bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-Generation Sequencing-Based Evaluation of the Actionable Mutational Landscape in Solid Tumors: the “MOZART” Prospective Observational Study
Authors: Schettini Francesco , Sirico Marianna , Loddo Marco , Williams Gareth H , Hardisty Keeda-Marie , Scorer Paul , Thatcher Robert , Rivera Pablo , Milani Manuela , Strina Carla , Ferrero Giuseppina , Ungari Marco , Bottin Cristina , Zanconati Fabrizio , Manzini Nicolò , Aguggini Sergio , Tancredi Richard , Fiorio Elena , Fioravanti Antonio , Scaltriti Maurizio , Generali Daniele 
Published: February 2024

Abstract

Background
The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine mutations’ type, frequency and actionability and potential correlations with PD-L1 expression.
Methods
304 adult patients with heavily-pretreated metastatic cancers treated between 01/2019-03/2021 were recruited. The CLIA-/UKAS-accredit Oncofocus® assay targeting 505 genes was used on newly-obtained or archived biopsies. Chi-square, Kruskal-Wallis and Wilcoxon rank-sum test were used where appropriate. Results were significant for p < 0.05.
Results
A total of 237 tumors (78%) harbored actionable mutations. Tumors were positive for PD-L1 in 68.9% cases. The median number of mutant genes/tumor was of 2.0 (IQR: 1.0–3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%) and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found between PD-L1, ESCAT, age, sex and tumor mutational status. Sixty-two patients underwent targeted treatment, with 37.1% obtaining objective responses.
Conclusions
We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment.
Fractional order Jacobi wavelet-based numerical analysis of fractal-fractional multi-pantograph delay differential equation with variable coefficients
Authors: Singh Deepak , Verma Sag Ram 
Published: February 2024

Abstract

In this study, the fractal-fractional Caputo and Caputo-Fabrizio derivatives are used to formulate the fractal-fractional model of multi-pantograph delay differential equations with variable coefficients. The wavelet method is constructed to provide a numerical solution by using fractional-order Jacobi wavelets. This methodology relies on the operational matrix for fractal-fractional integration of fractional order Jacobi wavelets and the collocation method. We defined pseudo code and stability analysis of the proposed approach for the given model. The error analysis and comparison of the numerical results are also shown in the tables and graphs for the three illustrative examples. In the proposed methods, the data are obtained on different values of fractal \((\nu)\) and fractional \((\mu,\phi)\) parameters and it is noteworthy to point out that the classical case is recovered for \(\mu=1\) and \(\nu=1\).
Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation
Authors: Zeng Qiang , Liu Tingting , Qin Lilu , Wang Chen , Peng Guangbei , Liu Zhong , Tao Junfeng 
Published: February 2024

Abstract
Background:
Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.
Methods:
We performed differential gene expression analysis on Wilms tumor transcriptomic data from the GEO database and TARGET database. GO, KEGG, and GSEA pathways were utilized for the biological functional analysis. 9 of 24 hub genes were identified had prognosis-related by univariate Cox regression analysis. Nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. Finally, The key hub genes were validated in the TARGET-WT datasets, and cell function experiments were conducted to identify the gene's function in the WiT-49 cell.
Results:
The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.
Conclusions
Our study suggests that EMCN and CCNA1 as prognostic signatures associated with the progression of WT.
OTULIN-related conditions: Report of a new case and review of the literature using GenIA
Authors: Caballero-Oteyza Andrés , Crisponi Laura , Peng Xiao P. , Wang Hongying , Mrovecova Pavla , Olla Stefania , Siguri Chiara , Marnissi Farida , Jouhadi Zineb , Aksentijevich Ivona , Grimbacher Bodo , Proietti Michele 
Published: February 2024

