bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct from the COVID-19 crisis: research and innovation sparks in Brazil
Authors: Rosa Mário Fabrício Fleury , da Silva Everton Nunes , Pacheco Christina , Diógenes Marcos Vinícius Pereira , Millett Christopher , Gadelha Carlos Augusto Grabois , Santos Leonor Maria Pacheco 
Published: January 2021

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has spread throughout more than 160 countries, infecting millions of people worldwide. To address this health emergency, countries have organized the flow of production and innovation to reduce the impact on health. This article shows the response of the Brazilian scientific community to meet the urgent needs of the public unified health system [SUS], aiming to guarantee universal access to an estimated population of 211 million. By December 2020, Brazil had recorded more than six million cases and approximately 175,000 deaths.

Methods
We collected data on research, development and innovation projects carried out by 114 public universities (plus Oswaldo Cruz Foundation [Fiocruz] and Butantan Institute), as reported on their websites. Additionally, we examined the studies on COVID-19 approved by the National Comission for Research Ethics, as well as those reported on the Ministry of Education website as of May 15, 2020.

Results
The 789 identified projects were classified according to research categories as follows: development and innovation (n = 280), other types of projects (n = 226), epidemiologic research (n = 211), and basic research on disease mechanisms (n = 72). Most proposals focused on the development and innovation of personal protective equipment, medical devices, diagnostic tests, medicines and vaccines, which were rapidly identified as research priorities by the scientific community. Some promising results have been observed from phase III vaccine trials, one of which is conducted in partnership with Oxford University and another of which is performed with Sinovac Biotech. Both trials involve thousands of volunteers in their Brazilian arms and include technology transfer agreements with Fiocruz and the Butantan Institute, respectively. These vaccines proved to be safe and effective and were immediately licensed for emergency use. The provision of doses for the public health system, and vaccination, started on January 17, 2021.

Conclusions
The mobilized Brazilian scientific community has generated comprehensive research, development and innovation proposals to meet the most urgent needs. It is important to emphasize that this response was only possible due to decades of investment in research, development and innovation in Brazil. We need to reinforce and protect the Brazilian science, technology and innovation system from austerity policies that disregard health and knowledge as crucial investments for Brazilian society, in line with the constitutional right of universal health access and universal health coverage.
3D printed Ti6Al4V bone scaffolds with different pore structure effects on bone ingrowth
Authors: Deng Fuyuan , Liu Linlin , Li Zhong , Liu Juncai 
Published: January 2021

AbstractThe microstructure of porous scaffolds plays a vital role in bone regeneration, but its optimal shape is still unclear. In this study, four kinds of porous titanium alloy scaffolds with similar porosities (65%) and pore sizes (650 μm) and different structures were prepared by selective laser melting. Four scaffolds were implanted into the distal femur of rabbits to evaluate bone tissue growth in vivo. Micro-CT and hard tissue section analyses were performed 6 and 12 weeks after the operation to reveal the bone growth of the porous scaffold. The results show that diamond lattice unit (DIA) bone growth is the best of the four topological scaffolds. Through computational fluid dynamics (CFD) analysis, the permeability, velocity and flow trajectory inside the scaffold structure were calculated. The internal fluid velocity difference of the DIA structure is the smallest, and the trajectory of fluid flow inside the scaffold is the longest, which is beneficial for blood vessel growth, nutrient transport and bone formation. In this study, the mechanism of bone growth in different structures was revealed by in vivo experiments combined with CFD, providing a new theoretical basis for the design of bone scaffolds in the future.
Rare functional missense variants in CACNA1H: What can we learn from Writer’s cramp?
Authors: Huang Miaozhen , Nibbeling Esther A. R. , Lagrand Tjerk J. , Souza Ivana A. , Groen Justus L. , Gandini Maria A. , Zhang Fang-Xiong , Koelman Johannes H. T. M. , Adir Noam , Sinke Richard J. , Zamponi Gerald W. , Tijssen Marina A. J. , Verbeek Dineke S. 
Published: January 2021

