bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-146a-5p, targeting ErbB4, promotes 3T3-L1 preadipocyte differentiation through the ERK1/2/PPAR-γ signaling pathway
Authors: Wang Yifen , Zhang Jie , Chu Xueru , Wang Mengke , Xin Yongning , Liu Shousheng 
Published: June 2022

Abstract
Background
MicroRNAs (MiRNAs) are known to participate in preadipocyte differentiation, but the manner in which miR-146a-5p participates in this process remains unclear. This study was performed to examine the participation of miR-146a-5p in 3T3-L1 cell differentiation.

Material and Methods
miR-146a-5p expression was upregulated and down-regulated to examine effects on 3T3-L1 cell differentiation. Bioinformatics analysis was performed to predict its target genes, and the signaling pathway it regulates was identified by qRT-PCR and Western blotting. The expression of miR-146a-5p in epididymal adipose tissue from obese mice and in an obese mouse adipose cell model was examined by qRT-PCR.

Results
3T3-L1 cells differentiated into mature adipocytes successfully, as verified by increased areas of intracellular lipid droplets and elevated expression of mature adipocyte markers, and these cells had elevated miR-146a-5p expression. The intracellular lipid droplet and triglyceride contents and the expression of mature adipocyte markers were significantly increased in miR-146a-5p–overexpressing 3T3-L1 cells and markedly decreased in miR-146a-5p–inhibited 3T3-L1 cells. ErbB4 was a predicted target gene of miR-146a-5p. In miR-146a-5p–overexpressing 3T3-L1 cells, ErbB4 expression and ERK1/2 phosphorylation were decreased and the expression of PPAR-γ was increased; the opposite was observed in miR-146a-5p–inhibited 3T3-L1 cells. In addition, miR-146a-5p expression was significantly increased in the mouse epididymal adipose tissue and adipose cell model.

Conclusions
Upregulated miR-146a-5p expression was related to 3T3-L1 cell differentiation. MiR-146a-5p promoted 3T3-L1 cell differentiation by targeting ErbB4 and via the ERK1/2/PPAR-γ signaling pathway.
Microbial hydrogen “manufactory” for enhanced gas therapy and self-activated immunotherapy via reduced immune escape
Authors: Yan Hongyu , Fan Miao , Liu Huifang , Xiao Tingshan , Han Dandan , Che Ruijun , Zhang Wei , Zhou Xiaohan , Wang June , Zhang Chi , Yang Xinjian , Zhang Jinchao , Li Zhenhua 
Published: June 2022

Abstract
Background
As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect.

Results
Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape.

Conclusion
Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1.

Graphical Abstract
The benefits and challenges of taxing sugar in a small island state: an interrupted time series analysis
Authors: Segal Alexa Blair , Olney Jack , Case Kelsey K. , Sassi Franco 
Published: June 2022

Abstract
Background
Beverage and food taxes have become a popular ‘best buy’ public health intervention in the global battle to tackle noncommunicable diseases. Though many countries have introduced taxes, mainly targeting products containing sugar, there is great heterogeneity in tax design. For taxes levied as import tariffs, there is limited evidence of effectiveness in changing the price and sale of taxed products, while the evidence base is stronger for excise taxes levied as a fixed amount per quantity of product. This paper examines the effect of the Bermuda Discretionary Foods Tax, which was based on import tariff changes, on retail prices and sales of sugar-sweetened beverages (SSBs), and on selected fruits and vegetables that benefited from a tariff reduction.

Methods
We used weekly electronic point-of-sale data from a major food retailer in Bermuda. We assessed historical weekly sales and price data using an interrupted time series design on 2,703 unique products between the dates of January 2018 through January 2020, covering 103 weeks.

Results
By January 2020, the average price per ounce of SSBs increased by 26.0%, while the price of untaxed beverages (including waters and non-added sugar drinks) remained constant. The increasing price of SSBs was the sole observable structural driver of SSB market share, responsible for a decrease in the market share by nearly eight percentage points by the end of the study period. The subsidy on fruits and vegetables was ineffective in changing prices and sales, due to the relatively small 5% import tax decrease.

