bluuebunny/crossref_metadata_2025_split huggingface dataset:
The wide‐ranging phenotypes of ergosterol biosynthesis mutants, and implications for microbial cell factories
Authors: Johnston Emily J. , Moses Tessa , Rosser Susan J. 
Published: December 2019

AbstractYeast strains have been used extensively as robust microbial cell factories for the production of bulk and fine chemicals, including biofuels (bioethanol), complex pharmaceuticals (antimalarial drug artemisinin and opioid pain killers), flavours, and fragrances (vanillin, nootkatone, and resveratrol). In many cases, it is of benefit to suppress or modify ergosterol biosynthesis during strain engineering, for example, to increase thermotolerance or to increase metabolic flux through an alternate pathway. However, the impact of modifying ergosterol biosynthesis on engineered strains is discussed sparsely in literature, and little attention has been paid to the implications of these modifications on the general health and well‐being of yeast. Importantly, yeast with modified sterol content exhibit a wide range of phenotypes, including altered organization and dynamics of plasma membrane, altered susceptibility to chemical treatment, increased tolerance to high temperatures, and reduced tolerance to other stresses such as high ethanol, salt, and solute concentrations. Here, we review the wide‐ranging phenotypes of viable Saccharomyces cerevisiae strains with altered sterol content and discuss the implications of these for yeast as microbial cell factories.
Smart Contracts in Insurance: A Law and Futurology Perspective
Authors: Borselli Angelo 
Published: December 2019

AbstractSmart contracts are innovative contracts that differ from traditional ones in that they are self-executing, as they entail the possibility of representing contract terms in programming code that gets automatically executed on a blockchain or other distributed ledgers. Following the latest developments in blockchain technology, smart contracts have been the focus of growing attention and are currently among the major innovations that are taking place in financial services. This paper investigates the scope for their application in insurance both in the near and longer term, exploring the legal challenges that they pose. The analysis shows that in the near term smart contracts will be mainly exploited to automate underwriting, claims handling and payouts. It considers how the automation of these processes will operate at law and emphasises the impact that smart contracts can have especially on the reduction of transaction costs and on the very essence of the insurance contract—the insurer’s promise to pay. Building on current technological developments, the paper then turns to role that smart contracts can play in insurance in the longer term, advancing the prospect of the automation of the entire insurance contract. In particular, it argues that the interaction between smart contracts and artificial intelligence and machine learning can challenge traditional frameworks of thought such as incomplete contracting and, in the farther-distant future, will culminate in contracts that will both self-interpret and self-enforce their terms—what can be called the true smart contracts. The analysis identifies and addresses the main legal issues that can arise in this context, exploring how to strike a balance between the goal of fostering innovation and the need to ensure policyholder and investor protection.
Probeless non-invasive near-infrared spectroscopic bioprocess monitoring using microspectrometer technology
Authors: Zimmerleiter Robert , Kager Julian , Nikzad-Langerodi Ramin , Berezhinskiy Vladimir , Westad Frank , Herwig Christoph , Brandstetter Markus 
Published: December 2019

AbstractReal-time measurements and adjustments of critical process parameters are essential for the precise control of fermentation processes and thus for increasing both quality and yield of the desired product. However, the measurement of some crucial process parameters such as biomass, product, and product precursor concentrations usually requires time-consuming offline laboratory analysis. In this work, we demonstrate the in-line monitoring of biomass, penicillin (PEN), and phenoxyacetic acid (POX) in a Penicilliumchrysogenum fed-batch fermentation process using low-cost microspectrometer technology operating in the near-infrared (NIR). In particular, NIR reflection spectra were taken directly through the glass wall of the bioreactor, which eliminates the need for an expensive NIR immersion probe. Furthermore, the risk of contaminations in the reactor is significantly reduced, as no direct contact with the investigated medium is required. NIR spectra were acquired using two sensor modules covering the spectral ranges 1350–1650 nm and 1550–1950 nm. Based on offline reference analytics, partial least squares (PLS) regression models were established for biomass, PEN, and POX either using data from both sensors separately or jointly. The established PLS models were tested on an independent validation fed-batch experiment. Root mean squared errors of prediction (RMSEP) were 1.61 g/L, 1.66 g/L, and 0.67 g/L for biomass, PEN, and POX, respectively, which can be considered an acceptable accuracy comparable with previously published results using standard process spectrometers with immersion probes. Altogether, the presented results underpin the potential of low-cost microspectrometer technology in real-time bioprocess monitoring applications.
The Bacterial Flora Associated with the Polyphagous Aphid Aphis gossypii Glover (Hemiptera: Aphididae) Is Strongly Affected by Host Plants
Authors: Xu Shifen , Jiang Liyun , Qiao Gexia , Chen Jing 
Published: December 2019

