bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy
Authors: Novelli Giuseppe , Biancolella Michela , Mehrian-Shai Ruty , Colona Vito Luigi , Brito Anderson F. , Grubaugh Nathan D. , Vasiliou Vasilis , Luzzatto Lucio , Reichardt Juergen K. V. 
Published: May 2021

AbstractCOVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.
Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer’s disease
Authors: Zhang Xiao , O’Callaghan Paul , Li Honglian , Tan Yingxia , Zhang Ganlin , Barash Uri , Wang Xiaomin , Lannfelt Lars , Vlodavsky Israel , Lindahl Ulf , Li Jin-Ping 
Published: May 2021

AbstractDefective amyloid-β (Aβ) clearance from the brain is a major contributing factor to the pathophysiology of Alzheimer’s disease (AD). Aβ clearance is mediated by macrophages, enzymatic degradation, perivascular drainage along the vascular basement membrane (VBM) and transcytosis across the blood–brain barrier (BBB). AD pathology is typically associated with cerebral amyloid angiopathy due to perivascular accumulation of Aβ. Heparan sulfate (HS) is an important component of the VBM, thought to fulfill multiple roles in AD pathology. We previously showed that macrophage-mediated clearance of intracortically injected Aβ was impaired in the brains of transgenic mice overexpressing heparanase (Hpa-tg). This study revealed that perivascular drainage was impeded in the Hpa-tg brain, evidenced by perivascular accumulation of the injected Aβ in the thalamus of Hpa-tg mice. Furthermore, endogenous Aβ accumulated at the perivasculature of Hpa-tg thalamus, but not in control thalamus. This perivascular clearance defect was confirmed following intracortical injection of dextran that was largely retained in the perivasculature of Hpa-tg brains, compared to control brains. Hpa-tg brains presented with thicker VBMs and swollen perivascular astrocyte endfeet, as well as elevated expression of the BBB-associated water-pump protein aquaporin 4 (AQP4). Elevated levels of both heparanase and AQP4 were also detected in human AD brain. These findings indicate that elevated heparanase levels alter the organization and composition of the BBB, likely through increased fragmentation of BBB-associated HS, resulting in defective perivascular drainage. This defect contributes to perivascular accumulation of Aβ in the Hpa-tg brain, highlighting a potential role for heparanase in the pathogenesis of AD.
Aβ43 aggregates exhibit enhanced prion-like seeding activity in mice
Authors: Ruiz-Riquelme Alejandro , Mao Alison , Barghash Marim M. , Lau Heather H. C. , Stuart Erica , Kovacs Gabor G. , Nilsson K. Peter R. , Fraser Paul E. , Schmitt-Ulms Gerold , Watts Joel C. 
Published: May 2021

AbstractWhen injected into genetically modified mice, aggregates of the amyloid-β (Aβ) peptide from the brains of Alzheimer’s disease (AD) patients or transgenic AD mouse models seed cerebral Aβ deposition in a prion-like fashion. Within the brain, Aβ exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Aβ variants to the seeding behavior of Aβ aggregates remains unknown. Here, we have investigated the relative seeding activities of Aβ aggregates composed exclusively of recombinant Aβ38, Aβ40, Aβ42, or Aβ43. Cerebral Aβ42 levels were not increased in AppNL−F knock-in mice injected with Aβ38 or Aβ40 aggregates and were only increased in a subset of mice injected with Aβ42 aggregates. In contrast, significant accumulation of Aβ42 was observed in the brains of all mice inoculated with Aβ43 aggregates, and the extent of Aβ42 induction was comparable to that in mice injected with brain-derived Aβ seeds. Mice inoculated with Aβ43 aggregates exhibited a distinct pattern of cerebral Aβ pathology compared to mice injected with brain-derived Aβ aggregates, suggesting that recombinant Aβ43 may polymerize into a unique strain. Our results indicate that aggregates containing longer Aβ C-terminal variants are more potent inducers of cerebral Aβ deposition and highlight the potential role of Aβ43 seeds as a crucial factor in the initial stages of Aβ pathology in AD.
Assessments of the quality systems of pharmaceutical distributors: a remote approach to be applied in times of COVID-19 and beyond
Authors: Bourasseau Anthony , Lavergne Laurine , Ravinetto Raffaella 
Published: May 2021