AbstractWriter’s cramp (WC) is a task-specific focal dystonia that occurs selectively in the hand and arm during writing. Previous studies have shown a role for genetics in the pathology of task-specific focal dystonia. However, to date, no causal gene has been reported for task-specific focal dystonia, including WC. In this study, we investigated the genetic background of a large Dutch family with autosomal dominant‒inherited WC that was negative for mutations in known dystonia genes. Whole exome sequencing identified 4 rare variants of unknown significance that segregated in the family. One candidate gene was selected for follow-up, Calcium Voltage-Gated Channel Subunit Alpha1 H, CACNA1H, due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders. Targeted resequencing of CACNA1H in 82 WC cases identified another rare, putative damaging variant in a familial WC case that did not segregate. Using structural modelling and functional studies in vitro, we show that both the segregating p.Arg481Cys variant and the non-segregating p.Glu1881Lys variant very likely cause structural changes to the Cav3.2 protein and lead to similar gains of function, as seen in an accelerated recovery from inactivation. Both mutant channels are thus available for re-activation earlier, which may lead to an increase in intracellular calcium and increased neuronal excitability. Overall, we conclude that rare functional variants in CACNA1H need to be interpreted very carefully, and additional studies are needed to prove that the p.Arg481Cys variant is the cause of WC in the large Dutch family.
Ameliorative effect of recombinant human lactoferrin on the premature ovarian failure in rats after cyclophosphamide treatments
Authors: Li Shubin , Liu Mengnan , Ma Hongmeng , Jin Qin , Ma Yuzhen , Wang Chunyu , Ren Jingyu , Liu Gang , Dai Yanfeng 
Published: January 2021

AbstractThis study investigated the effect of recombinant human lactoferrin (rhLF) on the premature ovarian failure (POF) of rats. After cyclophosphamide treatments, the POF rats were divided into the following groups: normal control group (NC), low-dose group (LD), medium-dose group (MD) and high-dose group (HD) of rhLF. After drug administrations, the ovarian indexes and hormonal levels were detected. After follicle number count, the proliferation and apoptosis were analyzed with the expressions of genes related with oogenesis, reactive oxygen species (ROS) production and apoptosis detected, followed by the calculation of oxidative stress and protein expressions. After 4-hydroperoxy cyclophosphamide (4-HC) treatments, the effect of rhLF on the proliferation, ROS production and gene expressions of primary rat granulosa cells (GCs) cultured in vitro were detected. After mating, the fertilities of POF rats were recorded. The result showed that the rhLF administrations up-regulated the ovarian index with the number of developing follicles increased and the decreases of hormonal levels conferred. The Ki-67 intensities of the MD and HD groups were up-regulated with the Tunnel intensities decreased. The rhLF treatments significantly promoted the expression of oogenesis, antioxidant and anti-apoptosis related genes. The expression of Bax and Caspase 3 were decreased with the expression of Bcl-2 up-regulated after rhLF administrations. The in vitro treatments of rhLF effectively conferred the toxicity of 4-HC on primary rat GCs. The fertility assessment showed the rhLF treatments up-regulated the offspring’s’ folliculogenesis, which confirmed the ameliorative role of rhLF on the POF damages via the inhibition of ROS production in GCs.
Minimal genome-wide human CRISPR-Cas9 library
Authors: Gonçalves Emanuel , Thomas Mark , Behan Fiona M. , Picco Gabriele , Pacini Clare , Allen Felicity , Vinceti Alessandro , Sharma Mamta , Jackson David A. , Price Stacey , Beaver Charlotte M. , Dovey Oliver , Parry-Smith David , Iorio Francesco , Parts Leopold , Yusa Kosuke , Garnett Mathew J. 
Published: January 2021

AbstractCRISPR guide RNA libraries have been iteratively improved to provide increasingly efficient reagents, although their large size is a barrier for many applications. We design an optimised minimal genome-wide human CRISPR-Cas9 library (MinLibCas9) by mining existing large-scale gene loss-of-function datasets, resulting in a greater than 42% reduction in size compared to other CRISPR-Cas9 libraries while preserving assay sensitivity and specificity. MinLibCas9 provides backward compatibility with existing datasets, increases the dynamic range of CRISPR-Cas9 screens and extends their application to complex models and assays.
Acupuncture for Hashimoto thyroiditis: study protocol for a randomized controlled trial
Authors: Wang Shanze , Zhao Jiping , Zeng Weimei , Du Wanqing , Zhong Tenghui , Gao Hui , Xiao Yi , Yang Chao 
Published: January 2021

Abstract
Background
The incidence rate of Hashimoto thyroiditis (HT) has gradually increased in recent years. There has been no specific etiological treatment for HT. Even though with normal level of thyroid hormone, the patients may still suffer from various clinical symptoms, such as anterior neck discomfort, fatigue, and mood swings, which seriously impair their quality of life. Acupuncture has long been used in the treatment of thyroid diseases, but there has been no related standardized clinical study as of today. This study aims to assess the feasibility, efficacy, and safety of acupuncture for HT.

