bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac surgery outcome during the COVID-19 pandemic: a retrospective review of the early experience in nine UK centres
Authors: Sanders Julie , Akowuah Enoch , Cooper Jackie , Kirmani Bilal H. , Kanani Mazyar , Acharya Metesh , Jeganathan Reuben , Krasopoulos George , Ngaage Dumbor , Deglurkar Indu , Yiu Patrick , Kendall Simon , Oo Aung Ye 
Published: March 2021

Abstract
Background
Early studies conclude patients with Covid-19 have a high risk of death, but no studies specifically explore cardiac surgery outcome. We investigate UK cardiac surgery outcomes during the early phase of the Covid-19 pandemic.

Methods
This retrospective observational study included all adult patients undergoing cardiac surgery between 1st March and 30th April 2020 in nine UK centres. Data was obtained and linked locally from the National Institute for Cardiovascular Outcomes Research Adult Cardiac Surgery database, the Intensive Care National Audit and Research Centre database and local electronic systems. The anonymised datasets were analysed by the lead centre. Statistical analysis included descriptive statistics, propensity score matching (PSM), conditional logistic regression and hierarchical quantile regression.

Results
Of 755 included individuals, 53 (7.0%) had Covid-19. Comparing those with and without Covid-19, those with Covid-19 had increased mortality (24.5% v 3.5%, p < 0.0001) and longer post-operative stay (11 days v 6 days, p = 0.001), both of which remained significant after PSM. Patients with a pre-operative Covid-19 diagnosis recovered in a similar way to non-Covid-19 patients. However, those with a post-operative Covid-19 diagnosis remained in hospital for an additional 5 days (12 days v 7 days, p = 0.024) and had a considerably higher mortality rate compared to those with a pre-operative diagnosis (37.1% v 0.0%, p = 0.005).

Conclusions
To mitigate against the risks of Covid-19, particularly the post-operative burden, robust and effective pre-surgery diagnosis protocols alongside effective strategies to maintain a Covid-19 free environment are needed. Dedicated cardiac surgery hubs could be valuable in achieving safe and continual delivery of cardiac surgery.
A standard set of outcome measures for the comprehensive assessment of osteogenesis imperfecta
Authors: Nijhuis Wouter , Franken Anton , Ayers Kara , Damas Chantal , Folkestad Lars , Forlino Antonella , Fraschini Paolo , Hill Claire , Janus Guus , Kruse Richard , Lande Wekre Lena , Michiels Lieve , Montpetit Kathleen , Panzeri Leonardo , Porquet-Bordes Valerie , Rauch Frank , Sakkers Ralph , Salles Jean-Pierre , Semler Oliver , Sun Jony , To Michael , Tosi Laura , Yao Yangyang , Yeung Eric Hiu Kwong , Zhytnik Lidiia , Zillikens Maria Carola , Verhoef Marjolein 
Published: March 2021

Abstract
Background
Osteogenesis Imperfecta (OI) is a genetic disorder also known as ‘brittle bone disease’. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes thus making the comparison of outcome measures available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future.

Methods
The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search. After reviewing the outcomes extracted from the literature, trials and registries, the working group agreed on a final selection of domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups who prioritized the outcome domains by taking into account the items important to the OI community. All content was collected and analyzed and final domains were determined. A consensus of appropriate measuring instruments for each domain was reached with Delphi rounds. The entire approach was in line with the International Consortium for Health Outcomes Measurement ICHOM methodology.

Results
More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults.

Conclusion
The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set.
Disease monitoring programs of rare genetic diseases: transparent data sharing between academic and commercial stakeholders
Authors: Lochmüller Hanns , Ramirez Antonio Nino , Kakkis Emil 
Published: March 2021

