bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-acetylcysteine for cessation of tobacco smoking: rationale and study protocol for a randomised controlled trial
Authors: Arancini Lauren , Bortolasci Chiara C. , Dodd Seetal , Dean Olivia M. , Berk Michael 
Published: September 2019

Abstract

Background
Tobacco smoking is a highly prevalent, addictive behaviour and a key public health priority. However available cessation therapies have low quit and high relapse rates, indicating an urgent need for more effective treatments. Predicated on promising preclinical and pilot clinical data, this paper presents a rationale and protocol for the trial of N-acetylcysteine (NAC) as a novel anti-craving smoking cessation aid.

Methods
Current smokers (n = 120) of at least 10 cigarettes a day are recruited through online advertisements, print publications and dissemination of flyers. Participants are randomised on a 1:1 ratio to receive either 16-week treatment of 1.8 g/day of NAC or placebo with all participants receiving quit support from the online QuitCoach tool. Participants are attending visits at baseline, 8 and 16 weeks with a 42-week post-discontinuation follow-up. The primary outcome measure is sustained abstinence at six months after treatment based on self-reported rating scales and confirmed by exhaled carbon monoxide and salivary cotinine levels. Secondary outcomes are timing of the first lapse and relapse, between-group cigarette consumption, withdrawal symptoms, general wellbeing and mood/anxiety symptoms. Between-group differences in adverse events and subgroup analyses for variables including gender and Diagnostic Statistics Manual 5 diagnostics will also be investigated.

Discussion
The planned trial addresses an issue of major importance to human health and, if an effect is shown, may result in substantial changes to the management of smoking and nicotine addiction with overt public health implications.

Trial registration
Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303. Registered on 19 October 2017.
Performance of three delignifying pretreatments on hardwoods: hydrolysis yields, comprehensive mass balances, and lignin properties
Authors: Bhalla Aditya , Cai Charles M. , Xu Feng , Singh Sandip K. , Bansal Namita , Phongpreecha Thanaphong , Dutta Tanmoy , Foster Cliff E. , Kumar Rajeev , Simmons Blake A. , Singh Seema , Wyman Charles E. , Hegg Eric L. , Hodge David B. 
Published: September 2019

AbstractBackgroundIn this work, three pretreatments under investigation at the DOE Bioenergy Research Centers (BRCs) were subjected to a side-by-side comparison to assess their performance on model bioenergy hardwoods (a eucalyptus and a hybrid poplar). These include co-solvent-enhanced lignocellulosic fractionation (CELF), pretreatment with an ionic liquid using potentially biomass-derived components (cholinium lysinate or [Ch][Lys]), and two-stage Cu-catalyzed alkaline hydrogen peroxide pretreatment (Cu-AHP). For each of the feedstocks, the pretreatments were assessed for their impact on lignin and xylan solubilization and enzymatic hydrolysis yields as a function of enzyme loading. Lignins recovered from the pretreatments were characterized for polysaccharide content, molar mass distributions, β-aryl ether content, and response to depolymerization by thioacidolysis.ResultsAll three pretreatments resulted in significant solubilization of lignin and xylan, with the CELF pretreatment solubilizing the majority of both biopolymer categories. Enzymatic hydrolysis yields were shown to exhibit a strong, positive correlation with the lignin solubilized for the low enzyme loadings. The pretreatment-derived solubles in the [Ch][Lys]-pretreated biomass were presumed to contribute to inhibition of enzymatic hydrolysis in the eucalyptus as a substantial fraction of the pretreatment liquor was carried forward into hydrolysis for this pretreatment. The pretreatment-solubilized lignins exhibited significant differences in polysaccharide content, molar mass distributions, aromatic monomer yield by thioacidolysis, and β-aryl ether content. Key trends include a substantially higher polysaccharide content in the lignins recovered from the [Ch][Lys] pretreatment and high β-aryl ether contents and aromatic monomer yields from the Cu-AHP pretreatment. For all lignins, the13C NMR-determined β-aryl ether content was shown to be correlated with the monomer yield with a second-order functionality.ConclusionsOverall, it was demonstrated that the three pretreatments highlighted in this study demonstrated uniquely different functionalities in reducing biomass recalcitrance and achieving higher enzymatic hydrolysis yields for the hybrid poplar while yielding a lignin-rich stream that may be suitable for valorization. Furthermore, modification of lignin during pretreatment, particularly cleavage of β-aryl ether bonds, is shown to be detrimental to subsequent depolymerization.
Metabolic engineering of Bacillus amyloliquefaciens for enhanced production of S-adenosylmethionine by coupling of an engineered S-adenosylmethionine pathway and the tricarboxylic acid cycle
Authors: Ruan Liying , Li Lu , Zou Dian , Jiang Cong , Wen Zhiyou , Chen Shouwen , Deng Yu , Wei Xuetuan 
Published: September 2019

