bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suitable indications of eculizumab for patients with refractory generalized myasthenia gravis
Authors: Oyama Munenori , Okada Kensuke , Masuda Masayuki , Shimizu Yuko , Yokoyama Kazumasa , Uzawa Akiyuki , Kawaguchi Naoki , Ikeguchi Ryotaro , Hoshino Yasunobu , Hatano Taku , Ozawa Yukiko , Nakahara Jin , Aizawa Hitoshi , Kitagawa Kazuo , Hattori Nobutaka , Kuwabara Satoshi , Murai Hiroyuki , Suzuki Shigeaki 
Published: March 2020

Background: Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated damage at the neuromuscular junction. Recently, the REGAIN study showed that eculizumab was effective and well tolerated in patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG). However, there is no consensus regarding which kind of patients with gMG are selected to preferentially receive eculizumab. Methods: Between January and December 2018, we followed 1388 patients with MG at seven hospitals located in Tokyo and Chiba. We evaluated the clinical features of MG and the patients’ quality of life. Clinical status and severity were determined by the recommendations of the Myasthenia Gravis Foundation of America. Results: Of 1388 patients with MG, 12 (0.9%) patients received eculizumab. A total of 11 patients who were anti-acetylcholine receptor antibody-positive with refractory gMG (M:F = 3:8) completed the 26-week treatment with eculizumab. The disease subtypes represented included five cases of early onset MG, one of late-onset MG, and five of thymoma-associated MG. Overall, seven patients had experienced myasthenic crisis. The mean quantitative MG score ranged from 18.6 at baseline to 9.1 at week 26 ( p = 0.008). Similarly, the mean MG activities of daily living score ranged from 10.8 at baseline to 4.2 at week 26 ( p = 0.002). There were marked improvements in all patients’ quality of life status. Overall, seven patients were able to reduce the dose of prednisolone at week 26. All but one patient did not require additional rescue treatment. Overall, one patient with early onset MG could not continue the eculizumab treatment due to nausea and vertigo. Conclusion: We demonstrate that eculizumab provided remarkable benefits for refractory gMG in practical real-world experience as well as in the REGAIN study. Patients with refractory gMG with myasthenia crisis and thymoma-associated MG are suitable for eculizumab administration.
Antimicrobial therapy of 3 days or less is sufficient after successful ERCP for acute cholangitis
Authors: Haal Sylke , ten Böhmer Britt , Balkema Sebastiaan , Depla Annekatrien CTM , Fockens Paul , Jansen Jeroen M , Kuiken Sjoerd D , Liberov Boris I , van Soest Ellert , van Hooft Jeanin E , Sieswerda Elske , Voermans Rogier P 
Published: March 2020

BackgroundRecommendations for the duration of antimicrobial therapy in cholangitis after successful endoscopic biliary drainage vary. The aim of this study was to compare the occurrence of local infectious complications in patients with acute cholangitis treated with antibiotics for 3 days or less compared with 4 days or more.MethodsWe performed a retrospective multicentre study in seven hospitals in the Netherlands. Patients who received a successful biliary drainage by endoscopic retrograde cholangio‐pancreatography because of cholangitis due to common bile duct stones between 2012 and 2017 were included. The primary outcome was the occurrence of a local infectious complication within 3 months of endoscopic retrograde cholangio‐pancreatography. Secondary outcomes included Clostridioides difficile infection, total length of hospital stay and all‐cause mortality.ResultsA total of 426 patients with cholangitis were identified and 296 patients met all inclusion criteria. Therapy duration was ≤3 days in 137 patients (46.3%). During follow‐up, 41 patients (13.9%) developed a local infectious complication. