bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the Region-Technology Network as a Driver for Technological Innovation
Authors: O’Neale Dion R. J. , Hendy Shaun C. , Vasques Filho Demival 
Published: July 2021

Agglomeration and spillovers are key phenomena of technological innovation, driving regional economic growth. Here, we investigate these phenomena through technological outputs of over 4,000 regions spanning 42 countries, by analyzing more than 30 years of patent data (approximately 2.7 million patents) from the European Patent Office. We construct a bipartite network—based on revealed comparative advantage—linking geographic regions with areas of technology and compare its properties to those of artificial networks using a series of randomization strategies, to uncover the patterns of regional diversity and technological ubiquity. Our results show that the technological outputs of regions create nested patterns similar to those of ecological networks. These patterns suggest that regions need to dominate various technologies first (those allegedly less sophisticated), creating a diverse knowledge base, before subsequently developing less ubiquitous (and perhaps more sophisticated) technologies as a consequence of complementary knowledge that facilitates innovation. Finally, we create a map—the Patent Space Network—showing the interactions between technologies according to their regional presence. This network reveals how technology across industries co-appear to form several explicit clusters, which may aid future works on predicting technological innovation due to agglomeration and spillovers.
High Performance of SARS-Cov-2N Protein Antigen Chemiluminescence Immunoassay as Frontline Testing for Acute Phase COVID-19 Diagnosis: A Retrospective Cohort Study
Authors: Deng Qiaoling , Ye Guangming , Pan Yunbao , Xie Wen , Yang Gui , Li Zhiqiang , Li Yirong 
Published: July 2021

Objectives: COVID-19 emerged and rapidly spread throughout the world. Testing strategies focussing on patients with COVID-19 require assays that are high-throughput, low-risk of infection, and with small sample volumes. Antigen surveillance can be used to identify exposure to pathogens and measure acute infections.Methods: A total of 914 serum samples, collected from 309 currently infected COVID-19 patients, 48 recovered ones, and 410 non-COVID-19 patients, were used to measure N protein antigen levels by a chemilumineseent immunoassay. Diagnostic performances were analyzed in different periods after onset.Results: There was a high level of N protein antigen in COVID-19 patients (0.56 COI), comparing to the recovered patients (0.12 COI) and controls (0.19 COI). In receiver-operating characteristic curve analysis, the area under the curve of serum N protein antigen was 0.911 in the first week after onset. In this period, Sensitivity and specificity of serologic N protein antigen testing was 76.27 and 98.78%. Diagnosis performance of specific antibodies became better from the third week after onset. Subgroup analysis suggested that severe patients had higher levels of antigens than mild patients.Conclusions: High level of serum antigen suggested early infection and serious illness. Serum N protein antigen testing by chemiluminescence immunoassay is considered as a viable assay used to improve diagnostic sensitivity for current patients.
The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: a step towards a rapid automated screening
Authors: Shabalina Evgenya Y. , Skorova Ekaterina Yu , Chudakova D. A. , Anikin V. B. , Reshetov I. V. , Mynbaev O. A. , Petersen E. V. 
Published: July 2021

In vitro 3D cell culture systems utilizing multicellular tumor spheroids (MCTS) are widely used in translational oncology, including for studying cell migration and in personalized therapy. However, early stages of cellular migration from MCTS and cross-talk between spheroids are overlooked, which was addressed in the current study. Here, we investigated cell migration from MCTS derived from human non-small cell lung cancer (NSCLC) cell line A549 cultured on different substrates, collagen gel or plastic, at different time points. We found that migration starts at 4–16 h time points after the seeding and its speed is substrate-dependent. We also demonstrated that co-culture of two NSCLC-derived MCTS on collagen gel, but not on plastic, facilitates cell migration compared with single MTCS. This finding should be considered when designing MCTS-based functional assays for personalized therapeutic approach and drug screenings. Overall, our work characterizes the in vitro 3D cell culture model resembling NSCLC cell migration from the clusters of CTCs into surgical wound, and describes microscopy-based tools and approaches for image data analysis with a potential for further automation. These tools and approaches also might be used to predict patterns of CTCs migration based on ex vivo analysis of patient biopsy in a 3D culture system.
Association of Tau Pathology With Clinical Symptoms in the Subfields of Hippocampal Formation
Authors: Ge Xinting , Zhang Dan , Qiao Yuchuan , Zhang Jiong , Xu Junhai , Zheng Yuanjie 
Published: July 2021