Abstract

Background
S-Adenosylmethionine (SAM) is a critical cofactor involved in many biochemical reactions. However, the low fermentation titer of SAM in methionine-free medium hampers commercial-scale production. The SAM synthesis pathway is specially related to the tricarboxylic acid (TCA) cycle in Bacillus amyloliquefaciens. Therefore, the SAM synthesis pathway was engineered and coupled with the TCA cycle in B. amyloliquefaciens to improve SAM production in methionine-free medium.

Results
Four genes were found to significantly affect SAM production, including SAM2 from Saccharomyces cerevisiae, metA and metB from Escherichia coli, and native mccA. These four genes were combined to engineer the SAM pathway, resulting in a 1.42-fold increase in SAM titer using recombinant strain HSAM1. The engineered SAM pathway was subsequently coupled with the TCA cycle through deletion of succinyl-CoA synthetase gene sucC, and the resulted HSAM2 mutant produced a maximum SAM titer of 107.47 mg/L, representing a 0.59-fold increase over HSAM1. Expression of SAM2 in this strain via a recombinant plasmid resulted in strain HSAM3 that produced 648.99 mg/L SAM following semi-continuous flask batch fermentation, a much higher yield than previously reported for methionine-free medium.

Conclusions
This study reports an efficient strategy for improving SAM production that can also be applied for generation of SAM cofactors supporting group transfer reactions, which could benefit metabolic engineering, chemical biology and synthetic biology.
Identification of critical factors that significantly affect the dose-response in mosquitoes irradiated as pupae
Authors: Yamada Hanano , Maiga Hamidou , Juarez Jose , De Oliveira Carvalho Danilo , Mamai Wadaka , Ali Adel , Bimbile-Somda Nanwintoum Severin , Parker Andrew Gordon , Zhang Dongjing , Bouyer Jeremy 
Published: September 2019

AbstractBackgroundThe sterile insect technique (SIT) for use against mosquitoes consists of several steps including the production of the target species in large numbers, the separation of males and females, the sterilization of the males, and the packing, transport and release of the sterile males at the target site. The sterility of the males is the basis of the technique; for this, efficient and standardized irradiation methods are needed to ensure that the required level of sterility is reliably and reproducibly achieved. While several reports have found that certain biological factors, handling methods and varying irradiation procedures can alter the level of induced sterility in insects, few studies exist in which the methodologies are adequately described and discussed for the reproductive sterilization of mosquitoes. Numerous irradiation studies on mosquito pupae have resulted in varying levels of sterility. Therefore, we initiated a series of small-scale experiments to first investigate variable parameters that may influence dose-response in mosquito pupae, and secondly, identify those factors that potentially have a significantly large effect and need further attention.MethodsIn this study, we compiled the results of a series of experiments investigating variable parameters such as pupal age (Aedes aegypti), pupal size (Ae. aegypti), geographical origin of mosquito strains (Ae. aegyptiandAe. albopictus), exposure methods (in wetversusdry conditions,Ae. albopictus) and subsequently in lowversushigh oxygen environments [submerged in water (low O2(< 5 %)] and in air [high O2(~ 21 %)] on the radiosensitivity of male pupae (Ae. aegypti,Ae. albopictusandAnopheles arabiensis).ResultsResults indicate that radiosensitvity ofAe. aegyptidecreases with increasing pupal age (99% induced sterility in youngest pupae, compared to 93% in oldest pupae), but does not change with differences in pupal size (P = 0.94). Differing geographical origin of the same mosquito species did not result in variations in radiosensitivity inAe. aegyptipupae [Brazil, Indonesia, France (La Reunion), Thailand] orAe. albopictus[Italy, France (La Reunion)]. Differences in induced sterility were seen following irradiation of pupae that were in wetversusdry conditions, which led to further tests showing significant radioprotective effects of oxygen depletion during irradiation procedures in three tested mosquito species, as seen in other insects.ConclusionsThese findings infer the necessity to further evaluate significant factors and reassess dose-response for mosquitoes with controlled variables to be able to formulate protocols to achieve reliable and reproducible levels of sterility for application in the frame of the SIT.
Sex differences in fetal growth and immediate birth outcomes in a low-risk Caucasian population
Authors: Galjaard Sander , Ameye Lieveke , Lees Christoph C. , Pexsters Anne , Bourne Tom , Timmerman Dirk , Devlieger Roland 
Published: September 2019

