bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Characterisation of the Craniofacial Morphology of Infants Born With Zika Virus; Innovative Approach for Public Health Surveillance and Broad Clinical Applications
Authors: Ayoub Ashraf , de Freitas Silva Leonardo , Mossey Peter , Al-Rudainy Dhelal , de Mattos Adriana Marques , Garcia Júnior Idelmo Rangel , Quigley Alan , Ju Xiangyang 
Published: June 2021

Background: This study was carried out in response to the Zika virus epidemic, which constituted a public health emergency, and to the 2019 WHO calling for strengthened surveillance for the early detection of related microcephaly. The main aim of the study was to phenotype the craniofacial morphology of microcephaly using a novel approach and new measurements, and relate the characteristics to brain abnormalities in Zika-infected infants in Brazil to improve clinical surveillance.Methods: 3D images of the face and the cranial vault of 44 Zika-infected infants and matched healthy controls were captured using a 3D stereophotogrammetry system. The CT scans of the brain of the infected infants were analysed. Principal component analysis (PCA) was applied to characterise the craniofacial morphology. In addition to the head circumference (HC), a new measurement, head height (HH), was introduced to measure the cranial vault. The level of brain abnormality present in the CT scans was assessed; the severity of parenchymal volume loss and ventriculomegaly was quantified. Student's t-test and Spearman's Rho statistical test have been applied.Findings: The PCA identified a significant difference (p &lt; 0.001) between the cranial vaults and the face of the Zika infants and that of the controls. Spearman's rank-order correlation coefficients show that the head height (HH) has a strong correlation (0.87 in Zika infants; 0.82 in controls) with the morphology of the cranial vaults, which are higher than the correlation with the routinely used head circumference (HC). Also, the head height (HH) has a moderate negative correlation (−0.48) with the brain abnormalities of parenchymal volume loss.Interpretation: It is discovered that the head height (HH) is the most sensitive and discriminatory measure of the severity of cranial deformity, which should be used for clinical surveillance of the Zika syndrome, evaluation of other craniofacial syndromes and assessment of various treatment modalities.
The Significance of Duration of Exposure and Circulation of Fresh Air in SARS-CoV-2 Transmission Among Healthcare Workers
Authors: Vlacha Vasiliki , Feketea Gavriela , Petropoulou Athanasia , Trancá Sebastian Daniel 
Published: June 2021

Background: The true risk of infection after exposure to SARS-CoV-2 of healthcare workers (HCWs) in the workplace has not yet been established. This descriptive study analyzes the exposure characteristics of HCWs to SARS-CoV-2.Methods: In March 2020, at the beginning of the pandemic, a total of 58 HCWs in a regional hospital in Greece were exposed to three patients with symptomatic SARS-CoV-2 infection. These three index cases had taken part in an 8-day religious tour, during which 52 travelers spent 10 h every day in a tour bus. A study was made of the circumstances of the hospital exposure.Results: Of the 52 travelers in the bus, 48 contracted SARS-CoV2. None of the 58 HCW contacts developed symptoms related to COVID-19, although, 43% were exposed to a SARS-CoV-2 infected patient for more than 15 min, and 74% were within a distance of &lt;1 m, and half of the contacts were not wearing a surgical mask. Additional information was that 63% of the contacts were exposed in a room sized more than 15 m2, and in more than 80% of cases, the window or the door to the room was open during their exposure. In about one-third of the exposure events, the HCW contacts were not wearing a mask and were at a distance of &lt;1 m, and just under half of them were exposed for more than 15 min. One-fourth of the contacts underwent RT-PCR testing, and 11% IgG/IgM antibody testing for SARS-CoV-2, all of which were negative. All observed quarantine at home for 14 days.Conclusion: This observational study was made before the extent of the SARS-CoV-2 became apparent, and before routine preventive measures were observed by all HCWs. Comparing the conditions of exposure in the two different settings (bus vs. regional health facility), it is apparent that the duration of exposure and the small, enclosed nature of the bus are the distinguishing factors. In the healthcare setting, the elimination of both factors and the implementation of additional measures protected the exposed HCWs from contracting SARS-CoV-2 infection.
Correlation Between Electroretinogram and Visual Prognosis in Metallic Intraocular Foreign Body Injury
Authors: Mai Xiaoting , Ling Fangyi , Gong Yuting , Chen Jialin , Lin Hongjie , Chen Haoyu 
Published: June 2021

