bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Mouse VEGF Neutralization by Ranibizumab and Aflibercept
Authors: Ichiyama Yusuke , Matsumoto Riko , Obata Shumpei , Sawada Osamu , Saishin Yoshitsugu , Kakinoki Masashi , Sawada Tomoko , Ohji Masahito 
Published: October 2021

Abstract
There are many articles using bevacizumab, ranibizumab, and aflibercept as effective anti-vascular endothelial growth factor (VEGF) drugs in mice. However, it has been reported that bevacizumab lacks the ability to neutralize mouse VEGF. Here, we assessed the interaction between ranibizumab or aflibercept and mouse VEGF, both in vitro and in vivo. In vitro, we analyzed the interaction of mouse VEGF-A with aflibercept or ranibizumab as the primary antibody by Western blot, and observed immunoreactive bands for mouse VEGF-A in the aflibercept-probed blot, but not in the ranibizumab-probed blot. In vivo, we assessed the effect of intravitreal injection of ranibizumab and aflibercept on oxygen induced retinopathy and the effect of multiple intraperitoneal injections of ranibizumab and aflibercept on neonatal mice, and found that anti-VEGF effects were observed with aflibercept, but not with ranibizumab in both experiments. Our results suggest that aflibercept but not ranibizumab interacts with mouse VEGF. When conducting experiments using anti-VEGF drugs in mice, aflibercept is suitable, but ranibizumab is not.
Enhancement of Membrane Vesicle Production by Disrupting the degP Gene in Meiothermus Ruber H328
Authors: ASANO Yuki , ONISHI Manato , NISHI Kaito , KAWASAKI Kazunori , Watanabe Kunihiko 
Published: October 2021

Abstract
The phenomenon of membrane vesicle (MV) production is known to be common to all bacterial cells. Although MVs are expected to be employed in a variety of applications, improving MV productivity is essential for applications. Since the deletion of the degP gene, a periplasmic dual-function protease and chaperone, in Escherichia coli has successfully improved MV production capacity, we tried to enhance MV productivity in the thermophilic M. ruber H328 by deleting the degP gene. One gene (mrH_0331) was selected for degP gene from the H328 genome and we constructed the mutant strain DdegP by deleting the degP gene of the H328 strain that was replaced with the htk gene showing thermophilic kanamaycin resistance by homologous recombination. The mutant strain DdegP exhibited smooth growth but a lower level of turbidity at 60ºC although there was no difference in growth at 55ºC between the wild strain and the mutant strain. Finally, we have confirmed that incubation at 60°C increases MV in the mutant strain DdegP strain about fivefold by using two fluorescent dyes, DiI and FM4-64, which is followed by TEM analysis. The deletion of the degP gene presumably causes an increase in denatured proteins at 60°C, leading to enhanced MV production. Meanwhile, the S-layer protein included in the outer membrane of the H328 strain increased in the MV fraction prepared from the mutant cells incubated at 60°C. This indicates that this method is effective for MV production and that degP deletion enhances it in strain H328.
Today’s Referral Is Tomorrow’s Repeat Patient: Referrals Between Medical Outpatient Clinics in a Hospital
Authors: Safi Mariam , Clay-Williams Robyn , Thude Bettina Ravnborg , Vaisman Julija , Brandt Frans 
Published: October 2021

