bluuebunny/crossref_metadata_2025 huggingface dataset:
Site vs. core laboratory variability in computed tomographic angiography-derived SYNTAX scores in the SYNTAX III trial
Authors: Katagiri Yuki , Andreini Daniele , Miyazaki Yosuke , Takahashi Kuniaki , Komiyama Hidenori , Mushtaq Saima , Sonck Jeroen , Schoors Danny , Maisano Francesco , Kaufman Philipp A , Leal Ingrid , Lindeboom Wietze , Piek Jan J , Wykrzykowska Joanna J , Morel Marie-Angele , Bartorelli Antonio L , Onuma Yoshinobu , Serruys Patrick W ,   the SYNTAX III REVOLUTION Investigators
Published: May 2020

Aims 

To investigate the variability between site and core laboratory (CL) calculation of the anatomical SYNTAX score (SS) based on coronary computed tomography angiography (CTA) alone and functional SS based on coronary CTA and fractional flow reserve derived from computed tomography (FFRCT) in the SYNTAX III trial.

Methods and results 

The SYNTAX III trial was a multicentre, international study that included 223 patients with three-vessel disease with or without left main involvement. Functional SS was computed by subtracting non-flow limiting stenoses (FFRCT > 0.80) from anatomical SS. SS was combined with clinical information to generate the SYNTAX score II (SS II) that provides treatment recommendations. The mean anatomical SS based on coronary CTA alone was 33.4 ± 12.7 by sites and 37.1 ± 13.4 by CL (P < 0.001). The mean functional SS based on coronary CTA and FFRCT was 30.5 ± 13.0 by sites and 33.3 ± 13.6 by CL (P < 0.001). The intraclass correlation coefficient was 0.49 [95% confidence interval (CI) 0.37–0.59) in anatomical SS and 0.62 (95% CI 0.52–0.70) in functional SS. The Cohen’s κ comparing treatment recommendation between sites and CL was 0.68 (95% CI 0.58–0.78) based on anatomical SS and 0.71 (95% CI 0.60–0.82) based on functional SS.

Conclusion 

The mean anatomical SS derived from coronary CTA alone and functional SS based on coronary CTA and FFRCT were higher when assessed by the CL than by the sites themselves. However, substantial agreement in treatment recommendation by SS II between sites and CL was demonstrated.

Clinical Trials.gov Identifier

NCT02385279.
Glycogen storage cardiomyopathy (PRKAG2): diagnostic findings of standard and advanced echocardiography techniques
Authors: Pena José Luiz Barros , Santos Wander Costa , Siqueira Maria Helena Albernaz , Sampaio Isaac Hermes , Moura Isabel Cristina Gomes , Sternick Eduardo Back
Published: May 2020

Aims 

Describe the findings obtained using standard echocardiography (Echo) and deformation indices (2D and 3D speckle tracking strain) in patients (Pts) with PRKAG2 cardiomyopathy. Seek to identify any peculiar characteristics and possible strain patterns that may distinguish this condition from other causes of left ventricular hypertrophy (LVH).

Methods and results 

Thirty Pts with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) male, mean age 39.1± 15.4 years old, were examined using standard, speckle tracking (STE), and 3D Echo. Pacemaker (PM) had been implanted in 12 (40%) Pts with a mean age of 38.1 ± 13 years. Hypertrophy was found in varying degrees in 18 (86%) Pts. Seven Pts (24%) presented 3D ejection fraction (EF) below normal limits. Diastolic function was abnormal in 17 (63%) Pts. Global longitudinal strain (GLS) on 2D measured −16.4% ± 5.3%. GLS measured −13.2% ± 4.8%, global radial strain 40.8% ± 13.8%, global circumferential strain (GCS) −16.1% ± 4.4%, and global area strain −26.1% ± 6.7% by 3D Echo offline analyses. Pts with PM presented lower EF and GCS compared with those without PM. EF/GLS measured 3.65 ± 1.00. In the bull's eye map, a strain pattern similar to stripes in 18 (60%) Pts was identified, which might be a differentiating signal among LVH.

Conclusion 

Echocardiography is a valuable tool in detecting diffuse and focal myocardial abnormalities in PRKAG2 cardiomyopathy. The deformation indices are especially revealing because they may help distinguish this rare infiltrative disease, thereby favouring early diagnosis, enhanced treatment, and improved outcome.
Association between renin–angiotensin system inhibitors and COVID-19 complications
Authors: Liabeuf Sophie , Moragny Julien , Bennis Youssef , Batteux Benjamin , Brochot Etienne , Schmit Jean Luc , Lanoix Jean-Philippe , Andrejak Claire , Ganry Olivier , Slama Michel , Maizel Julien , Mahjoub Yazine , Masmoudi Kamel , Gras-Champel Valérie
Published: May 2020

Aims

To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.