Purpose: This study aims to investigate the correlation between electroretinogram (ERG) and visual outcome in eyes with metallic intraocular foreign body (IOFB) injury.Methods: Cases with metallic IOFB injuries with preoperative ERG from January 2008 to May 2020 were reviewed retrospectively. Five ERG responses were recorded, including rod response, maximal response, oscillatory potentials, cone response, and 30-Hz flicker. The results were compared between the affected and the contralateral eyes. All patients received surgery to remove IOFBs. The correlation between amplitudes, implicit times, and grades of ERG with final best-corrected visual acuity (BCVA) was analyzed.Results: A total of 33 eyes of 33 patients were included. The eyes with IOFB had generally delayed implicit time and reduced amplitude in all waves. The maximum change was found in oscillatory potentials S3 and N1 (0.42 ± 0.42 and 1.95 ± 1.97 of the fellow eyes, respectively, p &lt; 0.05). All amplitudes were negatively correlated with the final BCVA (rs: −0.676 to −0.459, all p &lt; 0.05). In contrast, all implicit times were positively correlated with final BCVA, although, some of them were not statistically significant (rs: 0.035 to 0.687). Among them, oscillatory potential P3 has the highest correlation coefficient (rs = 0.687, p &lt; 0.001). All grades of ERG waves were statistically correlated with the final BCVA (rs: −0.596 to −0.664, all p &lt; 0.001).Conclusions: ERG can be used to assess visual outcome in metallic IOFB injury after surgery. Oscillatory potentials provided the most significant responses.
Prognosis and Concurrent Genomic Alterations in Patients With Advanced NSCLC Harboring MET Amplification or MET Exon 14 Skipping Mutation Treated With MET Inhibitor: A Retrospective Study
Authors: Liu Li , Kalyani Farhin Shaheed , Yang Haiyan , Zhou Chunhua , Xiong Yi , Zhu Songlin , Yang Nong , Qu Jingjing 
Published: June 2021

BackgroundMET amplification or METex14 skipping mutations are uncommon oncogenic events in NSCLC patients. Clinicopathological characteristics, concurrent gene alterations, and prognosis of MET TKIs in these patients are yet to be elucidated.MethodsWe retrospectively analyzed the genomic profiles of 43 MET amplifications or 31 METex14 skipping mutations in NSCLC patients with no previous treatment with EGFR TKIs. Survival outcomes were analyzed in evaluable patients receiving MET TKI treatment: MET amplification cohort (n = 29) and METex14 skipping mutation cohort (n = 29).ResultsAmong evaluable patients, a shorter PFS was observed in the MET amplification cohort than in the METex14 skipping mutation cohort (7.0 months vs. 11.0 months, P = 0.043). Concurrent mutations in both cohorts resulted in a statistically significant shorter PFS (MET amplification: 3.5 months versus 8.0 months, P = 0.038, METex14 skipping mutation: 7.0 versus NR months, P = 0.022). However, a statistically significant OS (17.0 months versus 20.0 months, P = 0.044) was only observed in the MET amplification cohort. TP53, the most common concurrent mutation in both cohorts, was associated with worse survival outcomes as compared to the wild type. The MET amplification cohort with a concurrent PIK3CA mutation exhibited primary resistance to MET TKIs and showed disease progression (80%).ConclusionMET TKIs could be a better treatment option for patients with METex14 skipping mutations. Concurrent mutations may deteriorate the PFS of MET TKIs in NSCLC patients with MET amplification or METex14 skipping mutations. PIK3CA mutations may confer primary resistance to MET TKIs in patients with MET amplification.
Therapeutic Response of Soft Tissue Sarcoma With Novel SS18-POU5F1 Fusion: A Case Report
Authors: Liu Zengjun , Yuan Hongtu , Han Mingyong 
Published: June 2021

A novel SS18-POU5F1 fusion gene was recently reported in soft tissue sarcoma occurring in three adolescent and young adult patients. Herein, we firstly reported the treatment response of SS18-POU5F1 sarcoma to immune checkpoint inhibitor, angiogenesis inhibitor, chemotherapy and radiotherapy. Our patient demonstrated no response to various systemic therapies including immune checkpoint inhibitor, angiogenesis inhibitor and chemotherapy. However, we noted that the SS18-POU5F1 sarcoma had a quick, robust but transient clinical response to radiotherapy. Further studies are needed to elucidate the mechanism underlying the different tumor response to radiotherapy and systemic therapy in this kind of tumor.
Prognostic Value of Pretreatment Overweight/Obesity and Adipose Tissue Distribution in Resectable Gastric Cancer: A Retrospective Cohort Study
Authors: Gu Lihu , Zhang Yangfan , Hong Jiaze , Xu Binbin , Yang Liuqiong , Yan Kun , Zhang Jingfeng , Chen Ping , Zheng Jianjun , Lin Jie 
Published: June 2021