AbstractAphids live in symbiosis with a variety of bacteria, including the obligate symbiont Buchnera aphidicola and diverse facultative symbionts. The symbiotic associations for one aphid species, especially for polyphagous species, often differ across populations. In the present study, by using high-throughput 16S rRNA sequencing, we surveyed in detail the microbiota in natural populations of the cotton aphid Aphis gossypii in China and assessed differences in bacterial diversity with respect to host plant and geography. The microbial community of A. gossypii was dominated by a few heritable symbionts. Arsenophonus was the most dominant secondary symbiont, and Spiroplasma was detected for the first time. Statistical tests and ordination analyses showed that host plants rather than geography seemed to have shaped the associated symbiont composition. Special symbiont communities inhabited the Cucurbitaceae-feeding populations, which supported the ecological specialization of A. gossypii on cucurbits from the viewpoint of symbiotic bacteria. Correlation analysis suggested antagonistic interactions between Buchnera and coexisting secondary symbionts and more complicated interactions between different secondary symbionts. Our findings lend further support to an important role of the host plant in structuring symbiont communities of polyphagous aphids and will improve our understanding of the interactions among phytophagous insects, symbionts, and environments.
Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination
Authors: Baekgaard Josefine S. , Christensen Rasmus Ejlersgaard , Lee Jae Moo , Eid Ahmed I. , Eskesen Trine G. , Steinmetz Jacob , Rasmussen Lars S. , King David R. , Velmahos George C. 
Published: December 2019

AbstractBackgroundThe objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination.MethodsWe prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS.ResultsA total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center.ConclusionsTime to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.
IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications
Authors: Granai Massimo , Amato Teresa , Di Napoli Arianna , Santi Raffaella , Vergoni Federica , Di Stefano Gioia , Mancini Virginia , Kovalchuk Sofya , Cencini Emanuele , Carta Alberto Giulio , Aversa Sara , Ziepert Marita , Cevenini Gabriele , Lazzi Stefano , Leoncini Lorenzo , Bellan Cristiana 
Published: December 2019

AbstractThe precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL.
Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients
Authors: Ladfors Susanne Westphal , Lindahl Jenny K. , Hansson Sverker , Brandström Per , Andersson Rune , Jertborn Marianne , Lindh Magnus , Woxenius Susanne , Friman Vanda 
Published: December 2019

Abstract
Background
Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation.

Methods
A retrospective study of 58 children aged 1–17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months.

Results
At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7–13).

Conclusions
CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.
Vitamin D assessment in perioperative medicine and critical care
Authors: Zajic Paul , Heschl Stefan , Schörghuber Michael , Srekl-Filzmaier Petra , Stojakovic Tatjana , Weixler Viktoria , Zelzer Sieglinde , Amrein Karin 
Published: December 2019

Summary
Background
There is controversy about the impact of acute illness on vitamin D levels. This study was carried out to assess the influence of perioperative fluid loading on 25-hydroxy-vitamin D [25(OH)D] levels. The study evaluated the clinical utility of a commonly available chemiluminescence assay (ECLIA, IDS-iSYS) and liquid chromatography/mass spectrometry (LC-MS/MS) in the diagnosis of vitamin D deficiency in this setting.

