bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation science in nutrition: a summary and synthesis
Authors: Sarma Haribondhu 
Published: February 2021

AbstractObjective:This paper aimed to summarise and critically synthesise the key findings of the articles included in the supplement entitled ‘Nutrition Implementation Science: The Experience of a Large-Scale Home Fortification in Bangladesh’.Design:Commentary, summary and synthesis.Settings:Low- and middle-income country.Results:The supplement included six articles, including this summary paper. The second article presented an implementation science framework that facilitated conceptualising and evaluating the home-fortification programme in Bangladesh implemented by the Bangladesh Rural Advancement Committee (BRAC). The framework encompasses five components: identifying an ‘effective’ intervention; scaling-up and implementation fidelity; course corrections during implementation and assessing the implementation’s effectiveness; promoting sustainability of interventions and consideration of a concurrent evaluation to identify ‘effective’ interventions and to assess the process and outcome indicators of implementation. The other four articles in this supplement addressed the different components of the framework. For example, the third article addressed the implementation fidelity of a home-fortification programme, and the fourth article described the use of concurrent evaluation to course correct the implementation plan that resulted in improved implementation fidelity. The fifth article explained the outcome of course correction in the programme coverage, and the sixth article described the cost-effectiveness of the BRAC home-fortification programme.Conclusions:Overall, the supplement provides a comprehensive understanding of nutrition implementation science, which is very new in the field. The lessons learned in this supplement may enhance the capacity of researchers, policymakers and key stakeholders in the nutrition field to scale up new nutrition interventions and sustain them until malnutrition is alleviated.
Designing online grocery stores to support healthy eating for weight loss
Authors: Harnack Lisa , Redden Joseph , French Simone , Sherwood Nancy E , Rivera Gabrielle , Valluri Sruthi , Tahir Muna 
Published: February 2021

AbstractObjectives:The current study aimed to identify features to include in online grocery stores to support healthful food purchasing by those striving to lose weight.Design:A Value Proposition Design approach was used to gain shopper insights, devise potential online grocery store features and obtain feedback on these features.Setting:Telephone interviews were conducted to gain insight into shoppers’ needs and perceptions. Results were used by the research team to identify potential online grocery shopping features that may support healthful purchase decisions, and interviews were conducted with a different sample of shoppers to gather feedback on features.Participants:Insight (n 25) and feedback (n 25) interviews were conducted with convenience samples of adults trying to lose weight.Results:Participants were primarily female, white, college educated and with obesity or overweight. Online grocery features devised by the research team based on findings from the insight interviews included (1) shopping cart nutrition rating tool; (2) healthy meal planning tool; (3) interactive healthy eating inspiration aisle and (4) healthy shopping preference settings option. Findings from the feedback interviews indicated that the healthy meal planning tool, healthy shopping preference settings option and shopping cart nutrition rating tool features were positively rated by most participants.Conclusions:There are multiple features grocers should consider including in their online stores to attract and support customers striving to eat healthy for weight loss.
Exome-wide age-of-onset analysis reveals exonic variants in ERN1 and SPPL2C associated with Alzheimer’s disease
Authors: He Liang , Loika Yury , Park Yongjin ,   Genotype Tissue Expression (GTEx) consortium, Bennett David A. , Kellis Manolis , Kulminski Alexander M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