Abstract
Background Lack of understanding of inter-department and inter-speciality referral processes in Danish hospitals is contributing to unnecessary referrals and inefficient use of a health service already stretched and under pressure. An inefficient referral process is associated with over testing and repetitive testing, delayed treatment, patient confusion, ineffective use of physician and hospital service, and impaired patient outcomes. Despite a growing awareness in the literature and in practice of issues related to referrals, there has been relatively little research on referrals between specialists in hospital outpatient clinics and how it can be improved. This study aimed to describe the referral patterns to and within the Medical Department at the University Hospital of Southern Denmark. The Medical Department consists of the following medical specialist outpatient clinics: nephrology, pulmonology, endocrinology, cardiovascular, wound outpatient clinic, and a day hospital. Methods Two specialist physicians assessed all referrals to the medical specialist outpatient clinics over one month (from 01 September 2019 to 30 September 2019) using data drawn from the Danish electronic patient record system (Cosmic). Data on referral pattern, and patient age and sex, were statistically analysed to identify and characterise patterns of referral. Results 471(100%) referrals were included in the study. 49.5 % (233) of the referrals were from the hospital and 50.5 % (238) from general practitioners (GPs). Of the 233 referrals from the hospitals, 31% (72) were from the Medical Department.Conclusion The high rate of referrals from hospitals and referrals from own Medical Department or outpatient clinics illustrates the need for improvement on the inter-department referral process to provide joint care for multi-morbidity patients managed in multiple hospital outpatient clinics. Improved collaboration between specialists has the potential to improve health outcomes, timely access to care and more appropriate healthcare resource utilisation.
Vanillin Attenuates Pro-Inflammatory Factors in tMCAO Mice Model Via Inhibiting of TLR4/NF-kB Signal Pathway
Authors: Zhang Lei , Wang Ping , Li Chunyi , Liao Guolei , Huang Yihuan , Lv Xuxian , Liu Xudong , Chen Wenli 
Published: October 2021

Abstract
Purpose

Vanillin has been reported to reduce hippocampal neuronal death in rats of global cerebral ischemia. However, the immunoregulatory mechanism of vanillin in ischemic mice is still unclear. Hence, this study aims to investigate the role of vanillin in transient middle cerebral artery occlusion (tMCAO) mice.
Methods

Transient cerebral ischemic stroke was induced by tMCAO surgery following by reperfusion in mice. After 24 hours of ischemia/reperfusion, Berderson scoring and TTC staining were used to evaluate neurological deficit and infarct volume, respectively. Furthermore, the expression of cytokines in ipsilateral hemisphere were detected by qPCR, ELISA and immunofluorescence. In vitro, LPS-stimulated primary and BV2 microglia cells were used to mimic neuroinflammation after ischemic stroke. Similarly, the expression of cytokines was detected by qPCR and ELISA. In addition, Western blotting was performed to evaluate the expression of Toll-like receptor 4 (TLR4), nuclear factor-κ-gene binding p65 (NF-κB p65) and phosphorylated NF-κB p65.
Results

Vanillin reduced infarct volume and improved motor function after ischemia/reperfusion. IL-1β and TNF-α were decreased in ischemic brain tissue of tMCAO mice after vanillin treatment. Similar changes were confirmed using the in vitro LPS-stimulated microglia cell model. Moreover, the decreasing expression of pro-inflammatory cytokines in vanillin group were related to TLR4/NF-κB signal pathway.
Conclusions

Taken together, vanillin decreased activation of microglia by inhibiting TLR4 /NF-κB signal pathway, and then reduced expression of pro-inflammatory cytokines IL-1β and TNF-α, which finally reduced infarct volume and improve motor function in tMCAO mice.
Association Between HDL Cholesterol and Incident Cognitive Impairment in Black and White Adults in The Reasons For Geographic and Racial Differences in Stroke Study
Authors: Rosenson Robert , Cushman Mary , McKinley Emily C. , Muntner Paul , Wang Zhixin , Vaisar Tomas , Heinecke Jay , Tangney Christy , Judd Suzanne , Colantonio Lisandro D. 
Published: October 2021

Abstract
BACKGROUND:

Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with incident cognitive impairment (ICI) in some, but not all studies.
METHODS:

We examine the association between HDL-C and ICI among 18,378 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants without cognitive impairment or stroke at baseline in 2003 to 2007, and who did not have a stroke event during follow-up.
RESULTS:

Over a median follow-up of 9.6 years, 1,359 participants developed ICI. In fully adjusted models, the RR for ICI was 1.51 (95% CI 1.06, 2.15) in White women and 1.25 (95% CI 0.95, 1.65) in Black women. The association was not statistically significant afrter adjustment for triglycerides. There was no evidence of an association between HDL-C and ICI among White or Black men.
CONCLUSIONS:

