bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the genetic variability of host resilience to endo and ectoparasites under natural infestation, in Nellore cattle
Authors: Gouveia Gabriela Canabrava , Ribeiro Virgínia Mara Pereira , Fortes Marina Rufino Salinas , Raidan Fernanda Santos Silva , Reverter-Gomez Antonio , de Moraes Mariana Mamedes , de Araújo Andresa Eva Melo , Gonçalves Daniel Resende , Silva Marcos Vinicius Gualberto Barbosa da , Toral Fabio Luiz Buranelo 
Published: January 2021

Abstract
Background:

Host resilience (HR) to parasites can affect growth in pastured raised cattle. This study is a detailed investigation of the genetic mechanisms of HR to ticks (TICK), gastrointestinal nematodes (GIN), and Eimeria spp. (EIM) under natural infestation. HR was defined as the slope coefficient of random regression models of body weight (BW) when TICK, GIN, and EIM burdens were used as environmental gradients. The BW was evaluated in five measurement events (ME): when animals were 331, 385, 443, 498, and 555 days old on average. 7307 BW records were available from 1712 animals weighted at least in one ME. Out of those, 1075 animals had valid genotypic information after quality control analysis that were used in genome-wide association studies (GWAS) and GWAS meta-analyses to identify genomic regions associated with HR.
Results:

Both the genetic correlations between intercept and HR to each parasite, and the genetic correlations between BW measured in animals submitted to different parasite burden indicated that there was genotype x parasite burden interaction for BW, and selection for BW under environment with controlled parasite burden might be an efficient strategy to improve both, BW and HR. Furthermore, there was no impact of age of measurement on genetic variance estimates for HR to different parasites. However, genetic correlation between HR to the same parasite measured in different ages ranged from low to moderate in magnitude, with a posteriori means (high posterior density interval with 90% of samples) varying from 0.13 (-0.05; 0.35) to 0.40 (0.15; 0.63) for TICK, from 0.11 (-0.06; 0.29) to 0.52 (0.37; 0.67) for GIN and from 0.25 (0.07; 0.43) to 0.56 (0.34; 0.77) for EIM. These results indicate the importance of age of measurement in studies on HR.
Conclusions:

HR to GIN and EIM can be used as a complementary tool to parasitic control management, and a multiple trait selection method that combine BW and HR to parasites should be used in parasitic endemic areas to avoid economic losses due parasitic diseases.
Unmet need for contraception and associated factors among women with cardiovascular disease having follow-up at Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia: a cross-sectional study
Authors: Mechal Negalign , Negash Mustefa , Bizuneh Hailemichael , Abubeker Ferid A 
Published: January 2021

Abstract
Background

Pregnancies complicated by cardiovascular disease carry a high risk of morbidity and mortality. Contraception offers a unique opportunity to avoid unintended pregnancy and/or optimize preconception cardiac health status. Such planning will also allow possible modification of medical therapy that can be detrimental to the growing fetus. However, unmet need for contraception can become a barrier to achieving these goals. This research was aimed to determine the rate of unmet need for contraceptives and associated factors among women with cardiovascular disease.
Methods

A facility-based cross-sectional study was conducted from February 1 – May 31/2020. A convenient sampling technique was used to enroll 284 reproductive age women with cardiovascular disease having follow-up at Saint Paul’s Hospital Millennium Medical College. Data was collected through an exit interview using a structured and pretested questionnaire. Descriptive, bivariate, and multivariate methods were used to analyze the level of unmet need and its associated factors.
Results

The overall unmet need for contraception was 36%. The majority of the respondents lack counseling on contraception use. The most common reasons for non-use of a contraceptive method was fear of drug side effects and drug interaction. Unmet need for contraception was found to be more likely among those who have not been counseled on contraceptive utilization (AOR 6.7, CI 1.8–24.7) and those who lack partner support on contraception use (AOR = 6.2, CI: 1.91–19.8). Unmet need was also found to be more likely among women who have never used contraception before (AOR = 3.2, CI 1.12–8.92).
Conclusion

