bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acetate as substrate for l-malic acid production with Aspergillus oryzae DSM 1863
Authors: Kövilein Aline , Umpfenbach Julia , Ochsenreither Katrin 
Published: February 2021

Abstract
Background
Microbial malic acid production is currently not able to compete economically with well-established chemical processes using fossil resources. The utilization of inexpensive biomass-based substrates containing acetate could decrease production costs and promote the development of microbial processes. Acetate is a by-product in lignocellulosic hydrolysates and fast pyrolysis products or can be synthesized by acetogens during syngas fermentation. For the fermentation of these substrates, a robust microorganism with a high tolerance for biomass-derived inhibitors is required. Aspergillus oryzae is a suitable candidate due to its high tolerance and broad substrate spectrum. To pave the path towards microbial malic acid production, the potential of acetate as a carbon source for A. oryzae is evaluated in this study.

Results
A broad acetate concentration range was tested both for growth and malic acid production with A. oryzae. Dry biomass concentration was highest for acetic acid concentrations of 40–55 g/L reaching values of about 1.1 g/L within 48 h. Morphological changes were observed depending on the acetate concentration, yielding a pellet-like morphology with low and a filamentous structure with high substrate concentrations. For malic acid production, 45 g/L acetic acid was ideal, resulting in a product concentration of 8.44 ± 0.42 g/L after 192 h. The addition of 5–15 g/L glucose to acetate medium proved beneficial by lowering the time point of maximum productivity and increasing malic acid yield. The side product spectrum of cultures with acetate, glucose, and cultures containing both substrates was compared, showing differences especially in the amount of oxalic, succinic, and citric acid produced. Furthermore, the presence of CaCO3, a pH regulator used for malate production with glucose, was found to be crucial also for malic acid production with acetate.

Conclusions
This study evaluates relevant aspects of malic acid production with A. oryzae using acetate as carbon source and demonstrates that it is a suitable substrate for biomass formation and acid synthesis. The insights provided here will be useful to further microbial malic acid production using renewable substrates.
Melatonin levels in the Alzheimer’s disease continuum: a systematic review
Authors: Nous Amber , Engelborghs Sebastiaan , Smolders Ilse 
Published: February 2021

Abstract
Background
The search for new Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets. Melatonin might be an interesting biomarker as an inverse correlation between CSF melatonin levels, and severity of the neuropathology as measured by Braak stages has been described. Melatonin can be measured in different body fluids, such as CSF, blood, saliva and urine.

Objectives
The aim of this systematic review was to review all available studies regarding melatonin levels in different body fluids in the AD continuum and give an extensive overview of reported outcomes.

Methods
We included papers comparing melatonin levels between healthy controls and human patients belonging to the AD continuum. A systematic search of PubMed and Web of Science led to inclusion of 20 full-length English papers following exclusion of duplicates.

Results
This systematic literature search showed that disruptions in melatonin levels occur with age, but also in AD when compared to age-matched controls. Night-time melatonin levels were found to be lower in CSF and blood of AD patients as compared to controls. Literature was not conclusive regarding alterations in blood daytime melatonin levels or regarding saliva melatonin in AD patients. Decreased total and night-time melatonin production has been described in urine of AD patients.

Conclusion
Our systematic review shows evidence for disruptions in (night-time) melatonin levels in AD as compared to age-matched controls. Although more studies are needed to understand the contribution of disruption of the melatonergic system to the pathophysiology of AD, the potential anti-AD effects that have been attributed to melatonin, renders research on this topic relevant for the discovery of potential future treatment effects of melatonin for AD. The use of melatonin as potential blood biomarker for disease progression should also be further investigated.
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome
Authors: Petruschke Hannes , Schori Christian , Canzler Sebastian , Riesbeck Sarah , Poehlein Anja , Daniel Rolf , Frei Daniel , Segessemann Tina , Zimmerman Johannes , Marinos Georgios , Kaleta Christoph , Jehmlich Nico , Ahrens Christian H. , von Bergen Martin 
Published: February 2021