Low HDL-C was associated with a higher risk of ICI in White and Black women in models not including triglycerides.
A Visual Discrimination of Existing States of Virus Capsid Protein by a Giant Molybdate Cluster
Authors: Xue Yarong , Wei Mingfen , Fu Dingyi , Wu Yuqing , Sun Bo , Yu Xianghui , Wu Lixin 
Published: October 2021

Abstract

This study reports a unique phenomenon, the opposite color response of a giant polyoxometalate, (NH4)42[Mo132O372(CHCOO)30] (H2O)72 ([Mo132]), to the existing states of human papillomavirus (HPV) major capsid protein, L1-pentamer (L1-p) and virus-like particles (VLPs). The color responses originate from the different assembly forms between [Mo132] and the capsid protein, which were inspected and separated by using CsCl gradient centrifugation, and validated in detail by sodium dodecyl sulfate polyacrylamide gel-electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscopy (TEM) images. The intrinsic mechanism difference between them were investigated in depth by using the XPS-based semi-quantitative analysis and the well designed peptides, which reveal the key points of L1 determining the charge-transfer ratio between Mo(V) to Mo(VI), and consequently the levels of [Mo132] hypochromicity in different assemblies. Such unique phenomenon is significant as it supplies a colorimetry approach to directly distinguish the existing states of HPV capsid protein and would be significant in the quality assay of HPV vaccine and existing states of other virus in future.
Dissecting Impacts of Nutrition on Epistasis and Ethnicity-Specific Effects of Calibrated Factor VIII Level in the Multiethnic Study of Atherosclerosis
Authors: Alamin Md. , Zhu Jun , Lou Xiangyang , Xu Haiming 
Published: October 2021

Abstract
Background
Cardiovascular disease (CVD) is determined mainly by genetic predisposition and environmental factors such as diet. Factor VIII (FVIII) is an informative intermediate phenotype concerning atherosclerosis. An elevated plasma level of FVIII is considered a significant risk factor for CVD, providing an earlier subclinical measure to predict CVD liability. However, many studies have been investigated using the Multi-Ethnic Study of Atherosclerosis data, but very few studies have studied FVIII and nutrition factors together using a linear mixed model. A genome-wide association study (GWAS) was conducted using a mixed linear model including epistatic genetic effects, ethnicity-specific effects, and one cofactor (nutrition), aiming to investigate novel loci associated with Factor VIII level and the contribution due to the nutrition factor by comparing genetic effects of single nucleotide polymorphisms (SNPs) detected in the baseline and conditional models.
Results
A total of five quantitative trait SNPs at five genes have been identified in this study related to nutrition entirely or partially. One SNP (rs13428770) was associated with red blood cell count, two were in protein-coding genes, and the other two were in unknown non-coding RNA (ncRNA) genes associated with the FVIII level individually or epistatically. Two ethnicity-specific epistasis effect (rs17326624 × rs1468382) is identified in the European-American and African-American population. Bioinformatics analysis results showed that various Gene Ontology (GO) terms and pathways are associated with FVIII and nutrients in this study. The vital role of FVIII was further documented by the fact that the detected genetic factors are associated with CVD.
Conclusions
This study used a novel approach considering QTS by ethnicity interaction effects and applied conditional mapping by setting different kinds of nutrition as a cofactor in the statistic model. The nutrition factors strongly influence the genetic effects of detected SNPs, although the exact mechanism remains unidentified. This study offered that ethnicity-specific response needs to be considered in personal medical treatment and might reveal the impacts on specific QTS effects due to nutrition.
The “Direct Tip Injection in Occlusive Lesions (DIOL)” Fashion.
Authors: Haraguchi Takuya , Fujita Tsutomu , Kashima Yoshifumi , Masanaga Tsujimoto , Watanabe Tomohiko , Sugie Takuro , Hachinohe Daisuke , Kaneko Umihiko , Kobayashi Ken , Kanno Daitaro , Sato Katsuhiko 
Published: October 2021

