bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Decrypting an interchromosomal insertion associated with Marfan’s syndrome: how optical genome mapping emphasizes the morbid burden of copy-neutral variants
Authors: Bonaglia Maria Clara , Salvo Eliana , Sironi Manuela , Bertuzzo Sara , Errichiello Edoardo , Mattina Teresa , Zuffardi Orsetta 
Published: September 2023

Optical genome mapping (OGM), which allows analysis of ultra-high molecular weight (UHMW) DNA molecules, represents a response to the restriction created by short-read next-generation-sequencing, even in cases where the causative variant is a neutral copy-number-variant insensitive to quantitative investigations. This study aimed to provide a molecular diagnosis to a boy with Marfan syndrome (MFS) and intellectual disability (ID) carrying a de novo translocation involving chromosomes 3, 4, and 13 and a 1.7 Mb deletion at the breakpoint of chromosome 3. No FBN1 alteration explaining his Marfan phenotype was highlighted. UHMW gDNA was isolated from both the patient and his parents and processed using OGM. Genome assembly was followed by variant calling and annotation. Multiple strategies confirmed the results. The 3p deletion, which disrupted ROBO2, (MIM*602431) included three copy-neutral insertions. Two came from chromosome 13; the third contained 15q21.1, including the FBN1 from intron-45 onwards, thus explaining the MFS phenotype. We could not attribute the ID to a specific gene variant nor to the reshuffling of topologically associating domains (TADs). Our patient did not have vesicular reflux-2, as reported by missense alterations of ROBO2 (VUR2, MIM#610878), implying that reduced expression of all or some isoforms has a different effect than some of the point mutations. Indeed, the ROBO2 expression pattern and its role as an axon-guide suggests that its partial deletion is responsible for the patient’s neurological phenotype. Conclusion: OGM testing 1) highlights copy-neutral variants that could remain invisible if no loss of heterozygosity is observed and 2) is mandatory before other molecular studies in the presence of any chromosomal rearrangement for an accurate genotype-phenotype relationship.
PheWAS and cross-disorder analysis reveal genetic architecture, pleiotropic loci and phenotypic correlations across 11 autoimmune disorders
Authors: Topaloudi Apostolia , Jain Pritesh , Martinez Melanie B. , Bryant Josephine K. , Reynolds Grace , Zagoriti Zoi , Lagoumintzis George , Zamba-Papanicolaou Eleni , Tzartos John , Poulas Konstantinos , Kleopa Kleopas A. , Tzartos Socrates , Georgitsi Marianthi , Drineas Petros , Paschou Peristera 
Published: September 2023

IntroductionAutoimmune disorders (ADs) are a group of about 80 disorders that occur when self-attacking autoantibodies are produced due to failure in the self-tolerance mechanisms. ADs are polygenic disorders and associations with genes both in the human leukocyte antigen (HLA) region and outside of it have been described. Previous studies have shown that they are highly comorbid with shared genetic risk factors, while epidemiological studies revealed associations between various lifestyle and health-related phenotypes and ADs.MethodsHere, for the first time, we performed a comparative polygenic risk score (PRS) - Phenome Wide Association Study (PheWAS) for 11 different ADs (Juvenile Idiopathic Arthritis, Primary Sclerosing Cholangitis, Celiac Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Myasthenia Gravis, Type 1 Diabetes, Systemic Lupus Erythematosus, Vitiligo Late Onset, Vitiligo Early Onset) and 3,254 phenotypes available in the UK Biobank that include a wide range of socio-demographic, lifestyle and health-related outcomes. Additionally, we investigated the genetic relationships of the studied ADs, calculating their genetic correlation and conducting cross-disorder GWAS meta-analyses for the observed AD clusters.ResultsIn total, we identified 508 phenotypes significantly associated with at least one AD PRS. 272 phenotypes were significantly associated after excluding variants in the HLA region from the PRS estimation. Through genetic correlation and genetic factor analyses, we identified four genetic factors that run across studied ADs. Cross-trait meta-analyses within each factor revealed pleiotropic genome-wide significant loci.DiscussionOverall, our study confirms the association of different factors with genetic susceptibility for ADs and reveals novel observations that need to be further explored.
A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis
Authors: Coto-Segura Pablo , Segú-Vergés Cristina , Martorell Antonio , Moreno-Ramírez David , Jorba Guillem , Junet Valentin , Guerri Filippo , Daura Xavier , Oliva Baldomero , Cara Carlos , Suárez-Magdalena Olaya , Abraham Sonya , Mas José Manuel 
Published: September 2023

BackgroundPsoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized anin silicoapproach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles.MethodsWe built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug.ResultsThe combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed.ConclusionOur study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses.
Global research of artificial intelligence in strabismus: a bibliometric analysis
Authors: Zhou Ziying , Zhang Xuan , Tang Xiajing , Grzybowski Andrzej , Ye Juan , Lou Lixia 
Published: September 2023

PurposeTo analyze the global publications on artificial intelligence (AI) in strabismus using a bibliometric approach.MethodsThe Web of Science Core Collection (WoSCC) database was used to retrieve all of the publications on AI in strabismus from 2002 to 2023. We analyzed the publication and citation trend and identified highly-cited articles, prolific countries, institutions, authors and journals, relevant research domains and keywords. VOSviewer (software) and Bibliometrix (package) were used for data analysis and visualization.ResultsBy analyzing a total of 146 relevant publications, this study found an overall increasing trend in the number of annual publications and citations in the last decade. USA was the most productive country with the closest international cooperation. The top 3 research domains were Ophthalmology, Engineering Biomedical and Optics. Journal of AAPOS was the most productive journal in this field. The keywords analysis showed that “deep learning” and “machine learning” may be the hotspots in the future.ConclusionIn recent years, research on the application of AI in strabismus has made remarkable progress. The future trends will be toward optimized technology and algorithms. Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.
Molecular typing and characterization of Staphylococcus aureus isolates from burn wound infections in Fujian, China
Authors: Hong Xiaolan , Zhou Shaobo , Dai Xubo , Xie Dandan , Cai Yuanyuan , Zhao Guimei , Li Bin 
Published: September 2023

BackgroundStaphylococcus aureus (S. aureus) is the most common causative agent of burn wound infection, that often leads to high morbidity and mortality. However, there is not enough knowledge about the molecular epidemiology and antimicrobial susceptibility of S. aureus isolates from burn wound infections in Fujian, China.MethodsBetween 2016 and 2021, 90 S. aureus isolates were collected from burn wound infections in Fujian, China, including 59 methicillin-resistant (MRSA) strains and 31 methicillin-susceptible (MSSA) strains. These were investigated for molecular characteristics, virulence genes, biofilms, and antimicrobial susceptibility. All the isolates were genotyped by multilocus sequence typing (MLST), spa typing, agr typing, and SCCmec typing. Conventional PCR was performed for the detection of virulence genes. Biofilm formation capacity was assessed by tissue culture plate assay (TCP). The antimicrobial susceptibility of the isolates was evaluated using the dilution method.ResultsIn total, 37 sequence types (ST) and 34 Staphylococcal protein A (spa) types (including a new type named spa-t20720) were identified based on multilocus sequence typing (MLST) and spa typing, respectively. CC8-ST239-t030-agrI-SCCmecIII (57.6%,34/59) and CC7-ST7-t091-agrI (16.1%, 5/31) represented the main clone of MRSA and MSSA isolates, respectively. Antibiotic susceptibility testing identified a significant difference in resistance rates between ST239 and non-ST239 isolates (p &lt; 0.05). Twelve virulence genes were detected, of which the most common were icaA and icaD (both 100%), followed by icaB and icaC (both 96.7%), icaR (95.6%), lukED (81.1%), lukAB (62.2%), pvl (50%), hlgBC (26.7%), and eta (4.4%). Moreover, lukAB, hlgBC, agrI, and agrIII were significantly correlated with burn severity (p &lt; 0.05). MRSA isolates were less likely, compared with MSSA isolates, to carry pvl, lukAB, and hlgBC (p &lt; 0.05). A new spa type, t20720, was identified that contains pvl, lukED, lukAB, hlgBC, icaA, icaB, icaC, icaD, and icaR genes and has strong biofilm formation ability.ConclusionCC8-ST239-t030-agrI-SCCmecIII and CC7-ST-7-t091-agrI were the prevalent molecular signatures of MRSA and MSSA isolates from burn wound infections in Fujian, China, respectively. The newly identified spa-t20720 isolate, which carries a wide range of virulence genes and has strong biofilm formation ability, requires special clinical attention.
Knowledge and awareness of stroke and associated factors in the Saudi general population: a cross-sectional study
Authors: Alzayer Reem , Barakat Muna , Jirjees Feras , Alhamdan Aqeelah , Aloraifej Shatha , Cherri Sara , Mansour Sara , El Khatib Sami , Kharaba Zelal , Rahal Mohamad , Hallit Souheil , Malaeb Diana , Hosseini Hassan 
Published: September 2023