AbstractBackgroundThe intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities.ResultsWe created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx.ConclusionsWe outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.
Improvement in resolution of fiber-laser photoacoustic tomography based on a virtual-point concept
Authors: Bai Xue , Li Xu , Ma Jun , Guan Bai-Ou 
Published: February 2021

AbstractIn this study, a virtual-point concept was introduced into fiber-laser photoacoustic tomography to improve the elevational image resolution. The flexible fiber laser was bent into an arc shape to conform to the ultrasound wavefront, which formed an ultrasound focus at the center of the arc. The synthetic aperture focusing technique was utilized to reconstruct the images; as a result, the elevational resolution particularly within the out-of-focus region was considerably improved compared to the resolution of an image retrieved by multiplexing the PA time-resolved signals with sound velocity. The all-optical fiber-laser photoacoustic tomography system with a high spatial resolution has potential for various applications, including biomedical research and preclinical/clinical diagnosis.
High Prevalence of Weight Gain in Childhood Brain Tumor Survivors and Its Association With Hypothalamic-Pituitary Dysfunction
Authors: van Schaik Jiska , van Roessel Ichelle M. A. A. , Schouten-van Meeteren Netteke A. Y. N. , van Iersel Laura , Clement Sarah C. , Boot Annemieke M. , Claahsen-van der Grinten Hedi L. , Fiocco Marta , Janssens Geert O. , van Vuurden Dannis G. , Michiels Erna M. , Han Sen K. S. , van Trotsenburg Paul A. S. P. , Vandertop Peter W. P. , Kremer Leontien C. M. , van Santen Hanneke M. 
Published: February 2021

PURPOSE Childhood brain tumor survivors (CBTS) are at risk for developing obesity, which negatively influences cardiometabolic health. The prevalence of obesity in CBTS may have been overestimated in previous cohorts because of inclusion of children with craniopharyngioma. On the contrary, the degree of weight gain may have been underestimated because of exclusion of CBTS who experienced weight gain, but were neither overweight nor obese. Weight gain may be an indicator of underlying hypothalamic-pituitary (HP) dysfunction. We aimed to study prevalence of and risk factors for significant weight gain, overweight, or obesity, and its association with HP dysfunction in a national cohort of noncraniopharyngioma and nonpituitary CBTS. METHODS Prevalence of and risk factors for significant weight gain (body mass index [BMI] change ≥ +2.0 standard deviation score [SDS]), overweight, or obesity at follow-up, and its association with HP dysfunction were studied in a nationwide cohort of CBTS, diagnosed in a 10-year period (2002-2012), excluding all craniopharyngioma and pituitary tumors. RESULTS Of 661 CBTS, with a median age at follow-up of 7.3 years, 33.1% had significant weight gain, overweight, or obesity. Of the CBTS between 4 and 20 years of age, 28.7% were overweight or obese, compared with 13.2% of the general population between 4 and 20 years of age. BMI SDS at diagnosis, diagnosis of low-grade glioma, diabetes insipidus, and central precocious puberty were associated with weight gain, overweight, or obesity. The prevalence of HP dysfunction was higher in overweight and obese CTBS compared with normal-weight CBTS. CONCLUSION Overweight, obesity, and significant weight gain are prevalent in CBTS. An increase in BMI during follow-up may be a reflection of HP dysfunction, necessitating more intense endocrine surveillance.
Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies
Authors: Giusto Kiersten , Wanczyk Heather , Jensen Todd , Finck Christine 
Published: February 2021

ABSTRACT
Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.
Modified chromosome structure caused by phosphomimetic H2A modulates the DNA damage response by increasing chromatin mobility in yeast
Authors: García Fernández Fabiola , Lemos Brenda , Khalil Yasmine , Batrin Renaud , Haber James E. , Fabre Emmanuelle 
Published: February 2021

