bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing role of EMS –analyses of non-conveyed and conveyed patients in Finland
Authors: Paulin Jani , Kurola Jouni , Salanterä Sanna , Moen Hans , Guragain Nischal , Koivisto Mari , Käyhkö Niina , Aaltonen Venla , Iirola Timo 
Published: May 2020

Abstract
Background
Emergency Medical Services (EMS) and Emergency Departments (ED) have seen increasing attendance rates in the last decades. Currently, EMS are increasingly assessing and treating patients without the need to convey patients to health care facility. The aim of this study was to describe and compare the patient case-mix between conveyed and non-conveyed patients and to analyze factors related to non-conveyance decision making.

Methods
This was a prospective study design of EMS patients in Finland, and data was collected between 1st June and 30th November 2018. Adjusted ICPC2-classification was used as the reason for care. NEWS2-points were collected and analyzed both statistically and with a semi-supervised information extraction method. EMS patients’ geographic location and distance to health care facilities were analyzed by urban–rural classification.

Results
Of the EMS patients (40,263), 59.8% were over 65 years of age and 46.0% of the patients had zero NEWS2 points. The most common ICPC2 code was weakness/tiredness, general (A04), as seen in 13.5% of all patients. When comparing patients between the non-conveyance and conveyance group, a total of 35,454 EMS patients met the inclusion criteria and 14,874 patients (42.0%) were not conveyed to health care facilities. According the multivariable logistic regression model, the non-conveyance decision was more likely made by ALS units, when the EMS arrival time was in the evening or night and when the distance to the health care facility was 21-40 km. Furthermore, younger patients, female gender, whether the patient had used alcohol and a rural area were also related to the non-conveyance decision. If the patient’s NEWS2 score increased by one or two points, the likelihood of conveyance increased. When there was less than 1 h to complete a shift, this did not associate with either non-conveyance or conveyance decisions.

Conclusions
The role of EMS might be changing. This warrants to redesign the chain-of-survival in EMS to include not only high-risk patient groups but also non-critical and general acute patients with non-specific reasons for care. Assessment and on-scene treatment without conveyance can be called the “stretched arm of the emergency department”, but should be planned carefully to ensure patient safety.
A novel biocatalyst, Enterobacter aerogenes LU2, for efficient production of succinic acid using whey permeate as a cost-effective carbon source
Authors: Szczerba Hubert , Komoń-Janczara Elwira , Dudziak Karolina , Waśko Adam , Targoński Zdzisław 
Published: May 2020

AbstractBackgroundSuccinic acid (SA), a valuable chemical compound with a broad range of industrial uses, has become a subject of global interest in recent years. The bio-based production of SA by highly efficient microbial producers from renewable feedstock is significantly important, regarding the current trend of sustainable development.ResultsIn this study, a novel bacterial strain, LU2, was isolated from cow rumen and recognized as an efficient producer of SA from lactose. Proteomic and genetic identifications as well as phylogenetic analysis were performed, and strain LU2 was classified as anEnterobacter aerogenesspecies. The optimal conditions for SA production were 100 g/L lactose, 10 g/L yeast extract, and 20% inoculum at pH 7.0 and 34 °C. Under these conditions, approximately 51.35 g/L SA with a yield of 53% was produced when batch fermentation was conducted in a 3-L stirred bioreactor. When lactose was replaced with whey permeate, the highest SA concentration of 57.7 g/L was achieved with a yield and total productivity of 62% and 0.34 g/(L*h), respectively. The highest productivity of 0.67 g/(L*h) was observed from 48 to 72 h of batch fermentation, whenE.aerogenesLU2 produced 16.23 g/L SA.ConclusionsThis study shows that the newly isolated strainE.aerogenesLU2 has great potential as a new biocatalyst for producing SA from whey permeate.
Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression
Authors: Larsson Chatarina , Cordeddu Lina , Siggens Lee , Pandzic Tatjana , Kundu Snehangshu , He Liqun , Ali Muhammad Akhtar , Pristovšek Nuša , Hartman Karin , Ekwall Karl , Sjöblom Tobias 
Published: May 2020