AbstractIt has recently been suggested that registries for rare neuromuscular diseases should be formed and governed exclusively by physicians and patients in an effort to limit conflicts of interest. Enacting such an approach would not only be challenging logistically and financially, but it would also exclude the involvement of sponsors, who are an integral component of drug development within the current compliance framework. Therefore, as an alternative to traditional registries, we propose the use of a better collaborative model for post-marketing follow-up that includes all stakeholders. We developed the concept of Disease Monitoring Programs (DMPs), which are designed to monitor disease manifestations over a 10-year period whether on a sponsored drug or not, and ensure consistent collection, ownership sharing and governance of data.
The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement
Authors:   ERN-EYE study group, Black Graeme C. , Sergouniotis Panagiotis , Sodi Andrea , Leroy Bart P. , Van Cauwenbergh Caroline , Liskova Petra , Grønskov Karen , Klett Artur , Kohl Susanne , Taurina Gita , Sukys Marius , Haer-Wigman Lonneke , Nowomiejska Katarzyna , Marques João Pedro , Leroux Dorothée , Cremers Frans P. M. , De Baere Elfride , Dollfus Hélène 
Published: March 2021

Abstract
Background
Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states.

Main body
Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing.

Short conclusion
Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.
Radially patterned transplantable biodegradable scaffolds as topographically defined contact guidance platforms for accelerating bone regeneration
Authors: Gwon Yonghyun , Park Sunho , Kim Woochan , Han Taeseong , Kim Hyoseong , Kim Jangho 
Published: March 2021

Abstract
Background
The healing of large critical-sized bone defects remains a clinical challenge in modern orthopedic medicine. The current gold standard for treating critical-sized bone defects is autologous bone graft; however, it has critical limitations. Bone tissue engineering has been proposed as a viable alternative, not only for replacing the current standard treatment, but also for producing complete regeneration of bone tissue without complex surgical treatments or tissue transplantation. In this study, we proposed a transplantable radially patterned scaffold for bone regeneration that was defined by capillary force lithography technology using biodegradable polycaprolactone polymer.

Results
The radially patterned transplantable biodegradable scaffolds had a radial structure aligned in a central direction. The radially aligned pattern significantly promoted the recruitment of host cells and migration of osteoblasts into the defect site. Furthermore, the transplantable scaffolds promoted regeneration of critical-sized bone defects by inducing cell migration and differentiation.

Conclusions
Our findings demonstrated that topographically defined radially patterned transplantable biodegradable scaffolds may have great potential for clinical application of bone tissue regeneration.
Efficacy and safety of condylectomy with minimally invasive surgery in the treatment of interdigital corns of the lesser toes compared to conservative treatment
Authors: Marti‐Martinez Luis M. , Lorca‐Gutierrez Rubén , Sánchez‐Pérez Salvador Pedro , Garcia‐Campos Jonatan , Fernández Ehrling Nadia , Ferrer‐Torregrosa Javier 
Published: March 2021

AbstractBackgroundMinimally invasive surgery (MIS) procedures cause less trauma to the patient and might improve recovery. This study aimed to determine the efficacy and safety of condylectomy with MIS to treat interdigital corns of the lesser toes.MethodsThis prospective cohort study was conducted in seven podiatry centers. Patients with interdigital corns of the lesser toes, progressing for more than a year, with one or more recurrences in the last year following conservative treatments were eligible. The recruited patients were classified according to their treatment: conservative or surgical (condylectomy with MIS) and were compared. Patient satisfaction, pain, the clinical and functional status of the foot and the appearance of sequelae were assessed at 3 and 6 months after treatment.ResultsAt 6 months, patients in the surgical treatment group showed no pain on pressure, which significantly differed from the conservative treatment group (p <  0.001). They also improved clinical and functional status of the foot, reaching values comparable to those of the standard population. No paresthesia, joint stiffness or instability, toe malalignment, or corn transfer to a contiguous site resulted from the surgical treatment.ConclusionsCondylectomy with MIS is effective and safe to treat interdigital corns of the lesser toes.
Clinical implementation of an oncology‐specific family health history risk assessment tool
Authors: Fung Si Ming , Wu R. Ryanne , Myers Rachel A. , Goh Jasper , Ginsburg Geoffrey S. , Matchar David , Orlando Lori A. , Ngeow Joanne 
Published: March 2021

Abstract
Background
The presence of hereditary cancer syndromes in cancer patients can have an impact on current clinical care and post-treatment prevention and surveillance measures. Several barriers inhibit identification of hereditary cancer syndromes in routine practice. This paper describes the impact of using a patient-facing family health history risk assessment platform on the identification and referral of breast cancer patients to genetic counselling services.

