bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomous decisions by couples in reproductive care
Authors: Matar Amal , Höglund Anna T. , Segerdahl Pär , Kihlbom Ulrik 
Published: April 2020

AbstractBackgroundPreconception Expanded Carrier Screening (ECS) is a genetic test offered to a general population or to couples who have no known risk of recessive and X-linked genetic diseases and are interested in becoming parents. A test may screen for carrier status of several autosomal recessive diseases at one go. Such a program has been piloted in the Netherlands and may become a reality in more European countries in the future. The ethical rationale for such tests is that they enhance reproductive autonomy. The dominant conception of autonomy is individual-based. However, at the clinic, people deciding on preconception ECS will be counselledtogetherand are expected to make a joint decision, asa couple. The aim of the present study was to develop an understanding of autonomous decisions made by couples in the context of reproductive technologies in general and of preconception ECS in particular. Further, to shed light on what occurs in reproductive clinics and suggest concrete implications for healthcare professionals.Main textBased on the shift in emphasis from individual autonomy to relational autonomy, a notion ofcouple autonomywas suggested and some features of this concept were outlined. First, that both partners are individually autonomous and that the decision is reached through a communicative process. In this process each partner should feel free to express his or her concerns and preferences, so no one partner dominates the discussion. Further, there should be adequate time for the couple to negotiate possible differences and conclude that the decision is right for them. The final decision should be reached through consensus of both partners without coercion, manipulation or miscommunication. Through concrete examples, the suggested notion of couple autonomy was applied to diverse clinical situations.ConclusionsA notion of couple autonomy can be fruitful for healthcare professionals by structuring their attention to and support of a couple who is required to make an autonomous joint decision concerning preconception ECS. A normative implication for healthcare staff is to allow the necessary time for decision-making and to promote a dialogue that can increase the power of the weaker part in a relationship.
Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries
Authors: Degeling Chris , Carter Stacy M. , van Oijen Antoine M. , McAnulty Jeremy , Sintchenko Vitali , Braunack-Mayer Annette , Yarwood Trent , Johnson Jane , Gilbert Gwendolyn L. 
Published: April 2020

Abstract
Background
Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies – pathogen whole genome sequencing (WGS) and Big Data analytics – promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy.

Method
Four community juries were convened in two demographically different Sydney municipalities and two regional cities in New South Wales, Australia (western Sydney, Wollongong, Tamworth, eastern Sydney) to elicit the views of well-informed community members on the acceptability and legitimacy of:
making pathogen WGS and linked administrative data available for public health researchusing this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems
Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts.

Results
Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems.

Conclusions
Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.
Comparison of statistical and machine learning models for healthcare cost data: a simulation study motivated by Oncology Care Model (OCM) data
Authors: Mazumdar Madhu , Lin Jung-Yi Joyce , Zhang Wei , Li Lihua , Liu Mark , Dharmarajan Kavita , Sanderson Mark , Isola Luis , Hu Liangyuan 
Published: April 2020

Abstract
Background
The Oncology Care Model (OCM) was developed as a payment model to encourage participating practices to provide better-quality care for cancer patients at a lower cost. The risk-adjustment model used in OCM is a Gamma generalized linear model (Gamma GLM) with log-link. The predicted value of expense for the episodes identified for our academic medical center (AMC), based on the model fitted to the national data, did not correlate well with our observed expense. This motivated us to fit the Gamma GLM to our AMC data and compare it with two other flexible modeling methods: Random Forest (RF) and Partially Linear Additive Quantile Regression (PLAQR). We also performed a simulation study to assess comparative performance of these methods and examined the impact of non-linearity and interaction effects, two understudied aspects in the field of cost prediction.

Methods
The simulation was designed with an outcome of cost generated from four distributions: Gamma, Weibull, Log-normal with a heteroscedastic error term, and heavy-tailed. Simulation parameters both similar to and different from OCM data were considered. The performance metrics considered were the root mean square error (RMSE), mean absolute prediction error (MAPE), and cost accuracy (CA). Bootstrap resampling was utilized to estimate the operating characteristics of the performance metrics, which were described by boxplots.

Results
RF attained the best performance with lowest RMSE, MAPE, and highest CA for most of the scenarios. When the models were misspecified, their performance was further differentiated. Model performance differed more for non-exponential than exponential outcome distributions.