Abstract
Background
The histone 3 lysine 4 (H3K4) monomethylase KMT2C is mutated across several cancer types; however, the effects of mutations on epigenome organization, gene expression, and cell growth are not clear. A frequently recurring mutation in colorectal cancer (CRC) with microsatellite instability is a single nucleotide deletion within the exon 38 poly-A(9) repeat (c.8390delA) which results in frameshift preceding the functional carboxy-terminal SET domain. To study effects of KMT2C expression in CRC cells, we restored one allele to wild type KMT2C in the two CRC cell lines RKO and HCT116, which both are homozygous c.8390delA mutant.

Results
Gene editing resulted in increased KMT2C expression, increased H3K4me1 levels, altered gene expression profiles, and subtle negative effects on cell growth, where higher dependence and stronger effects of KMT2C expression were observed in RKO compared to HCT116 cells. Surprisingly, we found that the two RKO and HCT116 CRC cell lines have distinct baseline H3K4me1 epigenomic profiles. In RKO cells, a flatter genome-wide H3K4me1 profile was associated with more increased H3K4me1 deposition at enhancers, reduced cell growth, and more differential gene expression relative to HCT116 cells when KMT2C was restored. Profiling of H3K4me1 did not indicate a highly specific regulation of gene expression as KMT2C-induced H3K4me1 deposition was found globally and not at a specific enhancer sub-set in the engineered cells. Although we observed variation in differentially regulated gene sets between cell lines and individual clones, differentially expressed genes in both cell lines included genes linked to known cancer signaling pathways, estrogen response, hypoxia response, and aspects of immune system regulation.

Conclusions
Here, KMT2C restoration reduced CRC cell growth and reinforced genome-wide H3K4me1 deposition at enhancers; however, the effects varied depending upon the H3K4me1 status of KMT2C deficient cells. Results indicate that KMT2C inactivation may promote colorectal cancer development through transcriptional dysregulation in several pathways with known cancer relevance.
SMILES-based deep generative scaffold decorator for de-novo drug design
Authors: Arús-Pous Josep , Patronov Atanas , Bjerrum Esben Jannik , Tyrchan Christian , Reymond Jean-Louis , Chen Hongming , Engkvist Ola 
Published: May 2020

AbstractMolecular generative models trained with small sets of molecules represented as SMILES strings can generate large regions of the chemical space. Unfortunately, due to the sequential nature of SMILES strings, these models are not able to generate molecules given a scaffold (i.e., partially-built molecules with explicit attachment points). Herein we report a new SMILES-based molecular generative architecture that generates molecules from scaffolds and can be trained from any arbitrary molecular set. This approach is possible thanks to a new molecular set pre-processing algorithm that exhaustively slices all possible combinations of acyclic bonds of every molecule, combinatorically obtaining a large number of scaffolds with their respective decorations. Moreover, it serves as a data augmentation technique and can be readily coupled with randomized SMILES to obtain even better results with small sets. Two examples showcasing the potential of the architecture in medicinal and synthetic chemistry are described: First, models were trained with a training set obtained from a small set of Dopamine Receptor D2 (DRD2) active modulators and were able to meaningfully decorate a wide range of scaffolds and obtain molecular series predicted active on DRD2. Second, a larger set of drug-like molecules from ChEMBL was selectively sliced using synthetic chemistry constraints (RECAP rules). In this case, the resulting scaffolds with decorations were filtered only to allow those that included fragment-like decorations. This filtering process allowed models trained with this dataset to selectively decorate diverse scaffolds with fragments that were generally predicted to be synthesizable and attachable to the scaffold using known synthetic approaches. In both cases, the models were already able to decorate molecules using specific knowledge without the need to add it with other techniques, such as reinforcement learning. We envision that this architecture will become a useful addition to the already existent architectures for de novo molecular generation.
Use of static and dynamic [18F]-F-DOPA PET parameters for detecting patients with glioma recurrence or progression
Authors: Zaragori Timothée , Ginet Merwan , Marie Pierre-Yves , Roch Véronique , Grignon Rachel , Gauchotte Guillaume , Rech Fabien , Blonski Marie , Lamiral Zohra , Taillandier Luc , Imbert Laëtitia , Verger Antoine 
Published: May 2020

