bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and opportunities of bioprocessing 5-aminolevulinic acid using genetic and metabolic engineering: a critical review
Authors: Yi Ying-Chen , Shih I-Tai , Yu Tzu-Hsuan , Lee Yen-Ju , Ng I-Son 
Published: October 2021

Abstract5-Aminolevulinic acid (5-ALA), a non-proteinogenic five-carbon amino acid, has received intensive attentions in medicine due to its approval by the US Food and Drug Administration (FDA) for cancer diagnosis and treatment as photodynamic therapy. As chemical synthesis of 5-ALA performed low yield, complicated processes, and high cost, biosynthesis of 5-ALA via C4 (also called Shemin pathway) and C5 pathway related to heme biosynthesis in microorganism equipped more advantages. In C4 pathway, 5-ALA is derived from condensation of succinyl-CoA and glycine by 5-aminolevulic acid synthase (ALAS) with pyridoxal phosphate (PLP) as co-factor in one-step biotransformation. The C5 pathway involves three enzymes comprising glutamyl-tRNA synthetase (GltX), glutamyl-tRNA reductase (HemA), and glutamate-1-semialdehyde aminotransferase (HemL) from α-ketoglutarate in TCA cycle to 5-ALA and heme. In this review, we describe the recent results of 5-ALA production from different genes and microorganisms via genetic and metabolic engineering approaches. The regulation of different chassis is fine-tuned by applying synthetic biology and boosts 5-ALA production eventually. The purification process, challenges, and opportunities of 5-ALA for industrial applications are also summarized.
Crop host signatures reflected by co-association patterns of keystone Bacteria in the rhizosphere microbiota
Authors: Lewin Simon , Francioli Davide , Ulrich Andreas , Kolb Steffen 
Published: October 2021

Abstract
Background
The native crop bacterial microbiota of the rhizosphere is envisioned to be engineered for sustainable agriculture. This requires the identification of keystone rhizosphere Bacteria and an understanding on how these govern crop-specific microbiome assembly from soils. We identified the metabolically active bacterial microbiota (SSU RNA) inhabiting two compartments of the rhizosphere of wheat (Triticum aestivum L.), barley (Hordeum vulgare L.), rye (Secale cereale), and oilseed rape (Brassica napus L.) at different growth stages.

Results
Based on metabarcoding analysis the bacterial microbiota was shaped by the two rhizosphere compartments, i.e. close and distant. Thereby implying a different spatial extent of bacterial microbiota acquirement by the cereals species versus oilseed rape. We derived core microbiota of each crop species. Massilia (barley and wheat) and unclassified Chloroflexi of group ‘KD4-96’ (oilseed rape) were identified as keystone Bacteria by combining LEfSe biomarker and network analyses. Subsequently, differential associations between networks of each crop species’ core microbiota revealed host plant-specific interconnections for specific genera, such as the unclassified Tepidisphaeraceae ‘WD2101 soil group’.

Conclusions
Our results provide keystone rhizosphere Bacteria derived from for crop hosts and revealed that cohort subnetworks and differential associations elucidated host species effect that was not evident from differential abundance of single bacterial genera enriched or unique to a specific plant host. Thus, we underline the importance of co-occurrence patterns within the rhizosphere microbiota that emerge in crop-specific microbiomes, which will be essential to modify native crop microbiomes for future agriculture and to develop effective bio-fertilizers.
Organising labour market integration support for refugees in Austria and Sweden during the Covid-19 pandemic
Authors: Bešić Almina , Diedrich Andreas , Aigner Petra 
Published: October 2021