Unmet need for contraception was high in this high-risk population group. Tailored counseling can alleviate fear and concerns about contraceptive use. Appropriate strategies that enhance male partner involvement should also be implemented.
Long non-coding RNA GAS5 aggravate renal epithelial cell apoptosis in cisplatin-induced AKI by regulating miR-205-5p
Authors: Zhang Min , Bi Hui , Wang Shaoyan , Sun Xuejuan , Li Yinan 
Published: January 2021

Abstract
Introduction: The present study focuses on the interaction between long non-coding RNA GAS5 and microRNA-205-5p and their roles in cisplatin-induced acute kidney injury. Methods: Human kidney tubular cells (HK-2) were used to simulate acute renal injury induced by cisplatin with the consequent fluctuating expression levels of GAS5 and MIR-205-5p being determined respectively. Furthermore, the modulating effects of miR-205-5p and GAS5 in cisplatin-induced apoptosis of renal tubular epithelial cells and the possible binding sites between them were evaluated. Results: The results depicted that the expression of GAS5 was significantly up-regulated after AKI induced by cisplatin, while inhibiting the increase of expression would alleviate the apoptotic-promoting effect of cisplatin on renal tubular epithelial cells. MIR-205-5p is negatively regulated by GAS5, thus down-regulation of GAS5 will consequently elevate the expression of miR-205-5p and further alleviate the damage of HK-2 cells induced by cisplatin. Conclusions: In conclusion, in cisplatin-induced AKI, the expression of GAS5 was increased and consequently inhibited that of miR-205-5p by direct binding, which eventually aggravate the renal tubular epithelial injury, indicating their potential of being important diagnostic markers and therapeutic targets in the treatment of cisplatin-induced AKI.
D614G substitution at the hinge region enhances the stability of trimeric SARS-CoV-2 spike protein
Authors: Yazhini Arangasamy , Sidhanta Das Swayam Prakash , Sriniva Narayanaswamy 
Published: January 2021

Abstract
Background

Spike protein is a key player in the SARS-CoV-2 infection by mediating primary contact between the virus and host cell surface. In the current COVID-19 pandemic, a variant of SARS-CoV-2 having D614G substitution in the spike protein has become dominant world-wide. Initial characterization of the virus shows that the G614 variant is more infectious and has higher fitness than the ancestral (D614) variant. In this study, we analyzed the significance of the D614G substitution on the protein flexibility, inter-residue interaction energies and thermostability of the spike protein trimer.
Results

Using Gaussian network model-based normal mode analysis, we demonstrate that D614G substitution occurs at hinge region that facilitates domain-domain motions between receptor binding domain and S2 region of the spike protein. Further, in-silico mutagenesis and inter-residue energy calculations reveal that contacts involving D614 are energetically frustrated whereas contacts involving G614 are energetically favourable implying the substitution strengthens intra- as well as inter-protomers association. Upon glycine substitution, free energy difference (ΔΔG) is -2.6 kcal/mol for closed and − 2.0 kcal/mol for 1-RBD up conformation i.e., thermodynamic stability has increased. When we perform reverse mutation in the structures of spike protein having G614 substitution, we observe that the free energy difference is 6.6 kcal/mol and 6.3 kcal/mol for closed and 1-RBD up conformations respectively indicating lowered thermodynamic stability. Together, these observations suggest that D614G substitution could modulate the flexibility of spike protein and confer enhanced thermodynamic stability.
Conclusion

Our results on protein flexibility and energetic basis of enhanced stability hint that G614 likely increases the availability of functional form of spike trimer thereby associated to increased infectivity.
Planning and optimising a digital intervention to protect older adults’ cognitive health
Authors: Essery Rosie , Pollet Sebastien , Smith Kirsten A. , Mowbray Fiona , Slodkowska-Barabasz Joanna , Denison-Day James , Hayter Victoria , Bradbury Katherine , Grey Elisabeth , Western Max J. , Milton Alexander , Hunter Cheryl , Ferrey Anne E. , Müller Andre Matthias , Stuart Beth , Mutrie Nanette , Griffin Simon , Kendrick Tony , Brooker Helen , Gudgin Bernard , Phillips Rosemary , Stokes Tom , Niven John , Little Paul , Yardley Lucy 
Published: January 2021