Objective: To delineate the relationship between clinical symptoms and tauopathy of the hippocampal subfields under different amyloid statuses.Methods: One hundred and forty-three subjects were obtained from the ADNI project, including 87 individuals with normal cognition, 46 with mild cognitive impairment, and 10 with Alzheimer’s disease (AD). All subjects underwent the tau PET, amyloid PET, T1W, and high-resolution T2W scans. Clinical symptoms were assessed by the Neuropsychiatric Inventory (NPI) total score and Alzheimer’s Disease Assessment Scale cognition 13 (ADAS-cog-13) total score, comprising memory and executive function scores. The hippocampal subfields including Cornu Ammonis (CA1–3), subiculum (Sub), and dentate gyrus (DG), as well as the adjacent para-hippocampus (PHC) and entorhinal cortex (ERC), were segmented automatically using the Automatic Segmentation of Hippocampal Subfields (ASHS) software. The relationship between tauopathy/volume of the hippocampal subfields and assessment scores was calculated using partial correlation analysis under different amyloid status, by controlling age, gender, education, apolipoprotein E (APOE) allele ɛ4 carrier status, and, time interval between the acquisition time of tau PET and amyloid PET scans.Results: Compared with amyloid negative (A−) group, individuals from amyloid positive (A+) group are more impaired based on the Mini-mental State Examination (MMSE; p = 3.82e-05), memory (p = 6.30e-04), executive function (p = 0.0016), and ADAS-cog-13 scores (p = 5.11e-04). Significant decrease of volume (CA1, DG, and Sub) and increase of tau deposition (CA1, Sub, ERC, and PHC) of the hippocampal subfields of both hemispheres were observed for the A+ group compared to the A- group. Tauopathy of ERC is significantly associated with memory score for the A- group, and the associated regions spread into Sub and PHC for the A+ group. The relationship between the impairment of behavior or executive function and tauopathy of the hippocampal subfield was discovered within the A+ group. Leftward asymmetry was observed with the association between assessment scores and tauopathy of the hippocampal subfield, which is more prominent for the NPI score for the A+ group.Conclusion: The associations of tauopathy/volume of the hippocampal subfields with clinical symptoms provide additional insight into the understanding of local changes of the human HF during the AD continuum and can be used as a reference for future studies.
Updated Trends in Imaging Practices for Pancreatic Neuroendocrine Tumors (PNETs): A Systematic Review and Meta-Analysis to Pave the Way for Standardization in the New Era of Big Data and Artificial Intelligence
Authors: Partouche Ephraïm , Yeh Randy , Eche Thomas , Rozenblum Laura , Carrere Nicolas , Guimbaud Rosine , Dierickx Lawrence O. , Rousseau Hervé , Dercle Laurent , Mokrane Fatima-Zohra 
Published: July 2021

PurposeMedical imaging plays a central and decisive role in guiding the management of patients with pancreatic neuroendocrine tumors (PNETs). Our aim was to synthesize all recent literature of PNETs, enabling a comparison of all imaging practices.Methodsbased on a systematic review and meta-analysis approach, we collected; using MEDLINE, EMBASE, and Cochrane Library databases; all recent imaging-based studies, published from December 2014 to December 2019. Study quality assessment was performed by QUADAS-2 and MINORS tools.Results161 studies consisting of 19852 patients were included. There were 63 ‘imaging’ studies evaluating the accuracy of medical imaging, and 98 ‘clinical’ studies using medical imaging as a tool for response assessment. A wide heterogeneity of practices was demonstrated: imaging modalities were: CT (57.1%, n=92), MR (42.9%, n=69), PET/CT (13.3%, n=31), and SPECT/CT (9.3%, n=15). International imaging guidelines were mentioned in 2.5% (n=4/161) of studies. In clinical studies, imaging protocol was not mentioned in 30.6% (n=30/98) of cases and only mentioned imaging modality without further information in 63.3% (n=62/98), as compared to imaging studies (1.6% (n=1/63) of (p&lt;0.001)). QUADAS-2 and MINORS tools deciphered existing biases in the current literature.ConclusionWe provide an overview of the updated current trends in use of medical imaging for diagnosis and response assessment in PNETs. The most commonly used imaging modalities are anatomical (CT and MRI), followed by PET/CT and SPECT/CT. Therefore, standardization and homogenization of PNETs imaging practices is needed to aggregate data and leverage a big data approach for Artificial Intelligence purposes.
Dural and Multiple Brain Metastases From Basaloid Nasopharyngeal Carcinoma: Case Report and Literature Review
Authors: Geng Xiaotao , Hao Furong , Han Guiyan , Zhang Yaping , Qin Peiyan 
Published: July 2021