AbstractThis paper addresses the question of how the Covid-19 pandemic has affected the labour market integration support (LMIS) organised for refugees in Austria and Sweden, and the potential consequences of the changes unfolding. LMIS for refugees is a complex phenomenon involving actors at different interwoven levels—the macro-national level, the meso-organisational level and the micro-individual level. However, the complexities and consequences of such processes for the labour market integration of refugees have so far received limited attention. The current Covid-19 pandemic actualises the need to gain a better understanding of how integration support is organised across the different levels and how the pandemic itself impacts such support. Thus, the article seeks to understand how the pandemic affects the LMIS organised for refugees in Austria and Sweden, two countries with a large refugee population and diverging responses to the pandemic. Based on 29 semi-structured interviews and three focus group workshops, the results highlight in particular three developments: (a) a further entrenching of broader, macro-national level developments related to integration support already underway prior to the pandemic; (b) further mainstreaming of activities; and (c) increased volatility of work. Overall, the pandemic has brought to the fore the interrelation of different levels in the organising of LMIS for refugees and has contributed to a stabilisation of already ongoing activities.
Successful treatment of bepridil-induced intraoperative torsades de pointes by isoproterenol infusion
Authors: Shimano Ken , Chang Kyungho , Hara Yoshiki , Yasuda Atsushi , Sawamura Shigehito 
Published: October 2021

Abstract
Background
Several types of antiarrhythmic drugs are known to induce QT prolongation and torsades de pointes.

Case presentation
An 84-year-old man was scheduled for open gastrectomy for residual cancer. He had been prescribed bepridil for atrial fibrillation that converted to sinus rhythm with prolonged QT interval in the operating room. After the surgery was initiated under general and epidural anesthesia, the patient’s heart rate decreased to 50/min and multifocal premature ventricular contractions appeared, followed by several episodes of torsades de pointes, each lasting for 5 to 15 s. Infusion of isoproterenol was started (0.01 μg/kg/min), and the heart rate was maintained at around 80/min. Premature ventricular contractions disappeared, and torsades de pointes did not recur during the surgery. The operation was completed uneventfully. The serum bepridil concentration was found to be extremely high postoperatively.

Conclusions
Bepridil-induced intraoperative episodes of torsades de pointes were successfully treated by increasing the heart rate with isoproterenol.
Bacterial community dynamics during embryonic development of the little skate (Leucoraja erinacea)
Authors: Mika Katelyn , Okamoto Alexander S. , Shubin Neil H. , Mark Welch David B. 
Published: October 2021

Abstract
Background
Microbial transmission from parent to offspring is hypothesized to be widespread in vertebrates. However, evidence for this is limited as many evolutionarily important clades remain unexamined. There is currently no data on the microbiota associated with any Chondrichthyan species during embryonic development, despite the global distribution, ecological importance, and phylogenetic position of this clade. In this study, we take the first steps towards filling this gap by investigating the microbiota associated with embryonic development in the little skate, Leucoraja erinacea, a common North Atlantic species and popular system for chondrichthyan biology.

Methods
To assess the potential for bacterial transmission in an oviparous chondrichthyan, we used 16S rRNA amplicon sequencing to characterize the microbial communities associated with the skin, gill, and egg capsule of the little skate, at six points during ontogeny. Community composition was analyzed using the QIIME2 pipeline and microbial continuity between stages was tracked using FEAST.

Results
We identify site-specific and stage-specific microbiota dominated by the bacterial phyla Proteobacteria and Bacteroidetes. This composition is similar to, but distinct from, that of previously published data on the adult microbiota of other chondrichthyan species. Our data reveal that the skate egg capsule harbors a highly diverse bacterial community–particularly on the internal surface of the capsule–and facilitates intergenerational microbial transfer to the offspring. Embryonic skin and external gill tissues host similar bacterial communities; the skin and gill communities later diverge as the internal gills and skin denticles develop.

Conclusions
Our study is the first exploration of the chondrichthyan microbiota throughout ontogeny and provides the first evidence of vertical transmission in this group.
A cell-based drug discovery assay identifies inhibition of cell stress responses as a new approach to treatment of epidermolysis bullosa simplex
Authors: Tan Tong San , Common John E. A. , Lim John S. Y. , Badowski Cedric , Firdaus Muhammad Jasrie , Leonardi Steven S. , Lane E. Birgitte 
Published: October 2021