Abstract
Background By 2050 worldwide dementia prevalence is expected to triple, rising to 152 million. Affordable, scalable interventions are required to support protective behaviours such as physical activity, cognitive training and healthy eating. This paper outlines the development of ‘Active Brains’: a multi-domain digital behaviour change intervention to reduce cognitive decline amongst older adults, and key findings arising from this process. Methods A theory-, evidence- and person-based approach to intervention development was undertaken. Scoping reviews and behavioural analysis contributed to intervention planning. Optimisation involved qualitative interviews with 52 older adults with higher and lower cognitive performance scores. Data were analysed thematically and informed changes.Results The development process synthesised findings from planning and optimisation activities. Scoping reviews and qualitative interviews suggested that the same intervention content should be suitable for individuals with higher and lower cognitive performance. Qualitative findings revealed that maintaining independence and enjoyment motivated engagement in intervention-targeted behaviours, whereas managing ill health was a potential barrier. Social support for engaging in such activities could provide motivation, but was not desirable for all. These findings informed development of highly acceptable intervention content and functionality for target users.Conclusions A digitally-delivered intervention with minimal support appears acceptable and potentially engaging to older adults with higher and lower levels of cognitive performance. As well as informing our own intervention, the insights obtained through our development process may be useful for others working with, and developing interventions for, older adults and/or those with cognitive impairment.
Evaluation of a multidisciplinary lipid clinic to improve the care of individuals with severe lipid conditions: a RE-AIM Framework Analysis
Authors: Jones Laney K , McMinn Megan , Kann David , Lesko Michael , Sturm Amy C. , Walters Nicole , Chen Nan , Fry Kerrianne , Brownson Ross C. , Gidding Samuel S. , Williams Marc S. , Rahm Alanna Kulchak 
Published: January 2021

Abstract
Background. Individuals with complex dyslipidemia, or those with medication intolerance, are often difficult to manage in primary care. They require the additional attention, expertise, and adherence counseling that occurs in multidisciplinary lipid clinics (MDLCs). We conducted a program evaluation of the first year of a newly implemented MDLC utilizing the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to provide empirical data not only on program effectiveness, but also on components important to local sustainability and future generalizability.Methods. The purpose of the MDLC is to increase uptake of guideline-based care for lipid conditions. Established in 2019, the MDLC provides care via a centralized clinic location within the healthcare system. Primary care providers and cardiologists were invited to refer individuals with lipid conditions. Using a pre/post study design, we evaluated implementation outcomes from the MDLC using the RE-AIM framework. Results. In 2019, 420 referrals were made to the MDLC (reach). Referrals were made by 19% (148) of the 796 active cardiology and primary care providers; with an average of 35 patient referrals per month in 2019 (SD 12) (adoption). The MDLC saw 83 patients in 2019 (reach). Additionally, 50% (41/82) had at least one follow-up MDLC visit and 12% (10/82) had two or more follow-up visits in 2019 (implementation). In patients seen by the MDLC, we found improved diagnosis of specific lipid conditions (FH, hypertriglyceridemia, and dyslipidemia), increased prescribing of evidence-based therapies, high rates of medication prior authorization approvals, and significant reductions in lipid levels by lipid condition subgroup (effectiveness). Over time, the operations team decided to transition from in-person follow-up to telehealth appointments to increase capacity and sustain the clinic (maintenance).Conclusions. Despite limited reach and adoption of the MDLC, we found a large intervention effect that included improved diagnosis, increased prescribing of guideline-recommended treatments, and clinically significant reduction of lipid levels. Attention to factors including solutions to decrease the large burden of unseen referrals, discussion of the appropriate number and duration of visits, and sustainability of the clinic model could aid in enhancing the success of the MDLC and improving outcomes for more patients throughout the system.
Comparing syngeneic and autochthonous models of breast cancer to identify tumor immune components that correlate with response to immunotherapy in breast cancer
Authors: Lal Jessica Castrillon , Mehta Anita K. , Townsend Madeline G. , Oliwa Madisson , Miller Eric , Sotayo Alaba , Cheney Emily , Mittendorf Elizabeth A. , Letai Anthony , Guerriero Jennifer L. 
Published: January 2021