Abstract
Background: The successful intervention for peripheral artery disease is limited by complex chronic total occlusions (CTOs). During CTO wiring, without the use of intravascular or extravascular ultrasound, the guidewire position is unclear, except for calcified lesions showing the vessel path. To solve this problem, we propose a novel guidewire crossing with plaque modification method for complex occlusive lesions, named the “Direct tip Injection in Occlusive Lesions (DIOL)” fashion.Main text: The “DIOL” fashion utilizes the hydraulic pressure of tip injection with a general contrast media through a microcatheter or an over-the-wire balloon catheter within CTOs. The purposes of this technique are 1) to visualize the “vessel road” of the occlusion from expanding a microchannel, subintimal, intramedial, and periadventitial space with contrast agent and 2) to modify plaques within CTO to advance CTO devices safely and easily. This technique creates dissections by hydraulic pressure. Antegrade-DIOL may create dissections which extend to and compress a distal lumen, especially in below-the-knee arteries. A gentle tip injection with smaller contrast volume (1-2 ml) should be used to confirm the tip position which is inside or outside of a vessel. On the other hand, retrograde-DIOL is used with a forceful tip injection of moderate contrast volume up to 5-ml to visualize vessel tracks and to modify the plaques to facilitate the crossing of CTO devices. Case-1 involved a severe claudicant due to right superficial femoral artery occlusion. After the conventional bidirectional subintimal procedure failed, we performed two times of retrograde-DIOL fashion, and the bidirectional subintimal planes were successfully connected. After two stents implantation, a sufficient flow was achieved without complications and restenosis for two years. Case-2 involved multiple wounds in the heel due to ischemia caused by posterior tibial arterial occlusion. After the conventional bidirectional approach failed, retrograde-DIOL was performed and retrograde guidewire successfully crossed the CTO, and direct blood flow to the wounds was obtained after balloon angioplasty. The wounds heeled four months after the procedure without reintervention.Conclusions: The DIOL fashion is a useful and effective method to facilitate CTO treatment.
Three Types Halogen Bond Interaction Studied Between Pyrazine And XF
Authors: Wu Junyong , Yan Hua , Chen Hao , Jin Yanxian , Zhong Aiguo , Wang Zhaoxu , Dai Guoliang 
Published: October 2021

Abstract
Except σ-type and π-type halogen bond, a new type of the parallel halogen bond interactions between pyrazine (C4H4N2) and XF (X=F,Cl,Br and I) have been discovered at the MP2/aug-cc-pVTZ level. Through comparing the calculated interaction energy,we can know that the π-type halogen bonding interactions are weaker than the corresponding σ-type halogen bonding interactions, and parallel halogen-bond interactions are weaker than the corresponding π-type halogen bonding interactions in C4H4N2-XF complexes. SAPT analysis shows that the electrostatic energy are the major source of the attraction for the σ-type halogen bonding interactions while the parallel halogen-bond interactions are mainly dispersion energy. For the π-type halogen bonding interactions in C4H4N2-XF(X=F and Cl) complexes, electrostatic energy are the major source of the attraction, while in C4H4N2-XF(X=Br and I) complexes the electrostatic term, induction and dispersion play equally important role in the total attractive interaction.NBO analysis, AIM theory and Conceptual DFT are also be utilized.
The latest research trends in primary biliary cholangitis: A bibliometric analysis
Authors: Zhao Yu , Yin Zhenjie , Du Huang , Huang Kangming , Zhang Fajing , Chen Hongbin 
Published: October 2021

Abstract
Background and aims: The bibliometric analysis uses the citation count of an article to measure its impact in the scientific community, but no study has been undertaken to determine the most influential papers in the field of primary biliary cholangitis (PBC). This study aimed to investigate the global research interest regarding PBC in dentistry using a bibliometric approach.Methods: We searched the Web of Science Core Collection database to find the top 100 most cited (T100) articles focusing on PBC. The information about each article including citations, authors, journals, countries, institutions, and keywords was recorded for bibliometric analysis.Results: The T100 articles related to PBC were published from 1983 to 2019 and were originated from 26 countries. A total of 805 different authors were from 342 different institutions, and articles written by them were published in 35 journals. The five most frequently occurring keywords were “biochemical response”, “ursodeoxycholic acid”, “primary biliary cirrhosis”, “antimitochondrial antibody”, and “autoimmunity”. The T100 articles were classified into different research focuses: pathogenesis (41%), treatment (20%), prognosis (12%), epidemiology (9%), diagnosis (8%) and others (10%). These 100 articles included 32 observational studies, 29 basic research articles, 15 reviews, eight meta-analyses, 12 clinical trials, and four clinical guidelines.Conclusions: This report presents major advances and changes in research regarding PBC. The single treatment method entered a bottleneck period, and combined treatment with immunosuppressant, local therapy, and surgery will become the next research focus to identify possible beneficial treatment combinations.
Theoretically Investigation On The Roughness Profile of The Machined Surface After Flank Milling
Authors: Fei Jixiong , Lin Bin , Yan Shuai 
Published: October 2021