BackgroundNasopharyngeal carcinoma is an endemic head and neck cancer in Southern China. The common metastases organs involve bone, lung, and liver. Metastases in the dura and at multiple locations in the brain after a diagnosis of nasopharyngeal carcinoma are extremely rare.Case PresentationWe present a case of a 66-year-old man who initially complained of nasal congestion, epistaxis, and hearing impairment. The biopsy of the nasopharynx lesion showed basaloid squamous cell carcinoma. Eight months after conventional therapy, the patient was admitted to our hospital again with the complaint of a headache. A PET/CT scan was performed, revealing multiple metastases. A biopsy of subcutaneous soft tissue from the right upper arm was consistent with the previous biopsy. Palliative chemotherapy was administered. Thereafter, the patient had sudden dysfunction of the right side of the body. MRI demonstrated dural and multiple brain metastases. The therapeutic regimen then consisted of whole-brain radiotherapy, anti-angiogenesis therapy, and immunotherapy.ConclusionsThis case highlights the diagnosis and treatment of uncommon metastases of nasopharyngeal carcinoma. Clinicians should remain vigilant for metastases during the treatment and follow-up periods.
Ubiquitin-Like Protein UBD Promotes Cell Proliferation in Colorectal Cancer by Facilitating p53 Degradation
Authors: Su Hongbin , Qin Mengdi , Liu Qiang , Jin Bo , Shi Xianjun , Xiang Zheng 
Published: July 2021

PurposeUbiquitin D (UBD) is a member of the ubiquitin-like modifier (UBL) family and is highly expressed in a variety of cancers including colorectal cancer (CRC). However, the mechanisms of its regulatory roles in CRC are largely elusive. In this study, we revealed the effect of UBD on the proliferation of CRC.MethodsThe expression of UBD in clinical tissue samples of CRC and seven CRC cell lines was detected using qRT-PCR, immunohistochemistry (IHC) and Western blotting. CCK-8, colony formation, EdU and flow cytometry assays were used to detect the functional changes of CRC cells transfected with UBD stable expression plasmids in vitro. A xenograft model was constructed to assess the effect of UBD on the growth of CRC cells in vivo. The connection between UBD and p53 was analyzed using Western blotting, immunoprecipitation, proteasome inhibition assay and Cycloheximide (CHX) chase assay.ResultsUBD was overexpressed in CRC tumor tissues compared with nontumor tissues, and its overexpression was positively associated with the tumor size and TNM stage of CRC patients. Functionally, UBD significantly accelerated CRC cell viability and proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, UBD interacted with p53 in CRC cells, downregulated the expression of p53 by regulating its degradation, shortened the p53 half-life, thereby further affecting the decrease in p21 and the increase in Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6. Moreover, in vivo experiments showed that UBD-induced tumor growth in nude mice was dependent on a decrease in p53.ConclusionsOur study proved that UBD mediates the degradation of p53, thereby facilitating the growth of CRC cells and ultimately promoting the progression of CRC. Therefore, UBD may be a potential therapeutic target and a promising prognostic biomarker for CRC.
National Divergences in Perinatal Palliative Care Guidelines and Training in Tertiary NICUs
Authors: Boan Pion Antonio , Baenziger Julia , Fauchère Jean-Claude , Gubler Deborah , Hendriks Manya J. 
Published: July 2021