Abstract

Background
According to the WHO Multicentre Growth Reference Study Group recommendations, boys and girls have different growth trajectories after birth. Our aim was to develop gender-specific fetal growth curves in a low-risk population and to compare immediate birth outcomes.

Methods
First, second, and third trimester fetal ultrasound examinations were conducted between 2002 and 2012. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancies, Caucasian ethnicity, and confirmation of gestational age by a crown-rump length (CRL) measurement in the first trimester. Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to align the time frames of the longitudinal fetal measurements, corresponding with the methods of the postnatal growth curves of the WHO MGRS Group.

Results
A total of 27,680 complete scans were selected from the astraia© ultrasound database representing 12,368 pregnancies. Gender-specific fetal growth curves for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were derived. The HC and BPD were significantly larger in boys compared to girls from 20 weeks of gestation onwards (p < 0.001) equating to a 3-day difference at 20–24 weeks. Boys were significantly heavier, longer, and had greater head circumference than girls (p < 0.001) at birth. The Apgar score at 1 min (p = 0.01) and arterial cord pH (p < 0.001) were lower in boys.

Conclusions
These longitudinal fetal growth curves for the first time allow integration with neonatal and pediatric WHO gender-specific growth curves. Boys exceed head growth halfway of the pregnancy, and immediate birth outcomes are worse in boys than girls. Gender difference in intrauterine growth is sufficiently distinct to have a clinically important effect on fetal weight estimation but also on the second trimester dating. Therefore, these differences might already play a role in early fetal or immediate neonatal management.
Stability-preserving model order reduction for linear stochastic Galerkin systems
Authors: Pulch Roland 
Published: September 2019

Abstract
Mathematical modeling often yields linear dynamical systems in science and engineering. We change physical parameters of the system into random variables to perform an uncertainty quantification. The stochastic Galerkin method yields a larger linear dynamical system, whose solution represents an approximation of random processes. A model order reduction (MOR) of the Galerkin system is advantageous due to the high dimensionality. However, asymptotic stability may be lost in some MOR techniques. In Galerkin-type MOR methods, the stability can be guaranteed by a transformation to a dissipative form. Either the original dynamical system or the stochastic Galerkin system can be transformed. We investigate the two variants of this stability-preserving approach. Both techniques are feasible, while featuring different properties in numerical methods. Results of numerical computations are demonstrated for two test examples modeling a mechanical application and an electric circuit, respectively.
A convenient and efficient total solid-phase synthesis of DOTA-functionalized tumor-targeting peptides for PET imaging of cancer
Authors: Okarvi Subhani M. , AlJammaz Ibrahim 
Published: September 2019

Abstract

Introduction
An efficient and cost-effective synthesis of the metal chelating agents that couple to tumor-targeting peptides is required to enhance the process of preclinical research toward the clinical translation of molecular imaging agents. DOTA is one of the most widely used macrocyclic ligands for the development of new metal-based imaging and therapeutic agents owing to its ability to form stable and inert complexes under physiological conditions. Although solid-phase synthesis compatible DOTA-tris-(t-Bu ester) is a commercial product, it is expensive and contain chemical impurities. There is a need to explore new and cost-effective methods for the preparation of metal chelating agents, i.e., DOTA, directly on solid support to facilitate rapid, cost-effective, and high purity preparation of DOTA-linked peptides for imaging and therapy. In the present study, we describe a facile synthetic strategy of DOTA preparation and its linkage to peptides directly on solid-phase support.

