bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protective effects of phosphodiesterase-5 inhibitor, sildenafil on post-resuscitation cardiac dysfunction of cardiac arrest: by regulating the miR-155-5p and miR-145-5p
Authors: He Yong , Wang Guoxing , Li Chuang , Wang Yuxing , Zhang Qian 
Published: January 2021

Abstract
Background
MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.

Methods
Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury.

Results
Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.

Conclusions
Sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.
Alternatives to direct emergency department conveyance of ambulance patients: a scoping review of the evidence
Authors: Blodgett Joanna M. , Robertson Duncan J. , Pennington Elspeth , Ratcliffe David , Rockwood Kenneth 
Published: January 2021

Abstract
Background
The role of ambulance services is shifting, due in part to more intermediate, non-urgent patients who do not require direct emergency department conveyance, yet who cannot be safely left at home alone. Evidence surrounding the safety, effectiveness and efficiency of alternate care routes is not well known.

Methods
This scoping review sought to identify all studies that examined alternate routes of care for the non-urgent “intermediate” patient, as triaged on scene. Search terms for the sample (ambulances, paramedics, etc.) and intervention (e.g. referrals, alternate care route, non-conveyance) were combined. Articles were systematically searched using four databases and grey literature sources (February 2020). Independent researchers screened title-abstract and full text stages.

Results
Of 16,037 records, 41 examined alternate routes of care after triage by the on-scene paramedic. Eighteen articles considered quantitative patient data, 12 studies provided qualitative perspectives while 11 were consensus or opinion-based articles. The benefits of alternative schemes are well-recognised by patients, paramedics and stakeholders and there is supporting evidence for a positive impact on patient-centered care and operational efficiency. Challenges to successful use of schemes included: patient safety resulting from incorrect triage decisions, inadequate training, lack of formal partnerships between ambulance and supporting services, and insufficient evidence to support safe implementation or continued use. Studies often inaccurately defined success using proxies for patient safety (e.g. decision comparisons, rates of secondary contact). Finally, patients expressed willingness for such schemes but their preference must be better understood.

Conclusions
This broad summary offers initial support for alternate routes of care for intermediate, non-urgent patients. Even so, most studies lacked methodologically rigorous evidence and failed to evaluate safe patient outcomes. Some remedies appear to be available such as formal triage pathways, targeted training and organisational support, however there is an urgent need for more research and dissemination in this area.
Hospital-level intracranial pressure monitoring utilization and functional outcome in severe traumatic brain injury: a post hoc analysis of prospective multicenter observational study
Authors: Okazaki Tomoya , Kawakita Kenya , Kuroda Yasuhiro 
Published: January 2021

Abstract
Background
Several observational studies have shown that hospital-level intracranial pressure (ICP) monitoring utilization varies considerably in patients with severe traumatic brain injury (TBI). However, the relationship between hospital-level ICP monitoring utilization and clinical functional outcomes is unknown. This study examined whether patients with severe TBI treated at hospitals with high ICP monitoring utilization have better functional outcomes.

Methods
A post hoc analysis of the data from a prospective multicenter cohort study in Japan was undertaken, and included severe TBI patients (Glasgow Come Scale score ≤ 8). The primary exposure was hospital-level ICP monitoring utilization. Patients treated at hospitals with more than 80% ICP monitoring utilization were assigned to a high group and the others to a low group. The primary endpoint was a favorable functional outcome at 6 months after injury, defined as a Glasgow Outcome Scale score of good recovery or moderate disability. We conducted multiple logistic regression analyses adjusted for potential confounders.

Results
Of the 427 included patients, 60 were assigned to the high group and 367 to the low group. Multiple logistic regression analysis revealed that patients in the high group had significantly better functional outcome (adjusted odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.17–4.76; p = 0.016). Multiple logistic regression analysis adjusted for additional confounders supported this result (adjusted OR: 2.30; 95% CI: 1.07–4.92; p = 0.033).

