bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level
Authors: Wong Chee-Yin , Chang Yao-Ming , Tsai Yu-Shuen , Ng Wailap Victor , Cheong Soon-Keng , Chang Ting-Yu , Chung I-Fang , Lim Yang-Mooi 
Published: July 2020

AbstractBackgroundMesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.ResultsSeveral ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.ConclusionsA systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.
Identifying and exploring biohydrogenating rumen bacteria with emphasis on pathways including trans-10 intermediates
Authors: Dewanckele Lore , Jeyanathan Jeyamalar , Vlaeminck Bruno , Fievez Veerle 
Published: July 2020

Abstract
Background
Bacteria involved in ruminal formation of trans-10 intermediates are unclear. Therefore, this study aimed at identifying rumen bacteria that produce trans-10 intermediates from 18-carbon unsaturated fatty acids.

Results
Pure cultures of 28 rumen bacterial species were incubated individually in the presence of 40 μg/mL 18:3n-3, 18:2n-6 or trans-11 18:1 under control or lactate-enriched (200 mM Na lactate) conditions for 24 h. Of the 28 strains, Cutibacterium acnes (formerly Propionibacterium acnes) was the only bacterium found to produce trans-10 intermediates from 18:3n-3 and 18:2n-6, irrespective of the growth condition. To further assess the potential importance of this species in the trans-11 to trans-10 shift, different biomass ratios of Butyrivibrio fibrisolvens (as a trans-11 producer) and C. acnes were incubated in different growth media (control, low pH and 22:6n-3 enriched media) containing 40 μg/mL 18:2n-6. Under control conditions, a trans-10 shift, defined in the current study as trans-10/trans-11 ≥ 0.9, occurred when the biomass of C. acnes represented between 90 and 98% of the inoculum. A low pH or addition of 22:6n-3 inhibited cis-9, trans-11 CLA and trans-10, cis-12 CLA formation by B. fibrisolvens and C. acnes, respectively, whereby C. acnes seemed to be more tolerant. This resulted in a decreased biomass of C. acnes required at inoculation to induce a trans-10 shift to 50% (low pH) and 90% (22:6n-3 addition).

Conclusions
Among the bacterial species studied,C. acnes was the only bacterium that have the metabolic ability to produce trans-10 intermediates from 18:3n-3 and 18:2n-6. Nevertheless, this experiment revealed that it is unlikely that C. acnes is the only or predominant species involved in the trans-11 to trans-10 shift in vivo.
Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study
Authors: Nudel Ron , Christiani Camilla A. J. , Ohland Jessica , Uddin Md Jamal , Hemager Nicoline , Ellersgaard Ditte , Spang Katrine S. , Burton Birgitte K. , Greve Aja N. , Gantriis Ditte L. , Bybjerg-Grauholm Jonas , Jepsen Jens Richardt M. , Thorup Anne A. E. , Mors Ole , Werge Thomas , Nordentoft Merete 
Published: July 2020

Abstract
Background
One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects.

Results
Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10−8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis.

Conclusions
Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.
The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun
Authors: Alhuthali Hayaa Moeed , Bradshaw Tracey D. , Lim Kuan-Hon , Kam Toh-Seok , Seedhouse Claire H. 
Published: July 2020

Abstract
Background
Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

Methods
We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.

Results
AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).

Conclusions
This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.
Treatment outcomes of severe acute malnutrition and predictors of recovery in under-five children treated within outpatient therapeutic programs in Ethiopia: a systematic review and meta-analysis
Authors: Bitew Zebenay Workneh , Alemu Ayinalem , Worku Teshager 
Published: July 2020

Abstract
Background
Severe acute malnutrition affects around 17 million under-five children in the world, of which the highest burden is accounted by Sub-Saharan Africa where Ethiopia is found. Though there are few individual, inconsistent and inconclusive studies, there is no nationally representative study on treatment outcomes of SAM in outpatient therapeutic feeding programs of Ethiopia. This study aimed at estimating the pooled treatment outcomes and predictors of recovery rate among under- five children with SAM in Ethiopia.

Methods
Electronic databases (PubMed, Medline (EBSCOhost), EMBASE (Elsevier), CINAHL (EBSCOhost), web of science, Scopus, Science Direct and Food Science and Technology Abstracts (FSTA)), and grey literature sources (Google scholar, Mednar, World Cat and google) were used to retrieve articles. The random effect model was used to estimate the pooled treatment outcomes. Hazard ratios were used to determine the predictors of recovery rate. Cochran’s Q, I2, and univariate Meta regression were done for heterogeneity. Begg’s & Egger’s tests were used for publication bias.

