bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance of Yarrowia lipolytica to inhibitors commonly found in lignocellulosic hydrolysates
Authors: Konzock Oliver , Zaghen Simone , Norbeck Joakim 
Published: March 2021

Abstract
Background
Lignocellulosic material is a suitable renewable carbon and energy source for microbial cell factories, such as Yarrowia lipolytica. To be accessible for microorganisms, the constituent sugars need to be released in a hydrolysis step, which as a side effect leads to the formation of various inhibitory compounds. However, the effects of these inhibitory compounds on the growth of Y. lipolytica have not been thoroughly investigated.

Results
Here we show the individual and combined effect of six inhibitors from three major inhibitor groups on the growth of Y. lipolytica. We engineered a xylose consuming strain by overexpressing the three native genes XR, XDH, and XK and found that the inhibitor tolerance of Y. lipolytica is similar in glucose and in xylose. Aromatic compounds could be tolerated at high concentrations, while furfural linearly increased the lag phase of the cultivation, and hydroxymethylfurfural only inhibited growth partially. The furfural induced increase in lag phase can be overcome by an increased volume of inoculum. Formic acid only affected growth at concentrations above 25 mM. In a synthetic hydrolysate, formic acid, furfural, and coniferyl aldehyde were identified as the major growth inhibitors.

Conclusion
We showed the individual and combined effect of inhibitors found in hydrolysate on the growth of Y. lipolytica. Our study improves understanding of the growth limiting inhibitors found in hydrolysate and enables a more targeted engineering approach to increase the inhibitor tolerance of Y. lipolytica. This will help to improve the usage of Y. lipolytica as a sustainable microbial cell factory.
Improved node culture methods for rapid vegetative propagation of switchgrass (Panicum virgatum L.)
Authors: Wang Yongqin , Dong Weihong , Saha Malay C. , Udvardi Michael K. , Kang Yun 
Published: March 2021

Abstract
Background
Switchgrass (Panicum virgatum L.) is an important bioenergy and forage crop. The outcrossing nature of switchgrass makes it infeasible to maintain a genotype through sexual propagation. Current asexual propagation protocols in switchgrass have various limitations. An easy and highly-efficient vegetative propagation method is needed to propagate large natural collections of switchgrass genotypes for genome-wide association studies (GWAS).

Results
Micropropagation by node culture was found to be a rapid method for vegetative propagation of switchgrass. Bacterial and fungal contamination during node culture is a major cause for cultural failure. Adding the biocide, Plant Preservative Mixture (PPM, 0.2%), and the fungicide, Benomyl (5 mg/l), in the incubation solution after surface sterilization and in the culture medium significantly decreased bacterial and fungal contamination. In addition, “shoot trimming” before subculture had a positive effect on shoot multiplication for most genotypes tested. Using the optimized node culture procedure, we successfully propagated 330 genotypes from a switchgrass GWAS panel in three separate experiments. Large variations in shoot induction efficiency and shoot growth were observed among genotypes. Separately, we developed an in planta node culture method by stimulating the growth of aerial axillary buds into shoots directly on the parent plants, through which rooted plants can be generated within 6 weeks. By circumventing the tissue culture step and avoiding application of exterior hormones, the in planta node culture method is labor- and cost-efficient, easy to master, and has a high success rate. Plants generated by the in planta node culture method are similar to seedlings and can be used directly for various experiments.

Conclusions
In this study, we optimized a switchgrass node culture protocol by minimizing bacterial and fungal contamination and increasing shoot multiplication. With this improved protocol, we successfully propagated three quarters of the genotypes in a diverse switchgrass GWAS panel. Furthermore, we established a novel and high-throughput in planta node culture method. Together, these methods provide better options for researchers to accelerate vegetative propagation of switchgrass.
Use of volume controlled vs. pressure controlled volume guaranteed ventilation in elderly patients undergoing laparoscopic surgery with laryngeal mask airway
Authors: Wang Ping , Zhao Shihao , Gao Zongbin , Hu Jun , Lu Yao , Chen Jinbao 
Published: March 2021