AbstractBackgroundStatic [18F]-F-DOPA PET images are currently used for identifying patients with glioma recurrence/progression after treatment, although the additional diagnostic value of dynamic parameters remains unknown in this setting. The aim of this study was to evaluate the performances of static and dynamic [18F]-F-DOPA PET parameters for detecting patients with glioma recurrence/progression as well as assess further relationships with patient outcome.MethodsFifty-one consecutive patients who underwent an [18F]-F-DOPA PET for a suspected glioma recurrence/progression at post-resection MRI, were retrospectively included. Static parameters, including mean and maximum tumor-to-normal-brain (TBR) ratios, tumor-to-striatum (TSR) ratios, and metabolic tumor volume (MTV), as well as dynamic parameters with time-to-peak (TTP) values and curve slope, were tested for predicting the following: (1) glioma recurrence/progression at 6 months after the PET exam and (2) survival on longer follow-up.ResultsAll static parameters were significant predictors of glioma recurrence/progression (accuracy ≥ 94%) with all parameters also associated with mean progression-free survival (PFS) in the overall population (allp< 0.001, 29.7 vs. 0.4 months for TBRmax, TSRmax, and MTV). The curve slope was the sole dynamic PET predictor of glioma recurrence/progression (accuracy = 76.5%) and was also associated with mean PFS (p< 0.001, 18.0 vs. 0.4 months). However, no additional information was provided relative to static parameters in multivariate analysis.ConclusionAlthough patients with glioma recurrence/progression can be detected by both static and dynamic [18F]-F-DOPA PET parameters, most of this diagnostic information can be achieved by conventional static parameters.
The flow-metabolism ratio might predict treatment response and survival in patients with locally advanced esophageal squamous cell carcinoma
Authors: Zhao Kewei , Wang Chunsheng , Mao Qingfeng , Shang Dongping , Huang Yong , Ma Li , Yu Jinming , Li Minghuan 
Published: May 2020

Abstract
Background
Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC).

Methods
Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman’s rank correlation, Mann–Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan–Meier method, and Cox proportional hazards models.

Results
The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = − 0.547, p = 0.003) and TTP (r = − 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014).

Conclusions
The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.
Identification of a species-specific aminotransferase in Pediococcus acidilactici capable of forming α-aminobutyrate
Authors: Wenger Alexander , Schmidt Remo S. , Portmann Reto , Roetschi Alexandra , Eugster Elisabeth , Weisskopf Laure , Irmler Stefan 
Published: May 2020

AbstractDuring cheese ripening, the bacterial strain Pediococcus acidilactici FAM18098 produces the non-proteinogenic amino acid, α-aminobutyrate (AABA). The metabolic processes that lead to the biosynthesis of this compound are unknown. In this study, 10 P. acidilactici, including FAM18098 and nine Pediococcus pentosaceus strains, were screened for their ability to produce AABA. All P. acidilactici strains produced AABA, whereas the P. pentosaceus strains did not. The genomes of the pediococcal strains were sequenced and searched for genes encoding aminotransferases to test the hypothesis that AABA could result from the transamination of α-ketobutyrate. A GenBank and KEGG database search revealed the presence of a species-specific aminotransferase in P. acidilactici. The gene was cloned and its gene product was produced as a His-tagged fusion protein in Escherichia coli to determine the substrate specificity of this enzyme. The purified recombinant protein showed aminotransferase activity at pH 5.5. It catalyzed the transfer of the amino group from leucine, methionine, AABA, alanine, cysteine, and phenylalanine to the amino group acceptor α-ketoglutarate. Αlpha-ketobutyrate could replace α-ketoglutarate as an amino group acceptor. In this case, AABA was produced at significantly higher levels than glutamate. The results of this study show that P. acidilactici possesses a novel aminotransferase that might play a role in cheese biochemistry and has the potential to be used in biotechnological processes for the production of AABA.
Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease
Authors: Yan Yan , Liu Chunyan , Zhao Shimin , Wang Xinxu , Wang Jinling , Zhang Heping , Wang Yuzhen , Zhao Guofen 
Published: May 2020