BackgroundThis is a study aimed at exploring the relationship between pretreatment overweight/obesity, adipose tissue distribution, and long-term prognosis of gastric cancer.MethodsA total of 607 gastric cancer patients were involved in the retrospective cohort study. Overweight/obese patients were defined as body mass index (BMI) greater than 25 kg/m2, and adipose tissue distribution parameters, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio were measured at the level of the third lumbar vertebra using computerized tomography images within 15 days before the surgery. Multiple Cox regression models were applied to evaluate the association between overweight/obesity and disease-specific survival (DSS) of gastric cancer, and covariates including age, gender, T stage, N stage, and chemotherapy were adjusted. Furthermore, multiple Cox regression models were performed to evaluate the association between adipose tissue distribution parameters and DSS of gastric cancer; except for covariates mentioned above, overweight/obesity was adjusted additionally.ResultsOverweight/obesity was a predictive factor (HR = 0.61, 95% CI: 0.37–0.99) for the prognosis of gastric cancer. After additionally adjusting for overweight/obesity, high SAT percentage was an independent protective factor (HR = 0.59, 95% CI: 0.36–0.96), while high VAT percentage (HR = 1.68, 95% CI: 1.06–2.68) and high VAT/SAT ratio (HR = 1.99, 95% CI: 1.19–3.34) were independent risk factors for DSS of gastric cancer. Compared with other patients (overweight/obesity with low VAT/SAT ratio group, non-overweight/obesity or high VAT/SAT ratio group), patients in the non-overweight/obesity with high VAT/SAT ratio group had a worse prognosis (HR = 1.89, 95% CI: 1.28–2.77).ConclusionThese results suggest that overweight/obesity is a predictive factor for the prognosis of gastric cancer. The VAT/SAT ratio could be used as a promising prognostic factor for gastric cancer. Therefore, in preoperative evaluation of gastric cancer patients, attention should be paid not only to BMI but also to adipose tissue distribution.
Expression of Glycolysis-Related Proteins in Cancer of Unknown Primary Origin
Authors: Bonatelli Murilo , Fornari Isabella Fernandes , Bernécule Priscila Neves , Pinheiro Lara Esquiapatti , Costa Ricardo Filipe Alves , Longatto-Filho Adhemar , Junior João Neif Antonio , Silva Eduardo Caetano Albino , Cárcano Flávio Mavignier , Pinheiro Céline 
Published: June 2021

IntroductionCancer of unknown primary origin (CUP) is defined as metastatic cancer without identification of the primary site. Considering that only 15–20% of patients with CUP show a favorable outcome, identifying biomarkers may help improve the clinical management of patients who do not respond well to conventional therapies. In this context, the study of the metabolic profile of CUP may pave the way to establish new biomarkers and/or therapeutic targets; therefore, this study aimed to characterize the expression of metabolism-related proteins in CUP.Materials and MethodsThe expression of monocarboxylate transporters MCT1, MCT2 and MCT4, their chaperone CD147, the glucose transporter GLUT1 and the pH regulator CAIX was evaluated by immunohistochemistry in a series of 118 CUP patients, and the results were associated with the available clinicopathological information.ResultsThe metabolism-related proteins MCT1, MCT4, CD147, GLUT1 and CAIX were expressed in a critical portion of the CUP (approximately 20 to 70%). MCT1 and CD147 were both more frequently expressed in cases with lymph nodes as metastasis dominant sites (p = 0.001) as well as in samples from lymph nodes (p &lt;0.001 and p = 0.002, respectively), while MCT1 expression was more frequently expressed in squamous cell carcinomas (p = 0.045). A higher overall survival was observed in patients with tumors positive for GLUT1 and CAIX expression (p = 0.011 and p = 0.041, respectively), but none of the proteins was an independent prognostic factor for overall survival in multivariable analysis.ConclusionThe results suggest that a portion of CUPs present a hyperglycolytic phenotype, which is associated with higher overall survival.
An Original Ferroptosis-Related Gene Signature Effectively Predicts the Prognosis and Clinical Status for Colorectal Cancer Patients
Authors: Shao Yanfei , Jia Hongtao , Huang Ling , Li Shuchun , Wang Chenxing , Aikemu Batuer , Yang Guang , Hong Hiju , Yang Xiao , Zhang Sen , Sun Jing , Zheng Minhua 
Published: June 2021

