bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of human cytomegalovirus (HCMV) neutralizing antibodies with antibodies to the HCMV glycoprotein complexes
Authors: Shibamura Miho , Yoshikawa Tomoki , Yamada Souichi , Inagaki Takuya , Nguyen Phu Hoang Anh , Fujii Hikaru , Harada Shizuko , Fukushi Shuetsu , Oka Akira , Mizuguchi Masashi , Saijo Masayuki 
Published: April 2020

Abstract
Background
Human cytomegalovirus (HCMV) causes asymptomatic infections, but also causes congenital infections when women were infected with HCMV during pregnancy, and life-threatening diseases in immunocompromised patients. To better understand the mechanism of the neutralization activity against HCMV, the association of HCMV NT antibody titers was assessed with the antibody titers against each glycoprotein complex (gc) of HCMV.
Methods
Sera collected from 78 healthy adult volunteers were used. HCMV Merlin strain and HCMV clinical isolate strain 1612 were used in the NT assay with the plaque reduction assay, in which both the MRC-5 fibroblasts cells and the RPE-1 epithelial cells were used. Glycoprotein complex of gB, gH/gL complexes (gH/gL/gO and gH/gL/UL128-131A [PC]) and gM/gN were selected as target glycoproteins. 293FT cells expressed with gB, gM/gN, gH/gL/gO, or PC, were prepared and used for the measurement of the antibody titers against each gc in an indirect immunofluorescence assay (IIFA). The correlation between the IIFA titers to each gc and the HCMV-NT titers was evaluated.
Results
There were no significant correlations between gB-specific IIFA titers and the HCMV-NT titers in epithelial cells or between gM/gN complex-specific IIFA titers and the HCMV-NT titers. On the other hand, there was a statistically significant positive correlation between the IIFA titers to gH/gL complexes and HCMV-NT titers.
Conclusions
The data suggest that the gH/gL complexes might be the major target to induce NT activity against HCMV.
Using the drug repositioning approach to develop a novel therapy, tipepidine hibenzate sustained-release tablet (TS-141), for children and adolescents with Attention-Deficit/Hyperactivity Disorder
Authors: Saito Takuya , Yamashita Yushiro , Tomoda Akemi , Okada Takashi , Umeuchi Hideo , Iwamori Saki , Shinoda Satoru , Mizuno-Yasuhira Akiko , Urano Hidetoshi , Nishino Izumi , Saito Kazuhiko 
Published: April 2020

Abstract
Background
Asverin® (tipepidine hibenzate) has been used as an antitussive for > 50 years in Japan. Studies revealed that tipepidine modulates monoamine levels, by inhibiting G-protein-activated inwardly rectifying potassium (GIRK) channels, expecting the potential therapeutic effects of tipepidine for attention-deficit/hyperactivity disorder (ADHD) in recent years. In this study, TS-141, a sustained-release tablet of tipepidine, was developed for the treatment of ADHD through a drug repositioning approach.
Methods
The sustained-release profile of TS-141 in healthy adults was investigated, and tipepidine exposure in the plasma after the TS-141 administration was compared to that of Asverin in the phase I study. Phase II study was conducted to examine the effects of TS-141 30 (once a day), 60 (once a day), 120 mg (60 mg twice a day), or placebo, that is within the exposure in the maximum dosage of Asverin, in children and adolescents with ADHD, and was designed as an 8-week treatment, randomized, parallel group, double-blind, placebo-controlled trial recruiting 6–17-year-old children and adolescents diagnosed with ADHD. A total of 216 patients were randomized according to the CYP2D6 phenotype. The primary end-point was ADHD Rating Scale IV-J changes. Furthermore, effects of CYP2D6 phenotype on the efficacy in the subgroup analysis were investigated.
Results
TS-141 had the sustained-release profile, and the CYP2D6 phenotype had effects on the plasma exposure of tipepidine. ADHD RS-IV-J scores in all TS-141 dosages decreased from their baseline scores; however, no significant difference was observed in ADHD RS-IV-J score changes between the placebo and TS-141-administered groups. In patients with intermediate metabolizer CYP2D6, ADHD RS-IV-J score changes in the 120 mg group tended to be larger than that in the placebo group.
Conclusions
ADHD RS-IV-J changes on TS-141 may depend on the interaction between the TS-141 dose and CYP2D6 phenotype, suggesting that further clinical trials should be conducted with careful consideration of polymorphism. Drug repositioning approach of TS-141 was attempted at the same dose as that of antitussive; however, dose setting according to the indication was necessary.
Trial Registration
Phase I study: JapicCTI-205235 (Registered 25 March 2020), Phase II study: JapicCTI-163244 (Registered 9 May 2016), https://www.clinicaltrials.jp/cti-user/trial/Show.jsp
Surgical management of sarcoma in adolescent and young adult patients
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Oka Naohiro , Akagi Masao 
Published: April 2020