Methods and results

All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.

Conclusions

We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.
Nursing Home Culture Change Practices and Survey Deficiencies: A National Longitudinal Panel Study
Authors: Lepore Michael J , Lima Julie C , Miller Susan C
Published: May 2020

Background and Objectives

Nursing home (NH) adoption of culture change practices has substantially increased in recent decades. We examined how increasing adoption of culture change practices affected the prevalence of health, severe health, and quality of life (QoL) deficiencies.

Research Design and Methods

Novel data on culture change practice adoption from a nationally representative NH panel (N = 1,585) surveyed in 2009/2010 and 2016/2017 were used to calculate change in practice adoption scores in 3 culture change domains (resident-centered care, staff empowerment, physical environment). These data were linked to data on health, severe health, and QoL deficiencies and facility-level covariates. Multinomial logistic regression models, with survey weights and inverse probability of treatment weighting, examined how increased culture change practice adoption related to change in deficiencies.

Results

We generally observed less increase in deficiencies when culture change practices increased. However, after weighting and controlling for baseline deficiencies and culture change scores, we found few statistically significant effects. Still, results show increased physical environment practices resulted in a higher likelihood of decreases or no change (vs increases) in QoL deficiencies; increased resident-centered care practices resulted in decreases or no change (vs increases) in health deficiencies; and increased staff empowerment practices resulted in a higher likelihood of no change (vs increases) in severe health deficiencies.

Discussion and Implications

This study provides some evidence that culture change practices can help reduce the risk of increasing some types of deficiencies, but the impact of increases in each culture change domain related differently to different types of deficiencies.
halSynteny: a fast, easy-to-use conserved synteny block construction method for multiple whole-genome alignments
Authors: Krasheninnikova Ksenia , Diekhans Mark , Armstrong Joel , Dievskii Aleksei , Paten Benedict , O'Brien Stephen
Published: May 2020

Background

Large-scale sequencing projects provide high-quality full-genome data that can be used for reconstruction of chromosomal exchanges and rearrangements that disrupt conserved syntenic blocks. The highest resolution of cross-species homology can be obtained on the basis of whole-genome, reference-free alignments. Very large multiple alignments of full-genome sequence stored in a binary format demand an accurate and efficient computational approach for synteny block production.

Findings

halSynteny performs efficient processing of pairwise alignment blocks for any pair of genomes in the alignment. The tool is part of the HAL comparative genomics suite and is targeted to build synteny blocks for multi-hundred–way, reference-free vertebrate alignments built with the Cactus system.

Conclusions

halSynteny enables an accurate and rapid identification of synteny in multiple full-genome alignments. The method is implemented in C++11 as a component of the halTools software and released under MIT license. The package is available at https://github.com/ComparativeGenomicsToolkit/hal/.
Withering of tea leaves using heat pipe heat exchanger by utilizing low-temperature geothermal energy
Authors: Gunawan Yohanes , Putra Nandy , Hakim Imansyah Ibnu , Agustina Dinni , Mahlia Teuku Meurah Indra
Published: May 2020

The volume of Indonesian tea exports to the European Union (EU) decreased by 43% in 2014 because of the EU setting a maximum residue limit of anthraquinone (AQ) for tea as 0.02 mg/kg. The content of AQ in tea leaves increases when there is incomplete combustion in the combustion of firewood for the energy source of withering and drying of tea leaves. This study aims to develop and test a new concept for the direct use of low-temperature geothermal energy with a heat pipe heat exchanger (HPHE) for the withering of tea leaves as a solution for energy sources free from AQ. The geothermal fluid simulators use water, which is heated by heater and flowed by a pump. The HPHE used consists of 42 heat pipes and 181 fins. The heat pipe used has a length of 700 mm with an outer diameter of 10 mm. Each fin is made of aluminum with a thickness of 0.105 mm and a size of 76 × 345 mm2. The results show that the effectiveness of the HPHE varies from 66% to 79.59%. For 100 g of fresh tea leaves, the heating energy produced ranges from 15.21 W to 45.07 W, meaning it can wither tea leaves from 80% (w.b.) to 54% (w.b.) in a variety of 11 h 56 min to only 49.6 min. The Page mathematical model is the best model to represent the behavior of the tea leaves with this HPHE system.
Ceftriaxone treatment of spondylodiscitis and other serious infections with Cutibacterium acnes
Authors: Tiltnes Theo S , Kehrer Michala , Hughes Harriet , Morris Trefor E , Justesen Ulrik S
Published: May 2020

Objectives

To establish testing and treatment recommendations for a ceftriaxone once-daily dose regimen for systemic infections with Cutibacterium acnes.

Methods

A review of the literature and a retrospective evaluation of patients diagnosed with C. acnes spondylodiscitis and treated with ceftriaxone were performed. Ceftriaxone and penicillin MICs were determined for C. acnes isolates from blood and biopsies and the epidemiological cut-off (ECOFF) was determined with surveillance data from the UK Anaerobe Reference Laboratory in Cardiff.

Results

Limited clinical data exist from endocarditis and prosthetic joint infections using treatment with ceftriaxone 2 g once daily for C. acnes with ceftriaxone MICs ≤0.5 mg/L. In this case study, five patients were successfully treated with ceftriaxone as part of the treatment for spondylodiscitis with C. acnes. Ceftriaxone and penicillin MICs of the C. acnes isolates from the patients were 0.016–0.125 mg/L and 0.012–0.032 mg/L, respectively. The ceftriaxone ECOFF was 0.5 mg/L and the penicillin ECOFF was 0.25 mg/L based on available surveillance data.

Conclusions

From the data presented in this study it would be acceptable to consider treatment with a once-daily dose of ceftriaxone 2 g for systemic infections, including endocarditis, spondylodiscitis and prosthetic joint infections with C. acnes using a clinical breakpoint of ≤0.5 mg/L (the ECOFF). However, clinical data are still limited and the response of patients treated with ceftriaxone for serious infections with C. acnes should be monitored closely.
Pharmacokinetics of lopinavir/ritonavir oral solution to treat COVID-19 in mechanically ventilated ICU patients
Authors: Lê Minh Patrick , Jaquet Pierre , Patrier Juliette , Wicky Paul-Henri , Le Hingrat Quentin , Veyrier Marc , Kauv Juliette , Sonneville Romain , Visseaux Benoit , Laouénan Cédric , Bouadma Lila , Descamps Diane , de Montmollin Etienne , Peytavin Gilles , Timsit Jean-François
Published: May 2020

Background

The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000–8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir.

Objectives

To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir.

Patients and methods

Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored.

Results

Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928–32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394–32 735).

Conclusions

In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.
Evaluating patient attitudes to increased patient engagement with antimicrobial stewardship: a quantitative survey
Authors: Hughes Gerry , O’Toole Eilis , Talento Alida Fe , O’Leary Aisling , Bergin Colm
Published: May 2020

Background

Antimicrobial stewardship (AMS) describes interventions designed to optimize antimicrobial therapy, minimize adverse treatment consequences and reduce the spread of antimicrobial resistance (AMR). Previous research has investigated the patient’s role in healthcare infection prevention but the patient’s role in AMS has not been extensively explored.

Objectives

To investigate the willingness of hospital inpatients to question staff about prudent antimicrobial use in an Irish hospital and evaluate the impact of patient and public involvement in research (PPI) on this study.

Methods

A survey was co-designed with the hospital Patient Representative Group (PRG) to evaluate patient willingness to engage with prudent antimicrobial treatment. A random sample of 200 inpatients was selected to self-complete the survey using pen and paper. PRG members provided feedback on their involvement.

Results

Of the 200 inpatients randomly selected to participate, 120 did not fulfil the inclusion criteria. Of the remaining 80, 67 participated (response 84%). Median respondent age was 58 years, 30% were employed and 30% had a third-level education degree. Over 90% had not heard of AMS while just over 50% had not heard of AMR. Patients preferred asking factual questions rather than challenging ones but did not have a preference in asking questions of doctors compared with nurses. Older patients were less likely to ask questions. PRG members reported an overall positive experience as research collaborators.

Conclusions

Future patient-centred AMS interventions should empower patients to ask about antimicrobial treatment, in particular the older patient cohort. PPI is a valuable component of patient-centred research.
Predicting complications of diabetes mellitus using advanced machine learning algorithms
Authors: Ljubic Branimir , Hai Ameen Abdel , Stanojevic Marija , Diaz Wilson , Polimac Daniel , Pavlovski Martin , Obradovic Zoran
Published: May 2020

Objective

We sought to predict if patients with type 2 diabetes mellitus (DM2) would develop 10 selected complications. Accurate prediction of complications could help with more targeted measures that would prevent or slow down their development.

Materials and Methods

Experiments were conducted on the Healthcare Cost and Utilization Project State Inpatient Databases of California for the period of 2003 to 2011. Recurrent neural network (RNN) long short-term memory (LSTM) and RNN gated recurrent unit (GRU) deep learning methods were designed and compared with random forest and multilayer perceptron traditional models. Prediction accuracy of selected complications were compared on 3 settings corresponding to minimum number of hospitalizations between diabetes diagnosis and the diagnosis of complications.

Results

The diagnosis domain was used for experiments. The best results were achieved with RNN GRU model, followed by RNN LSTM model. The prediction accuracy achieved with RNN GRU model was between 73% (myocardial infarction) and 83% (chronic ischemic heart disease), while accuracy of traditional models was between 66% – 76%.