Methods
This is a randomized, black-controlled assessor-blinded pilot trial. A total of 60 patients will be recruited and divided into the experimental group (n = 30) or the control group (n = 30). The experimental group will undergo acupuncture therapy (penetration needling of Hand-Yangming meridian, PNHM) for 16 weeks, followed by a 16-week follow-up period, and the control group will first go through an observation period for 16 weeks, followed by a 16-week compensation PNHM therapy. The primary outcome will be the change of the concentrations of anti-thyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), and thyroid hormone, including total thyroxine (FT4), free thyroxine (FT3), and thyroid-stimulating hormone (TSH). The secondary outcome measurements include the thyroid-related quality of life questionnaire short-form (ThyPRO-39), The Mos 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HAD). Data collection will be performed before the start of the study (the baseline assessment) and at weeks 8, 16, 24, and 32.

Discussion
The study is designed to assess the feasibility and effectiveness of PNHM in reducing the thyroid antibody level and improving the quality of life of HT patients with hypothyroidism or subclinical hypothyroidism. Results of this trial will assist further analyses on whether the acupuncture treatment can alleviate symptoms for patients with HT.

Trial registration
Acupuncture-Moxibustion Clinical Trial Registry AMCTR-IOR-19000308 (ChiCTR1900026830). Registered on 23 October 2019.
Evaluation of a panel of tumor-specific differentially-methylated DNA regions in IRF4, IKZF1 and BCAT1 for blood-based detection of colorectal cancer
Authors: Young Graeme P. , Symonds Erin L. , Nielsen Hans Jørgen , Ferm Linnea , Christensen Ib J. , Dekker Evelien , van der Vlugt Manon , Mallant-Hent Rosalie C. , Boulter Nicky , Yu Betty , Chan Michelle , Tevz Gregor , LaPointe Lawrence C. , Pedersen Susanne K. 
Published: January 2021

Abstract
Background
Differentially-methylated regions (DMRs) are characteristic of colorectal cancer (CRC) and some occur more frequently than common mutations. This study aimed to evaluate the clinical utility of assaying circulating cell-free DNA for methylation in BCAT1, IKZF1 and IRF4 for detection of CRC.

Methods
A multiplexed real-time PCR assay targeting DMRs in each of the three genes was developed. Assay accuracy was explored in plasma specimens banked from observational cross-sectional trials or from volunteers scheduled for colonoscopy or prior to CRC surgery.

Results
1620 specimens were suitable for study inclusion including 184 and 616 cases with CRC and adenomas, respectively, and 820 cases without neoplasia (overall median age, 63.0 years; 56% males). Combining the PCR signals for all targeted DMRs returned the best sensitivity for CRC (136/184, 73.9%, 95% CI 67.1–79.7), advanced adenomas (53/337, 15.7%, 95% CI 12.0–20.1) and high-grade dysplastic (HGD) adenomas (9/35, 25.7%, 95% CI 14.0–42.3) with a 90.1%, specificity for neoplasia (739/820, 95% CI 87.9–92.0, p < 0.01). Detection of methylation in all three genes were more likely in CRC cases than those without it (OR 28.5, 95% CI 7.3–121.2, p < 0.0001). Of the 81 positive cases without neoplasia, 62 (76.5%) were positive by a single PCR replicate only and predominantly due to detection of methylated BCAT1 (53.2%). Single replicate positivity was significantly higher than that in CRC (26/136, 19.1%, p < 0.0001), and single BCAT1 replicate positivity was more likely in cases without neoplasia than in CRC (OR 17.7, 95% CI 6.6–43.3, p < 0.0001). When a positive result was limited to those with ≥ 1 PCR replicate positive for either IKZF1 or IRF4, or at least two replicates positive for BCAT1, the multi-panel test maintained a high sensitivity for CRC (131/184, 71.2%, 95% CI 64.3–77.3) and HGD adenomas (8/35, 22.9%, 95% CI 11.8–39.3, p = 0.029) but improved specificity significantly (772/820, 94.1%, 95% CI 92.3–95.6, p < 0.0001 vs. any PCR replicate positive).

