bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid-β1–43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations
Authors: Perrone Federica , Bjerke Maria , Hens Elisabeth , Sieben Anne , Timmers Maarten , De Roeck Arne , Vandenberghe Rik , Sleegers Kristel , Martin Jean-Jacques , De Deyn Peter P. , Engelborghs Sebastiaan , van der Zee Julie , Van Broeckhoven Christine , Cacace Rita ,   on behalf of the BELNEU Consortium, Goeman Johan , Crols Roeland , Dermaut Bart , Ivanoiu Adrian , Hanseeuw Bernard , Deryck Olivier , Bergmans Bruno , Versijpt Jan , Pharmaceutica Janssen , Saido Takaomi 
Published: September 2020

Abstract
Background
Alzheimer’s disease (AD) mutations in amyloid precursor protein (APP) and presenilins (PSENs) could potentially lead to the production of longer amyloidogenic Aβ peptides. Amongst these, Aβ1–43 is more prone to aggregation and has higher toxic properties than the long-known Aβ1–42. However, a direct effect on Aβ1–43 in biomaterials of individuals carrying genetic mutations in the known AD genes is yet to be determined.

Methods
N = 1431 AD patients (n = 280 early-onset (EO) and n = 1151 late-onset (LO) AD) and 809 control individuals were genetically screened for APP and PSENs. For the first time, Aβ1–43 levels were analysed in cerebrospinal fluid (CSF) of 38 individuals carrying pathogenic or unclear rare mutations or the common PSEN1 p.E318G variant and compared with Aβ1–42 and Aβ1–40 CSF levels.
The soluble sAPPα and sAPPβ species were also measured for the first time in mutation carriers.

Results
A known pathogenic mutation was identified in 5.7% of EOAD patients (4.6% PSEN1, 1.07% APP) and in 0.3% of LOAD patients. Furthermore, 12 known variants with unclear pathogenicity and 11 novel were identified. Pathogenic and unclear mutation carriers showed a significant reduction in CSF Aβ1–43 levels compared to controls (p = 0.037; < 0.001). CSF Aβ1–43 levels positively correlated with CSF Aβ1–42 in both pathogenic and unclear carriers and controls (all p < 0.001). The p.E318G carriers showed reduced Aβ1–43 levels (p < 0.001), though genetic association with AD was not detected. sAPPα and sAPPβ CSF levels were significantly reduced in the group of unclear (p = 0.006; 0.005) and p.E318G carriers (p = 0.004; 0.039), suggesting their possible involvement in AD. Finally, using Aβ1–43 and Aβ1–42 levels, we could re-classify as “likely pathogenic” 3 of the unclear mutations.

Conclusion
This is the first time that Aβ1–43 levels were analysed in CSF of AD patients with genetic mutations in the AD causal genes. The observed reduction of Aβ1–43 in APP and PSENs carriers highlights the pathogenic role of longer Aβ peptides in AD pathogenesis. Alterations in Aβ1–43 could prove useful in understanding the pathogenicity of unclear APP and PSENs variants, a critical step towards a more efficient genetic counselling.
A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth
Authors: Tu Geraldine Xue En , Ho Yoon Khei , Ng Zhi Xu , Teo Ke Jia , Yeo Tseng Tsai , Too Heng-Phon 
Published: September 2020

AbstractBackgroundMesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs. However, this is limited by the inherent issues of safety, high cost and demanding manufacturing processes. The aim of this study is to identify a facile, scalable in production and highly efficient non-viral method to transiently engineer MSCs for prolonged and exceptionally high expression of a fused transgene: yeast cytosine deaminase::uracil phosphoribosyl-transferase::green fluorescent protein (CD::UPRT::GFP).MethodsMSCs were transfected with linear polyethylenimine using a cpg-free plasmid encoding the transgene in the presence of a combination of fusogenic lipids and β tubulin deacetylase inhibitor (Enhancer). Process scalability was evaluated in various planar vessels and microcarrier-based bioreactor. The transfection efficiency was determined with flow cytometry, and the therapeutic efficacy of CD::UPRT::GFP expressing MSCs was evaluated in cocultures with temozolomide (TMZ)-sensitive or TMZ-resistant human glioblastoma cell lines. In the presence of 5-fluorocytosine (5FC), the 5-fluorouracil-mediated cytotoxicity was determined by performing colometric MTS assay. In vivo antitumor effects were examined by local injection into subcutaneous TMZ-resistant tumors implanted in the athymic nude mice.ResultsAt > 90% transfection efficiency, the phenotype, differentiation potential and tumour tropism of MSCs were unaltered. High reproducibility was observed in all scales of transfection. The therapeutically modified MSCs displayed strong cytotoxicity towards both TMZ-sensitive and TMZ-resistant U251-MG and U87-MG cell lines only in the presence of 5FC. The effectiveness of this approach was further validated with other well-characterized and clinically annotated patient-derived GBM cells. Additionally, a long-term suppression (> 30 days) of the growth of a subcutaneous TMZ-resistant U-251MG tumour was demonstrated.ConclusionsCollectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.
Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: implications of a transcriptomic study
Authors: Gao Xiugong , Li Rong , Cahan Patrick , Zhao Yang , Yourick Jeffrey J. , Sprando Robert L. 
Published: September 2020

Abstract
Background
Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level.

Methods
HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays.

Results
HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepatocyte differentiation track and characterized the expression of some key marker genes in major stages of hepatocyte differentiation. In addition, HLC_SM were scored with CellNet, a bioinformatics tool quantifying how closely engineered cell populations resemble their target cell type, and compared to primary human hepatocytes (PHHs), adult liver tissue, fetal liver tissue, HLCs differentiated using GFs (HLC_GF), and commercially available HLCs. Similar to HLC_GF, HLC_SM displayed a mixed phenotype of fetal and adult hepatocytes and had relatively low expression of metabolic enzymes, transporters, and nuclear receptors compared to PHHs. Finally, the differentially expressed genes in HLC_SM compared to HLC_GF and to PHHs were analyzed to identify pathways and upstream transcription regulators which could potentially be manipulated to improve the differentiation of HLCs.

Conclusions
Overall, the present study demonstrated the usefulness of the SM-based hepatocyte differentiation method, offered new insights into the molecular basis of hepatogenesis and associated gene regulation, and suggested ways for further improvements in hepatocyte differentiation in order to obtain more mature HLCs that could be used in toxicological studies.
Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington’s disease transgenic mouse
Authors: Niu Li , Li Li , Yang Shiming , Wang Weixi , Ye Cuifang , Li He 
Published: September 2020

AbstractBackgroundHuntington’s disease (HD) is a neurodegenerative disease that involves a complex combination of psychiatric, cognitive and motor impairments. Synaptic dysfunction has been implicated in HD pathogenesis. However, the mechanisms have not been clearly delineated. Synaptic vesicular zinc is closely linked to modulating synaptic transmission and maintaining cognitive ability. It is significant to assess zinc homeostasis for further revealing the pathogenesis of synaptic dysfunction and cognitive impairment in HD.ResultsHistochemical staining by autometallography indicated that synaptic vesicular zinc was decreased in the hippocampus, cortex and striatum of N171-82Q HD transgenic mice. Analyses by immunohistochemistry, Western blot and RT-PCR found that the expression of zinc transporter 3 (ZnT3) required for transport of zinc into synaptic vesicles was obviously reduced in these three brain regions of the HD mice aged from 14 to 20 weeks and BHK cells expressing mutant huntingtin. Significantly, dual-luciferase reporter gene and chromatin immunoprecipitation assays demonstrated that transcription factor Sp1 could activate ZnT3 transcription via its binding to the GC boxes in ZnT3 promoter. Moreover, mutant huntingtin was found to inhibit the binding of Sp1 to the promoter of ZnT3 and down-regulate ZnT3 expression, and the decline in ZnT3 expression could be ameliorated through overexpression of Sp1.ConclusionsThis is first study to reveal a significant loss of synaptic vesicular zinc and a decline in ZnT3 transcriptional activity in the HD transgenic mice. Our work sheds a novel mechanistic insight into pathogenesis of HD that mutant huntingtin down-regulates expression of ZnT3 through inhibiting binding of Sp1 to the promoter of ZnT3 gene, causing disruption of synaptic vesicular zinc homeostasis. Disrupted vesicular zinc ultimately leads to early synaptic dysfunction and cognitive deficits in HD. It is also suggested that maintaining normal synaptic vesicular zinc concentration is a potential therapeutic strategy for HD.
Eigenvalues of s-type operators on $C(p)$ equipped with a pre-quasi norm
Authors: Bakery Awad A. , Mohamed Elsayed A. E. 
Published: September 2020