ABSTRACT
In the skin fragility disorder epidermolysis bullosa simplex (EBS), mutations in keratin 14 (K14, also known as KRT14) or keratin 5 (K5, also known as KRT5) lead to keratinocyte rupture and skin blistering. Severe forms of EBS are associated with cytoplasmic protein aggregates, with elevated kinase activation of ERK1 and ERK2 (ERK1/2; also known as MAPK3 and MAPK1, respectively), suggesting intrinsic stress caused by misfolded keratin protein. Human keratinocyte EBS reporter cells stably expressing GFP-tagged EBS-mimetic mutant K14 were used to optimize a semi-automated system to quantify the effects of test compounds on keratin aggregates. Screening of a protein kinase inhibitor library identified several candidates that reduced aggregates and impacted on epidermal growth factor receptor (EGFR) signalling. EGF ligand exposure induced keratin aggregates in EBS reporter keratinocytes, which was reversible by EGFR inhibition. EBS keratinocytes treated with a known EGFR inhibitor, afatinib, were driven out of activation and towards quiescence with minimal cell death. Aggregate reduction was accompanied by denser keratin filament networks with enhanced intercellular cohesion and resilience, which when extrapolated to a whole tissue context would predict reduced epidermal fragility in EBS patients. This assay system provides a powerful tool for discovery and development of new pathway intervention therapeutic avenues for EBS.
Convergent evolution of skin surface microarchitecture and increased skin hydrophobicity in semi-aquatic anole lizards
Authors: Baeckens Simon , Temmerman Marie , Gorb Stanislav N. , Neto Chiara , Whiting Martin J. , Van Damme Raoul 
Published: October 2021

ABSTRACTAnimals that habitually cross the boundary between water and land face specific challenges with respect to locomotion, respiration, insulation, fouling and waterproofing. Many semi-aquatic invertebrates and plants have developed complex surface microstructures with water-repellent properties to overcome these problems, but equivalent adaptations of the skin have not been reported for vertebrates that encounter similar environmental challenges. Here, we document the first evidence of evolutionary convergence of hydrophobic structured skin in a group of semi-aquatic tetrapods. We show that the skin surface of semi-aquatic species of Anolis lizards is characterized by a more elaborate microstructural architecture (i.e. longer spines and spinules) and a lower wettability relative to closely related terrestrial species. In addition, phylogenetic comparative models reveal repeated independent evolution of enhanced skin hydrophobicity associated with the transition to a semi-aquatic lifestyle, providing evidence of adaptation. Our findings invite a new and exciting line of inquiry into the ecological significance, evolutionary origin and developmental basis of hydrophobic skin surfaces in semi-aquatic lizards, which is essential for understanding why and how the observed skin adaptations evolved in some and not other semi-aquatic tetrapod lineages.
A semi-automatic approach for longitudinal 3D upper airway analysis using voxel-based registration
Authors: Diaconu Alexandru , Holte Michael Boelstoft , Cattaneo Paolo Maria , Pinholt Else Marie 
Published: October 2021

Objectives: To propose and validate a reliable semi-automatic approach for three-dimensional (3D) analysis of the upper airway (UA) based on voxel-based registration (VBR). Methods: Post-operative cone beam computed tomography (CBCT) scans of 10 orthognathic surgery patients were superimposed to the pre-operative CBCT scans by VBR using the anterior cranial base as reference. Anatomic landmarks were used to automatically cut the UA and calculate volumes and cross-sectional areas (CSA). The 3D analysis was performed by two observers twice, at an interval of two weeks. Intraclass correlations and Bland-Altman plots were used to quantify the measurement error and reliability of the method. The relative Dahlberg error was calculated and compared with a similar method based on landmark re-identification and manual measurements. Results: Intraclass correlation coefficient (ICC) showed excellent intra- and inter-observer reliability (ICC ≥ 0.995). Bland-Altman plots showed good observer agreement, low bias and no systematic errors. The relative Dahlberg error ranged between 0.51 and 4.30% for volume and 0.24 and 2.90% for CSA. This was lower when compared with a similar, manual method. Voxel-based registration introduced 0.05–1.44% method error. Conclusions: The proposed method was shown to have excellent reliability and high observer agreement. The method is feasible for longitudinal clinical trials on large cohorts due to being semi-automatic.
A cross-sectional study of the relationship between delayed healthcare utilisation and chronic conditions among older adults during the COVID-19 pandemic in Ireland
Authors: Hennelly Niamh , Lalor Georgia , Gibney Sarah , Kenny Rose Anne , Ward Mark 
Published: October 2021