Conclusion
The multi-panel methylation assay differentiates cases with CRC from those without it and does so with high specificity when criteria for BCAT1 detection are applied. The marker panel is flexible and studies in those at average risk for CRC are now warranted to determine which panel configuration best suits screening goals.
Trial registration: ACTRN12611000318987. Registered 25 March 2011, https://www.anzctr.org.au/ ACTRN12611000318987.
Health and support service needs of individuals with disability from culturally and linguistically diverse backgrounds: a scoping review protocol
Authors: Pho Jacqueline Nhu Quynh , Tan Aidan Christopher , Chaudhary Katrina , Hines Sonia , Ellison Caroline , Isaac Vivian , Lim David 
Published: January 2021

AbstractBackgroundAll individuals should have the right to engage meaningfully in occupations that meet their aspirations and life goals as well as promote their health and well-being. For individuals with disability, meaningful engagement in occupations is supported by timely, effective, and adaptive health and support services. However, research has revealed multiple barriers preventing utilization of these services by individuals with disability from culturally and linguistically diverse (CALD) backgrounds. This review aims to identify gaps and solutions in health and support services of individuals with disability from CALD backgrounds to meaningfully engage in occupations.MethodsA scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. A detailed search strategy will be used to search CINAHL, PubMed, Embase, Scopus, PsycInfo, JBI, and Cochrane Library, as well as grey literature in Trove, Mednar, and OpenGrey from January 1974 onwards. Two reviewers will independently screen all citations and full-text articles for eligibility against specific inclusion and exclusion criteria. Potential conflicts will be resolved through discussion. Data will be extracted and presented in a diagrammatic or tabular form accompanied by a narrative summary.DiscussionThe scoping review will present the health and support service needs of individuals with disability from CALD backgrounds and will extend the current reviews as it focuses the engagement in meaningful occupation. Findings from this review have the potential to inform local policy discussions and practice-based disability care.Systematic review registrationOpen Science Framework (10.17605/OSF.IO/HW2FB).
LncRNA NEAT1 promotes nucleus pulposus cell matrix degradation through regulating Nrf2/ARE axis
Authors: Li Cheng , Ma Xinjian , Ni Chenfei , Xu Jingyan , Xie Yinfei , Kan Junwei , Wei Xiaoli 
Published: January 2021

AbstractBackgroundThis study aimed to assess the role and mechanism of lncRNA NEAT1 in intervertebral disc degeneration (IVD).MethodsLncRNA profile (GSE56081) between IVD and healthy control was downloaded from the Gene Expression Omnibus (GEO) database and analyzes differential lncRNA expression. Expression of lncRNA NEAT1 in IVD tissue and TNF-α/IL-1β-stimulated nucleus pulposus cells were further measured by RT-PCR. The lncRNA NEAT1 overexpression plasmids (pcDNA-NEAT1) were constructed and transfected into nucleus pulposus cells. Catabolic biomarkers (MMP-3 and MMP-13), anabolic biomarkers (Col II and Aggrecan) and Nrf2 expression were further measured. To further investigate the function of Nrf2, nucleus pulposus cells were pretreated with or without 25 μM tert-Butylhydroquinone (TBHQ), a Nrf2 activator, for 18 h and subsequently cotreated with pcDNA-NEAT1.ResultsA total of 1432 lncRNAs were differentially expressed in GSE56081. Bioinformatic analysis found that these lncRNAs mainly enriched in Nrf2/ARE signaling pathway. LncRNA NEAT1 was highly expressed in IVD tissues than that of healthy control. Moreover, TNF-α/IL-1β induced a time- and dose-dependent increase in the mRNA expression of lncRNA NEAT1 in the nucleus pulposus cells. Overexpression of lncRNA NEAT1 abates promotes nucleus pulposus cells proliferation but induces matrix degradation. Meanwhile, nucleus and cytoplasm Nrf2 expression was significantly down-regulated by lncRNA NEAT1 upregulation. Nrf2 activator (TBHQ) could partially reverse the inhibitory effects of overexpression of lncRNA NEAT1 on matrix degradation.ConclusionCollectively, our data unveiled the lncRNA NEAT1 promotes matrix degradation by regulating Nrf2/ARE signaling pathway, suggesting a potential therapeutic for IVD in the future.
Zone-dependent acute circulatory changes in abdominal organs and extremities after resuscitative balloon occlusion of the aorta (REBOA): an experimental model
Authors: Halvachizadeh Sascha , Mica Ladislav , Kalbas Yannik , Lipiski Miriam , Canic Marko , Teuben Michel , Cesarovic Nikola , Rancic Zoran , Cinelli Paolo , Neuhaus Valentin , Pape Hans- Christoph , Pfeifer Roman 
Published: January 2021