AbstractBackgroundThe peak inspiratory pressure (PIP) is crucial in mechanical ventilation with supraglottic airway device (SAD). Pressure-controlled ventilation volume-guaranteed (PCV-VG), delivering a preset tidal volume with the lowest required airway pressure, is being increasingly used during general anesthesia. In this study, we compared respiratory mechanics and circulatory parameters between volume-controlled ventilation (VCV) and PCV-VG in elderly patients undergoing laparoscopic surgery using the laryngeal mask airway supreme (LMA).MethodsEighty participants scheduled for laparoscopic surgery were enrolled in this prospective, randomized clinical trial. The participants were randomly assigned to receive VCV or PCV-VG. PIP, dynamic compliance (Cdyn) and mean inspiratory pressure (Pmean) were recorded at 5 min after induction of anesthesia (T1), 5 min after pneumoperitoneum(T2), 30 and 60 min after pneumoperitoneum (T3 and T4). Data including other respiratory variables, hemodynamic variables, and arterial blood gases were also collected. The difference in PIP between VCV and PCV-VG was assessed as the primary outcome.ResultsPIP was significantly lower at T2, T3, and T4 in both groups compared with T1 (allP <  0.0001), and it was significantly lower in the PCV-VG group than the VCV group at T2, T3, and T4 (allP <  0.001). Cydn was decreased at T2, T3, and T4 in two groups compared with T1 (allP <  0.0001), but it was higher in PCV-VG group than in VCV group at T2, T3, and T4 (allP <  0.0001). There were on statistically significant differences were found between the groups for other respiratory and hemodynamic variables.ConclusionIn elderly patients who underwent laparoscopic surgery using an LMA, PCV-VG was superior to VCV in its ability to provide ventilation with lower peak inspiratory pressure and greater dynamic compliance.
Multi-centre implementation of an Educational program to improve the Cardiac Arrest diagnostic accuracy of ambulance Telecommunicators and survival outcomes for sudden cardiac arrest victims: the EduCATe study design and methodology
Authors: Vaillancourt Christian , Charette Manya , Naidoo Sarika , Taljaard Monica , Church Matthew , Hodges Stephanie , Leduc Shannon , Christenson Jim , Cheskes Sheldon , Dainty Katie , Feldman Michael , Goldstein Judah , Tallon John , Helmer Jennie , Sibley Aaron , Spidel Matthew , Blanchard Ian , Garland Jim , Cyr Kathryn , Brehaut Jamie , Dorian Paul , Lacroix Colette , Zambon Sandra , Thiruganasambandamoorthy Venkatesh 
Published: March 2021

Abstract
Background
Sudden cardiac death remains a leading cause of mortality in Canada, resulting in more than 35,000 deaths annually. Most cardiac arrest victims collapse in their own home (85% of the time) and 50% are witnessed by a family member or bystander. Survivors have a quality of life similar to the general population, but the overall survival rate for out-of-hospital cardiac arrest (OHCA) rarely exceeds 8%. Victims are almost four times more likely to survive when receiving bystander CPR, but bystander CPR rates have remained low in Canada over the past decade, not exceeding 15–25% until recently. Telecommunication-assisted CPR instructions have been shown to significantly increase bystander CPR rates, but agonal breathing may be misinterpreted as a sign of life by 9–1-1 callers and telecommunicators, and is responsible for as much as 50% of missed OHCA diagnoses.
We sought to improve the ability and speed with which ambulance telecommunicators can recognize OHCA over the phone, initiate timely CPR instructions, and improve survival.

Methods
In this multi-center national study, we will implement and evaluate an educational program developed for ambulance telecommunicators using a multiple baseline interrupted time-series design. We will compare outcomes 12 months before and after the implementation of a 20-min theory-based educational video addressing barriers to recognition of OHCA while in the presence of agonal breathing. Participating Canadian sites demonstrated prior ability to collect standardized data on OHCA. Data will be collected from eligible 9–1-1 recordings, paramedic documentation and hospital medical records. Eligible cases will include suspected or confirmed OHCA of presumed cardiac origin in patients of any age with attempted resuscitation.