Conclusions
RF outperformed Gamma GLM and PLAQR in predicting overall and top decile costs. RF demonstrated improved prediction under various scenarios common in healthcare cost modeling. Additionally, RF did not require prespecification of outcome distribution, nonlinearity effect, or interaction terms. Therefore, RF appears to be the best tool to predict average cost. However, when the goal is to estimate extreme expenses, e.g., high cost episodes, the accuracy gained by RF versus its computational costs may need to be considered.
Integrating public preferences into national reimbursement decisions: a descriptive comparison of approaches in Belgium and New Zealand
Authors: Leopold Christine , Lu Christine Y. , Wagner Anita K. 
Published: April 2020

Abstract
Background
Public health care payer organizations face increasing pressures to make transparent and sustainable coverage decisions about ever more expensive prescription drugs, suggesting a need for public engagement in coverage decisions. However, little is known about countries’ approaches to integrating public preferences in existing funding decisions. The aim of this study was to describe how Belgium and New Zealand used deliberative processes to engage the public and to identify lessons learned from these countries’ approaches.

Methods
To describe two countries’ deliberative processes, we first reviewed key country policy documents and then conducted semi-structured interviews with five leaders of the processes from Belgium and New Zealand. We assessed each country’s rationales for and approaches to engaging the public in pharmaceutical coverage decisions and identified lessons learned. We used qualitative content analysis of the interviews to describe key themes and subthemes.

Results
In both countries, the national public payer organization initiated and led the process of integrating public preferences into national coverage decision making. Reimbursement criteria considered outdated and changing societal expectations prompted the change. Both countries chose a deliberative process of public engagement with a multi-year commitment of many stakeholders to develop new reimbursement processes. Both countries’ new reimbursement processes put a stronger emphasis on quality of life, the separation of individual versus societal perspectives, and the importance of final reimbursement decisions being taken in context rather than based largely on cost-effectiveness thresholds.

Conclusions
To face the growing financial pressure of sustainable funding of medicines, Belgium’s and New Zealand’s public payers have developed processes to engage the public in defining the reimbursement system’s priorities. Although these countries differ in context and geographic location, they came up with overlapping lessons learnt which include the need for 1) political commitment to initiate change, 2) broad involvement of all stakeholders, and 3) commitment of all to engage in a long-term process. To evaluate these changes, further research is required to understand how coverage decisions in systems with and without public engagement differ.
Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017
Authors: Vold Jørn Henrik , Skurtveit Svetlana , Aas Christer , Chalabianloo Fatemeh , Kloster Pia Synnøve , Johansson Kjell Arne , Fadnes Lars Thore 
Published: April 2020

Abstract
Background
Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017.

Methods
Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models.

Results
Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20–23) diazepam equivalents in 2013 to 17 mg (95% CI: 16–17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309–421) in 2013 to 386 mg (95% CI: 349–423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1–3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6–3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs.

Conclusion
The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.
Understanding hand hygiene behaviour in the intensive care unit to inform interventions: an interview study
Authors: Lambe Kathryn , Lydon Sinéad , Madden Caoimhe , McSharry Jenny , Marshall Rebecca , Boylan Ruth , Hehir Aoife , Byrne Molly , Tujjar Omar , O’Connor Paul 
Published: April 2020

Abstract
Background
Improving hand hygiene (HH) compliance is one of the most important, but elusive, goals of infection control. The purpose of this study was to use the capability (C), opportunity (O), motivation (M), and behaviour (B; COM-B) model and the theoretical domains framework (TDF) to gain an understanding of the barriers and enablers of HH behaviours in an intensive care unit (ICU) in order to identify specific interventions to improve HH compliance.

Methods
A semi-structured interview schedule was developed based upon the COM-B model. This schedule was used to interview a total of 26 ICU staff: 12 ICU nurses, 11 anaesthetic specialist registrars, and three anaesthetic senior house officers.

Results
Participants were confident in their capabilities to carry out appropriate HH behaviours. The vast majority of participants reported having the necessary knowledge and skills, and believed they were capable of carrying out appropriate HH behaviours. Social influence was regarded as being important in encouraging HH compliance by the interviewees- particularly by nurses. The participants were motivated to carry out HH behaviours, and it was recognised that HH was an important part of their job and is important in preventing infection. It is recommended that staff are provided with targeted HH training, in which individuals receive direct and individualised feedback on actual performance and are provided guidance on how to address deficiencies in HH compliance at the bedside at the time at which the HH behaviour is performed. Modelling of appropriate HH behaviours by senior leaders is also suggested, particularly by senior doctors. Finally, appropriate levels of staffing are a factor that must be considered if HH compliance is to be improved.