Background: Many healthcare services were cancelled or postponed during the coronavirus 2019 (COVID-19) pandemic, likely impacting the management of chronic conditions prevalent among older adults in Ireland. Methods: Data from the Irish Longitudinal Study on Ageing COVID-19 study and previous waves were used. Taking healthcare demand into account, the relationship between delayed healthcare utilisation among older adults (≥50) with chronic conditions was examined. Further analyses examined the reasons for delays in healthcare utilisation, and whether they were the result of the reduced availability of healthcare services or participant decisions. Results: In total, 31.6% of participants reported experiencing healthcare delay. The first analysis found that older adults with two or more chronic conditions were more likely to have experienced healthcare delay than those with no chronic conditions (odds ratio (OR): 1.46, 95% confidence interval (CI): 1.11, 1.90). The second analysis found that older adults with two or more chronic conditions were more likely to have healthcare delayed by the provider (OR: 1.73, 95% CI: 1.16, 2.56), and were also more likely to delay their own healthcare (OR: 1.62, 95% CI: 1.14, 2.29) than older adults with no chronic conditions. Additionally, people aged 70 years and over, females, those with problematic alcohol consumption, those with third-level education, those who had visited the GP and those who reported polypharmacy were all more likely to experience healthcare delay, while older adults living with others and those living outside Dublin were less likely to experience healthcare delay. Conclusion: COVID-19 has had a significant impact on the healthcare utilisation of older adults in Ireland, with some groups of older adults impacted more than others. Policy and practice must now focus on how the healthcare needs of these groups can be best served. Further research is required to understand the impact of healthcare delays on health outcomes.
Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study
Authors: Crone Michael , Randell Paul , Herm Zoey , Anand Arthi , Missaghian-Cully Saghar , Perelman Loren , Pantelidis Panagiotis , Freemont Paul 
Published: October 2021

Background: Diagnostic laboratories are currently required to provide routine testing of asymptomatic staff and patients as a part of their clinical screening for SARS-CoV-2 infection. However, these cohorts display very different disease prevalence from symptomatic individuals and testing capacity for asymptomatic screening is often limited. Group testing is frequently proposed as a possible solution to address this; however, proposals neglect the technical and operational feasibility of implementation in a front-line diagnostic laboratory. Methods: Between October and December 2020, as a seven-week proof of concept, we took into account scientific, technical and operational feasibility to design and implement an adaptive pooling strategy in an NHS diagnostic laboratory in London (UK). We assessed the impact of pooling on analytical sensitivity and modelled the impact of prevalence on pooling strategy. We then considered the operational constraints to model the potential gains in capacity and the requirements for additional staff and infrastructure. Finally, we developed a LIMS-agnostic laboratory automation workflow and software solution and tested the technical feasibility of our adaptive pooling workflow. Results: First, we determined the analytical sensitivity of the implemented SARS-CoV-2 assay to be 250 copies/mL. We then determined that, in a setting with limited analyser capacity, the testing capacity could be increased by two-fold with pooling, however, in a setting with limited reagents, this could rise to a five-fold increase. These capacity increases could be realized with modest additional resource and staffing requirements whilst utilizing up to 76% fewer plastic consumables and 90% fewer reagents. Finally, we successfully implemented a plate-based pooling workflow and tested 920 patient samples using the reagents that would usually be required to process just 222 samples. Conclusions: Adaptive pooled testing is a scientifically, technically and operationally feasible solution to increase testing capacity in frontline NHS diagnostic laboratories.
3D reconstruction and positioning of surface features based on a monocular camera and geometric constraints
Authors: Hou Guanyu , Zhang Weibin , Wu Bin , He Rongfang 
Published: October 2021