Abstract
Background
Adequate quality systems throughout pharmaceutical supply chains are crucial to protect individuals and communities from substandard and falsified medical products. Thus, pharmaceutical distributors are regularly assessed by qualified experts. Since the COVID-19 pandemic has forced a suspension of normal activities, remote assessments via videoconferencing may represent a temporary alternative to on-site audits. We exploratorily evaluated the feasibility of remote assessments of pharmaceutical distributors, located in a low- or middle-income country hard-to reach during the COVID-19 pandemic.

Methods
We conducted pilot remote assessments of four conveniently selected distributors. The expert was remotely connected via videoconference, and supported by an in-country assessment facilitator (ICAF), who had received ad hoc training and was present at the assessed facility. First, the remote expert assessed the quality assurance (QA) activities and rated their compliance with the standards of the World Health Organization Good Storage & Distribution Practices (GSDP), as per routine practice. Second, s/he assessed the completeness, clarity and accuracy of data collected remotely, first per distributor, and then in aggregated form.

Results
Data completeness was assessed by the expert as excellent, while clarity and accuracy were good. Overall data quality (a combination of completeness, clarity and accuracy) was good, with no major differences across QA activities, nor across distributors. Contextual limitations included poor internet connection, language barriers, and distributors’ lack of familiarity with QA terminology.

Conclusions
Our findings are exploratory and cannot be extrapolated to other contexts, nor to other types of audits. Nonetheless, this pilot experience suggests that a well-planned remote assessment of pharmaceutical distributors, conducted with the support of a well-trained onsite ICAF, can provide data of acceptable quality, allowing to assess GSDP-compliance and to make temporary decisions about licensing or purchasing. Purchasers and policy makers should read the results of remote assessments in light of their intrinsic limitations. At the moment, onsite assessments remain the gold standards, but this could change in the longer term, with improved information technology and in light of the need to avoid unnecessary travels. Furthermore, remote assessments could be considered for routine pre-screening candidates for on-site assessments, and for targeted follow-up of on-site assessment.
Promoting N2 electroreduction to ammonia by fluorine-terminating Ti3C2Tx MXene
Authors: Ding Yu , Zhang Junbo , Guan Anxiang , Wang Qihao , Li Si , Al-Enizi Abdullah M. , Qian Linping , Zhang Lijuan , Zheng Gengfeng 
Published: May 2021

AbstractTwo-dimensional MXene-based materials are potential of presenting unique catalytic performances of electrocatalytic reactions. The surface functionalization of MXene-based catalysts is attractive for developing efficient electrocatalysts toward nitrogen reduction reaction. Herein, we reported a Ti3C2Tx MXene with a medium density of surface functionalized fluorine terminal groups, as an excellent N2 reduction reaction electrocatalyst with enhanced adsorption and activation of N2. The Ti3C2Tx MXene catalyst showed a production rate of ammonia as 2.81 × 10–5 μmol·s−1·cm−2, corresponding to a partial current density of 18.3 μA·cm−2 and a Faradic efficiency of 7.4% at − 0.7 V versus reversible hydrogen electrode in aqueous solutions at ambient conditions, substantially exceeding similar Ti3C2Tx MXene catalysts but with higher or lower densities of surface fluorine terminal groups. Our work suggests the capability of developing surface functionalization toolkit for enhancing electrochemical catalytic activities of two-dimensional MXene-based materials.
Laparoscopic partial liver resection for hepatocellular carcinoma arising from Fontan-associated liver disease: a case report
Authors: Iwata Miku , Sakamoto Katsunori , Ito Chihiro , Sakamoto Akimasa , Uraoka Mio , Nagaoka Tomoyuki , Tamura Kei , Funamizu Naotake , Takai Akihiro , Ogawa Kohei , Takada Yasutsugu 
Published: May 2021

Abstract
Background
The Fontan procedure (FP) is a palliative surgery for functional single ventricle. The Fontan circulation maintains pulmonary circulation by a high central venous pressure, leading to chronic congestive liver. The number of patients diagnosed with hepatocellular carcinoma (HCC) arising from liver fibrosis and cirrhosis after FP is increasing. Several reports have described surgical treatment for HCC after FP, but few have described laparoscopic surgery.