Methods
In this prospective observational pilot study in adult patients undergoing cardiovascular surgery on cardiopulmonary bypass (CPB), blood samples drawn at preoperative baseline (t1), after weaning from CPB (t2), on intensive care unit (ICU) admission (t3) and on the first (t4) and second (t5) postoperative days were analyzed.

Results
A total of 26 patients (130 samples) were included in this study. Fluid loading by CPB led to a median reduction of 25(OH)D by −22.6% (range −54.5% to −19.5%) between t1 and t2. Cohen’s kappa (κ) for method agreement for vitamin D deficiency (tested cut-off values 20 ng/ml and 12 ng/ml), was κ = 0.291 (p < 0.001) and κ = 0.469 (p < 0.001), respectively. The mean difference between measurements by ECLIA and LC-MS/MS was 4.8 ng/ml (±5.7), Pearson’s r for correlation was 0.73 (p < 0.001). The biologically inactive C3-epimer did not contribute to 25(OH)D levels assessed by LC-MS/MS.

Conclusion
The 25(OH)D measurements by chemiluminescence assays can noticeably deviate from those measured by LC-MS/MS, which can be considered the unequivocal gold standard. These assays may still be acceptably reliable in the screening for vitamin D deficiency, especially in the setting of low vitamin D levels. Stricter definitions, e.g. serum 25(OH)D levels lower than 12 ng/ml, may be used to diagnose deficiency with low false positive rate.

Trial Registration
DRKS00009216, German Clinical Trials Registry (www.drks.de)
The Premonitory Urge for Tics Scale in a large sample of children and adolescents: psychometric properties in a developmental context. An EMTICS study
Authors:   and the EMTICS collaborative group, Openneer Thaïra J. C. , Tárnok Zsanett , Bognar Emese , Benaroya-Milshtein Noa , Garcia-Delgar Blanca , Morer Astrid , Steinberg Tamar , Hoekstra Pieter J. , Dietrich Andrea 
Published: December 2019

AbstractPremonitory urges are uncomfortable physical sensations preceding tics that occur in most individuals with a chronic tic disorder. The Premonitory Urge for Tics Scale (PUTS) is the most frequently used self-report measure to assess the severity of premonitory urges. We aimed to evaluate the psychometric properties of the PUTS in the largest sample size to date (n = 656), in children aged 3–16 years, from the baseline measurement of the longitudinal European Multicenter Tics in Children Study (EMTICS). Our psychometric evaluation was done in three age-groups: children aged 3–7 years (n = 103), children between 8 and 10 years (n = 253), and children aged 11–16 years (n = 300). The PUTS exhibited good internal reliability in children and adolescents, also under the age of 10, which is younger than previously thought. We observed significant but small correlations between the severity of urges and severity of tics and obsessive–compulsive symptoms, and between severity of urges and ratings of attention-deficit/hyperactivity disorder and internalizing and externalizing behaviors, however, only in children of 8–10 years. Consistent with previous results, the 10th item of the PUTS correlated less with the rest of the scale compared to the other items and, therefore, should not be used as part of the questionnaire. We found a two-factor structure of the PUTS in children of 11 years and older, distinguishing between sensory phenomena related to tics, and mental phenomena as often found in obsessive–compulsive disorder. The age-related differences observed in this study may indicate the need for the development of an age-specific questionnaire to assess premonitory urges.
Screening tools for early neuropsychological impairment after aneurysmal subarachnoid hemorrhage
Authors: Rautalin Ilari M. , Sebök Martina , Germans Menno R. , Korja Miikka , Dannecker Noemi , Zindel-Geisseler Olivia , Brugger Peter , Regli Luca , Stienen Martin N. 
Published: December 2019

Abstract
Background
Although most aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from neuropsychological disabilities, outcome estimation is commonly based only on functional disability scales such as the modified Rankin Scale (mRS). Moreover, early neuropsychological screening tools are not used routinely.

Objective
To study whether two simple neuropsychological screening tools identify neuropsychological deficits (NPDs), among aSAH patients categorized with favorable outcome (mRS 0—2) at discharge.