AbstractDespite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer’s disease (AD), its underlying biological mechanisms are still elusive. The discovery of novel AD-associated genetic variants, particularly in coding regions and from APOEε4 non-carriers, is critical for understanding the pathology of AD. In this study, we carried out an exome-wide association analysis of age-of-onset of AD with ~20,000 subjects and placed more emphasis on APOEε4 non-carriers. Using Cox mixed-effects models, we find that age-of-onset shows a stronger genetic signal than AD case-control status, capturing many known variants with stronger significance, and also revealing new variants. We identified two novel variants, rs56201815, a rare synonymous variant in ERN1, and rs12373123, a common missense variant in SPPL2C in the MAPT region in APOEε4 non-carriers. Besides, a rare missense variant rs144292455 in TACR3 showed the consistent direction of effect sizes across all studies with a suggestive significant level. In an attempt to unravel their regulatory and biological functions, we found that the minor allele of rs56201815 was associated with lower average FDG uptake across five brain regions in ADNI. Our eQTL analyses based on 6198 gene expression samples from ROSMAP and GTEx revealed that the minor allele of rs56201815 was potentially associated with elevated expression of ERN1, a key gene triggering unfolded protein response (UPR), in multiple brain regions, including the posterior cingulate cortex and nucleus accumbens. Our cell-type-specific eQTL analysis using ~80,000 single nuclei in the prefrontal cortex revealed that the protective minor allele of rs12373123 significantly increased the expression of GRN in microglia, and was associated with MAPT expression in astrocytes. These findings provide novel evidence supporting the hypothesis of the potential involvement of the UPR to ER stress in the pathological pathway of AD, and also give more insights into underlying regulatory mechanisms behind the pleiotropic effects of rs12373123 in multiple degenerative diseases including AD and Parkinson’s disease.
Neurosteroid allopregnanolone (3α,5α-THP) inhibits inflammatory signals induced by activated MyD88-dependent toll-like receptors
Authors: Balan Irina , Aurelian Laure , Schleicher Riana , Boero Giorgia , O’Buckley Todd , Morrow A. Leslie 
Published: February 2021

AbstractWe have shown that endogenous neurosteroids, including pregnenolone and 3α,5α-THP inhibit toll-like receptor 4 (TLR4) signal activation in mouse macrophages and the brain of alcohol-preferring (P) rat, which exhibits innate TLR4 signal activation. The current studies were designed to examine whether other activated TLR signals are similarly inhibited by 3α,5α-THP. We report that 3α,5α-THP inhibits selective agonist-mediated activation of TLR2 and TLR7, but not TLR3 signaling in the RAW246.7 macrophage cell line. The TLR4 and TLR7 signals are innately activated in the amygdala and NAc from P rat brains and inhibited by 3α,5α-THP. The TLR2 and TLR3 signals are not activated in P rat brain and they are not affected by 3α,5α-THP. Co-immunoprecipitation studies indicate that 3α,5α-THP inhibits the binding of MyD88 with TLR4 or TLR7 in P rat brain, but the levels of TLR4 co-precipitating with TRIF are not altered by 3α,5α-THP treatment. Collectively, the data indicate that 3α,5α-THP inhibits MyD88- but not TRIF-dependent TLR signal activation and the production of pro-inflammatory mediators through its ability to block TLR-MyD88 binding. These results have applicability to many conditions involving pro-inflammatory TLR activation of cytokines, chemokines, and interferons and support the use of 3α,5α-THP as a therapeutic for inflammatory disease.
Inhibition of intervertebral disc disease progression via the circPKNOX1–miR-370-3p–KIAA0355 axis
Authors: Huang Yizhen , Gao Jun , Wang Jianle , Ye Huali , Yao Teng , Xu Yining , Chen Zizheng , Shen Shuying , Ma Jianjun 
Published: February 2021