Methods
Bombesin (BN) peptides were functionalized with DOTA chelator prepared from cyclen precursor on solid-phase and from commercial DOTA-tris and radiolabeled with 68Ga. In vitro BN/GRP receptor binding affinities of the corresponding radiolabeled peptides were determined by saturation binding assays on human breast MDA-MB-231, MCF7, T47D, and PC3 prostate cancer cells. Pharmacokinetics were studied in Balb/c mice and in vivo tumor targeting in MDA-MB-231 tumor-bearing nude mice.

Results
DOTA was prepared successfully from cyclen on solid-phase support, linked specifically to BN peptides and resultant DOTA-coupled peptides were radiolabeled efficiently with 68Ga. The binding affinities of all the six BN peptides were comparable and in the low nanomolar range. All 68Ga-labeled peptides showed high metabolic stability in plasma. These radiopeptides exhibited rapid pharmacokinetics in Balb/c mice with excretion mainly through the urinary system. In nude mice, MDA-MB-231 tumor uptake profiles were slightly different; the BN peptide with Ahx spacer and linked to DOTA through cyclen exhibited higher tumor uptake (2.32% ID/g at 1 h post-injection) than other radiolabeled BN peptides investigated in this study. The same leading BN peptide also displayed favorable pharmacokinetic profile in Balb/c mice. The PET images clearly visualized the MDA-MB-231 tumor.

Conclusions
DOTA prepared from cyclen on solid-phase support showed comparable potency and efficiency to DOTA-tris in both in vitro and in vivo evaluation. The synthetic methodology described here allows versatile, site-specific introduction of DOTA into peptides to facilitate the development of DOTA-linked molecular imaging and therapy agents for clinical translation.
End-user experiences with two incident and injury reporting systems designed for led outdoor activities - challenges for implementation of future data systems
Authors: Finch Caroline F. , Goode Natassia , Shaw Louise , Salmon Paul M. 
Published: September 2019

AbstractBackgroundInjury and incident (near miss) prevention is heavily dependent upon robust and high-quality data systems. Evaluations of surveillance systems designed to report factors associated with incidents and injuries are essential to understand their value, as well as to improve their performance and efficiency. Despite, this there have been few such evaluations published in the peer-review literature.MethodsThe attitudes and experiences of industry representatives who used one of two variants of an incident and injury surveillance system to collect injury and incident data for the led outdoor activity setting were obtained through an online self-report survey following a 12-month trial. Survey respondents were 18 representatives of 33 organisations who were users of a comprehensive incident reporting and surveillance system – the Understanding and Preventing Led Outdoor Accidents Data System Software Tool (UPLOADS-ST) - and six out of 11 users of a modified system (UPLOADS-Lite). The survey collected information on user experiences in relation to system training, accessibility, ease of use, security, feedback and perceived value to the sector of collating and reporting data across organisations.FindingsOnly four UPLOADS-ST responding users found the system easy to use and just three considered entering incident reports to be easy. However, many considered the training on reporting incidents to be sufficient and that the incident reports contained relevant details. Fewer than half of respondents (seven for UPLOADS-ST, three for UPLOADS-Lite) believed entering data was a good use of staff time and resources. Nonetheless, a majority of respondents (seven for UPLOADS-ST, five for UPLOADS-Lite) found the reporting format easy to read and felt the information provided was useful for their organisation.ConclusionsUsability barriers to incident reporting were identified, particularly for UPLOADS-ST, including time constraints and user friendliness. The majority of users believed aggregating and reporting incident and injury data across organisations would be of value in making the led outdoor activity sector safer. Improving the utility of the surveillance systems will assist in ensuring their sustainability in the led outdoor activity sector.
Comparison of video demonstrations and bedside tutorials for teaching paediatric clinical skills to large groups of medical students in resource-constrained settings
Authors: George Ann , Blaauw Duane , Green-Thompson Lionel , Hajinicolaou Christina , Lala Nilesh , Parbhoo Kiran , Rodda John , Velaphi Sithembiso , Kala Udai , Vallabh Preeteeben , Dangor Ziyaad , Lala Sanjay G. 
Published: September 2019