Discussion

The number of hospitalizations was an important factor for the prediction accuracy. Experiments with 4 hospitalizations achieved significantly better accuracy than with 2 hospitalizations. To achieve improved accuracy deep learning models required training on at least 1000 patients and accuracy significantly dropped if training datasets contained 500 patients. The prediction accuracy of complications decreases over time period. Considering individual complications, the best accuracy was achieved on depressive disorder and chronic ischemic heart disease.

Conclusions

The RNN GRU model was the best choice for electronic medical record type of data, based on the achieved results.
Two Multivariate Calibration Models for Assay of Niacin in Complex Mixtures with Its Official Impurities: A Pharmaceutical Application
Authors: Naguib Ibrahim A , Abdallah Fatma F
Published: May 2020

Background

Niacin (NIA) is a water-soluble vitamin and the primary treatment of pellagra. No analytical method was found to assess NIA in complex mixtures with its official impurities.

Objective

Two validated, accurate, and selective chemometric models were developed to assay NIA in the presence of its four official impurities, including pyridine, a nephrotoxic and hepatotoxic substance. Additionally, the two selective chemometric models were compared by processing UV spectra in the range 220–305 nm and applying partial least squares regression (PLSR) and support vector regression (SVR) models.

Method

A five levels five factors experimental design was chosen to exhibit a training set of 25 mixtures that had numerous variable percentages of tested substances. A test set consisting of 10 mixtures was designed to confirm the predictive power of the suggested models.

Results

The presented results substantiate the strength of the developed multivariate calibration models to assay NIA specifically with high selectivity and accuracy (100.02 ± 1.312 and 100.04 ± 1.272 for PLSR and SVR models, respectively). The root mean square error of prediction for the validation set mixtures was applied as a main comparison tool and it was found to be 0.2016 and 0.1890 for PLSR and SVR models, respectively.

Conclusions

The results of the developed models and the reported HPLC method were statistically compared, where F-values and Student's t-tests did not show significant difference in regards to accuracy and precision. The SVR model proved to be more accurate than the PLSR model, producing a high generalization capacity, while PLSR was easy to implement and fast.

Highlights
Serena Partridge’s ‘Accessories’: Fabricating Uncertainty in the Brontë Parsonage Museum
Authors: Pouliot Amber
Published: May 2020

The 1861 sale of the Brontës’ personal effects sent relic hunters scrambling to collect the material remains of the famous family. In the second half of the nineteenth century, the collection, preservation, and veneration of relics, particularly those associated with a writer’s private, domestic life, were important aspects of literary celebrity culture and commemoration, and both the Brontë Society and the original Brontë Museum were established to collect material remains. Yet when Virginia Woolf visited the museum in 1904, she viewed Charlotte Brontë’s clothing, shoes, and accessories with considerable unease. Anticipating the concerns of the literary establishment, Woolf feared that access to Brontë’s material remains would encourage the domestic cult which had formed around her following the publication of Elizabeth Gaskell’s The Life of Charlotte Brontë (1857). She feared it would diminish the importance of Brontë’s writing by privileging a narrative of domestic rather than literary labour. This essay considers the creative-critical intervention of Serena Partridge’s ‘Accessories’ (2016), a collection of newly created pseudo-relics of Charlotte Brontë, framed by semi-fictional narratives that dramatize the construction, use, and significance of her personal possessions. I argue that ‘Accessories’ and biographical fiction are analogous modes of engaging with Brontë’s legacy. They respond to the anxieties articulated by Woolf through the fabrication – both literal and literary – of new pseudo-relics that (rather than emphasizing Brontë’s perceived conventional, domestic femininity) enable multiple interpretive possibilities while simultaneously acknowledging the contingent nature of our understanding of her experience.
WARPFIELD-EMP: The self-consistent prediction of emission lines from evolving H ii regions in dense molecular clouds
Authors: Pellegrini E W , Rahner D , Reissl S , Glover S C O , Klessen R S , Rousseau-Nepton L , Herrera-Camus R
Published: May 2020

We present the warpfield emission predictor, warpfield-emp, which couples the 1D stellar feedback code warpfield with the cloudy H iiregion/PDR code and the polaris radiative transfer code, in order to make detailed predictions for the time-dependent line and continuum emission arising from the H ii region and PDR surrounding an evolving star cluster. warpfield-emp accounts for a wide range of physical processes (photoionization, stellar winds, supernovae, radiation pressure, gravity, thermal conduction, radiative cooling, dust extinction etc.) and yet runs quickly enough to allow us to explore broad ranges of different model parameters. We compare the results of an extensive set of models with SITELLE observations of a large sample of H ii regions in NGC 628 and find very good agreement, particularly for the highest signal-to-noise observations. We show that our approach of modelling individual clouds from first principles (instead of in terms of dimensionless quantities such as the ionization parameter) allows us to avoid long-standing degeneracies in the interpretation of H ii region diagnostics and enables us to relate these diagnostics to important physical parameters such as cloud mass or cluster age. Finally, we explore the implications of our models regarding the reliability of simple metallicity diagnostics, the properties of long-lived embedded clusters, and the role played by winds and supernovae in regulating H ii region and PDR line emission.
mCSM-membrane: predicting the effects of mutations on transmembrane proteins
Authors: Pires Douglas E V , Rodrigues Carlos H M , Ascher David B
Published: May 2020