AbstractWe investigate some new topological properties of the multiplication operator on$C(p)$C(p)defined by Lim (Tamkang J. Math. 8(2):213–220, 1977) equipped with the pre-quasi-norm and the pre-quasi-operator ideal formed by this sequence space ands-numbers.
On modeling of coronavirus-19 disease under Mittag-Leffler power law
Authors: Bushnaq Samia , Shah Kamal , Alrabaiah Hussam 
Published: September 2020

AbstractThis paper investigates a new model on coronavirus-19 disease (COVID-19) with three compartments including susceptible, infected, and recovered class under Mittag-Leffler type derivative. The mentioned derivative has been introduced by Atangana, Baleanu, and Caputo abbreviated as$(\mathcal{ABC})$(ABC). Upon utilizing fixed point theory, we first prove the existence of at least one solution for the considered model and its uniqueness. Also, some results about stability of Ulam–Hyers type are also established. By applying a numerical technique called fractional Adams–Bashforth (AB) method, we develop a scheme for the approximate solutions to the considered model. Using some real available data, we perform the concerned numerical simulation corresponding to different values of fractional order.
Diversity of antibiotics in hospital and municipal wastewaters and receiving water bodies and removal efficiency by treatment processes: a systematic review protocol
Authors: Ebrahimi Seyedeh Masoumeh , Dehghanzadeh Reyhani Reza , Asghari-JafarAbadi Mohammad , Fathifar Zahra 
Published: September 2020

AbstractBackgroundAntibiotics are extensively discharged into the environment through sewages. These emergent contaminants cause health and environmental risks by toxicity, allergic impacts, non-biodegradability and more importantly advancing antibiotic resistance. Antibiotics are hardly removed by conventional treatment processes and frequently are being reported in aquatic environments. The systematic review outlined in this protocol will compile and synthesize literature on the variety and concentrations of antibiotics in wastewaters and receiving water resources. Also, the review will address the efficiency of treatment processes in elimination of antibiotics from aqueous solutions. Outcomes of the study could help wastewater treatment plant engineers with providing reliable design data and outline a road map for future researches.MethodsThe review will be performed according to the Collaboration for Environmental Evidence (CEE) guidelines for systematic review and evidence synthesis in environmental management, and will be reported according to ROSES reporting standards for systematic evidence syntheses. The published articles will be screened by considering the defined inclusion and exclusion criteria at the title, abstract and full-text levels. Included studies will be exposed to a critical appraisal for validity and quality assessment. The articles will be assessed on the susceptibility to bias and the studies with high bias will be excluded from the data synthesis. The data from included studies will be combined into a narrative synthesis. Random effect Meta-analysis will be conducted due to the likely range of underlying effects. If the heterogeneity exists, the source of heterogeneity will be sought by met-regression and subgroup analyses.
What are the effects of climate variability and change on ungulate life-histories, population dynamics, and migration in North America? A systematic map protocol
Authors: Malpeli Katherine C. , Weiskopf Sarah R. , Thompson Laura , Hardy Amanda R. 
Published: September 2020

