bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretion of a low and high molecular weight β-glycosidase by Yarrowia lipolytica
Authors: Swietalski Paul , Hetzel Frank , Seitl Ines , Fischer Lutz 
Published: May 2020

Abstract
Background
The secretory production of recombinant proteins in yeast simplifies isolation and purification but also faces possible complications due to the complexity of the secretory pathway. Therefore, correct folding, maturation and intracellular transport of the recombinant proteins are important processing steps with a higher effort needed for complex and large proteins. The aim of this study was to elucidate the secretion potential of Yarrowia lipolytica for low and high molecular weight β-glycosidases in a comparative cultivation approach.

Results
A low sized β-glucosidase from Pyrococcus furiosus (CelB; 55 kDa) and a large sized β-galactosidase isolated from the metagenome (M1; 120 kDa) were integrated into the acid extracellular protease locus using the CRISPR–Cas9 system to investigate the size dependent secretion of heterologous proteins in Y. lipolytica PO1f. The recombinant strains were cultivated in the bioreactor for 78 h and the extra- and intracellular enzyme activities were determined. The secretion of CelB resulted in an extracellular volumetric activity of 187.5 µkatoNPGal/Lmedium, while a volumetric activity of 2.98 µkatoNPGal/Lmedium was measured during the M1 production. However, when the amount of functional intra- and extracellular enzyme was investigated, the high molecular weight M1 (85%) was secreted more efficiently than CelB (27%). Real-time PCR experiments showed a linear correlation between the transcript level and extracellular activity for CelB, while a disproportional high mRNA level was observed regarding M1. Interestingly, mass spectrometry data revealed the unexpected secretion of two endogenous intracellular glycolytic enzymes, which is reported for the first time for Y. lipolytica.

Conclusion
The results of this study provide deeper insights into the secretion potential of Y. lipolytica. A secretion limitation for the low-size CelB was observed, while the large size M1 enzyme was produced in lower amounts but was secreted efficiently. It was shown for the first time that Y. lipolytica is a promising host for the secretion of heterologous high molecular weight proteins (> 100 kDa), although the total secreted amount has to be increased further.
Inhibition of germinal vesicle breakdown using IBMX increases microRNA-21 in the porcine oocyte
Authors: Hale Benjamin J. , Li Yunsheng , Adur Malavika K. , Ross Jason W. 
Published: May 2020

Abstract
Background
Germinal vesicle breakdown (GVBD) occurs during oocyte meiotic maturation, a period when transcriptional processes are virtually inactive. Thus, the maturing oocyte is reliant on processes such as post-transcriptional gene regulation (PTGR) to regulate the mRNA and protein repertoire. MicroRNA (miRNA) are a class of functional small RNA that target mRNA to affect their abundance and translational efficiency. Of particular importance is miRNA-21 (MIR21) due to its role in regulating programmed cell death 4 (PDCD4). The objective of this study was to characterize the abundance and regulation of MIR21 in relation to GVBD.

Methods
Oocytes were collected from aspirated porcine tertiary follicles. Relative abundance of mature MIR21 was quantified at 0, 8, 16, 24, 32, and 42 h of in vitro (IVM) with or without treatment with 3-isobutyl-1-methylxanthine (IBMX).

Results
IBMX increased abundance of MIR21 at 24 h approximately 30-fold compared to control oocytes (P < 0.05), and the induced increase in MIR21 abundance at 24 h was concomitant with premature depletion of PDCD4 protein abundance. To characterize the effect of artificially increasing MIR21 on oocyte competence without inhibiting GVBD, a MIR21 mimic, scrambled microRNA negative control, or nuclease free water was micro-injected into denuded oocytes at 21 h of IVM. The maturation rate of oocytes injected with synthetic MIR21 (63.0 ± 7.5%) was higher than oocytes injected with negative controls (P < 0.05).

Conclusions
Inhibition of nuclear meiotic maturation via IBMX significantly increased MIR21 and decreased its target, PDCD4. Injection of a MIR21 mimic increased oocyte maturation rate. Our results indicate MIR21 is active and important during meiotic maturation of the oocyte.
Learning sites for health system governance in Kenya and South Africa: reflecting on our experience
Authors:   The RESYST/DIAHLS learning site team
Published: May 2020

Abstract
Background
Health system governance is widely recognised as critical to well-performing health systems in low- and middle-income countries. However, in 2008, the Alliance for Health Policy and Systems Research identified governance as a neglected health systems research issue. Given the demands of such research, the Alliance recommended applying qualitative approaches and institutional analysis as well as implementing cross-country research programmes in engagement with policy-makers and managers. This Commentary reports on a 7-year programme of work that addressed these recommendations by establishing, in partnership with health managers, three district-level learning sites that supported real-time learning about the micro-practices of governance – that is, managers’ and health workers’ everyday practices of decision-making.