IntroductionStroke is a major cause of death and disability globally and in Saudi Arabia as well. Prevention and management of stroke depend highly on raising knowledge and awareness about the disease.PurposeThe purpose of this study was to evaluate Saudi adult's knowledge and awareness about stroke and determine the associated factors.Materials and methodsA cross-sectional online survey was conducted in May–July 2022 among Saudi citizens. Assessments of stroke knowledge about risk factors, symptoms, and response to stroke symptoms were evaluated. Logistic regression was conducted to assess the association between the socio-demographic characteristics and knowledge.ResultsA total of 389 participants were enrolled with the majority (81.7%) being male participants. Less than half of the study subjects (43.3%) identified four out of five correct answers related to general knowledge about stroke. Almost all the participants were able to identify at least one risk factor associated with stroke. The majority of the participants (81.2%) believed that physical inactivity was the most common risk factor associated with stroke. Approximately three-quarters of participants considered difficulty speaking and understanding speech, followed by the sudden loss of consciousness as the most common stroke manifestation. Participants with a history of hypertension, dyslipidemia, and obesity had significantly higher odds of identifying at least one early stroke symptom (OR 2.271 [95% CI 1.402 3.677], 2.059 [95% CI 1.273 3.328], and 2.665 [95% CI 1.431 4.963], respectively).ConclusionOur study revealed that participants have good knowledge about stroke. Nonetheless, further efforts are required to raise awareness and educate the public to optimize and ensure better treatment outcomes.
CNS-LAND score: predicting early neurological deterioration after intravenous thrombolysis based on systemic responses and injury
Authors: Jin Huijuan , Bi Rentang , Zhou Yifan , Xiao Qinghui , Li Min , Sun Shuai , Zhou Jinghua , Hu Jichuan , Huang Ming , Li Yanan , Hong Candong , Chen Shengcai , Chang Jiang , Wan Yan , Hu Bo 
Published: September 2023

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase &gt;4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT.
Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial
Authors: Mahajan Abhishek , Unde Himangi , Sable Nilesh P. , Shukla Shreya , Vaish Richa , Patil Vijay , Agarwal Ujjwal , Agrawal Archi , Noronha Vanita , Joshi Amit , Kapoor Akhil , Menon Nandini , Agarwal Jai Prakash , Laskar Sarbani Ghosh , Dcruz Anil Keith , Chaturvedi Pankaj , Pai Prathamesh , Rane Swapnil Ulhas , Bal Munita , Patil Asawari , Prabhash Kumar 
Published: September 2023

ObjectiveInterpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation.MethodsRetrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status.ResultsOut of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%.ConclusionThe accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.
Validation of the Arabic version of the general medication adherence scale in patients with type 2 diabetes mellitus in Jordan
Authors: Islam Md. Ashraful , El-Dahiyat Faris , Nouri Ahmed , Alefan Qais , Naqvi Atta Abbas 
Published: September 2023

Background: Medication adherence is a major challenge for patients with diabetes. Adherence rates are often low, and this can lead to poor glycaemic control and increased risk of complications. There are a number of tools available to measure medication adherence, but few have been validated in Arabic-speaking populations.Aim: This study aimed to validate the Arabic version of the General Medication Adherence Scale in patients with type 2 diabetes in Jordan.Methods: A cross-sectional study was conducted for 3 months among patients attending diabetes mellitus outpatient clinic in Irbid, Jordan. The validation procedure included confirmatory factor analysis (CFA) and equation modelling (SEM). Fit indices, namely, goodness of fit index (GFI), Tucker Lewis index (TLI), comparative fit index (CFI), and root mean square error of approximation (RMSEA) were observed. Corrected item-total correlation (ITC) was reported. Reliability was assessed using Cronbach’s alpha (α) and α value based on item deletion was also carried out. Intraclass correlation coefficient (ICC) was reported. Data were analyzed using IBM SPSS v23 and IBM AMOS v25.Results: Data from 119 participants were gathered. The mean adherence score was 27.5 (±6) ranging from 6 to 33. More than half of the patients were adherent to their therapy (n = 79, 66.4%). The reliability of the scale (n = 11) was 0.907, and ICC ranged from 0.880—0.930: 95% CI. The following values were observed in CFA; χ2 = 62.158, df = 41, χ2/df = 1.516, GFI = 0.913, AGFI = 0.860, TLI = 0.960, CFI = 0.971 and RMSEA = 0.066. A total of 10 out of 11 items had corrected ITC &gt;0.5. The α remained between 0.89–0.92 during item deletion.Conclusion: The results obtained in this study suggest that the scale is valid and reliable in measuring adherence to medications in the studied sample of patients with diabetes. This scale can be used by clinicians in Jordan to assess adherence and may further aide in evaluating interventions to improve adherence rates in persons with type 2 diabetes.
The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress
Authors: Lv Xuefeng , Jia Yanyan , Li Jinpeng , Deng Shu , Yuan Enwu 
Published: September 2023

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail.Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated.Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways.Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.