Conclusion
Treatment at hospitals with high ICP monitoring utilization for severe TBI patients could be associated with better functional outcome.
Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: study protocol for a randomized controlled trial
Authors: Di Gregorio Francesco , La Porta Fabio , Casanova Emanuela , Magni Elisabetta , Bonora Roberta , Ercolino Maria Grazia , Petrone Valeria , Leo Maria Rosaria , Piperno Roberto 
Published: January 2021

AbstractBackgroundLeft hemispatial neglect (LHN) is a neuropsychological syndrome often associated with right hemispheric stroke. Patients with LHN have difficulties in attending, responding, and consciously representing the right side of space. Various rehabilitation protocols have been proposed to reduce clinical symptoms related to LHN, using cognitive treatments, or on non-invasive brain stimulation. However, evidence of their benefit is still lacking; in particular, only a few studies focused on the efficacy of combining different approaches in the same patient.MethodsIn the present study, we present the SMART ATLAS trial (StimolazioneMAgneticaRipetitivaTranscranica nell’ATtenzioneLAteralizzata dopoStroke), a multicenter, randomized, controlled trial with pre-test (baseline), post-test, and 12 weeks follow-up assessments based on a novel rehabilitation protocol based on the combination of brain stimulation and standard cognitive treatment. In particular, we will compare the efficacy of inhibitory repetitive-transcranial magnetic stimulation (r-TMS), applied over the left intact parietal cortex of LHN patients, followed by visual scanning treatment, in comparison with a placebo stimulation (SHAM control) followed by the same visual scanning treatment, on visuospatial symptoms and neurophysiological parameters of LHN in a population of stroke patients.DiscussionOur trial results may provide scientific evidence of a new, relatively low-cost rehabilitation protocol for the treatment of LHN.Trial registrationClinicalTrials.govNCT04080999. Registered on September 2019.
Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial)
Authors: Bandak Elisabeth , Overgaard Anders F. , Kristensen Lars Erik , Ellegaard Karen , Guldberg-Møller Jørgen , Bartholdy Cecilie , Hunter David J. , Altman Roy D. , Christensen Robin , Bliddal Henning , Henriksen Marius 
Published: January 2021

Abstract
Background
Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the ‘active’ ingredients are unknown. Designing and executing an adequate and ‘blindable placebo’ version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used ‘state-of-art’ exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.

Methods
In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients’ global assessment of disease impact, physical performance tests, and presence of knee joint swelling.

Discussion
This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.

Trial registration
www.ClinicalTrials.govNCT03843931. Prospectively registered on 18 February 2019.
Efficacy of prophylactic methylprednisolone on reducing the risk of post-extubation stridor in patients after an emergency intubation: study protocol for a randomized controlled trial
Authors: Wang Jingyi , Walline Joseph Harold , Yin Lu , Dai Yili , Dai Jiayuan , Zhu Huadong , Yu Xuezhong , Xu Jun 
Published: January 2021

Abstract
Background
Post-extubation stridor (PES) is one of the most common complications of invasive respiratory support, with severe cases leading to possible extubation failure (reintubation within 48 h) and increased mortality. Previous studies confirmed that prophylactic corticosteroids play an important role in reducing the risk of PES and extubation failure. However, few studies have looked at the efficacy of corticosteroids on preventing PES in patients after an emergency intubation.

Aim
To evaluate whether a single dose of methylprednisolone given over a set timeframe before extubation is effective in preventing PES in patients after an emergency intubation.

Methods
A multicenter, randomized, placebo-controlled trial will be performed in an emergency department (ED) setting. The trial will include 132 patients who fail a cuff-leak test (CLT) prior to the intervention. Patients will be randomly assigned to either intravenous methylprednisolone (40 mg) or placebo 4 h prior to extubation. Other eligible patients who pass the CLT will be included in a non-intervention (observation) group. The primary endpoint is the incidence of PES within 48 h after extubation. Secondary endpoints include oxygen therapy, respiratory support requirements, reintubation secondary to PES, adverse effects within 48 h after extubation, hospital length of stay, and hospital mortality.

Discussion
Patients who are intubated on an emergency basis have a higher risk of intubation-related complications. Previous studies have examined treatment regimens involving more than 10 different variations on corticosteroid treatments for PES prevention, while for ED therapy, only a simple and effective treatment would be appropriate. Corticosteroid administration is usually accompanied by adverse effects; thus, this study will be important for further risk stratification among intubated ED patients.