Case presentation
The patient was a 31-year-old man who had undergone the FP for single right ventricle at 3 years. Several liver masses were detected at 30 years. A liver mass in segment 3 showed increasing size concomitant with increasing alpha-fetoprotein concentration, and a solitary HCC 15 mm in diameter was diagnosed. The tumor was located on the liver surface, abutting the origin of the left hepatic vein. Laparoscopic partial liver resection was performed. The postoperative course was uneventful and the patient was discharged on postoperative day 3. The patient remained disease-free on follow-up after 7 months.

Conclusions
Although we had some concerns, such as difficulty managing general anesthesia and easy venous bleeding due to high central venous pressure, laparoscopic partial liver resection was performed with safe exposure of the left hepatic vein.
Making the patient voice heard in a research consortium: experiences from an EU project (IMI-APPROACH)
Authors: Taylor Jane , Dekker Sjouke , Jurg Diny , Skandsen Jon , Grossman Maureen , Marijnissen Anne-Karien , Ladel Christoph , Mobasheri Ali , Larkin Jon , Weinans Harrie , Kanter-Schlifke Irene ,   on behalf of the APPROACH research consortium and APPROACH Principal Investigators, Marijnissen Anne-Karien , Ladel Christoph , Mobasheri Ali , Larkin Jon , Weinans Harrie 
Published: May 2021

Abstract
APPROACH is an EU-wide research consortium with the goal to identify different subgroups of knee osteoarthritis to enable future differential diagnosis and treatment. During a 2-year clinical study images, biomarkers and clinical data are collected from people living with knee osteoarthritis and data are analyzed to confirm patterns that can indicate such different subgroups. A Patient Council (PC) has been set up at project initiation and consists of five people from Norway, The Netherlands and UK. Initially, this group of individuals had to learn how to effectively work with each other and with the researchers. Today, the PC is a strong team that is fully integrated in the consortium and acknowledged by researchers as an important sounding board.
The article describes this journey looking at formal processes of involvement – organizational structure, budget, meetings – and more informal processes such as building relationships and changing researcher perceptions. It describes how the PC helped improve the experience and engagement of study participants by providing input to the clinical protocol and ensuring effective communication (e.g. through direct interactions with participants and newsletters). Furthermore, the PC is helping with dissemination of results and project advocacy, and overall provides the patient perspective to researchers. Additionally, the authors experienced and describe the intangible benefits such as a shift in researcher attitudes and a sense of community and purpose for PC members. Importantly, learnings reported in this article also include the challenges, such as effective integration of the PC with researchers’ work in the early phase of the project.

Trial registration
US National Library of Medicine, NCT03883568, retrospectively registered 21 March 2019.
Involving older adults in technology research and development discussions through dialogue cafés
Authors: Lund Anne , Holthe Torhild , Halvorsrud Liv , Karterud Dag , Johannessen Adele Flakke , Lovett Hilde Margrethe , Thorstensen Erik , Casagrande Flávia Dias , Zouganeli Evi , Norvoll Reidun , Forsberg Ellen Marie 
Published: May 2021

Abstract
Background
Citizen involvement is important for ensuring the relevance and quality of many research and innovation efforts. Literature shows that inadequate citizen involvement poses an obstacle during the research, development, and implementation of assistive technology. Previous studies have addressed the advantages and disadvantages of citizen engagement in health research and technology development, and there is concern about how to ensure valuable engagement to avoid situations where they don’t have influence. Frail older adults are often excluded from being active partners in research projects.
The overall objective of this commentary is to describe a case where dialogue cafés was used as a method for involving assisted living residents in technology discussions, elaborating on the following research question: In what ways are dialogue cafés useful for directing research and development and for engaging residents in assisted living facilities in assistive technology discussions?