Abstract
Background
Climate is an important driver of ungulate life-histories, population dynamics, and migratory behaviors, and can affect the growth, development, fecundity, dispersal, and demographic trends of populations. Changes in temperature and precipitation, and resulting shifts in plant phenology, winter severity, drought and wildfire conditions, invasive species distribution and abundance, predation, and disease have the potential to directly or indirectly affect ungulates. However, ungulate responses to climate variability and change are not uniform and vary by species and geography. Here, we present a systematic map protocol aiming to describe the abundance and distribution of evidence on the effects of climate variability and change on ungulate life-histories, population dynamics, and migration in North America. This map will help to identify knowledge gaps and clusters of evidence, and can be used to inform future research directions and adaptive management strategies.

Methods
We will catalogue evidence on how climate variability and change affect the life-histories, population dynamics, and migration patterns of the fifteen ungulate species native to North America. We will search both academic and grey literature, using academic journal databases and specialist websites. Articles will be screened for inclusion at the title/abstract and full-text levels, and data will be extracted from articles that pass the full-text review. These data will be summarized quantitatively, visually, and with a narrative review to describe the distribution and abundance of evidence on the effects of climate variability and change on ungulates in North America.
Identification of novel molecular markers of mastitis caused by Staphylococcus aureus using gene expression profiling in two consecutive generations of Chinese Holstein dairy cattle
Authors: Wang Di , Liu Lei , Augustino Serafino M. A. , Duan Tao , Hall Thomas J. , MacHugh David E. , Dou Jinhuan , Zhang Yi , Wang Yachun , Yu Ying 
Published: September 2020

AbstractBackgroundMastitis in dairy cows caused byStaphylococcus aureusis a major problem hindering economic growth in dairy farms worldwide. It is difficult to prevent or eliminate due to its asymptomatic nature and long persistence of infection. Although transcriptomic responses of bovine mammary gland cells to pathogens that cause mastitis have been studied, the common responses of peripheral blood leukocytes toS. aureusinfection across two consecutive generations of dairy cattle have not been investigated.MethodsIn the current study, RNA-Seq was used to profile the transcriptomes of peripheral blood leukocytes sampled fromS. aureus-infected mothers and theirS. aureus-infected daughters, and also healthy non-infected mothers and their healthy daughters. Differential gene expression was evaluated as follows: 1)S. aureus-infected cows versus healthy non-infected cows (S vs. H, which include all the mothers and daughters), 2)S. aureus-infected mothers versus healthy non-infected mothers (SM vs. HM), and 3)S. aureus-infected daughters versus healthy non-infected daughters (SMD vs. HMD).ResultsAnalysis of all identified expressed genes in the four groups (SM, SMD, HM, and HMD) showed thatEPOR,IL9,IFNL3,CCL26,IL26were exclusively expressed in both the HM and HMD groups, and that they were significantly (P <  0.05) enriched for the cytokine-cytokine receptor interaction pathway. A total of 17, 13 and 10 differentially expressed genes (DEGs) (FDRPadj.< 0.1 and |FC| > 1.2) were detected in the three comparisons, respectively. DEGs withP <  0.05 and |FC| > 2 were used for functional enrichment analyses. For the S vs. H comparison, DEGs detected includedCCL20,IL13andMMP3, which are associated with the IL-17 signaling pathway. In the SM vs. HM and SMD vs. HMD comparisons, five (BLA-DQB,C1R,C2,FCGR1A, andKRT10) and six (BLA-DQB,C3AR1,CFI,FCAR,FCGR3A, andLOC10498484) genes, respectively, were involved in theS. aureusinfection pathway.ConclusionsOur study provides insights into the transcriptomic responses of bovine peripheral blood leukocytes across two generations of cattle naturally infected withS. aureus. The genes highlighted in this study could serve as expression biomarkers for mastitis and may also contain sequence variation that can be used for genetic improvement of dairy cattle for resilience to mastitis.
The relationship of smartphone addiction with psychological distress and neuroticism among university medical students
Authors: Lei Leonard Yik-Chuan , Ismail Muhd Al-Aarifin , Mohammad Jamilah Al-Muhammady , Yusoff Muhamad Saiful Bahri 
Published: September 2020