Significant efforts have been invested into understanding and predicting the molecular consequences of mutations in protein coding regions, however nearly all approaches have been developed using globular, soluble proteins. These methods have been shown to poorly translate to studying the effects of mutations in membrane proteins. To fill this gap, here we report, mCSM-membrane, a user-friendly web server that can be used to analyse the impacts of mutations on membrane protein stability and the likelihood of them being disease associated. mCSM-membrane derives from our well-established mutation modelling approach that uses graph-based signatures to model protein geometry and physicochemical properties for supervised learning. Our stability predictor achieved correlations of up to 0.72 and 0.67 (on cross validation and blind tests, respectively), while our pathogenicity predictor achieved a Matthew's Correlation Coefficient (MCC) of up to 0.77 and 0.73, outperforming previously described methods in both predicting changes in stability and in identifying pathogenic variants. mCSM-membrane will be an invaluable and dedicated resource for investigating the effects of single-point mutations on membrane proteins through a freely available, user friendly web server at http://biosig.unimelb.edu.au/mcsm_membrane.
Cause of death for people with end-stage kidney disease withdrawing from treatment in Australia and New Zealand
Authors: Khou Victor , De La Mata Nicole L , Morton Rachael L , Kelly Patrick J , Webster Angela C
Published: May 2020

Background

Withdrawal from renal replacement therapy is common in patients with end-stage kidney disease (ESKD), but end-of-life service planning is challenging without population-specific data. We aimed to describe mortality after treatment withdrawal in Australian and New Zealand ESKD patients and evaluate death-certified causes of death.

Methods

We performed a retrospective cohort study on incident patients with ESKD in Australia, 1980–2013, and New Zealand, 1988–2012, from the Australian and New Zealand Dialysis and Transplant registry. We estimated mortality rates (by age, sex, calendar year and country) and summarized withdrawal-related deaths within 12 months of treatment modality change. Certified causes of death were ascertained from data linkage with the Australian National Death Index and New Zealand Mortality Collection database.

Results

Of 60 823 patients with ESKD, there were 8111 treatment withdrawal deaths and 26 207 other deaths over 381 874 person-years. Withdrawal-related mortality rates were higher in females and older age groups. Rates increased between 1995 and 2013, from 1142 (95% confidence interval 1064–1226) to 2706/100 000 person-years (95% confidence interval 2498–2932), with the greatest increase in 1995–2006. A third of withdrawal deaths occurred within 12 months of treatment modality change. The national death registers reported kidney failure as the underlying cause of death in 20% of withdrawal cases, with other causes including diabetes (21%) and hypertensive disease (7%). Kidney disease was not mentioned for 18% of withdrawal patients.

Conclusions

Treatment withdrawal represents 24% of ESKD deaths and has more than doubled in rate since 1988. Population data may supplement, but not replace, clinical data for end-of-life kidney-related service planning.
Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results
Authors: Kraaij Tineke , Arends Eline J , van Dam Laura S , Kamerling Sylvia W A , van Daele Paul L A , Bredewold Obbo W , Ray Argho , Bakker Jaap A , Scherer Hans U , Huizinga Tom J W , Rabelink Ton J , van Kooten Cees , Teng Y K Onno
Published: May 2020

Background

Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF).

Methods

Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN).

Results

In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + ≤7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as ‘non-responders’ due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA+ patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19+ B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20+ B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier.

Conclusions

Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM.
The impact of EGFR mutation status and single brain metastasis on the survival of non-small-cell lung cancer patients with brain metastases
Authors: Fujita Yuya , Kinoshita Manabu , Ozaki Tomohiko , Takano Koji , Kunimasa Kei , Kimura Madoka , Inoue Takako , Tamiya Motohiro , Nishino Kazumi , Kumagai Toru , Kishima Haruhiko , Imamura Fumio
Published: May 2020

Background

Molecular and genetic alterations of non-small-cell lung cancer (NSCLC) now play a vital role in patient care of this neoplasm. The authors focused on the impact of epidermal growth factor receptor mutation (EGFR-mt) status on the survival of patients after brain metastases (BMs) from NSCLC. The purpose of the study was to understand the most desirable management of BMs from NSCLC.