Objectives:Despite established principles of perinatal palliative care (PnPC), implementation into practice has shown inconsistencies. The aim of this study was to assess PnPC services, examine healthcare professionals (HCPs) awareness and availability of PnPC guidelines, and describe HCPs satisfaction with PC and guidelines.Material and Methods:A nationwide survey was conducted in Swiss tertiary NICUs between April-November 2019. Data were examined by descriptive statistics and linear regression models.Results:Overall response rate was 54% (65% physicians; 49% nurses; 72% psychosocial staff). Half of professionals (50%) received education in PC during their medical/nursing school, whereas 36% indicated they obtained further training in PnPC at their center. PnPC guidelines were available in 4/9 centers, with 68% HCPs being aware of the guideline. Professionals who had access to a PnPC team (P= 0.001) or were part of the nursing (P= 0.003) or psychosocial staff (P= 0.001) were more likely aware of having a guideline. Twenty-eight percent indicated being satisfied with PC in their center. Professionals with guideline awareness (P= 0.025), further training (P= 0.001), and access to a PnPC team (P&lt; 0.001) were more likely to be satisfied, whereas HCPs with a nursing background (P&lt; 0.001) were more likely to be dissatisfied. A majority expressed the need for a PnPC guideline (80%) and further PC training (94%).Conclusion:This study reveals lacking PnPC guidelines and divergences regarding onsite opportunities for continued training across Swiss level III NICUs. Extending PnPC guidelines and training services to all centers can help bridge the barriers created by fragmented practice.
Mechanisms of Impaired Lung Development and Ciliation in Mannosidase-1-Alpha-2 (Man1a2) Mutants
Authors: Ningappa Mylarappa , Adenuga Morayooluwa , Ngo Kim A. , Mohamed Nada , Narayanan Tejaswini , Prasadan Krishna , Ashokkumar Chethan , Das Jishnu , Schmitt Lori , Hartman Hannah , Sehrawat Anuradha , Salgado Claudia M. , Reyes-Mugica Miguel , Gittes George K. , Lo Cecilia W. , Subramaniam Shankar , Sindhi Rakesh 
Published: July 2021

BackgroundCiliary defects cause heterogenous phenotypes related to mutation burden which lead to impaired development. A previously reported homozygous deletion in the Man1a2 gene causes lethal respiratory failure in newborn pups and decreased lung ciliation compared with wild type (WT) pups. The effects of heterozygous mutation, and the potential for rescue are not known.PurposeWe hypothesized that survival and lung ciliation, (a) would decrease progressively in Man1a2+/− heterozygous and Man1a2–/– null newborn pups compared with WT, and (b) could be enhanced by gestational treatment with N-Acetyl-cysteine (NAC), an antioxidant.MethodsMan1a2+/– adult mice were fed NAC or placebo from a week before breeding through gestation. Survival of newborn pups was monitored for 24 h. Lungs, liver and tails were harvested for morphology, genotyping, and transcriptional profiling.ResultsSurvival (p = 0.0001, Kaplan-Meier) and percent lung ciliation (p = 0.0001, ANOVA) measured by frequency of Arl13b+ respiratory epithelial cells decreased progressively, as hypothesized. Compared with placebo, gestational NAC treatment enhanced (a) lung ciliation in pups with each genotype, (b) survival in heterozygous pups (p = 0.017) but not in WT or null pups. Whole transcriptome of lung but not liver demonstrated patterns of up- and down-regulated genes that were identical in living heterozygous and WT pups, and completely opposite to those in dead heterozygous and null pups. Systems biology analysis enabled reconstruction of protein interaction networks that yielded functionally relevant modules and their interactions. In these networks, the mutant Man1a2 enzyme contributes to abnormal synthesis of proteins essential for lung development. The associated unfolded protein, hypoxic and oxidative stress responses can be mitigated with NAC. Comparisons with the developing human fetal lung transcriptome show that NAC likely restores normal vascular and epithelial tube morphogenesis in Man1a2 mutant mice.ConclusionSurvival and lung ciliation in the Man1a2 mutant mouse, and its improvement with N-Acetyl cysteine is genotype-dependent. NAC-mediated rescue depends on the central role for oxidative and hypoxic stress in regulating ciliary function and organogenesis during development.
Smoking Cessation Experience in Indonesia: Does the Non-smoking Wife Play a Role?
Authors: Ayuningtyas Dyah A. , Tuinman Marrit A. , Prabandari Yayi S. , Hagedoorn Mariët 
Published: July 2021