Methods
This was a hybrid implementation-effectiveness study completed in breast cancer clinics. English-literate patients not previously referred for genetic counselling and/or gone through genetic testing were offered enrollment. Consented participants were provided educational materials on family health history collection, entered their family health history into the platform and completed a satisfaction survey. Upon completion, participants and their clinicians were given personalized risk reports. Chart abstraction was done to identify actions taken by patients, providers and genetic counsellors.

Results
Of 195 patients approached, 102 consented and completed the study (mean age 55.7, 100 % women). Sixty-six (65 %) met guideline criteria for genetic counseling of which 24 (36 %) were referred for genetic counseling. Of those referred, 13 (54 %) participants attended and eight (33 %) completed genetic testing. On multivariate logistic regression, referral was not associated with age, cancer stage, or race but was associated with clinical provider (p = 0.041). Most providers (71 %) had higher referral rates during the study compared to prior. The majority of participants found the experience useful (84 %), were more aware of their health risks (83 %), and were likely to recommend using a patient-facing platform to others (69 %).

Conclusions
65 % of patients attending breast cancer clinics in this study are at-risk for hereditary conditions based on current guidelines. Using a patient-facing risk assessment platform enhances the ability to identify these patients systematically and with widespread acceptability and recognized value by patients. As only a third of at-risk participants received referrals for genetic counseling, further understanding barriers to referral is needed to optimize hereditary risk assessment in oncology practices.

Trial Registration
NIH Clinical Trials registry, NCT04639934. Registered Nov 23, 2020 -- Retrospectively registered.
Comparison of clinical outcomes between nurse practitioner and registrar-led medical emergency teams: a propensity-matched analysis
Authors: Gupta Sachin , Balachandran Mayurathan , Bolton Gaby , Pratt Naomi , Molloy Jo , Paul Eldho , Tiruvoipati Ravindranath 
Published: March 2021

Abstract
Objective
Medical emergency teams (MET) are mostly led by physicians. Some hospitals are currently using nurse practitioners (NP) to lead MET calls. These are no studies comparing clinical outcomes between these two care models. To determine whether NP-led MET calls are associated with lower risk of acute patient deterioration, when compared to intensive care (ICU) registrar (ICUR)-led MET calls.

Methods
The composite primary outcome included recurrence of MET call, occurrence of code blue or ICU admission within 24 h. Secondary outcomes were mortality within 24 h of MET call, length of hospital stay, hospital mortality and proportion of patients discharged home. Propensity score matching was used to reduce selection bias from confounding factors between the ICUR and NP group.

Results
A total of 1343 MET calls were included (1070 NP, 273 ICUR led). On Univariable analysis, the incidence of the primary outcome was higher in ICUR-led MET calls (26.7% vs. 20.6%, p = 0.03). Of the secondary outcome measures, mortality within 24 h (3.4% vs. 7.7%, p = 0.002) and hospital mortality (12.7% vs. 20.5%, p = 0.001) were higher in ICUR-led MET calls. Propensity score-matched analysis of 263 pairs revealed the composite primary outcome was comparable between both groups, but NP-led group was associated with reduced risk of hospital mortality (OR 0.57, 95% CI 0.35–0.91, p = 0.02) and higher likelihood of discharge home (OR 1.55, 95% CI 1.09–2.2, p = 0.015).