Abstract

OTULIN encodes an eponymous linear deubiquitinase (DUB), which through the regulation of M1-Ub dynamics, is essential for controlling inflammation as a negative regulator of the canonical NF-𝛋B signaling pathway. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative effects. In this manuscript, we report the identification of a novel homozygous missense mutation, p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype. We go on to systematically review the literature for OTULIN-related human disease phenotypes by using the GenIA databaseto collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. We show how GenIA facilitates comprehensive synthesis across genotypic, phenotypic, and mechanistic data, enabling a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and the drafting of diagnostic and management guidelines; but it also identifies outstanding knowledge gaps and raises additional questions for future investigation.
Choroidal and Retinal Changes in Patients with Allergic Rhinoconjunctivitis
Authors: Akcal Omer , Suleymanzade Matin , Isik Burcu , Ersoz Mehmet Giray 
Published: February 2024

Abstract
PURPOSE
Allergic rhinoconjunctivitis (ARC) is an allergic upper respiratory tract disease characterized by sneezing, runny nose, nasal congestion and ocular and nasal itching due to inflammation of the nasal and conjunctival mucosa. There are no studies evaluating both the choroidal and retinal areas in ARC patients. Our objective was to evaluate patients with ARC at the time of diagnosis and before initiating treatment using Optical Coherence Tomography (OCT).
METHODS
This prospective cross-sectional study included 30 patients with ARC who presented to the Pediatric Allergy & Immunology Outpatient Clinic and 30 healthy control individuals. OCT scans were captured with Cirrus HD OCT-5000 (Carl Zeiss, Jena, Germany) in the enhanced depth imaging (EDI) mode.
RESULTS
Of the study population, 66.7% (n=20) of patient group and 56.6% (n=17) of control group were female. The mean age was 13±2.3 and 13.9±1.8 years in the patient and control groups, respectively. The temporal subfoveal choroidal thickness was statistically significantly thinner in ARC patients with asthma (p=0.032). A robust negative correlation was found between minimum ganglion cell-inner plexiform layer (GCIPL) thickness and allergic eosinophil count (AEC) in patients with ARC (r: -0.551, p<0.0001).
CONCLUSION
In our study, the GCIPL thickness was lower in ARC patients. Similarly, although it did not reach statistical significance, the minimum GCIPL thickness was lower in our patient group with asthma compared to those without asthma. Our results suggest that multiple allergen sensitization and elevated eosinophils may influence GCIP thickness. However, both choroidal and retinal tissue might be impacted during chronic follow-up. Further studies are needed to support these findings.
Graph Fourier transform for spatial omics representation and analyses of complex organs
Authors: Chang Yuzhou , Liu Jixin , Jiang Yi , Ma Anjun , Yeo Yao Yu , Guo Qi , McNutt Megan , Krull Jodran , Rodig Scott J. , Barouch Dan H. , Nolan Garry , Xu Dong , Jiang Sizun , Li Zihai , Liu Bingqiang , Ma Qin 
Published: February 2024

Abstract

Spatial omics technologies are capable of deciphering detailed components of complex organs or tissue in cellular and subcellular resolution. A robust, interpretable, and unbiased representation method for spatial omics is necessary to illuminate novel investigations into biological functions, whereas a mathematical theory deficiency still exists. We present SpaGFT (Spatial Graph Fourier Transform), which provides a unique analytical feature representation of spatial omics data and elucidates molecular signatures linked to critical biological processes within tissues and cells. It outperformed existing tools in spatially variable gene prediction and gene expression imputation across human/mouse Visium data. Integrating SpaGFT representation into existing machine learning frameworks can enhance up to 40% accuracy of spatial domain identification, cell type annotation, cell-to-spot alignment, and subcellular hallmark inference. SpaGFT identified immunological regions for B cell maturation in human lymph node Visium data, characterized secondary follicle variations from in-house human tonsil CODEX data, and detected extremely rare subcellular organelles such as Cajal body and Set1/COMPASS. This new method lays the groundwork for a new theoretical model in explainable AI, advancing our understanding of tissue organization and function.
Analysis of the interaction of antimalarial agents with Plasmodium falciparum Glutathione Reductase through molecular mechanical calculations
Authors: Ferreira F. H. do C , Pinto L. R. , Oliveira B. A. , Daniel L. V. , Navarro M. , Delgado G. Y. Sánchez 
Published: February 2024