Paper focus
The paper’s specific focus is methodological and it seeks to prompt wider discussion about the long-term and engaged nature of learning-site work for governance research. It was developed through processes of systematic reflection within and across the learning sites. In the paper, we describe the learning sites and our research approach, and highlight the set of wider activities that spun out of the research partnership, which both supported the research and enabled it to reach wider audiences. We also separately present the views of managers and researchers about the value of this work and reflect carefully on four critiques of the overall approach, drawing on wider co-production literature.

Conclusions
Ultimately, the key lessons we draw from these experiences are that learning sites offer particular opportunities not only to understand the everyday realities of health system governance but also to support emergent system change led by health managers; the wider impacts of this type of research are enabled by working up the system as well as by infusing research findings into teaching and other activities, and this requires supportive organisational environments, some long-term research funding, recognising the professional and personal risks involved, and sustaining activities over time by paying attention to relationships; and working in multiple settings deepens learning for both researchers and managers. We hope the paper stimulates further reflection about research on health system governance and about co-production as a research approach.
Can consumer wearable activity tracker-based interventions improve physical activity and cardiometabolic health in patients with chronic diseases? A systematic review and meta-analysis of randomised controlled trials
Authors: Franssen Wouter M. A. , Franssen Gregor H. L. M. , Spaas Jan , Solmi Francesca , Eijnde Bert O. 
Published: May 2020

Abstract
Background
To date, it is unclear if consumer wearable activity trackers (CWATs), with or without behaviour multi-component strategies, effectively improve adherence to physical activity and health outcomes under free living conditions in populations with chronic diseases. Therefore, we systematically evaluated the efficacy of CWAT-based interventions to promote physical activity levels and cardiometabolic health in populations with chronic diseases.

Methods
Randomised controlled trials were collected from five bibliographic databases (PubMed, Embase, Web of Science, The Cochrane Central Register of Controlled Trials and CINAHL). Studies were eligible for inclusion if they evaluated a CWAT-based counselling intervention versus control intervention among patients with chronic respiratory diseases, type 2 diabetes mellitus, cardiovascular diseases, overweight/obesity, cognitive disorders, or sedentary older adults. Data were pooled using a random-effects model.

Results
After deduplication 8147 were identified of which 35 studies met inclusion criteria (chronic respiratory diseases: 7, type 2 diabetes mellitus: 12, cardiovascular diseases: 6, overweight/obesity: 3, cognitive disorders: 1, sedentary older adults: 6). Compared to control groups, CWAT-based interventions significantly increased physical activity by 2123 steps per day (95% confidence interval [CI], [1605–2641]; p < 0.001). In addition, CWAT-based interventions in these populations significantly decreased systolic blood pressure (− 3.79 mm Hg; 95% CI: [− 4.53, − 3.04] mm Hg; p < 0.001), waist circumference (− 0.99 cm; 95% CI: [− 1.48, − 0.50] cm; p < 0.001) and low-density lipoprotein cholesterol concentration (− 5.70 mg/dl; 95% CI: [− 9.24, − 2.15] mg/dl; p = 0.002).

Conclusion
CWAT-based interventions increase physical activity and have beneficial effects on important health-related outcomes such as systolic blood pressure, waist circumference and LDL cholesterol concentration in patients with chronic diseases.
The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery: a randomized study
Authors: Jiang Huiqi , Holm Jonas , Vidlund Mårten , Vanky Farkas , Friberg Örjan , Yang Yanqi , Svedjeholm Rolf 
Published: May 2020

Abstract
Background
Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP.

Methods
Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M l-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP.

Results
Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995–6260] vs. 6745 [3455–12,687] ng•L−1, p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426–7423] vs. 8430 [5370–14,100] ng•L−1, p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19–26] vs. 25 [22–46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170–500] vs. 560 [210–910] ng•L−1, p = 0.025).