Conclusions
The tax was largely passed through to consumers. However, several factors mitigated the impact of the tax on the prices paid for SSBs by consumers, including the specific design of the tax, price promotions and consumer responses. The experience of Bermuda provides important lessons for the planning of similar taxes in the future.
Prehabilitative resistance exercise reduces neuroinflammation and improves mitochondrial health in aged mice with perioperative neurocognitive disorders
Authors: Liu Yan , Chu John Man Tak , Ran You , Zhang Yan , Chang Raymond Chuen Chung , Wong Gordon Tin Chun 
Published: June 2022

Abstract
Background
Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus.

Methods
18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups.

Results
18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3β signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice.

Conclusions
Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway.
A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study
Authors: Stephens Robert J. , Evans Erin M. , Pajor Michael J. , Pappal Ryan D. , Egan Haley M. , Wei Max , Hayes Hunter , Morris Jason A. , Becker Nicholas , Roberts Brian W. , Kollef Marin H. , Mohr Nicholas M. , Fuller Brian M. 
Published: June 2022

Abstract
Background
Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

Study design and methods
Dual-center, retrospective cohort study conducted over 6 months (March–August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of − 3 to − 5 or Riker Sedation-Agitation Scale of 1–3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.

Results
391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65–7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19.

Conclusions
The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.
SCADIE: simultaneous estimation of cell type proportions and cell type-specific gene expressions using SCAD-based iterative estimating procedure
Authors: Tang Daiwei , Park Seyoung , Zhao Hongyu 
Published: June 2022

AbstractA challenge in bulk gene differential expression analysis is to differentiate changes due to cell type-specific gene expression and cell type proportions. SCADIE is an iterative algorithm that simultaneously estimates cell type-specific gene expression profiles and cell type proportions, and performs cell type-specific differential expression analysis at the group level. Through its unique penalty and objective function, SCADIE more accurately identifies cell type-specific differentially expressed genes than existing methods, including those that may be missed from single cell RNA-Seq data. SCADIE has robust performance with respect to the choice of deconvolution methods and the sources and quality of input data.
HA gene amino acid mutations contribute to antigenic variation and immune escape of H9N2 influenza virus
Authors: Zhu Rui , Xu Shunshun , Sun Wangyangji , Li Quan , Wang Shifeng , Shi Huoying , Liu Xiufan 
Published: June 2022

AbstractBased on differences in the amino acid sequence of the protein haemagglutinin (HA), the H9N2 avian influenza virus (H9N2 virus) has been clustered into multiple lineages, and its rapidly ongoing evolution increases the difficulties faced by prevention and control programs. The HA protein, a major antigenic protein, and the amino acid mutations that alter viral antigenicity in particular have always been of interest. Likewise, it has been well documented that some amino acid mutations in HA alter viral antigenicity in the H9N2 virus, but little has been reported regarding how these antibody escape mutations affect antigenic variation. In this study, we were able to identify 15 HA mutations that were potentially relevant to viral antigenic drift, and we also found that a key amino acid mutation, A180V, at position 180 in HA (the numbering for mature H9 HA), the only site of the receptor binding sites that is not conserved, was directly responsible for viral antigenic variation. Moreover, the recombinant virus with alanine to valine substitution at position 180 in HA in the SH/F/98 backbone (rF/HAA180V virus) showed poor cross-reactivity to immune sera from animals immunized with the SH/F/98 (F/98, A180), SD/SS/94 (A180), JS/Y618/12 (T180), and rF/HAA180V (V180) viruses by microneutralization (MN) assay. The A180V substitution in the parent virus caused a significant decrease in cross-MN titres by enhancing the receptor binding activity, but it did not physically prevent antibody (Ab) binding. The strong receptor binding avidity prevented viral release from cells. Moreover, the A180V substitution promoted H9N2 virus escape from an in vitro pAb-neutralizing reaction, which also slightly affected the cross-protection in vivo. Our results suggest that the A180V mutation with a strong receptor binding avidity contributed to the low reactors in MN/HI assays and slightly affected vaccine efficacy but was not directly responsible for immune escape, which suggested that the A180V mutation might play a key role in the process of the adaptive evolution of H9N2 virus.
Alternating 3 different influenza vaccines for swine in Europe for a broader antibody response and protection
Authors: Parys Anna , Vandoorn Elien , Chiers Koen , Van Reeth Kristien 
Published: June 2022