This paper proposes a 3D reconstruction and positioning method based on a single detecting camera and geometric constraint to evaluate the defect quantitatively. We realize the camera orientation through datum point coordinates acquired by a photogrammetry system and then solve the equation of the defect detection camera model and surface constraints to reconstruct the color point cloud in 3D space. To realize the reconstruction and orientation of defects on objects without marker points, the system is operated by a repetitive moving of robotic arms. Finally, the experiment achieves the reconstruction of three types of products with marker points and one of the same types of objects without marks. The experiment shows that this method can limit the accuracy of surface feature positioning to 0.7 mm, and relative accuracy of the area calculation to 0.125%.
Tobacco price and use following California Proposition 56 tobacco tax increase
Authors: Gunadi Christian , Benmarhnia Tarik , White Martha , Pierce John P. , McMenamin Sara B. , Leas Eric C. , Shi Yuyan 
Published: October 2021

Background
California Proposition 56 increased cigarette excise tax by $2 per pack with equivalent increases on non-cigarette tobacco products. We estimated the changes in cigarette price, cigarette use, and non-cigarette use following the implementation of Proposition 56 in California in 2017.

Methods
Seven waves of Tobacco Use Supplements to the Current Population Survey (TUS-CPS) 2011–2019 data were used to obtain state-level aggregate self-reported outcomes, including cigarette price per pack, current and daily cigarette use, cigarette consumption per day, and current and daily use of non-cigarette tobacco products (hookah, pipe, cigar, and smokeless tobacco). A modified version of a synthetic control method was used to create a “synthetic” California that best resembled pre-policy sociodemographic characteristics and outcome trends in California while correcting time-invariant pre-policy differences. Various sensitivity analyses were also conducted.

Results
The implementation of Proposition 56 was associated with an increase in self-reported cigarette price per pack in California ($1.844, 95%CI: $0.153, $3.534; p = 0.032). No evidence suggested that Proposition 56 was associated with the changes in the prevalence of current or daily cigarette use, cigarette consumption per day, or the prevalence of current or daily use of non-cigarette tobacco products.

Conclusion
Most of the cigarette tax increase following Proposition 56 in California was passed on to consumers. There is a lack of evidence that the implementation of Proposition 56 was associated with the changes in the use of cigarettes and other tobacco products such as hookah, pipe, cigar, and smokeless tobacco.
Impact of obesity on intensive care outcomes in patients with COVID-19 in Sweden—A cohort study
Authors: Sjögren Lovisa , Stenberg Erik , Thuccani Meena , Martikainen Jari , Rylander Christian , Wallenius Ville , Olbers Torsten , Kindblom Jenny M. 
Published: October 2021

Background
Previous studies have shown that a high body mass index (BMI) is a risk factor for severe COVID-19. The aim of the present study was to assess whether a high BMI affects the risk of death or prolonged length of stay (LOS) in patients with COVID-19 during intensive care in Sweden.

Methods and findings
In this observational, register-based study, we included patients with COVID-19 from the Swedish Intensive Care Registry admitted to intensive care units (ICUs) in Sweden. Outcomes assessed were death during intensive care and ICU LOS ≥14 days. We used logistic regression models to evaluate the association (odds ratio [OR] and 95% confidence interval [CI]) between BMI and the outcomes. Valid weight and height information could be retrieved in 1,649 patients (1,227 (74.4%) males) with COVID-19. We found a significant association between BMI and the risk of the composite outcome death or LOS ≥14 days in survivors (OR per standard deviation [SD] increase 1.30, 95%CI 1.16–1.44, adjusted for sex, age and comorbidities), and this association remained after further adjustment for severity of illness (simplified acute physiology score; SAPS3) at ICU admission (OR 1.30 per SD, 95%CI 1.17–1.45). Individuals with a BMI ≥ 35 kg/m2 had a doubled risk of the composite outcome. A high BMI was also associated with death during intensive care and a prolonged LOS in survivors assessed as separate outcomes.
The main limitations were the restriction to the first wave of the pandemic, and the lack of information on socioeconomic status as well as smoking.

Conclusions
In this large cohort of Swedish ICU patients with COVID-19, a high BMI was associated with increasing risk of death and prolonged length of stay in the ICU. Based on our findings, we suggest that individuals with obesity should be more closely monitored when hospitalized for COVID-19.