Abstract
Background
Smartphone plays a vital role in higher education as it serves as a device with multiple functions. Smartphone addiction was reported on the rise among college and university students. The addiction may result in unwanted consequences on their academic performance and psychological health. One factor that consistently relates to psychological distress and smartphone addiction is the neurotic personality trait. This study explored the relationship of smartphone addiction with psychological health and neuroticism among USM medical students.

Methods
A cross-sectional study was carried out on medical students in a public medical school. DASS-21, the neuroticism-subscale of USMaP-i and SAS-SV were administered to measure psychological distress, neuroticism, and smartphone addiction of the medical students. Spearman correlation was performed to examine the correlation between smartphone addiction with psychological distress and neuroticism. Simple linear regression was performed to investigate relationship factors of smartphone addiction.

Results
A total of 574 medical students participated in this study. The prevalence of smartphone addiction was 40.6%. It was higher among male (49.2%) compared to female (36.6%) medical students. The result showed a fair positive correlation between smartphone addiction and psychological health (rdepression = 0.277, p-value < 0.001; ranxiety = 0.312, p-value < 0.001; rstress = 0.329, p-value < 0.001). However, there was a poor positive correlation between smartphone addiction and neuroticism (r = 0.173, p-value < 0.001). The simple linear regression showed a significant increase in the levels of depression, anxiety, stress and neuroticism upon one unit increase in smartphone addiction (bdepression = 0.101, p-value < 0.001; banxiety = 0.120, p-value < 0.001; bstress = 0.132, p-value < 0.001; bneuroticism = 0.404, p-value < 0.05). These results indicated significant relationships between smartphone addiction, psychological health and neuroticism.

Conclusion
This study suggested a high prevalence of smartphone addiction among medical students, particularly in male medical students. The smartphone addiction might lead to psychological problems and the most vulnerable group is the medical student with the neurotic personality trait.
Saline versus 5% dextrose in water as a drug diluent for critically ill patients: a retrospective cohort study
Authors: Aoyagi Yukari , Yoshida Takuo , Uchino Shigehiko , Takinami Masanori , Uezono Shoichi 
Published: September 2020

Abstract
Background
The choice of intravenous infusion products for critically ill patients has been studied extensively because it can affect prognosis. However, there has been little research on drug diluents in this context. The purpose of this study is to evaluate the impact of diluent choice (saline or 5% dextrose in water [D5W]) on electrolyte abnormalities, blood glucose control, incidence of acute kidney injury (AKI), and mortality.

Methods
This before-after, two-group comparative, retrospective study enrolled adult patients who stayed for more than 48 h in a general intensive care unit from July 2015 to December 2018. We changed the default diluent for intermittent drug sets in our electronic ordering system from D5W to saline at the end of 2016.

Results
We included 844 patients: 365 in the D5W period and 479 in the saline period. Drug diluents accounted for 21.4% of the total infusion volume. The incidences of hypernatremia and hyperchloremia were significantly greater in the saline group compared to the D5W group (hypernatremia 27.3% vs. 14.6%, p < 0.001; hyperchloremia 36.9 % vs. 20.4%, p < 0.001). Multivariate analyses confirmed the similar effects (hypernatremia adjusted odds ratio (OR), 2.43; 95% confidence interval (CI), 1.54–3.82; hyperchloremia adjusted OR, 2.09; 95% CI, 1.31–3.34). There was no significant difference in the incidences of hyperglycemia, AKI, and mortality between the two groups.

Conclusions
Changing the diluent default from D5W to saline had no effect on blood glucose control and increased the incidences of hypernatremia and hyperchloremia.