AbstractBoth steatosis and inflammation are key pathological events in the progression of non-alcoholic fatty liver disease (NAFLD). Probiotics are beneficial for the prevention and treatment of NAFLD. Bifidobacterium animalis subsp. lactis V9 (V9) is a newly isolated strain with favorable probiotic properties. The study aims to evaluate the effects and mechanisms of V9 on the hepatic steatosis and inflammatory responses in a rat model of NAFLD induced by high-fat diets (HFD). Our results showed that administration of V9 significantly attenuated the HFD-induced increases in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, resulting in alleviated hepatic steatosis. V9 supplementation reduced the accumulation of hepatic triglyceride and free fatty acid,while increasing the levels of glycogen. Serum levels of glucose were also decreased in HFD rats administrated with V9. Meanwhile, the transcription of SREBP-1c and FAS was reduced, and the hepatic expression of phosphorylated-AMPK and PPAR-α was restored after V9 administration. V9 suppressed the production of inflammatory cytokines (e.g. IL-6, IL-1β, and TNF-α) in HFD-fed rats. The anti-inflammatory effects of V9 was found to be associated with the inhibition of hepatic expression of TLR4, TLR9, NLRP3, and ASC mRNA. Furthermore, the activation of ERK, JNK, AKT and NF-κB were suppressed by V9 treatment. These results indicate that Bifidobacterium lactis V9 improves NAFLD by regulating de novo lipid synthesis and suppressing inflammation through AMPK and TLR-NF-κB pathways, respectively.
Recruitment pattern of the diaphragm and extradiaphragmatic inspiratory muscles in response to different levels of pressure support
Authors: Roesthuis L. H. , van der Hoeven J. G. , van Hees H. W. H. , Schellekens W.-J. M. , Doorduin J. , Heunks L. M. A. 
Published: May 2020

Abstract
Background
Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm.

Methods
Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed.

Results
We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles.

Conclusions
Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.
Positive periodic solution for Nicholson’s blowfies systems with patch structure
Authors: Duan Feng , Du Bo 
Published: May 2020

AbstractA generalized Nicholson blowfies system with patch structure is studied. Some existence and asymptotic stability results of the positive periodic solution to the considered system are obtained by coincidence degree theory and some analysis techniques. Finally, two examples are given to show the effectiveness of the results in the present paper.
Population vulnerability to COVID-19 in Europe: a burden of disease analysis
Authors: Wyper Grant M. A. , Assunção Ricardo , Cuschieri Sarah , Devleesschauwer Brecht , Fletcher Eilidh , Haagsma Juanita A. , Hilderink Henk B. M. , Idavain Jane , Lesnik Tina , Von der Lippe Elena , Majdan Marek , Milicevic Milena S. , Pallari Elena , Peñalvo José L. , Pires Sara M. , Plaß Dietrich , Santos João V. , Stockton Diane L. , Thomsen Sofie Theresa , Grant Ian 
Published: May 2020

Abstract
Background
Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19.

Methods
Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability.

Results
Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made, the highest rates were observed for Bulgaria, Czechia, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden.

Conclusion
Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19.