AbstractThe molecular mechanism underlying the development of intervertebral disc disease (IVDD) is not completely understood. Circular RNAs (circRNAs) play a significant role in the occurrence and development of various diseases, and studies have shown that circPKNOX1 is involved in the compensatory response of extracellular matrix synthesis and secretion of the nucleus pulposus (NP) cells. However, the mechanism through which circRNAs regulate IVDD progression remains unclear; therefore, in this study, we explored the significance of circPKNOX1 in IVDD. The expression of circRNAs in NP cells of normal and degenerative patients was detected using microarray analysis, and the role of circPKNOX1 in IVDD was confirmed using RT-qPCR. The interaction networks of circRNAs, miRNAs, and miRNA target genes were detected using bioinformatics analysis, RNA fluorescence in situ hybridization, and immunofluorescence analysis. We found that the expression of circPKNOX1 decreased in IVDD cells. The expression of circPKNOX1 in NP cells, observed using RT-qPCR and western blotting, was consistent with that observed using array screening. Overexpression of circPKNOX1 increased the expression of collagen II, aggrecan, and SOX9 and decreased that of ADAMTS4, ADAMTS-5, MMP3, and MMP13. We further demonstrated that circPKNOX1 played the role of a sponge by competitively binding miR-370-3p to reverse the inhibition of KIAA0355 expression. Our findings indicated that circPKNOX1 affected the progression of IVDD by regulating the expression of KIAA0355 via miR-370-3p. Therefore, circPKNOX1-based therapy may serve as an effective IVDD treatment strategy.
GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study
Authors: Rodríguez-Valdés Patricio J. , Rehak Matus , Zur Dinah , Sala-Puigdollers Anna , Fraser-Bell Samantha , Lupidi Marco , Chhablani Jay , Cebeci Zafer , Laíns Inês , Chaikitmongkol Voraporn , Fung Adrian T. , Okada Mali , Unterlauft Jan Darius , Smadar Lital , Loewenstein Anat , Iglicki Matias , Busch Catharina 
Published: February 2021

AbstractTo analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.
(E)-N-(2-(3, 5-Dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) induces cytoprotection in CCD18-Co human colon fibroblast cells through Nrf2/ARE pathway activation
Authors: Tan Huan Huan , Thomas Noel Francis , Inayat-Hussain Salmaan Hussain , Chan Kok Meng 
Published: February 2021

AbstractCytoprotection involving the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is an important preventive strategy for normal cells against carcinogenesis. In our previous study, the chemopreventive potential of (E)-N-(2-(3, 5-Dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) has been elucidated through its cytoprotective effects against DNA and mitochondrial damages in the human colon fibroblast CCD-18Co cell model. Therefore this study aimed to investigate the molecular mechanisms underlying BK3C231-induced cytoprotection and the involvement of the Nrf2/ARE pathway. The cells were pretreated with BK3C231 before exposure to carcinogen 4-nitroquinoline N-oxide (4NQO). BK3C231 increased the protein expression and activity of cytoprotective enzymes namely NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST) and heme oxygenase-1 (HO-1), as well as restoring the expression of glutamate-cysteine ligase catalytic subunit (GCLC) back to the basal level. Furthermore, dissociation of Nrf2 from its inhibitory protein, Keap1, and ARE promoter activity were upregulated in cells pretreated with BK3C231. Taken together, our findings suggest that BK3C231 exerts cytoprotection by activating the Nrf2 signaling pathway which leads to ARE-mediated upregulation of cytoprotective proteins. This study provides new mechanistic insights into BK3C231 chemopreventive activities and highlights the importance of stilbene derivatives upon development as a potential chemopreventive agent.
A plant plasma-membrane H+-ATPase promotes yeast TORC1 activation via its carboxy-terminal tail
Authors: Saliba Elie , Primo Cecilia , Guarini Nadia , André Bruno 
Published: February 2021