Abstract

Malaria remains a significant global health challenge, with emerging resistance to current treatments necessitating the development of novel therapeutic strategies. P. falciparum Glutathione Reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarial drugs and dual drugs combining aminoquinoline derivatives with GR inhibitors using molecular docking and molecular dynamics simulations. Our findings reveal promising interactions between PfGR and antimalarial drugs, with the naphthoquinone Atovaquone (ATV) demonstrating particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity compared to reference inhibitors, suggesting their efficacy in inhibiting PfGR. Insights into their interaction mechanisms and structural dynamics are described. Overall, this research provides valuable insights into the potential of targeting PfGR and encourages further exploration of its role in the mechanisms of action of antimalarial drugs, including dual drugs, to enhance antiparasitic efficacy.
Analysis and Suppression of Offshore Wind Power Broadband Oscillation Based on HVDC Transmission Technology
Authors: Yang Zhangbin , Li Gang , Ding Yiwei , Peng Daixiao , Kaikai Zou , Ruan Lin 
Published: February 2024

Abstract

This paper explores the dynamics of large-scale offshore wind farms comprised of full-power variable frequency wind turbines, interconnected with flexible HVDC (High Voltage Direct Current) converter stations. These systems are susceptible to broad frequency oscillations due to the rapid response characteristics of power electronic devices, potentially compromising their operational safety and stability under various conditions. To mitigate the impact of these oscillations on offshore wind turbines and the connected systems, the study first outlines the structure and operational mode of the offshore wind power electronic system with flexible HVDC transmission. It then analyzes the mechanisms underlying these broad frequency oscillations. Subsequently, the paper presents a model construction and stability analysis for wind farms and flexible HVDC systems. It specifically focuses on offshore wind power systems with flexible HVDC transmission based on symmetric mono-polar topology, involving multiple branches and multiple wind farm access points. The research includes an in-depth oscillation analysis, supported by real-world case studies, demonstrating that strategically optimized control and protection strategies can effectively reduce the oscillation risks associated with wind farms connected through flexible HVDC systems, thereby ensuring their safe and stable operation.
Features of molecular self-assembled helix peptide nanotubes based on some amino acids molecules and their dipeptides: molecular modelling studies
Authors: Bystrov Vladimir 
Published: February 2024

Abstract
The paper considered the structural and dipole moments features of some amino acids that are important in the formation of the di-peptides and peptide nanotubes on their basis. The influence of the features of their chirality (left L and right D) and the alpha-helix conformations of amino acids also were taken into account. In particular, amino acids with aromatic rings were considered, such as phenylalanine (Phe/F), and branched-chain amino acids (BCAAs) Isoleucine (Ile/I), Leucine (Leu/L), as well as corresponding dipeptides based on them. On their basis, the features and properties of dipeptide structures and peptide nanotubes (PNTs) were investigated using computational molecular modeling and quantum-chemical semi-empirical calculations. Their polar, piezoelectric and photoelectronic properties and features were studied in details. The results of calculations of dipole moments and polarization, as well as piezoelectric coefficients and band gap width, for different types of helical peptide nanotubes are presented. The calculated values of the chirality indices of various nanotubes are given, depending on the chirality of the original dipeptides - the results obtained are consistent with the law of changes in the type of chirality as the hierarchy of molecular structures becomes more complex. Calculations were also carried out on the influence of water molecules in the internal cavity of nanotubes on their physical properties. Comparison of the results of these calculations by various computational chemistry methods with the available experimental data were also be given.
Diagnostic performance of a rapid immunochromatographic test for the simultaneous detection of antibodies to Theileria equi and Babesia caballi in horses and donkeys
Authors: Jongejan Frans , Du Cheng , Papadopoulos Elias , Blanda Valeria , Bella Santina , Canella Vincenza , Guercio Annalisa , Vicari Domenico , Tirosh-Levy Sharon , Steinman Amir , Baneth Gad , Keulen Sanna , Hulsebos Iris , Berger Laura , Wang Xiaojun 
Published: February 2024