Conclusions
Post hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings.
Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1
A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation
Authors: Goshi Noah , Morgan Rhianna K. , Lein Pamela J. , Seker Erkin 
Published: May 2020

Abstract
Background
Interactions between neurons, astrocytes, and microglia critically influence neuroinflammatory responses to insult in the central nervous system. In vitro astrocyte and microglia cultures are powerful tools to study specific molecular pathways involved in neuroinflammation; however, in order to better understand the influence of cellular crosstalk on neuroinflammation, new multicellular culture models are required.

Methods
Primary cortical cells taken from neonatal rats were cultured in a serum-free “tri-culture” medium formulated to support neurons, astrocytes, and microglia, or a “co-culture” medium formulated to support only neurons and astrocytes. Caspase 3/7 activity and morphological changes were used to quantify the response of the two culture types to different neuroinflammatory stimuli mimicking sterile bacterial infection (lipopolysaccharide (LPS) exposure), mechanical injury (scratch), and seizure activity (glutamate-induced excitotoxicity). The secreted cytokine profile of control and LPS-exposed co- and tri-cultures were also compared.

Results
The tri-culture maintained a physiologically relevant representation of neurons, astrocytes, and microglia for 14 days in vitro, while the co-cultures maintained a similar population of neurons and astrocytes, but lacked microglia. The continuous presence of microglia did not negatively impact the overall health of the neurons in the tri-culture, which showed reduced caspase 3/7 activity and similar neurite outgrowth as the co-cultures, along with an increase in the microglia-secreted neurotrophic factor IGF-1 and a significantly reduced concentration of CX3CL1 in the conditioned media. LPS-exposed tri-cultures showed significant astrocyte hypertrophy, increase in caspase 3/7 activity, and the secretion of a number of pro-inflammatory cytokines (e.g., TNF, IL-1α, IL-1β, and IL-6), none of which were observed in LPS-exposed co-cultures. Following mechanical trauma, the tri-culture showed increased caspase 3/7 activity, as compared to the co-culture, along with increased astrocyte migration towards the source of injury. Finally, the microglia in the tri-culture played a significant neuroprotective role during glutamate-induced excitotoxicity, with significantly reduced neuron loss and astrocyte hypertrophy in the tri-culture.

Conclusions
The tri-culture consisting of neurons, astrocytes, and microglia more faithfully mimics in vivo neuroinflammatory responses than standard mono- and co-cultures. This tri-culture can be a useful tool to study neuroinflammation in vitro with improved accuracy in predicting in vivo neuroinflammatory phenomena.
Guiding functional reorganization of motor redundancy using a body-machine interface
Authors: De Santis Dalia , Mussa-Ivaldi Ferdinando A. 
Published: May 2020

Abstract
Background
Body-machine interfaces map movements onto commands to external devices. Redundant motion signals derived from inertial sensors are mapped onto lower-dimensional device commands. Then, the device users face two problems, a) the structural problem of understanding the operation of the interface and b) the performance problem of controlling the external device with high efficiency. We hypothesize that these problems, while being distinct are connected in that aligning the space of body movements with the space encoded by the interface, i.e. solving the structural problem, facilitates redundancy resolution towards increasing efficiency, i.e. solving the performance problem.

Methods
Twenty unimpaired volunteers practiced controlling the movement of a computer cursor by moving their arms. Eight signals from four inertial sensors were mapped onto the two cursor’s coordinates on a screen. The mapping matrix was initialized by asking each user to perform free-form spontaneous upper-limb motions and deriving the two main principal components of the motion signals. Participants engaged in a reaching task for 18 min, followed by a tracking task. One group of 10 participants practiced with the same mapping throughout the experiment, while the other 10 with an adaptive mapping that was iteratively updated by recalculating the principal components based on ongoing movements.

Results
Participants quickly reduced reaching time while also learning to distribute most movement variance over two dimensions. Participants with the fixed mapping distributed movement variance over a subspace that did not match the potent subspace defined by the interface map. In contrast, participant with the adaptive map reduced the difference between the two subspaces, resulting in a smaller amount of arm motions distributed over the null space of the interface map. This, in turn, enhanced movement efficiency without impairing generalization from reaching to tracking.

Conclusions
Aligning the potent subspace encoded by the interface map to the user’s movement subspace guides redundancy resolution towards increasing movement efficiency, with implications for controlling assistive devices. In contrast, in the pursuit of rehabilitative goals, results would suggest that the interface must change to drive the statistics of user’s motions away from the established pattern and toward the engagement of movements to be recovered.