Conclusion
Acute patient deterioration was comparable between ICUR- and NP-led MET calls. NP-led MET calls were associated with lower hospital mortality and higher likelihood of discharge home.
Insights into the genome and secretome of Fusarium metavorans DSM105788 by cultivation on agro-residual biomass and synthetic nutrient sources
Authors: Brandt Sophie C. , Brognaro Hévila , Ali Arslan , Ellinger Bernhard , Maibach Katharina , Rühl Martin , Wrenger Carsten , Schlüter Hartmut , Schäfer Wilhelm , Betzel Christian , Janssen Stefan , Gand Martin 
Published: March 2021

AbstractBackgroundThe transition to a biobased economy involving the depolymerization and fermentation of renewable agro-industrial sources is a challenge that can only be met by achieving the efficient hydrolysis of biomass to monosaccharides. In nature, lignocellulosic biomass is mainly decomposed by fungi. We recently identified six efficient cellulose degraders by screening fungi from Vietnam.ResultsWe characterized a high-performance cellulase-producing strain, with an activity of 0.06 U/mg, which was identified as a member of theFusarium solanispecies complex linkage 6 (Fusarium metavorans), isolated from mangrove wood (FW16.1, deposited as DSM105788). The genome, representing nine potential chromosomes, was sequenced using PacBio and Illumina technology. In-depth secretome analysis using six different synthetic and artificial cellulose substrates and two agro-industrial waste products identified 500 proteins, including 135 enzymes assigned to five different carbohydrate-active enzyme (CAZyme) classes. TheF. metavoransenzyme cocktail was tested for saccharification activity on pre-treated sugarcane bagasse, as well as untreated sugarcane bagasse and maize leaves, where it was complemented with the commercial enzyme mixture Accellerase 1500. In the untreated sugarcane bagasse and maize leaves, initial cell wall degradation was observed in the presence of at least 196 µg/mL of the in-house cocktail. Increasing the dose to 336 µg/mL facilitated the saccharification of untreated sugarcane biomass, but had no further effect on the pre-treated biomass.ConclusionOur results show thatF. metavoransDSM105788 is a promising alternative pre-treatment for the degradation of agro-industrial lignocellulosic materials. The enzyme cocktail promotes the debranching of biopolymers surrounding the cellulose fibers and releases reduced sugars without process disadvantages or loss of carbohydrates.
Masting by beech trees predicts the risk of Lyme disease
Authors: Bregnard Cindy , Rais Olivier , Voordouw Maarten Jeroen 
Published: March 2021

AbstractBackgroundThe incidence of Lyme borreliosis and other tick-borne diseases is increasing in Europe and North America. There is currently much interest in identifying the ecological factors that determine the density of infected ticks as this variable determines the risk of Lyme borreliosis to vertebrate hosts, including humans. Lyme borreliosis is caused by the bacteriumBorrelia burgdorferisensu lato (s.l.) and in western Europe, the hard tickIxodes ricinusis the most important vector.MethodsOver a 15-year period (2004–2018), we monitored the monthly abundance ofI. ricinusticks (nymphs and adults) and theirB. burgdorferis.l. infection status at four different elevations on a mountain in western Switzerland. We collected climate variables in the field and from nearby weather stations. We obtained data on beech tree seed production (masting) from the literature, as the abundance ofIxodesnymphs can increase dramatically 2 years after a masting event. We used generalized linear mixed effects models and AIC-based model selection to identify the ecological factors that influence inter-annual variation in the nymphal infection prevalence (NIP) and the density of infected nymphs (DIN).ResultsWe found that the NIP decreased by 78% over the study period. Inter-annual variation in the NIP was explained by the mean precipitation in the present year, and the duration that the DNA extraction was stored in the freezer prior to pathogen detection. The DIN decreased over the study period at all four elevation sites, and the decrease was significant at the top elevation. Inter-annual variation in the DIN was best explained by elevation site, year, beech tree masting index 2 years prior and the mean relative humidity in the present year. This is the first study in Europe to demonstrate that seed production by deciduous trees influences the density of nymphs infected withB. burgdorferis.l. and hence the risk of Lyme borreliosis.ConclusionsPublic health officials in Europe should be aware that masting by deciduous trees is an important predictor of the risk of Lyme borreliosis.Graphical Abstract
Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study
Authors: Nicolas Patricia , Kiuru Caroline , Wagah Martin G. , Muturi Martha , Duthaler Urs , Hammann Felix , Maia Marta , Chaccour Carlos 
Published: March 2021

Abstract
Background
Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively.

Methods
We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification.

Results
Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin.

Conclusion
There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

Graphical Abstract