Discussion
The ability of telecommunication-assisted CPR instructions to improve bystander CPR and survival rates for OHCA victims is undeniable. The ability of telecommunicators to recognize OHCA over the phone is unequivocally impeded by relative lack of training on agonal breathing, and reluctance to initiate CPR instructions when in doubt. Our pilot data suggests the potential impact of this project will be to increase absolute OHCA recognition and bystander CPR rates by at least 10%, and absolute out-of-hospital cardiac arrest survival by 5% or more.

Trial registration
Prospectively registered on March 28, 2019 at ClinicalTrials.gov identifier: NCT03894059.
The impact of symptoms on quality of life before and after diagnosis of coeliac disease: the results from a Polish population survey and comparison with the results from the United Kingdom
Authors: Majsiak Emilia , Choina Magdalena , Golicki Dominik , Gray Alastair M. , Cukrowska Bożena 
Published: March 2021

AbstractBackgroundCoeliac disease (CD) is characterised by diverse clinical symptoms, which may cause diagnostic problems and reduce the patients’ quality of life. A study conducted in the United Kingdom (UK) revealed that the mean time between the onset of coeliac symptoms and being diagnosed was above 13 years. This study aimed to analyse the diagnostic process of CD in Poland and evaluate the quality of life of patients before and after CD diagnosis. In addition, results were compared to the results of the original study conducted in the UK.MethodsThe study included 2500 members of the Polish Coeliac Society. The patients were asked to complete a questionnaire containing questions on socio-demographic factors, clinical aspects and quality of life, using the EQ-5D questionnaire. Questionnaires received from 796 respondents were included in the final analysis.ResultsThe most common symptoms reported by respondents were bloating (75%), abdominal pain (72%), chronic fatigue (63%) and anaemia (58%). Anaemia was the most persistent symptom, with mean duration prior to CD diagnosis of 9.2 years, whereas diarrhoea was observed for the shortest period (4.7 years). The mean duration of any symptom before CD diagnosis was 7.3 years, compared to 13.2 years in the UK. CD diagnosis and the introduction of a gluten-free diet substantially improved the quality of life in each of the five EQ-5D-5L health dimensions: pain and discomfort, anxiety and depression, usual activities, self-care and mobility (p < 0.001), the EQ-Index by 0.149 (SD 0.23) and the EQ-VAS by 30.4 (SD 28.3) points.ConclusionsDuration of symptoms prior to the diagnosis of CD in Poland, although shorter than in the UK, was long with an average of 7.3 years from first CD symptoms. Faster CD diagnosis after the onset of symptoms in Polish respondents may be related to a higher percentage of children in the Polish sample. Introduction of a gluten-free diet improves coeliac patients’ quality of life. These results suggest that doctors should be made more aware of CD and its symptoms across all age groups.
Development and validation of a simple-to-use nomogram to predict liver metastasis in patients with pancreatic neuroendocrine neoplasms: a large cohort study
Authors: Pan Maoen , Yang Yuanyuan , Teng Tianhong , Lu Fengchun , Chen Yanchan , Huang Heguang 
Published: March 2021

Abstract
Background
Liver metastasis is an important prognostic factor for pancreatic neuroendocrine neoplasms (pNENs), but the relationship between the clinical features of patients with pNEN and liver metastasis remains undetermined. The aim of this study was to establish and validate an easy-to-use nomogram to predict liver-metastasis in patients with pNEN.

Methods
We obtained the clinicopathologic data of 2960 patients with pancreatic neuroendocrine neoplasms from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2016. Univariate and multivariate logistic regression were done to screen out independent influencing factors to establish the nomogram. The calibration plots and the area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of nomogram. Decision curve analysis (DCA) was applied to compare the novel model with the conventional predictive methods.