AbstractVideos are increasingly being used for teaching clinical skills in medical education. However, most reports on the effectiveness and benefits of videos in medical teaching have come from developed countries. Resource constraints in South African academic hospitals, together with increasing numbers, may apply pressure on the standard of clinical teaching. This study investigated the potential for using video demonstrations to replace the bedside teaching of introductory paediatric clinical examination skills to large groups of medical students. Sixty medical students were randomised to an experimental group that watched a video of a paediatric abdominal examination or to a control group that received a bedside tutorial on the same topic. Immediately afterwards, experienced assessors observed and scored the students in a clinical examination. Data were analysed for the non-inferiority of the video group scores within a 10% margin of the bedside group. Students’ and clinician educators’ perceptions of the two teaching methods and their views on how video instruction could be integrated into the clinical teaching programme were explored. Qualitative data were analysed thematically. The video teaching was non-inferior to the bedside teaching within the 10% margin and did not significantly affect the pass/fail or distinction rates. Students and clinician educators suggested that the videos be used for teaching basic concepts, allowing bedside tutorials to focus on applied learning. The findings have important implications for using video demonstrations to supplement the teaching of clinical skills to large groups of medical students across multiple variably-resourced settings.
Suicide and the psychiatrist
Authors: House Allan 
Published: September 2019

SummaryResearch into patient suicide indicates that it has an impact on the psychiatrists involved, but leaves a number of unanswered questions about which elements of the experience are most likely to cause problems, who is most at risk, what is the clinical or professional significance of any effect on the psychiatrist and how other professionals are affected. Despite these uncertainties, it is clear that a response is needed, with three bodies responsible in different ways for coordinating one: the relevant mental health trust, as employer; the Royal College of Psychiatrists, as the professional representative body; and the National Confidential Inquiry into Suicide and Safety in Mental Health, as mediator of social and professional impact.
Baseline Functional Connectivity Predicts Connectivity Changes Due to a Small Dose of Midazolam in Older Adults
Authors: Frölich Michael A. , White David M. , Kraguljac Nina V. , Lahti Adrienne C. 
Published: September 2019

BACKGROUND:
In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55–73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function.

METHODS:
We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults.

RESULTS:
Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration.

CONCLUSIONS:
Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults.
IL VIAGGIO: METODO D’INDAGINE ORIGINALE
Authors: Perra Livio 
Published: September 2019

In questo articolo l’autore analizza i viaggi di Montesquieu, dove si manifesta il trionfo del piacere della scoperta. Il viaggio è indagine della realtà sociale, politica e istituzionale. Le certezze e le nozioni iniziali sono riconsiderate o temprate dalle conferme dell’osservata realtà. Il viaggio con una vena di disincanto porta con sé il fascino di nuove idee e diventa strumento originale di analisi comparativa della realtà europea dell’epoca. L’autore vuole sottolineare l’imprescindibilità del viaggio nella formazione delle rifl essioni di Montesquieu. La teoria da sola non è suffi ciente, il barone de La Brède trova nel suo cammino per l’Europa l’ispirazione che solo l’osservazione empirica può dare. Scrutare la realtà da vicino diviene fondamentale, fa comprendere a Montesquieu come siano numerose le variabili che infl uenzano gli eventi e la politica di uno Stato. L’autore, dopo l’attenta analisi effettuata, giunge alla conclusione che alcune delle riflessioni contenute nel De l’Esprit des Lois, oltre che di derivazione libresca, sono figlie dell’originale metodo d’indagine costituito dai viaggi di Montesquieu.