AbstractHeterologous prime-boost vaccination with experimental or commercial influenza vaccines has been successful in various animal species. In this study, we have examined the efficacy of alternating 3 different European commercial swine influenza A virus (swIAV) vaccines: the trivalent Respiporc® FLU3 (TIV), the bivalent GRIPORK® (BIV) and the monovalent Respiporc® FLUpan H1N1 (MOV). Five groups of 6 pigs each received 3 vaccinations at 4–6 week intervals in a homologous or heterologous prime-boost regimen. A sixth group served as a mock-vaccinated challenge control. Four weeks after the last vaccination, pigs were challenged intranasally with a European avian-like H1N1 (1C.2.1) swIAV, which was antigenically distinct from the vaccine strains. One heterologous prime-boost group (TIV–BIV–MOV) had higher hemagglutination inhibition (HI) and neuraminidase inhibition antibody responses against a panel of antigenically distinct H1N1, H1N2 and H3N2 IAVs than the other heterologous prime-boost group (BIV–TIV–MOV) and the homologous prime-boost groups (3xTIV; 3xBIV; 3xMOV). Group TIV–BIV–MOV had seroprotective HI titers (≥ 40) against 56% of the tested viruses compared to 33% in group BIV–TIV–MOV and 22–39% in the homologous prime-boost groups. Post-challenge, group TIV–BIV–MOV was the single group with significantly reduced virus titers in all respiratory samples compared to the challenge control group. Our results suggest that the use of different commercial swIAV vaccines for successive vaccinations may result in broader antibody responses and protection than the traditional, homologous prime-boost vaccination regimens. In addition, the order in which the different vaccines are administered seems to affect the breadth of the antibody response and protection.
Characterization of siderophores from Escherichia coli strains through genome mining tools: an antiSMASH study
Authors: Cavas Levent , Kirkiz Ibrahim 
Published: June 2022

AbstractAlthough urinary tract infections (UTIs) affect many people, they are usually a disease observed in women. UTIs happen when exogenous and endogenous bacteria enter the urinary tract and colonize there. Cystitis and pyelonephritis occur when bacteria infect the bladder and the kidneys, respectively. UTIs become much serious if the bacteria causing the infection are antibiotic resistant. Since the pathogenic microorganisms have been adopted to current antibiotics via genetic variations, UTIs have become an even more severe health problem. Therefore, there is a great need for the discovery of novel antibiotics. Genome mining of nonpathogenic and pathogenic Escherichia coli strains for investigating secondary metabolites were conducted by the antiSMASH analysis. When the resulting secondary metabolites were examined, it was found that some of the siderophores are effective in UTIs. In conclusion, since the siderophore production in E. coli is directly related to UTIs, these molecules can be a good target for development of future pharmaceutical approaches and compounds. Siderophores can also be used in industrial studies due to their higher chelating affinity for iron.
How does the 120-year cycle mast seeding of dwarf bamboo affect the rodent population?
Authors: Suzuki Hanami , Kashiwagi Haruka , Kajimura Hisashi 
Published: June 2022

Abstract
Background
In 2017, large-scale flowering, seeding, and dying events of dwarf bamboo (Sasa borealis) occurred in a wide range in central Japan for the first time in 120 years. This phenomenon of S. borealis, like the mast seeding of trees, could be expected to provide a large amount of food for seed-eating rodents and gradually affect their ecology and population dynamics. We captured rodents in survey plots in a secondary broad-leaved forest with the phenomenon from 2018 to 2019 to investigate the species, the number of individuals, growing stage, sex, and body mass. In addition, we also compared the capture data for 2 years (2018–2019) with that for the mast seeding year (2017) and 6 years before it (2011–2016).