Results
A total of 2960 patients with pancreatic neuroendocrine neoplasms were included in the study. Among these, 1974 patients were assigned to the training group and 986 patients to the validation group. Multivariate logistic regression identified, tumor size, grade, other site metastasis, T stage and N stage as independent risk factors. The calibration plot showed good discriminative ability in the training and validation groups, with C-indexes of 0.850 for the training cohort and 0.846 for the validation cohort. The AUC values were 0.850 (95% CI 0.830–0.869) and 0.839 (95% CI 0.812–0.866), respectively. The nomogram total points (NTP) had the potential to stratify patients into low risk, medium risk and high risk (P < 0.001). Finally, comparing the nomogram with traditional prediction methods, the DCA curve showed that the nomogram had better net benefit.

Conclusions
Our nomogram has a good ability to predict liver metastasis of pancreatic neuroendocrine neoplasms, and it can guide clinicians to provide suitable prevention and treatment measures for patients with medium- and high-risk liver metastasis.
Association between in-hospital frailty and health-related quality of life after stroke: the Nor-COAST study
Authors: Wæhler Idunn Snorresdatter , Saltvedt Ingvild , Lydersen Stian , Fure Brynjar , Askim Torunn , Einstad Marte Stine , Thingstad Pernille 
Published: March 2021

Abstract
Background
Stroke survivors are known to have poorer health-related quality of life (HRQoL) than the general population, but less is known about characteristics associated with HRQoL decreasing through time following a stroke. This study aims to examine how in-hospital frailty is related to HRQoL from 3 to 18 months post stroke.

Method
Six hundred twenty-five participants hospitalised with stroke were included and followed up at 3 and/or 18 months post stroke. Stroke severity was assessed the day after admission with the National Institutes of Health Stroke Scale (NIHSS). A modified Fried phenotype was used to assess in-hospital frailty; measures of exhaustion, physical activity, and weight loss were based on pre-stroke status, while gait speed and grip strength were measured during hospital stay. HRQoL at 3- and 18-months follow-up were assessed using the five-level version of the EuroQol five-dimensional descriptive system (EQ-5D-5L) and the EuroQol visual analogue scale (EQ-5D VAS). We conducted linear mixed effect regression analyses unadjusted and adjusted for sex, age, and stroke severity to investigate the association between in-hospital frailty and post-stroke HRQoL.

Results
Mean (SD) age was 71.7 years (11.6); mean NIHSS score was 2.8 (4.0), and 263 (42.1%) were female. Frailty prevalence was 10.4%, while 58.6% were pre-frail. The robust group had EQ-5D-5L index and EQ-5D VAS scores at 3 and 18 months comparable to the general population. Also at 3 and 18 months, the pre-frail and frail groups had significantly lower EQ-5D-5L indices than the robust group (p <  0.001), and the frail group showed a larger decrease from 3 to 18 months in the EQ-5D-5L index score compared to the robust group (− 0.056; 95% CI − 0.104 to − 0.009; p = 0.021). There were no significant differences in change in EQ-5D VAS scores between the groups.

Conclusion
This study on participants mainly diagnosed with mild strokes suggests that robust stroke patients have fairly good and stable post-stroke HRQoL, while post-stroke HRQoL is impaired and continues to deteriorate among patients with in-hospital frailty. This emphasises the importance of a greater focus on frailty in stroke units.

Trial registration
ClinicalTrials.gov (NCT02650531).
Integrated bioinformatic analysis identifies UBE2Q1 as a potential prognostic marker for high grade serous ovarian cancer
Authors: Topno Rachel , Singh Ibha , Kumar Manoj , Agarwal Pallavi 
Published: March 2021

Abstract
Background
High grade serous ovarian cancer (HGSOC) accounts for nearly 60% of total cases of epithelial ovarian cancer. It is the most aggressive subtype, which shows poor prognosis and low patient survival. For better management of HGSOC patients, new prognostic biomarkers are required to facilitate improved treatment strategies and ensure suitable healthcare decisions.