Trial registration
Chictr.org.cn ChiCTR2000030349. Registered on 29 February 2020.
Modulating redox metabolism to improve isobutanol production in Shimwellia blattae
Authors: Acedos Miguel G. , de la Torre Isabel , Santos Victoria E. , García-Ochoa Félix , García José L. , Galán Beatriz 
Published: January 2021

Abstract
Background
Isobutanol is a candidate to replace gasoline from fossil resources. This higher alcohol can be produced from sugars using genetically modified microorganisms. Shimwellia blattae (p424IbPSO) is a robust strain resistant to high concentration of isobutanol that can achieve a high production rate of this alcohol. Nevertheless, this strain, like most strains developed for isobutanol production, has some limitations in its metabolic pathway. Isobutanol production under anaerobic conditions leads to a depletion of NADPH, which is necessary for two enzymes in the metabolic pathway. In this work, two independent approaches have been studied to mitigate the co-substrates imbalance: (i) using a NADH-dependent alcohol dehydrogenase to reduce the NADPH dependence of the pathway and (ii) using a transhydrogenase to increase NADPH level.

Results
The addition of the NADH-dependent alcohol dehydrogenase from Lactococcus lactis (AdhA) to S. blattae (p424IbPSO) resulted in a 19.3% higher isobutanol production. The recombinant strain S. blattae (p424IbPSO, pIZpntAB) harboring the PntAB transhydrogenase produced 39.0% more isobutanol than the original strain, reaching 5.98 g L−1 of isobutanol. In both strains, we observed a significant decrease in the yields of by-products such as lactic acid or ethanol.

Conclusions
The isobutanol biosynthesis pathway in S. blattae (p424IbPSO) uses the endogenous NADPH-dependent alcohol dehydrogenase YqhD to complete the pathway. The addition of NADH-dependent AdhA leads to a reduction in the consumption of NADPH that is a bottleneck of the pathway. The higher consumption of NADH by AdhA reduces the availability of NADH required for the transformation of pyruvate into lactic acid and ethanol. On the other hand, the expression of PntAB from E. coli increases the availability of NADPH for IlvC and YqhD and at the same time reduces the availability of NADH and thus, the production of lactic acid and ethanol. In this work it is shown how the expression of AdhA and PntAB enzymes in Shimwellia blattae increases yield from 11.9% to 14.4% and 16.4%, respectively.
Biomass, lipid accumulation kinetics, and the transcriptome of heterotrophic oleaginous microalga Tetradesmus bernardii under different carbon and nitrogen sources
Authors: Gao Baoyan , Wang Feifei , Huang Luodong , Liu Hui , Zhong Yuming , Zhang Chengwu 
Published: January 2021

Abstract
Background
Heterotrophic cultivation of microalgae has been proposed as a viable alternative method for novel high-value biomolecules, enriched biomass, and biofuel production because of their allowance of high cell density levels, as well as simple production technology. Tetradesmus bernardii, a newly isolated high-yielding oleaginous microalga under photoautotrophic conditions, is able to grow heterotrophically, meaning that it can consume organic carbon sources in dark condition. We investigated the effect of different carbon/nitrogen (C/N) ratios on the growth and lipid accumulation of T. bernardii in heterotrophic batch culture under two nitrogen sources (NaNO3 and CO(NH2)2). In addition, we conducted time-resolved transcriptome analysis to reveal the metabolic mechanism of T. bernardii in heterotrophic culture.

Results
T. bernardii can accumulate high biomass concentrations in heterotrophic batch culture where the highest biomass of 46.09 g/L was achieved at 100 g/L glucose concentration. The rate of glucose to biomass exceeded 55% when the glucose concentration was less than 80 g/L, and the C/N ratio was 44 at urea treatment. The culture was beneficial to lipid accumulation at a C/N ratio between 110 and 130. NaNO3 used as a nitrogen source enhanced the lipid content more than urea, and the highest lipid content was 45% of dry weight. We performed RNA-seq to analyze the time-resolved transcriptome of T. bernardii. As the nitrogen was consumed in the medium, nitrogen metabolism-related genes were significantly up-regulated to speed up the N metabolic cycle. As chloroplasts were destroyed in the dark, the metabolism of cells was transferred from chloroplasts to cytoplasm. However, storage of carbohydrate in chloroplast remained active, mainly the synthesis of starch, and the precursor of starch synthesis in heterotrophic culture may largely come from the absorption of organic carbon source (glucose). With regard to lipid metabolism, the related genes of fatty acid synthesis in low nitrogen concentration increased gradually with the extension of cultivation time.