Results
Nineteen articles with a total number of 23,395 under-five children with SAM were used for this meta-analysis. The pooled recovery, death, defaulter and non-recovery rates were 70% (95% CI: 64, 76), 2% (95% CI: 1, 2), 10% (95%CI: 7, 12), 15% (95% CI: 10, 20), respectively. Diarrhea (HR = 0.8, 95% CI: 0.75, 0.94), no edema (HR = 0.41, 95% CI: 0.33, 0.50) and amoxicillin (HR = 1.81, 95% CI: 1.18, 2.44) were independent predictors of recovery rate of children with SAM in Ethiopia. Publication year was found to be the potential source of heterogeneity between included studies.

Conclusion
The treatment outcomes of children with SAM from outpatient therapeutic feeding programs of Ethiopia are lower than the sphere guidelines, WHO and national recommendations. Diarrhea and no edema antagonized the recovery rate of children, while amoxicillin enhanced the recovery rate of children from SAM. Community health workers need to be trained. Especial attention should be given while treating children with diarrhea and severe wasting. Community mobilization is also recommended to improve community awareness about the therapeutic foods.
Pressure Support Ventilation (PSV) versus Neurally Adjusted Ventilatory Assist (NAVA) in difficult to wean pediatric ARDS patients: a physiologic crossover study
Authors: Spinazzola Giorgia , Costa Roberta , De Luca Daniele , Chidini Giovanna , Ferrone Giuliano , Piastra Marco , Conti Giorgio 
Published: July 2020

Abstract
Background
Neurally adjusted ventilatory assist (NAVA) is an innovative mode for assisted ventilation that improves patient-ventilator interaction in children. The aim of this study was to assess the effects of patient-ventilator interaction comparing NAVA with pressure support ventilation (PSV) in patients difficult to wean from mechanical ventilation after moderate pediatric acute respiratory distress syndrome (PARDS).

Methods
In this physiological crossover study, 12 patients admitted in the Pediatric Intensive Care Unit (PICU) with moderate PARDS failing up to 3 spontaneous breathing trials in less than 7 days, were enrolled. Patients underwent three study conditions lasting 1 h each: PSV1, NAVA and PSV2.

Results
The Asynchrony Index (AI) was significantly reduced during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.001). During the NAVA trial, the inspiratory and expiratory trigger delays were significantly shorter compared to those obtained during PSV1 and PSV2 trials (Delaytrinspp < 0.001, Delaytrexpp = 0.013). These results explain the significantly longer Timesync observed during the NAVA trial (p < 0.001). In terms of gas exchanges, PaO2 value significantly improved in the NAVA trial with respect to the PSV trials (p < 0.02). The PaO2/FiO2 ratio showed a significant improvement during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.004).

Conclusions
In this specific PICU population, presenting difficulty in weaning after PARDS, NAVA was associated with a reduction of the AI and a significant improvement in oxygenation compared to PSV mode.

Trial registration
ClinicalTrial.gov Identifier: NCT04360590 “Retrospectively registered”.
Is all-inside with suspensory cortical button fixation a superior technique for anterior cruciate ligament reconstruction surgery? A systematic review and meta-analysis
Authors: Fu Chun-Wei , Chen Wei-Cheng , Lu Yung-Chang 
Published: July 2020

Abstract
Background
To compare the clinical results of all-inside anterior cruciate ligament reconstruction (ACLR) using suspensory cortical button fixation and full tibial tunnel drilling.

Methods
Systematic searches were conducted of published literature up to November 2019 on PubMed, Embase, and Cochrane for studies comparing all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. Two reviewers independently determined eligibility, extracted the outcome data, and assessed the risk of bias of the eligible studies. The clinical outcome and graft reruptures were pooled by using random effects with mean differences and risk ratios for continuous and dichotomous variables, respectively.

Result
A total of nine studies (five randomized controlled trials and four comparative studies) involving 613 patients were included in the meta-analysis. The postoperative functional outcome, knee laxity measured with arthrometer, and graft reruptures were comparable between patients with all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. However, a significantly greater thickness of autologous tendon was used and less change in drilling tunnel diameter was noted in patients with suspensory cortical button graft fixation.

Conclusions
All-inside ACLR with suspensory cortical button fixation was not clinically superior to full tibial tunnel ACLR with interference screw fixation in functional outcomes, knee laxity measured with arthrometer, or rerupture rate. However, the advantage of using suspensory cortical button fixation was that a thicker graft could be used for reconstruction, and brought less tibia tunnel widening compared with bioabsorbable interference screw fixation.
An evaluation of continuous subcutaneous infusions across seven NHS acute hospitals: is there potential for 48-hour infusions?
Authors: Baker J. , Dickman A. , Mason S. , Bickerstaff M. , Jackson R. , McArdle A. , Lawrence I. , Stephenson F. , Paton N. , Kirk J. , Waters B. , Ellershaw J. 
Published: July 2020

Abstract
Background
Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals.

Methods
Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days.

Results
A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days.