Abstract
Background: The heterogeneity of the breast tumor microenvironment (TME) may contribute to the lack of durable responses to immune checkpoint blockade (ICB), however, mouse models to test this are currently lacking. Proper selection and use of preclinical models are necessary for rigorous, preclinical studies to rapidly move laboratory findings into the clinic to treat patients.Methods: We compared 3 versions of a common syngeneic and autochthonous mouse model to elucidate how tumor latency and TME heterogeneity contributes to ICB resistance. We performed comprehensive characterization of the TME using quantitative flow-cytometry and RNA expression analysis (NanoString) utilizing three distinct syngeneic breast cancer models, all derived from the MMTV-PyMT autochthonous model. A commonly used protocol was used to obtain tumor cells from MMTV-PyMT mice and 1E6, 1E5 or 1E4 cells were immediately injected into the mammary fat pad of FVB/NJ wild type mice. We then performed deep immunophenotyping and tested ICB efficacy in the 3 syngeneic models compared to the autochthonous model. Results: The 4 models had vastly different TMEs that correlated to ICB responses. We found that the number of cells used to generate syngeneic tumors significantly influences tumor latency, infiltrating leukocyte population and response to ICB. Compared to the autochthonous model, all 3 syngeneic models had significantly more tumor infiltrating lymphocytes (TILs; CD3+, CD4+, and CD8+) and higher proportions of PD-L1 positive myeloid cells, whereas the MMTV-PyMT model had the highest frequency of myeloid cells out of total leukocytes. Increased TILs correlated with response to anti-PD-L1 and anti-CTLA-4 therapy; but PD-L1expression on tumor cells or PD-1 expression of T-cells did not.Conclusions: These studies reveal that the commonly used syngeneic models have low concordance with the autochthonous model. We have identified ICB-sensitive and resistant syngeneic breast cancer models, generated from the same tumor cell inoculum, and find that only the 1E4 syngeneic model is representative of the slow growing, autochthonous model. Given the lack of benefit from ICB in breast cancer, the identification of robust murine models presented here provides the opportunity to further interrogate the TME for breast cancer treatment and provide novel insights into therapeutic combinations to overcome ICB resistance.
One-tube SARS-CoV-2 detection platform based on RT-RPA and CRISPR/Cas12a
Authors: Sun Yangyang , Yu Lei , Liu Chengxi , Ye Shanting , Chen Wei , Li Dechang , Huang Weiren 
Published: January 2021

Abstract
Background: COVID-19 has spread rapidly around the world, affecting a large percentage of the population. When lifting certain mandatory measures for an economic restart, robust surveillance must be established and implemented, with nucleic acid detection for SARS-CoV-2 as an essential component. Methods: We tried to develop a one-tube detection platform based on RT-RPA (Reverse Transcription and Recombinase Polymerase Isothermal Amplification) and DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) technology, termed OR-DETECTR, to detect SARS-CoV-2. We designed RT-RPA primers of the RdRp and N genes following the SARS-CoV-2 gene sequence. We optimized reaction components so that the detection process could be carried out in one tube. Specificity was demonstrated by detecting nucleic acid samples from pseudoviruses from seven human coronaviruses and Influenza A (H1N1). Clinical samples were used to validate the platform and all results were compared to rRT-PCR. RNA standards and pseudoviruses diluted by different gradients were used to demonstrate the detection limit. Additionally, we have developed a lateral flow assay based on OR-DETECTR for detecting COVID-19.Results: The OR-DETECTR detection process can be completed in one tube, which takes approximately 50 min. This method can specifically detect SARS-CoV-2 from seven human coronaviruses and Influenza A (H1N1), with a low detection limit of 2.5 copies/µl input (RNA standard) and 1 copy/µl input (pseudovirus). Results of six samples from SARS-CoV-2 patients, eight samples from patients with fever but no SARS-CoV-2 infection, and one mixed sample from 40 negative controls showed that OR-DETECTR is 100% consistent with rRT-PCR. The lateral flow assay based on OR-DETECTR can be used for the detection of COVID-19, and the detection limit is 2.5 copies/µl input.Conclusions: The OR-DETECTR platform for the detection of COVID-19 is rapid, accurate, tube closed, easy-to-operate, and free of large instruments.
FUNDAMENTAL LESSONS OF THE FIRST HUMAN VERTICAL ROCKET FLIGHT
Authors: Gooden Brett 
Published: January 2021