Abstract
Background
Equine piroplasmosis is caused by two tick-borne protozoan parasites, Theileria equi and Babesia caballi, which are clinically relevant in susceptible horses, donkeys, and mules. Moreover, equine piroplasmosis significantly constrains international trading and equestrian events. Rapidly diagnosing both parasites in carrier animals is essential for implementing effective control measures. Here, a rapid immunochromatographic test for the simultaneous detection of antibodies to T. equi and B. caballi was evaluated using samples from horses and donkeys collected in Greece, Israel and Italy. The results were compared with a competitive ELISA for detecting antibodies to both parasites using the same panel of samples.
Methods
Blood samples were collected from 255 horses and donkeys. The panel consisted of 129 horses sampled at four locations in northern Greece, 105 donkeys at four locations in Sicily and 21 horses at two locations in Israel. The rapid test and the cELISA were performed according to the manufacturer's instructions, and the results were subjected to a statistical analysis.
Results
The immunochromatographic test provided a result within 15 minutes and can be performed in the field, detecting both pathogens simultaneously. The overall coincidence rate between the rapid test and the cELISA for detecting antibodies against T. equi was 93% and 92.9% for B.caballi. The rapid test's sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for T.equi were above 91.5%. Sixteen samples were positive for both parasites in the rapid test and eight in the cELISA. Either test had no significant association between T. equi and B. caballi detection. The detection rates of both parasites were significantly higher in Italy than in Greece or Israel and in donkeys than in horses. The agreement for T.equi between the results of both tests was high in Greece (93.8%) and Italy (95.2%) and moderate in Israel (76.2%). For B.caballi, the specificity and NPV of the rapid test were high (94.2% and 98.3%, respectively), although the sensitivity and PPV were moderate (69.2% and 39.1%, respectively) due to the small sample size. However, for B. caballi, the sensitivity was higher with the rapid test.
Conclusions
The rapid test detected T.equi and B.caballi simultaneously in the field, potentially replacing laborious cELISA testing and is recommended for import/export purposes. The test can also be helpful for the differential diagnosis of clinical cases since seropositivity may rule out equine piroplasmosis since it does not indicate current or active infection.
Clinical Features of Chronic Tibial Osteomyelitis: A Single-center Retrospective Study of 282 Cases in Xinjiang, China
Authors: Huang Xiaoxia , Chen Jiahan , Li Qian , Liu Tao , Zhao Yan , Teng Yong 
Published: February 2024

Abstract
Objective:This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis.
Methods:A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification.
Results:Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21±15.68 years and was mainly concentrated in 41-50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling,pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA.
Conclusion:Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culturewas observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.
Feasibility Analysis of Line of Sight (LOS) Underwater Wireless Optical Communications (UWOCs) via Link Budget
Authors: Zayed M. Mokhtar , Shokair Mona , Elagooz Salah , Elshenawy Hamed 
Published: February 2024

Abstract

Optical Wireless Communications (OWCs) are capable of handling large data rate in the Internet of Underwater Things (IoUT) at low latency to be suitable for real time image and video applications. This paper presents communication link feasibility via link budget to determine the link communication range for three types of line-of-sight link configurations: point to point, diffused and modulating retro reflector link. The main aim of this paper studies a more realistic power link budget which is developed to take into account the following: LED Photo Source Lambertian radiation model, Beer Lambert pass loss model that includes absorption and scattering effects of water types, Spherical wave propagation model, photo detector which is modeled by active area model, transmitter projection optics (PO) gain and receiver collection optics (CO) gain. Moreover, this paper considers the effects of aquatic channels ‘scattering and absorption by using IM-DD OOK intensity modulation direct detection, LED and LD –PS based transmitter and SiPM-PD based receiver. The impact of different underwater environment, transmitter and receiver parameters will be investigated on the communication link range. Its range on the order of tens of meters could be achieved by the three link configurations. It is concluded from the analysis; line of sight point to point provides more communication range than diffused line of sight. Diffused line of sight is used when it is required to multicast from a node to several nodes. Modulating retro reflector provides moderate communication range and it is used when one party has more resources than the other one on the communication link. For medium distances, is determined by up to a hundred meter by placing multiple relay nodes between source node and destination node. The communication range is increased as increasing the active physical area of photodetector and transmitted power. The communication range in both clear sea water and clear ocean water is higher turbid water which is less since optical water suffers from higher attenuation. By using the multi hop concept, extended communication link range can be achieved.