Methods

This was a retrospective observational study analyzing 647 patients with NSCLC, including 266 patients with BMs, diagnosed at our institute between January 2008 and December 2015. EGFR mutation status, overall survival (OS) following diagnosis, OS following BMs, duration from diagnosis to BMs, and other factors related to OS and survival after BMs were measured.

Results

Among 647 patients, 252 (38.8%) had EGFR mutations. The rate and frequency of developing BMs were higher in EGFR-mt patients compared with EGFR wildtype (EGFR-wt) patients. EGFR-mt patients showed longer median OS (22 vs 11 months, P < .001) and a higher frequency of BMs. Univariate and multivariate analyses revealed that good performance status, presence of EGFR-mt, single BM, and receiving local therapies were significantly associated with favorable prognosis following BM diagnosis. Single metastasis, compared with multiple metastases, exhibited a positive impact on patient survival after BMs in EGFR-mt patients, but not in EGFR-wt NSCLC patients.

Conclusions

Single BM with EGFR-mt performed better than other groups. Furthermore, effective local therapies were recommended to achieve better outcomes.
A four-compartment model for the COVID-19 infection—implications on infection kinetics, control measures, and lockdown exit strategies
Authors: Wang Tianbing , Wu Yanqiu , Lau Johnson Yiu-Nam , Yu Yingqi , Liu Liyu , Li Jing , Zhang Kang , Tong Weiwei , Jiang Baoguo
Published: May 2020

Objective

To analyse the impact and repercussions of the surge in healthcare demand in response to the COVID-19 pandemic, assess the potential effectiveness of various infection/disease control measures, and make projections on the best approach to exit from the current lockdown.

Design

A four-compartment model was constructed for SARS-CoV-2 infection based on the Wuhan data and validated with data collected in Italy, the UK, and the US. The model captures the effectiveness of various disease suppression measures in three modifiable factors: (a) the per capita contact rate (β) that can be lowered by means of social distancing, (b) infection probability upon contacting infectious individuals that can be lowered by wearing facemasks, personal hygiene, etc., and (c) the population of infectious individuals in contact with the susceptible population, which can be lowered by quarantine. The model was used to make projections on the best approach to exit from the current lockdown.

Results

The model was applied to evaluate the epidemiological data and hospital burden in Italy, the UK, and the US. The control measures were identified as the key drivers for the observed epidemiological data through sensitivity analyses. Analysing the different lockdown exit strategies showed that a lockdown exit strategy with a combination of social separation/general facemask use may work, but this needs to be supported by intense monitoring which would allow re-introduction/tightening of the control measures if the number of new infected subjects increases again.

Conclusions and relevance

Governments should act early in a swift and decisive manner for containment policies. Any lockdown exit will need to be monitored closely, with regards to the potential of lockdown reimplementation. This mathematical model provides a framework for major pandemics in the future.
Node-Localized Transporters of Phosphorus Essential for Seed Development in Rice
Authors: Che Jing , Yamaji Naoki , Miyaji Takaaki , Mitani-Ueno Namiki , Kato Yuri , Shen Ren Fang , Ma Jian Feng
Published: May 2020

About 60–85% of total phosphorus (P) in cereal crops is finally allocated to seeds, where it is required for seed development, germination and early growth. However, little is known about the molecular mechanisms underlying P allocation to seeds. Here, we found that two members (OsPHO1;1 and OsPHO1;2) of the PHO1 gene family are involved in the distribution of P to seeds in rice. Both OsPHO1;1 and OsPHO1;2 were localized to the plasma membrane and showed influx transport activities for inorganic phosphate. At the reproductive stage, both OsPHO1;1 and OsPHO1;2 showed higher expression in node I, the uppermost node connecting to the panicle. OsPHO1;1 was mainly localized at the phloem region of diffuse vascular bundles (DVBs) of node I, while OsPHO1;2 was expressed in the xylem parenchyma cells of the enlarged vascular bundles (EVBs). In addition, they were also expressed in the ovular vascular trace, the outer layer of the inner integument (OsPHO1;1) and in the nucellar epidermis (OsPHO1;2) of caryopses. Knockout of OsPHO1;2, as well as OsPHO1;1 to a lesser extent, decreased the distribution of P to the seed, resulting in decreased seed size and delayed germination. Taken together, OsPHO1;2 expressed in node I is responsible for the unloading of P from the xylem of EVBs, while OsPHO1;1 is involved in reloading P into the phloem of DVBs for subsequent allocation of P to seeds. Furthermore, OsPHO1;1 and OsPHO1;2 expression in the caryopsis is important for delivering P from the maternal tissues to the filial tissues for seed development.
A Comparative Study of Laser In Situ Keratomileusis Flaps Created Using Single-Functional Versus Multifunctional Femtosecond Laser for Refractive Surgery
Authors: Colombo-Barboza Marcello N. , Colombo-Barboza Luiz R. , Colombo-Barboza Maria Margarida N. , Colombo-Barboza Guilherme N.
Published: May 2020

Purpose:

To compare laser in situ keratomileusis flaps created at the programmed target thickness of 120 μm using the LenSx multifunctional and the FS200 single-functional femtosecond lasers as evaluated by anterior segment optical coherence tomography (AS-OCT).