Conclusion
T. bernardii exhibited rapid growth and high lipid accumulation in heterotrophic culture. It may be a potential candidate for biomass and biofuel production. Transcriptome analysis showed that multilevel regulation ensured the conversion from carbon to the synthesis of carbohydrate and lipid.
High concentrations of membrane-fed ivermectin are required for substantial lethal and sublethal impacts on Aedes aegypti
Authors: Hadlett Max , Nagi Sanjay C. , Sarkar Manas , Paine Mark J. I. , Weetman David 
Published: January 2021

Abstract
Background
With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Blood containing the antihelminthic drug ivermectin has been shown to have lethal and sub-lethal effects on mosquitoes. Almost all work to date has been on Anopheles spp., but impacts on other anthropophagic vectors could provide new options for their control, or additional value to anti-malarial ivermectin programmes.

Methods
Using dose-response assays, we evaluated the effects of ivermectin delivered by membrane feeding on daily mortality (up to 14 days post-blood feed) and fecundity of an Indian strain of Aedes aegypti.

Results
The 7-day lethal concentration of ivermectin required to kill 50% of adult mosquitoes was calculated to be 178.6 ng/ml (95% confidence intervals 142.3–218.4) for Ae. aegypti, which is much higher than that recorded for Anopheles spp. in any previous study. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul).

Conclusion
Our results suggest that levels of ivermectin present in human blood at current dosing regimes in mass drug administration campaigns, or even those in a recent higher-dose anti-malaria trial, are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels of ivermectin in livestock blood is also unlikely to be an effective option for its control. However, other potential toxic impacts of ivermectin metabolites, accumulation in tissues, sublethal effects on behaviour, or antiviral action might increase the efficacy of ivermectin against Ae. aegypti and the arboviral diseases it transmits, and require further investigation.

Graphical Abstract
Canine infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp. in the United States, 2013–2019
Authors: Little Susan , Braff Jennifer , Place Joshua , Buch Jesse , Dewage Bhagya Galkissa , Knupp Andrew , Beall Melissa 
Published: January 2021

Abstract
Background
Dogs in the US are commonly infected with vector-borne pathogens, including heartworm and tick-borne disease agents. The geographic distribution of both arthropod vectors and the pathogens they transmit continues to expand.

Methods
To describe the current geographic distribution and prevalence of antigen of Dirofilaria immitis and antibody to Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp. in dogs, we summarized over 144 million test results from 2013 to 2019, inclusive, by county, state, and region. Canine seroprevalence by state was compared to population-adjusted human reports of tick-borne diseases.

Results
Results varied regionally, with D. immitis antigen and Ehrlichia spp. antibodies more frequently detected in the Southeast (2.6% and 5.2%, respectively) and antibody to B. burgdorferi and Anaplasma spp. most common in the Northeast (12.1% and 7.3%, respectively). Overall, percent positive test results to D. immitis decreased in the Southeast by 33.3% when compared to earlier summaries using the same strategy (from 3.9 to 2.6%). Geographic expansion of areas where dogs commonly test positive for Ehrlichia spp. was evident, likely because of a change in the test made in 2012 to allow detection of antibodies to E. ewingii concomitant with expansion of vector tick populations. Percent positive test results to Ehrlichia spp. increased in every region; this shift was particularly pronounced in the Southeast, where percent positive test results increased fourfold (from 1.3 to 5.2%). Continued geographic expansion of B. burgdorferi and A. phagocytophilum was apparent in the Northeast, Midwest, and Upper South, although canine seroprevalence of antibody to B. burgdorferi was much lower than prior surveys in many Lyme-endemic areas. Annual reports of human cases of Lyme disease, ehrlichiosis, and anaplasmosis were associated with percent positive canine results by state for the three tick-borne disease agents (R2 = 0.812, 0.521, and 0.546, respectively). Within endemic areas, percent positive test results for all three tick-borne agents demonstrated evidence of geographic expansion.

Conclusions
Large scale analysis of results from screening dogs in practice for evidence of vector-borne infections, including those with zoonotic importance, continues to be a valuable strategy for understanding geographic trends in infection risk over time.

Graphical Abstract