Abstract
Objective To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, surgical margin, local recurrence, metastasis, and final outcome were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, operation time, and intraoperative blood loss and surveyed features of cases of poor outcomes.Results The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with inadequate surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with a late-stage sarcomas, inadequate tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognosis. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining an adequate surgical margin are important.
Gut microbiota dysbiosis in stable coronary artery disease combined type 2 diabetes mellitus influence cardiovascular prognosis
Authors: Tian Ran , Liu Honghong , Feng Siqin , Xu Haopeng , Xing Haiping , Zhang Shuyang 
Published: April 2020

Abstract

Background : Host-microbiota interactions involving metabolic pathways have been linked to the pathogenesis of cardiovascular diseases like atherosclerotic disease and diabetes. Since stable coronary artery disease patients combined with diabetes mellitus have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development.Method : We used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined diabetes mellitus (SCAD+DM, n = 38), stable coronary artery disease (SCAD, n = 71), and healthy control (HC, n = 55). We connected microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers.Results: We investigated bacterial and metabolic signatures of diabetic and atherosclerotic phenotypes. SCAD+DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Meanwhile, our study addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. What’s more, we found that speciﬁc bacterial taxa Ruminococcus torques was predictive of cardiac survival outcomes.Conclusions: Overall, our study identified relationships between features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host–gut microbiota interplay in atherosclerotic cardiovascular pathogenesis.
Effect modification by ferritin on the relationship between inflammation and arterial stiffness in hypertensive patients with different glucose tolerance
Authors: Sciacqua Angela , Ventura Ettore , Tripepi Giovanni , Cassano Velia , D'Arrigo Graziella , Roumeliotis Stefanos , Maio Raffaele , Miceli Sofia , Perticone Maria , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco 
Published: April 2020

Abstract
Backgroud: Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance.Methods: We enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was definied by carotid-femoral pulse wave velocity (PWV).Results: Out of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin.Conclusion: Ferritin represents an independent predictor of AS in our study population and a strong effect modifier on the relationship between inflammation and PWV.
Involving Research Participants in a Pan-European Research Initiative: The EPAD Participant Panel Experience
Authors: Gregory Sarah , Bunnick Eline M , Callado Ana Belén , Carrie Isabelle , De Boer Casper , Duffus Julie , Fauria Karine , Forster Shona , Gove Dianne , Knezevic Iva , Pennetier Delphine , Saunders Stina , Sparks Sarah , Rice J. , Ritchie Craig W , Milne Richard 
Published: April 2020

Abstract
Background
Patient, public and participant involvement (PPPI) is increasingly acknowledged as a key pillar of successful research activity. PPPI can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage PPPI activities.
Methods
In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was established as a pan-European cohort study aiming at understanding risks for developing Alzheimer’s disease and building a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted PPPI involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting at least twice a year established in England, France, Scotland, Spain and The Netherlands, feeding into a central panel who met once a year at the project’s General Assembly. The local panels were governed by terms of reference which were adaptable to meet local needs. We discuss the recruitment opportunities employed by the centres and the set-up of the panels.
Results
Impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings.
Conclusions
The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.
Comparison of the Efficacy of Posterior-Anterior Screws, Anterior-Posterior Screws and a Posterior-Anterior Plate in the Fixation of Posterior Malleolar Fractures with a Fragment Size of ≥15% and &lt;15%
Authors: Wang Zheng , Sun Jianbin , Yan Jun , Gao Pengcheng , Zhang Hao , Yang Yong , Jin Qunhua 
Published: April 2020