ABSTRACT
In budding yeast and mammals, double-strand breaks (DSBs) trigger global chromatin mobility together with rapid phosphorylation of histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phosphomimetic H2A-S129E. We show that mimicking H2A phosphorylation leads to an increase in global chromatin mobility in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to downstream checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intrachromosomal distances observed in the H2A-S129E mutant are consistent with chromatin structural changes. Strikingly, in this context the Rad9-dependent checkpoint becomes dispensable. Moreover, increased chromatin dynamics in the H2A-S129E mutant correlates with improved DSB repair by non-homologous end joining and a sharp decrease in interchromosomal translocation rate. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DNA damage response and maintain genome integrity.
This article has an associated First Person interview with the first author of the paper.
Interest Rate Volatility and No-Arbitrage Affine Term Structure Models
Authors: Joslin Scott , Le Anh 
Published: February 2021

Within the affine framework, many have observed a tension between matching conditional first and second moments in dynamic term structure models (DTSMs). Although the existence of this tension is generally accepted, less understood is the mechanism that underlies it. We show that no arbitrage along with the rich information in the cross section of yields has strong implications for both the dynamics of volatility and the forecasts of yields. We show that this link implied by the absence of arbitrage—and not the factor structure per se—underlies the tension between first and second moments found in the literature. Adding to recent research that has suggested that no-arbitrage restrictions are nearly irrelevant in Gaussian DTSMs, our results show that no-arbitrage restrictions are potentially relevant when there is stochastic volatility. This paper was accepted by Gustavo Manso, finance.
Factors affecting health-related quality of life among Nepalese adults with mild traumatic brain injury
Authors: Aryal Shristi , Thosingha Orapan , Chayaput Prangtip 
Published: February 2021

Background: Mild traumatic brain injury (MTBI) is a stressful life event. Most patients recover, but a subset of patients experience somatic, cognitive and behavioural symptoms that affect health-related quality of life (HRQOL). Aims: To identify the level impact on HRQOL and to examine the associated factors of HRQOL among patients with MTBI. Methods: This was a correlational predictive study. Findings: The mean age of the participants was 33.89 years, with a range from 18 to 62 years. HRQOL was at amoderate level. In multiple regression analysis, social support (β = .419, p = .000), PCS severity (β = -.245, p = .003) and economic status (β = .167, p = .035) accounted for 36.3% of explained variance on HRQOL. Conclusions: Post-concussion symptoms after discharge should be evaluated, and patients' need for support must be thoroughly assessed.
Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis
Authors: Xu Hongzhen , Tong Lin , Gao Peng , Hu Yan , Wang Huijuan , Chen Zhimin , Fang Luo 
Published: February 2021

Background
A combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice.

Objective
To evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents.

Methods
The MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the earliest record date to September 2020 for randomized controlled trials in children and adolescents (≤18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO.

Results
Of the 1061 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66–0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.73; 95% CI 0.60–0.88; p = 0.0009; I2 = 4%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50–0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63–4.98).

Conclusion
IB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. The very low to high quality of evidence indicated that future well-designed double-blind RCTs with large sample are needed for research on evaluating the effectiveness of IB + salbutamol treatment for asthma in children and adolescents.
Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: A cross-sectional study
Authors: Kassie Ayelign Mengesha , Abate Biruk Beletew , Kassaw Mesfin Wudu , Getie Addisu , Wondmieneh Adam , Tegegne Kindie Mekuria , Ahmed Mohammed 
Published: February 2021