AbstractThe Target of Rapamycin Complex 1 (TORC1) involved in coordination of cell growth and metabolism is highly conserved among eukaryotes. Yet the signals and mechanisms controlling its activity differ among taxa, according to their biological specificities. A common feature of fungal and plant cells, distinguishing them from animal cells, is that their plasma membrane contains a highly abundant H+-ATPase which establishes an electrochemical H+ gradient driving active nutrient transport. We have previously reported that in yeast, nutrient-uptake-coupled H+ influx elicits transient TORC1 activation and that the plasma-membrane H+-ATPase Pma1 plays an important role in this activation, involving more than just establishment of the H+ gradient. We show here that the PMA2 H+-ATPase from the plant Nicotiana plumbaginifolia can substitute for Pma1 in yeast, to promote H+-elicited TORC1 activation. This H+-ATPase is highly similar to Pma1 but has a longer carboxy-terminal tail binding 14–3–3 proteins. We report that a C-terminally truncated PMA2, which remains fully active, fails to promote H+-elicited TORC1 activation. Activation is also impaired when binding of PMA2 to 14–3–3 s is hindered. Our results show that at least some plant plasma-membrane H+-ATPases share with yeast Pma1 the ability to promote TORC1 activation in yeast upon H+-coupled nutrient uptake.
Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations
Authors: Pawlowski Colin , Puranik Arjun , Bandi Hari , Venkatakrishnan A. J. , Agarwal Vineet , Kennedy Richard , O’Horo John C. , Gores Gregory J. , Williams Amy W. , Halamka John , Badley Andrew D. , Soundararajan Venky 
Published: February 2021

AbstractClinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Haemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), Varicella, pneumococcal conjugate (PCV13), Geriatric Flu, and hepatitis A/hepatitis B (HepA–HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI (0.32, 0.64), p-value: 6.9e−05). Overall, this study identifies existing approved vaccines which can be promising candidates for pre-clinical research and Randomized Clinical Trials towards combating COVID-19.
Postural adjustments impairments in elderly people with chronic low back pain
Authors: Garcez Daniela Rosa , da Silva Almeida Gizele Cristina , Silva Carlos Felipe Oliveira , de Souza Nascimento Tainá , de Athayde Costa e Silva Anselmo , Kleiner Ana Francisca Rozin , da Silva Souza Givago , Yamada Elizabeth Sumi , Callegari Bianca 
Published: February 2021

AbstractChronic low back pain (CLBP) is associated with postural control impairments and is highly prevalent in elderly people. The objective of this study is to verify whether anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are affected by CLBP in elderly people by assessing their postural control during a self-initiated perturbation paradigm induced by rapid upper arm movement when pointing to a target. The participants’ lower limb muscle onset and center of pressure (COP) displacements were assessed prior to perturbation and throughout the entire movement. T0 moment (i.e., the beginning of the movement) was defined as the anterior deltoid (DEL) onset, and all parameters were calculated with respect to it. The rectus femoris (RT), semitendinosus (ST), and soleous (SOL) showed delayed onset in the CLBP group compared with the control group: RF (control: − 0.094 ± 0.017 s; CLBP: − 0.026 ± 0.012 s, t = 12, p < 0.0001); ST (control: − 0.093 ± 0.013 s; CLBP: − 0.018 ± 0.019 s, t = 12, p < 0.0001); and SOL (control: − 0.086 ± 0.018 s; CLBP: − 0.029 ± 0.015 s, t = 8.98, p < 0.0001). In addition, COP displacement was delayed in the CLBP group (control: − 0.035 ± 0.021 s; CLBP: − 0.015 ± 0.009 s, t = 3; p = 0.003) and presented a smaller amplitude during APA COPAPA [control: 0.444 cm (0.187; 0.648); CLBP: 0.228 cm (0.096; 0.310), U = 53, p = 0.012]. The CLBP group required a longer time to reach the maximum displacement after the perturbation (control: 0.211 ± 0.047 s; CLBP 0.296 ± 0.078 s, t = 3.582, p = 0.0013). This indicates that CLBP elderly patients have impairments to recover their postural control and less efficient anticipatory adjustments. Our results suggest that people with CLBP have altered feedforward hip and ankle muscle control, as shown from the SOL, ST, and RT muscle onset. This study is the first study in the field of aging that investigates the postural adjustments of an elderly population with CLBP. Clinical assessment of this population should consider postural stability as part of a rehabilitation program.
Faecal bacterial composition in horses with and without free faecal liquid: a case control study
Authors: Lindroth Katrin M. , Dicksved Johan , Pelve Erik , Båverud Viveca , Müller Cecilia E. 
Published: February 2021