Conclusions
This study has demonstrated that short interviews with ICU staff, founded on appropriate behavioural change frameworks, can provide an understanding of HH behaviour. This understanding can then be applied to design interventions appropriately tailored to the needs of a specific unit, which will have an increased likelihood of improving HH compliance.
Perilesional photobiomodulation therapy and physical rehabilitation in post-operative recovery of dogs surgically treated for thoracolumbar disk extrusion
Authors: Bruno Enrico , Canal Sara , Antonucci Michela , Bernardini Marco , Balducci Federica , Musella Vincenzo , Mussoni Matteo , Spinella Giuseppe 
Published: April 2020

AbstractBackgroundRecent studies have reported contrasting results of the effects of laser therapy on post-operative intervertebral disk herniation, with a lack of evidence-based advantages of this modality within a rehabilitation protocol.The aim of this study was to report the clinical effects of photobiomodulation therapy within a post-operative rehabilitation protocol in dogs submitted to surgery for thoracolumbar disk extrusion. Twenty-four dogs were included in the study (12 dogs treated with laser therapy and rehabilitation protocol and 12 dogs treated with same rehabilitation protocol but without laser therapy).ResultsAll dogs treated with laser therapy showed improved neurological status (Modified Frankel Score more than 3 within 30 days of physiotherapy starting) if deep nociception on admission was maintained (P = 0.04). However, Kaplan-Meier analysis did not show any statistical difference in time to regain ambulatory ability, although there was a tendency for a shorter mean time of 14.2 ± 8.55 days in the laser group versus 24 ± 18.49 days in the no laser group.ConclusionsThe use of laser therapy in the post-operative rehabilitation of dogs affected by intervertebral disc extrusion and submitted to surgery for spinal decompression could help improve their neurological status.
CRISPR/Cas9-deaminase enables robust base editing in Rhodobacter sphaeroides 2.4.1
Authors: Luo Yufeng , Ge Mei , Wang Bolun , Sun Changhong , Wang Junyi , Dong Yuyang , Xi Jianzhong Jeff 
Published: April 2020

Abstract
Background
CRISPR/Cas9 systems have been repurposed as canonical genome editing tools in a variety of species, but no application for the model strain Rhodobacter sphaeroides 2.4.1 was unveiled.

Results
Here we showed two kinds of programmable base editing systems, cytosine base editors (CBEs) and adenine base editors (ABEs), generated by fusing endonuclease Cas9 variant to cytosine deaminase PmCDA1 or heterodimer adenine deaminase TadA–TadA*, respectively. Using CBEs, we were able to obtain C-to-T mutation of single and double targets following the first induction step, with the efficiency of up to 97% and 43%; while the second induction step was needed in the case of triple target, with the screening rate of 47%. Using ABEs, we were only able to gain A-to-G mutation of single target after the second induction step, with the screening rate of 30%. Additionally, we performed a knockout analysis to identify the genes responsible for coenzyme Q10 biosynthesis and found that ubiF, ubiA, ubiG, and ubiX to be the most crucial ones.

Conclusions
Together, CBEs and ABEs serve as alternative methods for genetic manipulation in Rhodobacter sphaeroides and will shed light on the fundamental research of other bacteria that are hard to be directly edited by Cas9-sgRNA.
Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice
Authors: Bai Liang , Gao Mengxue , Cheng Xiaoming , Kang Guangbo , Cao Xiaocang , Huang He 
Published: April 2020

Abstract
Background
Obesity is a major problem worldwide and severely affects public safety. As a metabolite of gut microbiota, endogenous butyric acid participates in energy and material metabolism. Considering the serious side effects and weight regain associated with existing weight loss interventions, novel strategies are urgently needed for prevention and treatment of obesity.