Methods
We performed genome wide expression analysis of HGSOC patient samples to identify differentially expressed genes (DEGs) using R based Limma package, Clust and other statistical tools. The identified DEGs were subjected to weighted gene co-expression network analysis (WGCNA) to identify co-expression patterns of relevant genes. Module trait and gene ontology analyses were performed to establish important gene co-expression networks and their biological functions. Overlapping the most relevant DEG cluster 4 with prominent WGCNA cyan module identified strongest correlation of UBE2Q1 with ovarian cancer and its prognostic significance on survival probability of ovarian cancer patients was investigated. The predictive value of UBE2Q1 as a potential biomarker was analysed by correlating its expression with 12-months relapse free survival of patients in response to platin/taxane, the standard first-line chemotherapy for ovarian cancer, and analysing area under the ROC curve.

Results
An integrated gene expression analysis and WGCNA, identified UBE2Q1 as a potential prognostic marker associated with poor relapse-free survival and response outcome to platin/taxane treatment of patients with high grade serous ovarian cancer.

Conclusions
Our study identifies a potential UBE2Q1 – B4GALT3 functional axis in ovarian cancer, where only the E2 conjugating enzyme showed a poor prognostic impact on the disease.
Etiologic distribution and clinical characteristics of pediatric diabetes in 276 children and adolescents with diabetes at a single academic center
Authors: Kim Ja Hye , Lee Yena , Choi Yunha , Kim Gu-Hwan , Yoo Han-Wook , Choi Jin-Ho 
Published: March 2021

Abstract
Background
The prevalence of monogenic diabetes is estimated to be 1.1–6.3% of patients with diabetes mellitus (DM) in Europe. The overlapping clinical features of various forms of diabetes make differential diagnosis challenging. Therefore, this study investigated the etiologic distribution and clinical characteristics of pediatric diabetes, including monogenic diabetes, who presented at a single tertiary center over the last 20 years.

Methods
This study included 276 consecutive patients with DM diagnosed before 18 years of age from January 2000 to December 2019 in Korea. Clinical features, biochemical findings, β-cell autoantibodies, and molecular characteristics were reviewed retrospectively.

Results
Of the 276 patients, 206 patients (74.6%), 49 patients (17.8%), and 21 patients (7.6%) were diagnosed with type 1 DM, type 2 DM, and clinically suspected monogenic diabetes, respectively. Among 21 patients suspected to have monogenic diabetes, 8 patients had clinical maturity-onset diabetes of the young (MODY), and the remaining 13 patients had other types of monogenic diabetes. Among them, genetic etiologies were identified in 14 patients (5.1%) from 13 families, which included MODY 5, transient neonatal DM, developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, Wolfram syndrome, Donohue syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, Fanconi-Bickel syndrome, Wolcott-Rallison syndrome, cystic fibrosis-related diabetes, and maternally inherited diabetes and deafness.

Conclusions
Genetically confirmed monogenic diabetes accounted for 5.1% of patients evaluated at a single tertiary center over 20-year period. Based on the findings for our sample, the frequency of mutations in the major genes of MODY appears to be low among pediatric patients in Korea. It is critical to identify the genetic cause of DM to provide appropriate therapeutic options and genetic counseling.
Predictors of a placebo response in patients with hand osteoarthritis: post-hoc analysis of two randomized controlled trials
Authors: Park Jin Kyun , Ahn Se Han , Shin Kichul , Lee Yun Jong , Song Yeong Wook , Lee Eun Bong 
Published: March 2021

Abstract
Background
Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA.

Methods
This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified.

Results
The mean improvement in the AUSCAN pain score was − 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: − 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, p = 0.001) and a worse AUSCAN stiffness (68.2 ± 20.5 vs. 57.5 ± 24.5, p = 0.008) at baseline than non-responders. Improvements in pain correlated with the baseline pain level (Pearson r = − 427, p < 0.001). Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response (OR: 1.054, 95% CI [1.019–1.089], p = 0.002).

Conclusions
High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.