AbstractFree faecal liquid (FFL) is a condition in horses which manifests as differential defecation of solid and liquid phases of faeces. The etiology of FFL is currently unknown, but deviances in the hindgut microbiota has been suggested to be of importance. The present study aimed to compare the faecal bacterial composition of farm-matched horses with (case, n = 50) and without (control, n = 50) FFL. Samples were collected at three different occasions. The V3 and V4 regions of the 16S rRNA gene were amplified and sequenced using Illumina sequencing. Also, samples were cultivated for detection ofClostridioides difficileandClostridium perfringens. Analysis revealed similar faecal bacterial composition between case and control horses, but an effect of sampling period (p = 0.0001). Within sampling periods, 14 genera were present in higher or lower proportions in case compared to control horses in at least one sampling period. Compared to controls, case horses had higher relative abundance ofAlloprevotella(adjusted p < 0.04) and lower relative abundance ofBacillusspp.(adjusted p < 0.03) in at least two sampling periods. All horses tested negative forC. difficileandC. perfringensby culture of faeces. Further studies are required to establish the clinical relevance of specific bacterial taxa in FFL.
Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
Authors: Mahoney Heather , Peterson Emily , Justin Hannah , Gonzalez David , Cardona Christopher , Stevanovic Korey , Faulkner John , Yunus Amara , Portugues Alexandra , Henriksen Amy , Burns Camden , McNeill Cameron , Gamsby Joshua , Gulick Danielle 
Published: February 2021

AbstractTime-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of the circadian system, either at the level of the master clock in the SCN or downstream, impairs hippocampus-dependent learning and memory. A number of kinases, including the serine-threonine casein kinase 1 (CK1) isoforms CK1δ/ε, regulate the timing of the circadian period through post-translational modification of clock proteins. Modulation of these circadian kinases presents a novel treatment direction for cognitive deficits through circadian modulation. Here, we tested the potential for PF-670462, a small molecule inhibitor of CK1δ/ε, to improve cognitive performance in C57BL/6J mice in an array of behavioral tests. Compared to vehicle-treated mice tested at the same time of the circadian day, mice treated with PF-670462 displayed better recall of contextual fear conditioning, made fewer working memory errors in the radial arm water maze, and trained more efficiently in the Morris Water Maze. These benefits were accompanied by increased expression of activity-regulated cytoskeleton-associated protein (Arc) in the amygdala in response to an acute learning paradigm. Our results suggest the potential utility of CK1δ/ε inhibition in improving time-of-day cognitive performance.
Chemokinesis-driven accumulation of active colloids in low-mobility regions of fuel gradients
Authors: Moran Jeffrey L. , Wheat Philip M. , Marine Nathan A. , Posner Jonathan D. 
Published: February 2021

AbstractMany motile cells exhibit migratory behaviors, such as chemotaxis (motion up or down a chemical gradient) or chemokinesis (dependence of speed on chemical concentration), which enable them to carry out vital functions including immune response, egg fertilization, and predator evasion. These have inspired researchers to develop self-propelled colloidal analogues to biological microswimmers, known as active colloids, that perform similar feats. Here, we study the behavior of half-platinum half-gold (Pt/Au) self-propelled rods in antiparallel gradients of hydrogen peroxide fuel and salt, which tend to increase and decrease the rods’ speed, respectively. Brownian Dynamics simulations, a Fokker–Planck theoretical model, and experiments demonstrate that, at steady state, the rods accumulate in low-speed (salt-rich, peroxide-poor) regions not because of chemotaxis, but because of chemokinesis. Chemokinesis is distinct from chemotaxis in that no directional sensing or reorientation capabilities are required. The agreement between simulations, model, and experiments bolsters the role of chemokinesis in this system. This work suggests a novel strategy of exploiting chemokinesis to effect accumulation of motile colloids in desired areas.