Abstract
Background To investigate the efficacy of posterior-anterior (PA), anterior-posterior (AP) screws and a PA plate in the fixation of posterior malleolar fractures (PMFs) with a fragment size of ≥ 15% and < 15%.MethodsThis is a retrospective study of the clinical data of 243 patients with unilateral ankle fractures involving the posterior malleolus. All patients were divided into two groups based on their fragment size, ≥ 15% (n = 136) and < 15% (n = 107). PA screws, AP screws and a posterior plate were used for fixation of PMF in the two groups. All patients were followed up at 1, 3, 6, and 12 months after surgery and thereafter at 6-month intervals. The primary outcomes were AOFAS and ROM, which were recorded at the final follow-up.Results The average follow-up time for all patients was 18.9 months and all fractures healed. There was no significant difference between the PA plate fixation, PA screw, and AP screw fixations in terms of AOFAS scores or ankle ROM in the fragment size of ≥ 15% group (P > 0.05). In the fragment size of < 15% group, there were statistically significant differences in the AOFAS scores and ankle ROM between the PA plate fixation and PA, AP screw fixation (P < 0.05); while no significant difference was observed between PA and AP screw fixation.Conclusion For PMFs with fragment size ≥ 15%, there was no significant difference in the outcomes between the three fixation methods. For PMF with fragmentation < 15%, the PA and AP screws both provided good fixation.
Expression Patterns of SREBF1 and SREBF2 in Liver and Adipose Tissues of Two Fat-Tailed Sheep Breeds
Authors: Liang Chen , Qiao Liying , Han Yongli , Liu Jianhua , Zhang Jianhai , Liu Wenzhong 
Published: April 2020

Abstract
Background

The fat-tailed sheep is raised largely in China and other countries due to its high adaptability to nutritionally challenging environments and disease resistance as well as fat deposition in tails. So the purpose of the study is to explore the expression pattern and regulation mechanism of sterol regulatory element binding proteins (SREBPs) in liver and adipose tissues of fat-tailed sheep bases on its role in fat metabolism and deposition with sheep grown and development.
Methods

Two representative Chinese fat-tailed sheep breeds i.e. Guangling Large Tailed (GLT) and Small Tailed Han (STH) were employed to evaluate the ontogenetic expressions of SREBF1 and SREBF2 from seven different adipose tissues and liver at 4, 6, 8, 10 and 12 month by real-time PCR. Five serum indicators were detected, and the function speculation of SREBP1 and SREBP2 were evaluated by bioinformatics approaches.
Results

Serum indicators, especially total cholesterol TC and non-esterified fatty acid (NEFA) showed obvious differences and dynamical changes with the different development ages, gender factors only had a significant effect on serum NEFA concentrations. Both SREBF1 and SREBF2 mRNA expression in sheep were significantly affected by breed, tissue, age factors, and show a significant positive correlation (r = 0.286). Merely the expression of SREBF1 gene in STH is significantly higher than that in GLT, but SREBF2 gene expression is opposite. The expressions of SREBF1/2 in liver are extremely higher than that in seven adipose tissues, the interaction of two factors between breed and month age, breed and tissue, and tissue and gender also significantly affects its expression. Subcellular locations and function prediction imply that SREBP1/2 expressions are closely related with metabolism processes in cells.
Conclusions

The mRNA expression profiling of SREBF1 and SREBF2 showing a breed-specific, gender-specific, and temporal and spatial expressions differences, which imply that SREBF1/2 play a crucial role in lipid metabolism regulation during growth and development of two fat-tailed sheep. This study provides a phenotypic basis for further revealing the genetic mechanism in lipid metabolism and fat deposition that causes differences in ovine tail types, which also provides a novel insight for improving quality of meat.
Neurological manifestations associated with COVID19: a review and a call for action
Authors: Leonardi Matilde , Padovani Alessandro , McArthur Justin Charles 
Published: April 2020