Methods:

This was a prospective, comparative, consecutive, blinded, nonrandomized study. Patients with stable refraction for over a year were consecutively allocated to the LenSx group or the FS200 group (n = 66; 33 patients in each group). All the patients underwent refractive surgery in both eyes. Previous eye surgery, ocular pathology associated with refractive errors, pregnancy, breastfeeding, and use of medication that causes ocular adverse effects constituted the exclusion criteria. Corneal topography, corneal tomography, dilated fundoscopy, applanation tonometry, ultrasonic pachymetry, dynamic and static refraction, visual acuity, and AS-OCT were evaluated before and after surgery. AS-OCT flap thickness was measured at 20 points on each cornea.

Results:

In the LenSx group, AS-OCT flap thickness differed significantly from the target thickness at 2 of 20 points (mean differences of 2.106 and 1.803 μm). In the FS200 group, 6 of 20 measurements differed significantly (mean differences ranging from 1.121 to 2.121 μm). The 2 lasers were similarly successful in creating regular and uniform flaps. The agreement between the 2 blinded examiners regarding the AS-OCT flap thickness measurements was excellent (intraclass correlation coefficient >0.75) in both groups.

Conclusions:

Both femtosecond lasers were safe and capable of creating highly reproducible, uniform, and regular flaps at the target preoperative thickness of 120 μm. The LenSx multifunctional femtosecond laser offers the advantage of allowing both cataract and corneal surgeries.
Dry Eye and Quantitative and Qualitative Changes of Meibomian Glands in Patients With Pemphigus
Authors: Kiyat Pelin , Palamar Melis , Gerceker Turk Bengu , Yagci Ayse
Published: May 2020

Purpose:

To evaluate dry eye and quantitative and qualitative changes of meibomian glands with meibography in patients with pemphigus.

Methods:

Twenty left eyes of 20 patients with pemphigus (group 1) and 20 left eyes of 20 age- and sex-matched healthy volunteers (group 2) were enrolled. Dry eye was evaluated with Oxford scale scoring, tear film breakup time, Schirmer 1 tests, and Ocular Surface Disease Index score assessments. Morphological changes and dropout ratio of meibomian glands were evaluated by upper and lower eyelid meibography (SL-D701; Topcon, IJssel, The Netherlands). Meibomian gland dropout ratio was scored for each eyelid from grade 0 (no loss) through grade 3 (lost area >2/3 of the total meibomian gland area).

Results:

The mean ages of group 1 and group 2 were 51.8 ± 11.1 (range: 32–73) and 50.4 ± 9.6 years (range: 32–70), respectively (P = 0.672). Schirmer 1 and tear film breakup time values were lower and Oxford and Ocular Surface Disease Index scores were higher in group 1 when compared with group 2, and the differences were statistically significant (P = 0.01, P < 0.001, P = 0.001, and P < 0.001, respectively). Upper eyelid, lower eyelid, and total eyelid meiboscore values were significantly higher in group 1 (P = 0.005, P = 0.018, and P = 0.002, respectively). Morphological changes in meibomian glands were detected in 16 eyes (80%) among group 1.

Conclusions:

Between patients with pemphigus and those who were healthy, there were significant differences in the results of dry eye tests and meibomian gland morphology. Patients with pemphigus should be monitored for dry eye and meibomian gland dysfunction and be promptly treated to prevent the serious consequences of dry eye.
Clinical manifestation of non-ketotic hyperglycemia chorea
Authors: Wang Weijing , Tang Xiaomei , Feng Hao , Sun Fenghui , Liu Lei , Rajah Gary B. , Yu Fengchun
Published: May 2020

Introduction:

Chorea is considered a special complication of diabetes mellitus. Here we report a case of chorea associated with non-ketotic hyperglycemia (NKH).

Patient concerns:

The patient was a 79-year-old Asian woman. She had a history of type 2 diabetes mellitus more than 30 years, but with a poor control of blood sugar. She complained of acute onset of right limb involuntary activities, and being admitted to neurology department.

Diagnosis:

The patient was then diagnosed with NKH chorea.

Interventions:

Intravenous infusion of insulin was given to reduce blood glucose. Haloperidol was used to control motor symptoms.

Outcomes:

Her symptoms improved quickly after treatment. In the past year, the patient's blood sugar was well controlled and her chorea did not recur.