Results
The mast seeding of S. borealis greatly increased the population size of rodents, especially Apodemus speciosus and A. argenteus. Conversely, Eothenomys smithii did not show such an increase. Most of the captured rodent individuals were already adults at the time of new capture, and the proportion of male juveniles was extremely low. These results suggest that the mast seeding of S. borealis created unusually rich food availability for the population concentration of rodents due to their immigration. However, body mass was not significantly different before and after the mast seeding. In addition, the increased populations of the two Apodemus species did not decline 2 years after the S. borealis masting, contrary to the previously reported decrease of rodent populations after tree masting.

Conclusions
Our results indicate that the mast seeding of S. borealis affected the population dynamics of Apodemus species over a long time and their individual composition of different growth stages. However, it did not affect their body mass.
Public expenditure for water facility and road transport infrastructure in Ethiopia: a comparison of impacts using an economy-wide model
Authors: Mosa Abdulaziz Abdulsemed 
Published: June 2022

Abstract
Background
Ethiopian government is investing in a wide range of pro-poor sectors but the economic effects of public investment widely vary across sectors. With a limited public resource, public investment across sectors has to be prioritized based on their potential socio-economic contributions and/or economy-wide benefits. Therefore, the objective of this study is to compare and explore the economy-wide returns of public expenditure on water facility and energy technology (such as improved cooking stoves) on the one hand and public expenditure on road infrastructure on the other hand.

Methods
The source of data for this study is the 2005/06 updated Social accounting matrix (SAM) of Ethiopia. The analysis applies the STAGE Computable General Equilibrium (CGE) model developed by McDonald (2007). This study analyses two policy scenarios; the first scenario is an increase in the total factor productivity (TFP) of water fetching and firewood collection activities due to public investment in water facility and improved cooking stoves and the second scenario is a decrease in the trade and transport margins due to public investment in road transport infrastructure. For ensuring the comparability of the return of public expenditure, the same amount of public capital is invested in both scenarios.

Results
The simulation outcome indicates that public investment in water facility and improved stoves results relatively higher domestic production in most sectors, larger household consumption, improved household welfare and improve in the major macroeconomic indicators (GDP, absorption, private consumption, and total domestic production) as compared to public investment in road transport infrastructure.

Conclusions
It is conducive to explore the potential economic contribution of public expenditure across the different pro-poor sectors before launching public investment in any specific sector. This will ensure limited public budgets are appropriately invested in the sector that can bring relatively highest economic-wide benefits to the wider society.
A focus group study of therapists’ views on using a novel neuroanimation virtual reality game to deliver intensive upper-limb rehabilitation early after stroke
Authors: Stockley Rachel C. , Christian Danielle L. 
Published: June 2022

Abstract
Background
Intensive training can significantly reduce upper-limb impairments after stroke but delivering interventions of sufficiently high intensity is extremely difficult in routine practice. The MindPod Dolphin® system is a novel neuroanimation experience which provides motivating and intensive virtual reality based training for the upper-limb. However several studies report that health professionals have reservations about using technology in rehabilitation. Therefore, this study sought to explore the views of therapists who had used this novel neuroanimation therapy (NAT) in a clinical centre to deliver intensive for the upper-limb of people after stroke in a phase 2 trial (SMARTS2).

Methods
Four therapists (three female, two physical and two occupational therapists) who delivered NAT participated in a focus group conducted by two independent researchers. The theoretical domains framework and COM-B behaviour change models informed the discussion schedule for the focus group. An inductive approach to content analysis was used. Recordings were transcribed, coded and thematically analysed. Generated key themes were cross-checked with participants.

Results
Whilst therapists had some initial concerns about using NAT, these were reduced by training, reference materials and face-to-face technical support. Therapists noted several significant benefits to using NAT including multi-system involvement, carry-over to functional tasks and high levels of patient engagement.

Conclusions
These findings illuminate key areas that clinicians, technology developers and researchers should consider when designing, developing and implementing NAT. Specifically, they highlight the importance of planning the implementation of rehabilitation technologies, ensuring technologies are robust and suggest a range of benefits that might be conferred to patients when using intensive NAT as part of rehabilitation for the upper-limb after stroke.