BackgroundEpilepsy is thought to be caused by witchcraft, evil spirit, and God’s punishment for sins in many developing countries. As a result, people with epilepsy and their families usually suffer from stigma, discrimination, depression, and other psychiatric problems. Thus, this study aimed to assess the quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia.MethodsAn institution-based cross-sectional study design was employed in this study. A simple random sampling technique was utilized. Health-related quality of life was measured based on the total score of the Quality of Life in Epilepsy Inventory (QOLIE-31) instrument. Data were entered into Epi-data 3.1 statistical package and exported to SPSS Version 20 for further analysis. Linear regression models were used to assess the relationship between quality of life and the independent variables. Statistically significant values were declared at a P-value of < 0.05.ResultsA total of 395 patients participated in the study making the response rate 98.5%. The mean age of the participants was 32.39 ±10.71 years. More than half, 199 (50.4%) of epileptic patients had an overall weighted average health related quality of life score of mean and above. Male sex (B=4.34, 95%CI, 0.41, 8.27, P=0.03), higher educational status (B=7.18, 95%CI, 1.39, 13.00, P=0.015) and age at onset of epilepsy (B=0.237, 95%CI, 0.02, 0.45, P=0.035) were associated with increased health related quality of life score. On the other hand, family history of epilepsy (B=-4.78, 95%CI,-9.24,-0.33, P=0.035), uncontrolled seizure (B=-11.08, 95%CI,-15.11,-7.05, P < 0.001), more than 5 pre-treatment number of seizures (B=-4.86, 95%CI,-8.91,-0.81, P=0.019), poor drug adherence (B=-11.65, 95%CI,-16.06,-7.23, P < 0.001), having moderate (B=-4.526, 95%CI,-8.59,-0.46, P=0.029) to sever (B = -12.84, 95%CI,-18.30,-7.37, P < 0.001) anxiety and depression, believing that epilepsy is caused by evil spirit (B=-7.04, 95%CI,-11.46,-2.61, P=0.002), drinking alcohol (B=-5.42, 95%CI,-10.72,-0.13, P = 0.045), and having other co-morbidities (B=-9.35, 95%CI,-14.35,-4.36, P < 0.001) were significantly negatively associated with the health related quality of life score among epileptic patients.ConclusionsOnly around half of the epileptic patients have a good health-related quality of life. In addition, multiple variables including family history, uncontrolled seizure, and poor drug adherence were associated with quality of life among epileptic patients. Hence, targeting these variables in epilepsy management is recommended.
Impact of surgeons’ experience and the single-shot perioperative antibiotic prophylaxis on outcome in stapedotomy
Authors: Brkic Faris F. , Erovic Boban M. , Onoprienko Arina , Janik Stefan , Riss Dominik , Lill Claudia , Grasl Stefan , Hamzavi Jafar-Sasan , Vyskocil Erich 
Published: February 2021

Background
The aim of this study was to evaluate whether surgeons´ experience and perioperative single-shot antibiotic prophylaxis affect outcome of patients undergoing stapes surgery.

Patients and methods
We retrospectively evaluated audiological outcomes and postoperative complications of 538 consecutive patients who underwent stapes surgery at a single tertiary referral center between 1990 and 2017. Effects of different clinical variables, including single-shot antibiotic prophylaxis and surgeons’ experience on outcome were assessed.

Results
538 patients underwent 667 stapedotomies and postoperative complication rate was 7.5% (n = 50). Air conduction and air-bone gap closure improved significantly after surgery (14.2 ± 14.8 dB, p = 0.001; 14.5 ± 12.8 dB, p = 0.001). Multivariate analysis revealed that 6 years or less of surgical experience was independently associated with a higher incidence of persisting or recurrent conductive hearing loss (p = 0.033, OR 5.13) but perioperative application of antibiotics had no significant effect on outcome.

Conclusion
First, clinical outcome regarding persisting or recurrent conductive hearing loss caused by incus necrosis and prosthesis luxation is linked to surgical performance. This underlines the need for a meticulous training and supervision of less experienced surgeons performing stapes surgery. Second, our results do not support the need for perioperative antibiotic prophylaxis in stapes surgery. Potential standard limitations of retrospective cohort studies (selection bias, confusion bias etc.) could play a role in interpreting our results. However, the probability for these limitations is minimized due to the large patient sample.