ObjectiveMore than 63% of Indonesian men are smokers, and smoking has long been a part of Indonesian culture and the concept of masculinity in Indonesian culture. Given the pro-smoking environment, we were interested in examining why smokers would willingly quit and whether their wives played a role in their quitting process as social factors are mentioned second most frequent as a reason for quitting smoking.DesignIn-depth interviews.MethodWe interviewed 11 couples (N = 22)—ex-smoking husbands and non-smoking wives—in Yogyakarta, Indonesia. The data were analysed by using the thematic analysis approach.ResultsFour themes were discussed: (1) reasons for stopping smoking, (2) the process of quitting smoking, (3) the wives’ attitudes toward smoking, and (4) the families’ attempts to make the (ex-)smokers quit. The most commonly cited reasons for quitting were family and personal motivation. The (ex-)smokers preferred to quit without assistance and in private. The wives’ attitude toward smoking ranged from dislike to tolerance, and most did not know when their husbands were trying to quit. Both husbands and wives reported that the wives did not influence the smoking cessation process.ConclusionIndonesian ex-smokers often had multiple reasons for quitting smoking. The process was typically difficult and kept private. While wives had little influence on the cessation process, they provided support and could institute a smoking ban in the house.
Factors Associated With Uptake of Iron Supplement During Pregnancy Among Women of Reproductive Age in Tanzania: an Analysis of Data From the 2015 to 2016 Tanzania Demographic and Health Survey and Malaria Indicators Survey
Authors: Moshi Fabiola Vincent , Millanzi Walter C. , Mwampagatwa Ipyana 
Published: July 2021

Background:Pregnant women are vulnerable to iron deficiency due to the fact that more iron is needed primarily to supply the growing fetus and placenta and to increase the maternal red cell mass. Little is known on the factors associated with uptake of iron supplement during pregnancy.Methods:The study used data from the 2015 to 2016 Tanzania Demographic and Health Survey and Malaria Indicators Survey. A total of 6,924 women of active reproductive age from 15 to 49 were included in the analysis. Both univariate and multiple regression analyses were used to determine factors associated with uptake of iron supplement during pregnancy.Results:Majority of the interviewed women 5,648 (81.6%) always took iron supplement during pregnancy, while a total of 1,276 (18.4%) women never took iron supplement during pregnancy. After controlling for confounders, the predictors for uptake of iron supplement during pregnancy were early antenatal booking (adjusted odds ratio, AOR = 1.603 at 95% CI = 1.362–1.887,p&lt; 0.001); rural residence (AOR = 0.711 at 95% CI = 0.159–0.526,p= 0.007); wealth index [rich (AOR = 1.188 at 95% CI = 0.986–1.432,p= 0.07)]—poor was the reference population; level of education [primary education (AOR = 1.187 at 95% CI = 1.013–1.391,p= 0.034)]—no formal education was the reference population; parity [para 2 to 4 (AOR = 0.807 at 95% CI = 0.668–0.974,p= 0.026), para 5 and above (AOR = 0.75 at 95% CI = 0.592–0.95,p= 0.017)], para 1 was the reference population; zones [mainland rural (AOR = 0.593 at 95% CI = 0.389–0.905,p= 0.015) and Unguja Island AOR = 0.63 at 95% CI = 0.431–0.92,p= 0.017]—mainland urban was the reference population; and current working status [working (AOR = 0.807 at 95% CI = 0.687–0.949,p= 0.009)].Conclusion:The study revealed that, despite free access to iron supplement during pregnancy, there are women who fail to access the supplement at least once throughout the pregnancy. The likelihood to fail to access iron supplement during pregnancy was common among pregnant women who initiated antenatal visits late, were from poor families, had no formal education, reside in rural settings, had high parity, were from mainland rural, and were in working status. Interventional studies are recommended in order to come up with effective strategies to increase the uptake of iron supplement during pregnancy.