Abstract
In this study, the roughness profile of a machined surface obtained via a flank milling process is thoroughly investigated through theoretical modeling and experimental demonstrations. First, the roughness profile of a machined surface generated by a single-tooth end milling cutter along a straight path is considered (without helical angle). The trajectory of a point on the cutting edge is constructed according to the cutting kinematics, and the roughness profile of the flank surface is theoretically extracted from the trajectory. The surface topography is constructed by integrating the roughness profile along the axial direction of the cutter. Based on the constructed roughness profile model, the effects of cutting parameters on the roughness profile are discussed, including those of the cutting speed, radial depth of the cut, and feed rate. In addition, the effects of cutter geometries including the cutter tooth number, tooth spacing angle, and helical angle on the roughness profile and surface topography are discussed. Further, roughness profiles are constructed for cutter feeds along different tool paths, such as round and curved paths. Finally, experiments are conducted to verify the method developed in this study. The results show that the roughness profile obtained from testing matches well with the theoretically modeled profile. Moreover, the methodology for constructing the roughness profile is compared to an existing approach, which shows that the method in this study is significantly faster.
Evolutionary Relic or a Curious Coincidence? A Mantisfly Emerging from a Mud-Dauber Nest.
Authors: Snyman Louwrens Pieter , Binoy Chereekandy 
Published: October 2021

Abstract
Mantispoidea exhibit a remarkably diverse morphology and life history for a relatively small group of insects, in part, complicating our understanding of its evolutionary history. Dietary specialisation of the larvae, however, seems to have played an important evolutionary role in this group. Symphrasinae (Rhachiberothidae) larvae are thought to be predators of aculeate Hymenoptera brood, while Mantispinae (Mantispidae) larvae are predators of spider eggs. Herewith the first observation of a Mantispinae adult emerging from the nest of a mud-dauber wasp (Sphecidae) is described. This is also the first genus record of Afromantispa Snyman & Ohl from the Oriental Region, including three new name combinations. The curious coincidence of a Mantispinae emerging from an aculeate wasp nest, the food source of a related taxon, is discussed in the light of our current understanding of Mantispoidea classification.
Background Factors Involved in the Epidemiology of Functional Constipation in the Japanese Population
Authors: Yamamoto Sayuri , Ohashi Wataru , Yamaguchi Yoshiharu , Inamoto Shunsuke , Koshino Akira , Sugiyama Tomoya , Nagao Kazuhiro , Tamura Yasuhiro , Izawa Shinya , Ebi Masahide , Usami Jun , Hamano Koichi , Izumi Junko , Wakita Yoshinori , Funaki Yasushi , Ogasawara Naotaka , Sasaki Makoto , Maekawa Masato , Kasugai Kunio 
Published: October 2021

Abstract
Background: Little is known about the prevalence and epidemiology of functional constipation (FC), a functional bowel disorder with symptoms of constipation. This study aimed to examine the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of individuals with and without FC and of individuals with a strong or weak awareness of constipation. Methods: An internet survey revealed that 262 (8.7%) out of 3,000 respondents from the general Japanese population were diagnosed with FC. Moreover, all respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared. Results: FC occurrence was associated with the elderly population, females, and homemakers. Its onset was associated with a change in the frequency of bowel movement, sensation of incomplete or hardly any evacuation, and the use of manual maneuvers, which are consequential clinical symptoms of FC. Subjects with FC also frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than individuals without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group.Conclusions: Based on the understanding of the characteristic features of FC, appropriate and comprehensive management considering the patient’s symptoms and lifestyle should be provided.