Method
Six dialogue cafés with assisted living residents as participants were carried out over a period of 3 years (2016–19). Reports that were written after each café by the group leaders and rapporteurs provide the material for the analyses in this paper.

Results
This study demonstrates an example of facilitating user involvement where the participants felt useful by contributing to research and discussions on assistive technology and where this contribution in fact directed the research and development in the overall Assisted Living Project.

Conclusion
This study demonstrated that dialogue cafés enable older residents at an assisted living facility to contribute with opinions about their needs and perspectives on assistive technologies. This negates the view of older adults as too frail to participate and demonstrates the importance of including and collaborating with older adults in research.
Development of the patient-oriented research curriculum in child health (PORCCH)
Authors: Macarthur Colin , Walsh Catharine M. , Buchanan Francine , Karoly Aliza , Pires Linda , McCreath Graham , Jones Nicola L. 
Published: May 2021

Abstract
Background
The Canadian Institutes for Health Research launched a national ‘Strategy for Patient-Oriented Research’ (SPOR) in 2011. Patient-oriented research is defined as a continuum of research that engages patients as partners, focuses on patient-identified priorities, and improves patient outcomes. Capacity development is a core element of SPOR. Barriers to patient-oriented research include unfamiliarity with the research process for patients and families and unfamiliarity with the methods of patient and family engagement for researchers.

Methods
The aim of the Patient-Oriented Research Curriculum in Child Health (PORCCH) is to build capacity in patient-oriented research in child health among patients and families, researchers, healthcare professionals, decision-makers, and trainees through a curriculum delivered via a series of interactive online modules (e-learning). A multi-disciplinary, multi-stakeholder steering committee, which included patients and families, guided the development of the curriculum and provided feedback on individual modules. The content, design, and development of each module were co-led by a parent and researcher in an equal partnership.

Results
PORCCH consists of a series of five modules. All modules are interactive and include video vignettes and knowledge comprehension questions. Access to the modules is free and each module takes approximately 30 min to complete. The five modules are: Research 101 (an Introduction to Patient-Oriented Research, parts 1 and 2), Patient Engagement 101 (an Introduction to Patient Engagement in Child Health Research, parts 1 and 2), and Research Ethics 101.

Conclusions
PORCCH was developed specifically to overcome recognized barriers to the engagement of patients and families in child health research. The aim of the curriculum is to build capacity in patient-oriented research in child health. The goal is for PORCCH to be a useful resource for all stakeholders involved in patient-oriented research: patients and families, researchers, healthcare professionals, decision-makers, and trainees.
Obstructs-equipped apparatus reduces cannibalism and improves larval survival of the Coccinellid, Harmonia axyridis (Coleoptera: Coccinellidae)
Authors: Sun Yuan-Xing , Hao Ya-Nan , Liu Chang-Zhong , Zhou Jing-Jiang , Wang Sen-Shan 
Published: May 2021

Abstract
Background
Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) is an important biocontrol agent in native region of Asia, while its high propensity for cannibalism causes great obstacles in mass production. Provisioning obstructs in rearing containers could decrease the cannibalism of ladybird beetles. In this study, three different patterns of obstructs (Con-A, Con-B, and Con-C) were designed and equipped in plastic Petri dishes (95.38 cm3) as rearing units, and their efficiency for H. axyridis larval survival was tested. The potential of the high-density rearing was then evaluated using the optimal units with 16, 24, or 32 larvae per unit (named 16-L, 24-L, or 32-L, respectively).