Methods
We reviewed 170 consecutive aSAH patients that were registered in a prospective institutional database. We included all patients graded by the mRS at discharge, and who had additionally been evaluated by a neuropsychologist and/or occupational therapist using the Montreal Cognitive Assessment (MoCA) and/or Rapid Evaluation of Cognitive Function (ERFC). The proportion of patients with scores indicative of NPDs in each test were reported, and spearman correlation tests calculated the coefficients between the both neuropsychological test results and the mRS.

Results
Of the 42 patients (24.7%) that were evaluated by at least one neuropsychological test, 34 (81.0%) were rated mRS 0—2 at discharge. Among these 34 patients, NPDs were identified in 14 (53.9%) according to the MoCA and 8 (66.7%) according to the ERFC. The mRS score was not correlated with the performance in the MoCA or ERFC.

Conclusion
The two screening tools implemented here frequently identified NPDs among aSAH patients that were categorized with favorable outcome according to the mRS. Our results suggest that MoCA or ERFC could be used to screen early NPDs in favorable outcome patients, who in turn might benefit from early neuropsychological rehabilitation.
The impact of wall thickness and curvature on wall stress in patient-specific electromechanical models of the left atrium
Authors: Augustin Christoph M. , Fastl Thomas E. , Neic Aurel , Bellini Chiara , Whitaker John , Rajani Ronak , O’Neill Mark D. , Bishop Martin J. , Plank Gernot , Niederer Steven A. 
Published: December 2019

AbstractThe left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA using patient-specific anatomical FE meshes with rule-based myofiber directions. The models of the LA were passively inflated to 10mmHg followed by simulation of the contraction phase of the atrial cardiac cycle. The FE models predicted maximum LA volumes of 156.5 mL, 99.3 mL and 83.4 mL and ejection fractions of 36.9%, 32.0% and 25.2%. The median wall thickness in the 3 cases was calculated as $$1.32\, \pm \,0.78$$1.32±0.78 mm, $$1.21\, \pm \,0.85$$1.21±0.85 mm, and $$0.74\,\pm \,0.34$$0.74±0.34 mm. The median curvature was determined as $$0.159\,\pm \,0.080$$0.159±0.080 $$\hbox {mm}^{-1}$$mm-1, $$0.165\,\pm \,0.079\,\hbox {mm}^{-1}$$0.165±0.079mm-1, and $$0.166\,\pm \,0.077\,\hbox {mm}^{-1}$$0.166±0.077mm-1. Following passive inflation, the correlation of wall stress with the inverse of wall thickness and curvature was 0.55–0.62 and 0.20–0.25, respectively. At peak contraction, the correlation of wall stress with the inverse of wall thickness and curvature was 0.38–0.44 and 0.16–0.34, respectively. In the LA, the 1st principal Cauchy stress is more dependent on wall thickness than curvature during passive inflation and both correlations decrease during active contraction. This emphasizes the importance of including the heterogeneous wall thickness in electromechanical FE simulations of the LA. Overall, simulation results and sensitivity analyses show that in complex atrial anatomy it is unlikely that a simple anatomical-based law can be used to estimate local wall stress, demonstrating the importance of FE analyses.
Aberrant mitochondrial function in ageing and cancer
Authors: Whitehall Julia C. , Greaves Laura C. 
Published: December 2019

AbstractAlterations in mitochondrial metabolism have been described as one of the major hallmarks of both ageing cells and cancer. Age is the biggest risk factor for the development of a significant number of cancer types and this therefore raises the question of whether there is a link between age-related mitochondrial dysfunction and the advantageous changes in mitochondrial metabolism prevalent in cancer cells. A common underlying feature of both ageing and cancer cells is the presence of somatic mutations of the mitochondrial genome (mtDNA) which we postulate may drive compensatory alterations in mitochondrial metabolism that are advantageous for tumour growth. In this review, we discuss basic mitochondrial functions, mechanisms of mtDNA mutagenesis and their metabolic consequences, and review the evidence for and against a role for mtDNA mutations in cancer development.