AbstractIntroductionResuscitative endovascular balloon occlusion of the aorta (REBOA) may be used in severely injured patients with uncontrollable bleeding. However, zone-dependent effects of REBOA are rarely described. We compared the short-term zone- and organ-specific microcirculatory changes in abdominal organs and the extremity during occlusion of the aorta in a standardized porcine model.MethodsMale pigs were placed under general anesthesia, for median laparotomy to expose intra-abdominal organs. REBOA placement occurred in Zone 1 (from origin left subclavian artery to celiac trunk), Zone 2 (between the coeliac trunk and most caudal renal artery) and Zone 3 (distal most caudal renal artery to aortic bifurcation). Local microcirculation of the intra-abdominal organs were measured at the stomach, colon, small intestine, liver, and kidneys. Furthermore, the right medial vastus muscle was included for assessment. Microcirculation was measured using oxygen-to-see device (arbitrary units, A.U). Invasive blood pressure measurements were recorded in the carotid and femoral artery (ipsilateral). Ischemia/Reperfusion (I/R)-time was 10 min with complete occlusion.ResultsAt baseline, microcirculation of intra-abdominal organs differed significantly (p < 0.001), the highest flow was in the kidneys (208.3 ± 32.9 A.U), followed by the colon (205.7 ± 36.2 A.U.). At occlusion in Zone 1, all truncal organs showed significant decreases (p < 0.001) in microcirculation, by 75% at the colon, and 44% at the stomach. Flow-rate changes at the extremities were non-significant (n.s). During occlusion in Zone 2, a significant decrease (p < 0.001) in microcirculation was observed at the colon (− 78%), small intestine (− 53%) and kidney (− 65%). The microcirculatory changes at the extremity were n.s. During occlusion in Zone 3, truncal and extremity microcirculatory changes were n.s.ConclusionAll abdominal organs showed significant changes in microcirculation during REBOA. The intra-abdominal organs react differently to the same occlusion, whereas local microcirculation in extremities appeared to be unaffected by short-time REBOA, regardless of the zone of occlusion.
Mungbean in Southeast Asia and East Africa: varieties, practices and constraints
Authors: Sequeros Teresa , Ochieng Justus , Schreinemachers Pepijn , Binagwa Papias H. , Huelgas Zenaida M. , Hapsari Ratri Tri , Juma Maurice Ogada , Kangile Joseph Rajabu , Karimi Rael , Khaririyatun Nur , Mbeyagala Emmanuel K. , Mvungi Henry , Nair Ramakrishnan Madhavan , Sanya Losira Nasirumbi , Nguyen Thi Tan Loc , Phommalath Siviengkhek , Pinn Thira , Simfukwe Esther , Suebpongsang Pornsiri 
Published: January 2021

AbstractBackgroundImproving the productivity of grain legumes is important to address global challenges of food security and soil degradation. This study’s objective was to quantify the adoption of improved mungbean (Vigna radiataL.) varieties and agricultural practices and to identify production constraints for six countries in Southeast Asia and three countries in East Africa.MethodsA Delphi method using expert elicitation was applied at subnational levels and then aggregated to national levels. Each panel employed repetitive and independent questioning of experts. The study organized 31 expert panels involving 387 experts across 9 countries.ResultsThe share of improved varieties in the planted area, as estimated by the expert panels, was 92% for the Philippines, 91% for Vietnam, 99% for Thailand, 84% for Cambodia, 60% for Indonesia, 35% for Laos, 91% for Kenya, 30% for Uganda and 25% for Tanzania. The average age of improved varieties was 19 years in Asia and 12 years in East Africa. Of the mungbean area in Southeast Asia, 61% was planted to varieties developed by the World Vegetable Center, but this was only 2% in East Africa. Production constraints generally included insect pests and plant diseases, unstable markets with low price and low market demand, and the lack of quality seed of suitable varieties.ConclusionsThere are ample opportunities to improve mungbean productivity through wider use of improved varieties and practices, which is important to meet the contemporary challenges of improving human nutrition and agricultural sustainability.