ABSTRACT
This paper examines the historic but tragic first human vertical rocket flight which took place in south-western Germany on 1 March 1945. The primary lesson learned from the flight was that, as a result of the combination of psychological and physiological stresses, a human pilot could not be expected to fly a vertically launched rocket manually. An autopilot would be essential for the guidance of the Natter rocket interceptor up to its operational altitude. No further human vertical rocket flights took place until 1961 when Major Yuri Gagarin was launched into orbit. In early April 1945 a fully operational Natter flew successfully into the lower stratosphere under the control of a three-axis autopilot and crewed with a dummy pilot. Both dummy pilot and rear fuselage were recovered successfully under separate parachutes. In less than a year the engineers and scientists in collaboration with aviation physicians and physiologists at research institutions across Germany had laid down the basic principles which still apply to human rocket flight today.
Sodium nanoparticles in alkali halide minerals: Why is villiaumite red and halite blue?
Authors: Calas Georges , Galoisy Laurence , Geisler Alexis 
Published: January 2021

Abstract
The presence of metal Na nanoparticles causes the bright, thermally unstable colors of villiaumite (NaF) and halite (NaCl). These nanoparticles have been suspected for a long time to be caused by external irradiation. Metal nanoparticles, often referred to as metal colloids, cause surface plasmon resonance effects, characterized by a single Lorentzian-shaped absorption band. The color of these minerals is due to metal Na nanoparticles of 2.5–3 nm. A key point is that the resonance wavelength, which corresponds to the maximum of the absorption band, is inversely related to the value of the refractive index of the embedding mineral. This causes the position of the main absorption band to be offset downward by 140 nm in halite relative to villiaumite. As a consequence, the optical transmission window is shifted from the long to the short wavelength domain, explaining the color of blue halite and red villiaumite, respectively. Similar refractive index dependence may explain the purple color of fluorite caused by metallic Ca nanoparticles. Finally, the origin of the villiaumite irradiation may be the presence of Th-rich (about 8.8 wt% ThO2) nano-inclusions, about 500 nm large, illustrating the specific geochemistry of peralkaline rocks where villiaumite is found.
Consumers' purchasing intentions for efficient water-saving products: the mediating effects of altruistic and egoistic values
Authors: Sarpong Kwabena Agyarko , Amankwaa Gordon , Frimpong Obeng , Xu Wanzhen , Cao Yunfei , Ni Xiaoni , Nkrumah Nana Kwame 
Published: January 2021

Abstract
Efficient water-saving appliances are an essential part of changing water consumption toward a more sustainable future. Unlike previous studies, this research focuses on egoistic and altruistic values as determinants of consumers' willingness to buy efficient water-saving appliances. In this study, a convenient sampling technique was used to solicit data from 308 potential consumers. Using a two-step structural equation model method for data analysis, the results show that both egoistic and altruistic values affect the willingness of consumers to purchase efficient water-saving appliances. However, compared with altruistic values, egoistic values had a greater influence on consumers' purchasing intention. From the Chinese perspective, this study is one of the primary efforts to understand the association and importance of ethical values and consumers' willingness to support water-saving innovations. The findings of this study put forward significant policy effects that could serve as a benchmark for measures that are likely to promote purchasing intentions toward efficient water-saving appliances.