Results
Larval survivals in obstructs-equipped units were generally higher than those in control, and significantly increased with the Con-C units (39.8% versus 74.2% at adult stage). With the Con-C units, the survivals were significantly higher at 16-L density (82.5%) than those at 24-L density (62.5%), but both were non-significantly different from those at 32-L density (70.0%). The weights of newly emerged adults (fit with the expected sex ratio of 1:1) at the higher densities were lower than those at 16-L density.

Conclusions
The results demonstrate that H. axyridis can be reared at a higher density (≈ 0.336 larvae/cm3) in a constrained unit and highlight the effects of obstructs in reducing cannibalism and improving insect survivals.
Composition, habitat preference and seasonal variation of malaria vector larval and pupa stage in Akure North Local Government Area of Ondo State, Nigeria
Authors: Olusi T. A. , Simon-Oke I. A. , Akeju A. V. 
Published: May 2021

Abstract
Background
The study of habitat preference and identification of malaria vector is one of the important steps in malaria control. Knowledge of local Anopheles mosquitoes capable of transmitting malaria parasites has contributed largely to the reduction in the menace caused by malaria infection. This present study examined the habitat nature and identified the species of Anopheles mosquitoes involved in malaria parasites transmission in the study area. Monthly collection and identification of the fourth larval stage was carried out from October 2018 to September 2019.

Result
The prevalence of An. gambiae complex and An. funestus larvae was 95.86 and 4.15%, respectively. The highest (14.17%) and the least (4.25%) number of larvae were collected in the month of November and May, respectively. Out of the total number of Anopheles mosquito larvae collected during the wet season, 69.77% of the larvae was collected from the clean habitat, while 30.23% was collected from the dirty habitats. During the dry season, the larvae dwell more in dirty aquatic habitat, with 64.74% of the larvae collected from the dirty habitats, while 35.27% was recorded from clean habitats. Statistically, there was no significant difference in the electrical conductivity when comparing both seasons (P = 0.19; X2 = 53.14). The average recorded electrical conductivity in dry and wet seasons were 350.76 µS/cm and 178.91 µS/cm, respectively. The pH recorded in dry and wet seasons were 6.78 and 7.04, respectively. There was no significant difference in the pH when both seasons were compared (P = 0.13; X2 = 54.89). The total dissolve solid where not significant different (P = 0.58; X2 = 13.35) when both seasons were compared. The temperature (P = 0.04; X2 = 43.54) and dissolve oxygen (P = 0.00; X2 = 30.09) were significantly different comparing dry and wet seasons in all the habitats where the immature stages of Anopheles mosquitoes were collected.

Conclusion
The study revealed major vector of malaria parasite in the study location, also the pattern of their breeding during dry and rainy season which is influenced by some selected ecological factors.
Effect of manure sources and rates on nitrogen replacement value, sesame yield and nutrient content under drip irrigation system
Authors: Abd El Lateef E. M. , Wali Asal M. , Abd El-Salam M. S. 
Published: May 2021

Abstract
Background
This work was conducted to investigate the effect of different manure types (compost, chicken manure and FYM) at 12, 24 and 48 m3 ha−1 with or without reduced N rate (72 kg ha−1) compared with N fertilizer levels: 0, 36, 72 and 108 kg ha−1 under drip irrigation system. Therefore, field trials were established in the summer seasons of 2018 and 2019 on a private farm, Belbais District, Sharkia Governorate, in a newly reclaimed soil (loomy calcareous). Sesame seed yield, oil content and macro- and micronutrients were determined.

Results
Highly significant effects due to organic sources applied were apparent on seed yield and yield components. Yield response to FYM at the lowest rate compared to the other two sources and rates was evident. Correlation analysis of the various yield characteristics with N fertilizer application was reported. Fertilizer replacement value in manure sources ranged between 30 and 62%. The chemical analysis of sesame seeds indicated that chemical composition of sesame seed was insensitive to the type of soil amendment.

Conclusion
It could be concluded from this study that the predictable benefits from manure application to sesame will increase farmer confidence in organic fertilizers reducing the reliance up on inorganic fertilizers for crop nutrition and improving the sesame seed nutrient content.