Conclusion
Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.
Differential influences of social support on app use for diabetes self-management – a mixed methods approach
Authors: Brew-Sam Nicola , Chib Arul , Rossmann Constanze 
Published: July 2020

Abstract
Background
Recent studies increasingly examine social support for diabetes self-management delivered via mHealth. In contrast to previous studies examining social support as an outcome of technology use, or technology as a means for delivering social support, this paper argues that social support has an impact on the use of diabetes mHealth apps. Specifically, we postulate differences between the impact of healthcare professional versus non-professional (family/friends) support on mobile app use for diabetes self-management.

Methods
This research employed a triangulation of methods including exploratory semi-structured face-to-face interviews (N = 21, Study 1) and an online survey (N = 65, Study 2) with adult type 1 and type 2 diabetes patients. Thematic analysis (Study 1) was used to explore the relevance of social support (by professionals versus non-professionals) for diabetes app use. Binary logistic regression (Study 2) was applied to compare healthcare decision-making, healthcare-patient communication, and the support by the personal patient network as predictors of diabetes app use, complemented by other predictors from self-management and technology adoption theory.

Results
The interviews (Study 1) demonstrated that (technology-supported) shared decision-making and supportive communication by healthcare professionals depended on their medical specialty. The personal patient network was perceived as either facilitating or hindering the use of mHealth for self-management. Binary logistic regression (Study 2) showed that the physician specialty significantly predicted the use of diabetes apps, with supervision by diabetes specialists increasing the likelihood of app use (as opposed to general practitioners). Additionally, specialist care positively related to a higher chance of shared decision-making and better physician-patient communication. The support by the personal patient network predicted diabetes app use in the opposite direction, with less family/friend support increasing the likelihood of app use.

Conclusion
The results emphasize the relevance of support by healthcare professionals and by the patient network for diabetes app use and disclose differences from the existing literature. In particular, the use of diabetes apps may increase in the absence of social support by family or friends (e.g., compensation for lack of support), and may decrease when such support is high (e.g., no perceived need to use technology).
Exploring the acceptability of controlled human infection with SARSCoV2—a public consultation
Authors: Gbesemete D. , Barker M. , Lawrence W. T. , Watson D. , de Graaf H. , Read R. C. 
Published: July 2020

AbstractRapid development of an effective vaccine for SARSCoV2 is a global priority. A controlled human infection model (CHIM) would accelerate the efficacy assessment of candidate vaccines. This strategy would require deliberate exposure of volunteers to SARSCoV2 with no currently available treatment and a small but definite risk of serious illness or death. This raises complex questions about the social and ethical acceptability of risk to individuals, given the potential benefit to the wider population, and as such, a study cannot be done without public involvement. We conducted a structured public consultation with 57 individuals aged 20–40 years to understand public attitudes to a CHIM, and pre-requisites for enrolment. The overall response to this strategy was positive, and many would volunteer altruistically. Carefully controlled infection is viewed as safer than natural exposure to wild virus. The prolonged social isolation required for the proposed CHIM is considered an obstacle but not insurmountable, with reasonable compensation and supportive care. Given the significant level of public interest, a CHIM should be done as open science with regular, controlled dissemination of information into the public domain. Importantly, there was a strong view that the final decision whether to conduct a CHIM should be in the hands of qualified and experienced clinician-scientists and the authorities.
Preference of individuals in the treatment strategies of acute myocardial infarction in China: a discrete choice experiment
Authors: Dai Weiqian , Liu Chang , Liu Jiahe , Lin Yaduan , Cheng Yu , Ming Wai-kit 
Published: July 2020

Abstract
Background
Acute myocardial infarction (AMI) is a significant cause of mortality and morbidity worldwide. Today, with increasing life quality and social economy, people pay much attention to the cost-effectiveness of a treatment strategy. This study investigated the preferences of individuals who would be potential caregivers or patients for AMI treatment in order to provide liable and instructive information for cardiologists and other related physicians.

Methods
A discrete choice experiment was conducted among people to assess preferences for hypothetical AMI treatment scenarios characterized by the attributes of treatment method, mortality within 5 years, complication rate within 1 year, treatment duration and expense. A conditional logit regression model and latent class analysis were used to interpret the collected data systematically. The relative importance of each attribute and willingness to pay of people on the trade-offs between different treatment strategies were estimated.

Results
Participants valued mortality within 5 years most highly (average importance: 40.9, 95%CI 0.447–0.530). Three classes of participants were identified: Class 1 placed the most importance on treatment duration, class 2 corresponded with the overall result while expense was regarded as the most important attribute in class 3. Individuals favored an intermediate treatment duration of about 10 days instead of the shortest (95% CI 1.044–1.248, P < 0.001). People’s characteristics (sex, age, marriage, education and income) affected their preferences (P < 0.01).

Conclusion
People considered a mortality rate within 5 years as the most crucial attribute in the MI treatment and preferred an intermediate treatment duration of about 10 days. Furthermore, the findings estimated the trade-offs acceptable to patients and heterogeneity in preferences for AMI treatment.