Abstract
While the epidemics of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidence is collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations or NeuroCOVID are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed in order to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID19, however many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID19 complications.
The impact of body mass index on short-term and long-term surgical outcomes of laparoscopic hepatectomy in liver carcinoma patients, a retrospective study
Authors: Zhao Lei , Wang Gang Jian , Kong Jingxia , Zhen Xing , Yu Xin 
Published: April 2020

Abstract
Background: To investigate the influence of body mass index (BMI) on the short-term and long-term outcomes including disease free survival (DFS) and overall survival (OS) rate in patients with liver carcinoma who underwent laparoscopic hepatectomy (LH) as primary treatment.Methods: Data were collected from 137 patients with liver carcinoma who underwent attempted LH between August 2003 and April 2014. Patients were classified into three groups depending on their BMI according to the WHO’s definition of obesity for Asia-Pacific region: underweight (BMI< 18.5kg/ m2, Group1), normal (18.5≤BMI< 23kg/m2, Group2), overweight (BMI≥ 23kg/m2, Group3) respectively. Short-term and long-term outcomes including overall survival (OS) and disease free survival (DFS) were compared across the BMI categories.Results: Of the 137 patients, 14 were underweight, 65 were normal weight, and 58 were overweight. The overall conversion rate of 137 patients was 20.44 %. Conversion rate in the three groups was 14.29%, 21.54% and 20.69 % (P=0.8284). The median follow-up duration was 26 months, 30 months, and 28 months, respectively. The mean postoperative hospital stay in the three groups were comparable (10.85±4.04, 11.57±5.56, and 10.88±5.70, P=0.76). The complications rate was much higher in Group 1 (42.85%) than that in Group 2 and Group 3 (20.08% and 17.2%, P=0.048). Underweight patients were more likely to develop grade III or higher postoperative complications (Clavien-Dindo classification) as compared to normal and overweight patients (P=0.042). Overweight patients had a longer 3- and 5-years DFS (41.4%, 36.2%) than those for underweight (21.4%, 14.3%) and normal weight (28.1%, 21.9%) patients (P=0.048, and 0.025). Overweight patients had a longer 5-years OS (44.8%) than those for underweight (28.6%) and normal weight (28.0%) patients (P=0.043).Conclusions: Being underweight was associated with an increased perioperative complication and being overweight has a better 3-, 5-years DFS and 5-years OS than those in under and normal weight patients with liver carcinoma who underwent LH.
Developing a Sociocultural Framework of Compliance: An Exploration of Factors Related to the Use of Early Warning Systems Among Acute Care Clinicians
Authors: Flenady Tracy , Dwyer Trudy , Sobolewska Agnieszka , Lagadec Danielle Le , Connor Justine , Signal Tania , Browne Matthew , Kahl Julie 
Published: April 2020

Abstract
Background: Early warning systems (EWS) are most effective when clinicians monitor patients’ vital signs and comply with the recommended escalation of care protocols once deterioration is recognised. Objectives: To explore sociocultural factors influencing acute care clinicians’ compliance with an early warning system commonly used in Queensland public hospitals in Australia. Methods: This interpretative qualitative study utilised inductive thematic analysis to analyse data collected from semi-structured interviews conducted with 30 acute care clinicians from Queensland, Australia.Results: This study identified that individuals and teams approached compliance with EWS in the context of 1) the use of EWS for patient monitoring; and 2) the use of EWS for the escalation of patient care. Individual and team compliance with monitoring and escalation processes is facilitated by intra and inter-professional factors such as acceptance and support, clear instruction, inter-disciplinary collaboration and good communication. Noncompliance with EWS can be attributed to intra and inter-professional hierarchy and poor communication. Conclusions: The overarching organisational context including the hospital’s embedded quality improvement and administrative protocols (training, resources and staffing) impact hospital-wide culture and influence clinicians’ and teams’ compliance or non-compliance with early warning system’s monitoring and escalation processes. Successful adoption of EWS relies on effective and meaningful interactions among multidisciplinary staff.