Lessons:

If there are sudden abnormal movements in patients, in addition to thinking of chorea, hepatolenticular degeneration and other diseases, we should also pay attention to blood sugar, especially in diabetic patients with poor blood sugar control and negative ketone, we should consider the possibility of NKK chorea.

Conclusions:

NKH chorea is a special complication of diabetes.
Use of siphon irrigation during burr-hole craniostomy to evacuate chronic subdural hematoma
Authors: Chen Song , Chen Zhen , Yang Bin , Xu Tao , Tu Xian-kun
Published: May 2020

Burr-hole craniostomy (BHC) is a widely accepted treatment for chronic subdural hematomas (CSDHs). This study adopted siphon irrigation to evacuate CSDHs and investigated its efficacy and safety as compared with the traditional irrigation used in BHC.

A retrospective cohort study was conducted at a center between January 2017 and December 2018. The data of 171 patients who underwent burr-hole craniostomy for CSDH were collected and analyzed. A total of 68 patients underwent siphon irrigation (siphon group) and 103 patients were treated by a traditional method (control group). A follow-up was conducted 6 months after the surgery.

No significant difference was observed in the baseline characteristics and preoperative computed tomography (CT) features of the 2 groups (P > .05). The postoperative CT features of the siphon group, which included the volume of hematoma evacuation (P = .034), hematoma evacuation rate (P < .001), recovery rate of the midline shift (P = .017), and occurrence of pneumocephalus (P = .037) were significantly different and better than those of the control group. The length of hospital stay after surgery of the siphon group was significantly shorter than that of the control group (P = .015). The Markwalder score of the siphon group was significantly superior to that of the control group on postoperative day 1 (P = .006). Although the recurrence rate in the siphon group (2/68, 2.5%) was lower than that in the control group (11/103, 8.9%), no statistically significant difference was observed between them (P = .069). Moreover, no significant differences were observed in terms of complications and mortality rate between the 2 groups.

There was no significant difference in the recurrence rate between the groups that underwent siphon irrigation and traditional irrigation. However, in comparison, siphon irrigation can better improve postoperative CT features, promote early recovery of neurological dysfunction after surgery, and shorten the length of hospital stay. This indicates that siphon irrigation may be a better therapeutic option in BHC for CSDH.
Analysis of knowledge bases and research hotspots of coronavirus from the perspective of mapping knowledge domain
Authors: Jia Qiulei , Shi Shuqing , Yuan Guozhen , Shi Jingjing , Shi Shuai , Hu Yuanhui
Published: May 2020

Background:

Coronaviruses have drawn attention since the beginning of the 21st century. Over the past 17 years, coronaviruses have triggered several outbreaks of epidemic in people, which brought great threats to global public health security. We analyzed the publications on coronavirus with bibliometrics software and qualitatively and quantitatively evaluated the knowledge base and hot topics of coronavirus research from 2003 to 2020.

Methods:

We explored the publications on coronavirus in the Web of Science core collection (WOSCC) from 2003 to 2020. Bibliometric analysis, evaluating knowledge base, and research hotspots were performed based on CiteSpace V (Drexel University, Chaomei Chen).

Results:

There were a total of 8433 publications of coronavirus. The research on coronavirus boomed when a novel coronavirus triggered outbreaks in people. The leading country was the United States, and the leading institution was the University of Hong Kong. The most productive researchers were: Yuen KY, Drosten C, Baric RS. The keywords analysis showed that SARS-CoV, infection, acute respiratory syndrome, antibody, receptor, and spike protein were research hotspots. The research categories analysis showed that virology, microbiology, veterinary sciences, infectious diseases, and biochemistry and molecular biology were hot research categories.

Conclusions:

Bibliometric analysis of the literature shows the research on coronavirus boomed when a novel coronavirus triggered outbreaks in people. With the end of the epidemic, the research tended to be cooling. Virus identification, pathogenesis, and coronavirus-mediated diseases attracted much attention. We must continue studying the viruses after an outbreak ended.
Effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3
Authors: Zhang Dan-feng , Zhao Dong-xu , Liu Xue-zhu , Li Jing , Hu Yu-hong , Dou Peng-hui
Published: May 2020

Background:

This study will investigate the effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3 (HOCC-SKOV3).

Methods:

We will retrieve potential studies from inception to the March 1, 2020 in Cochrane Library, MEDLINE, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge In-frastructure. There are not restrictions related to the language and publication status. This study will include case-controlled studies (CCSs) or randomized controlled studies (RCSs) that examine the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3. Two researchers will independently identify literatures, extract data, and appraise study quality. Any disagreements will be resolved by discussion with another researcher. RevMan 5.3 software will be placed to perform statistical analysis.

Results:

This study will summarize the present evidence to test the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3.

Conclusion:

It will provide evidence to investigate the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3, and will supply reference for further study.

Systematic review registration: INPLASY202040146.