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors in the world. Ferroptosis is a newly defined form of cell death, distinguished by different morphology, biochemistry, and genetics, and involved in CRC progression and treatment. This study aims to establish a predictive model to elucidate the relationship between ferroptosis and prognosis of CRC patients, to explore the potential value of ferroptosis in therapeutic options.MethodsThe ferroptosis-related genes were obtained from the GeneCards and FerrDb websites. The limma R package was used to screen the differential ferroptosis-related genes (DEGs) in CRC from The Cancer Genome Atlas (TCGA) dataset. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were to establish the 10-gene prognostic signature. The survival and receiver operating characteristic (ROC) curves were illustrated to evaluate the predictive effect of the signature. Besides, independent prognostic factors, downstream functional enrichment, drug sensitivity, somatic mutation status, and immune feature were analyzed. Moreover, all these conclusions were verified by using multiple datasets in International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO).ResultsTen ferroptosis-related gene signature (TFAP2C, SLC39A8, NOS2, HAMP, GDF15, FDFT1, CDKN2A, ALOX12, AKR1C1, ATP6V1G2) was established to predict the prognosis of CRC patients by Lasso cox analysis, demonstrating a good performance on Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) analyses. The CRC patients in the high- or low-risk group showed significantly different fractions of immune cells, such as macrophage cells and CD8+ T cells. Drug sensitivity and somatic mutation status like TP53 were also closely associated with the risk scores.ConclusionsIn this study, we identified a novel ferroptosis-related 10-gene signature, which could effectively predict the prognosis and survival time of CRC patients, and provide meaningful clinical implications for targeted therapy or immunotherapy. Targeting ferroptosis is a good therapeutic option for CRC patients. Further studies are needed to reveal the underlying mechanisms of ferroptosis in CRC.
Prevention of Neural Tube Defects in Europe: A Public Health Failure
Authors: Morris Joan K. , Addor Marie-Claude , Ballardini Elisa , Barisic Ingeborg , Barrachina-Bonet Laia , Braz Paula , Cavero-Carbonell Clara , Den Hond Elly , Garne Ester , Gatt Miriam , Haeusler Martin , Khoshnood Babak , Lelong Nathalie , Kinsner-Ovaskainen Agnieszka , Kiuru-Kuhlefelt Sonja , Klungsoyr Kari , Latos-Bielenska Anna , Limb Elizabeth , O'Mahony Mary T , Perthus Isabelle , Pierini Anna , Rankin Judith , Rissmann Anke , Rouget Florence , Sayers Gerardine , Sipek Antonin , Stevens Sarah , Tucker David , Verellen-Dumoulin Christine , de Walle Hermien E. K. , Wellesley Diana , Wertelecki Wladimir , Bermejo-Sanchez Eva 
Published: June 2021

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.
Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer
Authors: Cao Jing , Gong Jiao , Li Xinhua , Hu Zhaoxia , Xu Yingjun , Shi Hong , Li Danyang , Liu Guangjian , Jie Yusheng , Hu Bo , Chong Yutian 
Published: June 2021

Objectives: The pathogenesis of heterogeneity in gastric cancer (GC) is not clear and presents as a significant obstacle in providing effective drug treatment. We aimed to identify subtypes of GC and explore the underlying pathogenesis.Methods: We collected two microarray datasets from GEO (GSE84433 and GSE84426), performed an unsupervised cluster analysis based on gene expression patterns, and identified related immune and stromal cells. Then, we explored the possible molecular mechanisms of each subtype by functional enrichment analysis and identified related hub genes.Results: First, we identified three clusters of GC by unsupervised hierarchical clustering, with average silhouette width of 0.96, and also identified their related representative genes and immune cells. We validated our findings using dataset GSE84426. Subtypes associated with the highest mortality (subtype 2 in the training group and subtype C in the validation group) showed high expression of SPARC, COL3A1, and CCN. Both subtypes also showed high infiltration of fibroblasts, endothelial cells, hematopoietic stem cells, and a high stromal score. Furthermore, subtypes with the best prognosis (subtype 3 in the training group and subtype A in the validation group) showed high expression of FGL2, DLGAP1-AS5, and so on. Both subtypes also showed high infiltration of CD4+ T cells, CD8+ T cells, NK cells, pDC, macrophages, and CD4+ T effector memory cells.Conclusion: We found that GC can be classified into three subtypes based on gene expression patterns and cell composition. Findings of this study help us better understand the tumor microenvironment and immune milieu associated with heterogeneity in GC and provide practical information to guide personalized treatment.
In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model
Authors: Vossen M G , Pferschy S , Milacek C , Haidinger M , Karolyi Mario , Vass Zoltan , Burgmann Heinz , Maier-Salamon Alexandra , Wicha S G , Jäger W , Zeitlinger M , Stimpfl T , Wittek T , Thalhammer F 
Published: June 2021

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.