour de France and Tour de France Femmes
Authors: Sargent Charli , Jasinski Summer , Capodilupo Emily R. , Powers Jeremy , Miller Dean J. , Roach Gregory D. 
Published: April 2024

Abstract
Background
Sleep is a critical component of recovery, but it can be disrupted following prolonged endurance exercise. The objective of this study was to examine the capacity of male and female professional cyclists to recover between daily race stages while competing in the 2022 Tour de France and the 2022 Tour de France Femmes, respectively. The 17 participating cyclists (8 males from a single team and 9 females from two teams) wore a fitness tracker (WHOOP 4.0) to capture recovery metrics related to night-time sleep and autonomic activity for the entirety of the events and for 7 days of baseline before the events. The primary analyses tested for a main effect of ‘stage classification’—i.e., rest, flat, hilly, mountain or time trial for males and flat, hilly or mountain for females—on the various recovery metrics.

Results
During baseline, total sleep time was 7.2 ± 0.3 h for male cyclists (mean ± 95% confidence interval) and 7.7 ± 0.3 h for female cyclists, sleep efficiency was 87.0 ± 4.4% for males and 88.8 ± 2.6% for females, resting HR was 41.8 ± 4.5 beats·min−1 for males and 45.8 ± 4.9 beats·min−1 for females, and heart rate variability during sleep was 108.5 ± 17.0 ms for males and 119.8 ± 26.4 ms for females. During their respective events, total sleep time was 7.2 ± 0.1 h for males and 7.5 ± 0.3 h for females, sleep efficiency was 86.4 ± 1.2% for males and 89.6 ± 1.2% for females, resting HR was 44.5 ± 1.2 beats·min−1 for males and 50.2 ± 2.0 beats·min−1 for females, and heart rate variability during sleep was 99.1 ± 4.2 ms for males and 114.3 ± 11.2 ms for females. For male cyclists, there was a main effect of ‘stage classification’ on recovery, such that heart rate variability during sleep was lowest after mountain stages. For female cyclists, there was a main effect of ‘stage classification’ on recovery, such that the percentage of light sleep (i.e., lower-quality sleep) was highest after mountain stages.

Conclusions
Some aspects of recovery were compromised after the most demanding days of racing, i.e., mountain stages. Overall however, the cyclists obtained a reasonable amount of good-quality sleep while competing in these physiologically demanding endurance events. This study demonstrates that it is now feasible to assess recovery in professional athletes during multiple-day endurance events using validated fitness trackers.
Advancements in alveolar bone grafting and ridge preservation: a narrative review on materials, techniques, and clinical outcomes
Authors: Kim Suyoung , Kim Seong-Gon 
Published: April 2024

AbstractThis narrative review systematically explores the progression of materials and techniques in alveolar ridge preservation (ARP). We commence by delineating the evolution from traditional ARP methods to cutting-edge alternatives, including platelet-rich fibrin, injectable bone repair materials, and hydrogel systems. Critical examination of various studies reveals these innovative approaches not only accelerate bone healing but also significantly improve patient-reported outcomes, such as satisfaction, pain perception, and overall quality of life. Emphasis is placed on the correlation between advanced ARP techniques and enhanced patient comfort and clinical efficacy, underscoring their transformative potential in dental implantology. Highlighting the effectiveness of ARP, the implant survival rate over a span of 5 to 7 years was high, showcasing the reliability and success of these methods. Further, patients expressed high aesthetic satisfaction with the soft tissue outcome, evidenced by an average visual analog scale (VAS) score of 94. This positive aesthetic appraisal is linked to the clinical health of implants, potentially due to the employment of tooth-supported surgical guides. The economic analysis reveals a varied cost range for bone graft substitutes ($46.2 to $140) and socket sealing materials ($12 to $189), with a noteworthy correlation between the investment in barrier membranes and the diminished horizontal and vertical ridge resorption. This suggests that membrane usage significantly contributes to preserving ridge dimensions, offering a cost-effective strategy for enhancing ARP outcomes. In conclusion, this review illuminates the significant advancements in ARP, highlighting the shift towards innovative materials and techniques that not only promise enhanced bone regeneration and reduced healing times but also improve patient satisfaction and aesthetic outcomes. The documented high implant survival rate and the beneficial economic implications of membrane use further validate the effectiveness of contemporary ARP strategies, paving the way for their broader adoption in dental implantology.