Results
In the present study, we engineered Bacillus subtilis SCK6 to exhibited enhanced butyric acid production. Compared to the original Bacillus subtilis SCK6 strain, the genetically modified BsS-RS06550 strain had higher butyric acid production. The mice were randomly divided into four groups: a normal diet (C) group, a high-fat diet (HFD) group, an HFD + Bacillus subtilis SCK6 (HS) group and an HFD + BsS-RS06550 (HE) group. The results showed BsS-RS06550 decreased the body weight, body weight gain, and food intake of HFD mice. BsS-RS06550 had beneficial effects on blood glucose, insulin resistance and hepatic biochemistry. After the 14-week of experiment, fecal samples were collected for nontargeted liquid chromatography-mass spectrometry analysis to identify and quantify significant changes in metabolites. Sixteen potentially significant metabolites were screened, and BsS-RS06550 was shown to potentially regulate disorders in glutathione, methionine, tyrosine, phenylalanine, and purine metabolism and secondary bile acid biosynthesis.

Conclusions
In this study, we successfully engineered Bacillus subtilis SCK6 to have enhanced butyric acid production. The results of this work revealed that the genetically modified live bacterium BsS-RS06550 showed potential anti-obesity effects, which may have been related to regulating the levels of metabolites associated with obesity. These results indicate that the use of BsS-RS06550 may be a promising strategy to attenuate obesity.
Engineering of sugar transporters for improvement of xylose utilization during high-temperature alcoholic fermentation in Ogataea polymorpha yeast
Authors: Vasylyshyn Roksolana , Kurylenko Olena , Ruchala Justyna , Shevchuk Nadiya , Kuliesiene Neringa , Khroustalyova Galina , Rapoport Alexander , Daugelavicius Rimantas , Dmytruk Kostyantyn , Sibirny Andriy 
Published: April 2020

Abstract
Background
Xylose transport is one of the bottlenecks in the conversion of lignocellulosic biomass to ethanol. Xylose consumption by the wild-type strains of xylose-utilizing yeasts occurs once glucose is depleted resulting in a long fermentation process and overall slow and incomplete conversion of sugars liberated from lignocellulosic hydrolysates. Therefore, the engineering of endogenous transporters for the facilitation of glucose-xylose co-consumption is an important prerequisite for efficient ethanol production from lignocellulosic hydrolysates.

Results
In this study, several engineering approaches formerly used for the low-affinity glucose transporters in Saccharomyces cerevisiae, were successfully applied for earlier identified transporter Hxt1 in Ogataea polymorpha to improve xylose consumption (engineering involved asparagine substitution to alanine at position 358 and replacement of N-terminal lysine residues predicted to be the target of ubiquitination for arginine residues). Moreover, the modified versions of S. cerevisiae Hxt7 and Gal2 transporters also led to improved xylose fermentation when expressed in O. polymorpha.

Conclusions
The O. polymorpha strains with modified Hxt1 were characterized by simultaneous utilization of both glucose and xylose, in contrast to the wild-type and parental strain with elevated ethanol production from xylose. When the engineered Hxt1 transporter was introduced into constructed earlier advanced ethanol producer form xylose, the resulting strain showed further increase in ethanol accumulation during xylose fermentation. The overexpression of heterologous S. cerevisiae Gal2 had a less profound positive effects on sugars uptake rate, while overexpression of Hxt7 revealed the least impact on sugars consumption.
Long noncoding RNA BSN-AS2 induced by E2F1 promotes spinal osteosarcoma progression by targeting miR-654-3p/SYTL2 axis
Authors: Zhou Xianwei , Li Jitian , Teng Junyan , Liu Yufeng , Zhang Di , Liu Linyun , Zhang Wenming 
Published: April 2020

AbstractSpinal osteosarcoma (OS) is a rare and aggressive malignancy. Long noncoding RNA (lncRNA) BSN-AS2 has been shown to be an oncogenic gene in several cancers. However, the role and function of BSN-AS2 in spinal OS were unfamiliar. Our study identified that BSN-AS2 expression was boosted in spinal OS tissues and cell lines. Transcription factor E2F1 induced the upregulation of BSN-AS2 expression in spinal OS cells. Afterwards, loss-of-function assays indicated that BSN-AS2 depletion reduced cell proliferation, migration and invasion as well as promoted cell apoptosis in spinal OS. Thereafter, RIP, RNA pull down and luciferase reporter assays manifested BSN-AS2 could sponge miR-654-3p in spinal OS. After that, the binding effect of between miR-654-3p and SYTL2 was proved. Finally, rescue experiments illustrated that miR-654-3p inhibition or SYTL2 overexpression could counteract the inhibitory effect caused by BSN-AS2 deficiency on spinal OS progression. In conclusion, the availability of miR-654-3p was antagonized by E2F1-induced BSN-AS2 for SYTL2-meidated spinal OS progression.