Trial registration
ClinicalTrials.gov, NCT01608438, Registered 16 April 2012.
Metastatic non-functional paraganglioma to the lung
Authors: Abou Chaar Mohamad K. , Khanfer Aseel , Almasri Nidal M. , Abu Shattal Mohammad , Alibraheem Abdellatif O. , Al-Qudah Obada 
Published: May 2020

Abstract
Introduction
Paragangliomas are rare endocrine tumors that arise from the extra-adrenal autonomic paraganglia and sympathetic paragangliomas usually secret catecholamines and are located in the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In contrast, most parasympathetic paragangliomas are nonfunctional and located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Such neoplasms, although rare, are clinically important because they may recur after surgical resection and 10% of them give rise to metastases causing death with the lymphatic nodes, bones, liver, and lungs being the most common locations.

Case presentation
We present a case of a 26-year-old male patient that was diagnosed with paraganglioma of the right-frontal lobe infiltrating the falx and frontal bone which was diagnosed after suffering from a headache and abnormal vision. On initial work-up he was found to have right pulmonary nodules that increased in size after follow up and other nodules appeared in the contralateral lung. He underwent subtotal resection of the brain tumor and complete resection of the bilateral pulmonary nodules.

Conclusion
To our knowledge, paraganglioma is considered to be a rare entity in the central nervous system with very few cases being reported in the supratentorial region and no cases were reported of metastatic such paraganglioma to the lung.
Short-term outcomes of on- vs off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: a systematic review and meta-analysis
Authors: Guan Zhiyuan , Guan Xiaoqing , Gu Kaiyun , Lin Xuanqi , Lin Jin , Zhou Wenjun , Xu Ming , Wan Fen , Zhang Zhe , Song Chunli 
Published: May 2020

Abstract
Objectives
Does the manipulation of the off-pump CABG (OPCAB) in patient with depressed left ventricular function is better than on-pump CABG (ONCAB) approach in in-hospital mortality and morbidities? Here we undertook a meta-analysis of the best evidence available on the comparison of primary and second clinical outcomes of the off-pump and on-pump CABG.

Design
Systematic literature reviewer and meta-analysis.

Data sources
PubMed, EMBASE, Web of science and Cochrane Center Registry of Controlled Trials were searched the studies which comparing the use of the off-pump CABG(OPCAB) and on-pump CABG (ONCAB) for patients with LVD during January 1990.1 to January 2018.

Eligibility criteria
All observation studies and randomized controlled trials comparing on-pump and off-pump as main technique for multi-vessel coronary artery disease (defined as severe stenosis (>70%) in at least 2 major diseased coronary arteries) with left ventricular dysfunction(defined as ejection fraction (EF) 40% or less) were included.

Data extraction and synthesis
Authors will screen and select the studies extract the following data, first author, year of publication, trial characters, study design, inclusion and exclusion criteria, graft type, clinical outcome, assess the risk of bias and heterogeneity. Study-specific estimates will pool through the modification of the Newcastle-Ottawa scale for the quality of study and while leave-one-out analysis will be used to detect the impact of individual studies on the robustness of outcomes.

Results
Among the 987 screened articles, a total of 16 studies (32,354 patients) were included. A significant relationship between patient risk profile and benefits from OPCAB was found in terms of the 30-day mortality (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73–0.97; P = 0.02), stroke (OR, 0.69; 95% CI, 0.55–0.86; P = 0.00), myocardial infarction (MI) (OR, 0.71; 95% CI, 0.53–0.96; P = 0.02), renal failure (OR, 0.71; 95% CI, 0.55–0.93; P = 0.01), pulmonary complication (OR, 0.68; 95% CI, 0.52–0.90; P = 0.01), infection (OR, 0.67; 95% CI, 0.49–0.91; P = 0.00),postoperative transfusion (OR, 0.25; 95% CI, 0.08–0.84; P = 0.02) and reoperation for bleeding (OR, 0.56; 95% CI, 0.41–0.75; P = 0.00). There was no significant difference in atrial fibrillation (AF) (OR, 0.96;95%; CI, 0.78–1.41; P = 0.56) and neurological dysfunction (OR, 0.88; 95% CI, 0.49–1.57; P = 0.65).

Conclusions
Compared with the on-pump CABG with LVD, using the off-pump CABG is a better choice for patients with lower mortality, stroke, MI, RF, pulmonary complication, infection, postoperative transfusion and reoperation for bleeding. Further randomized studies are warranted to corroborate these observational data.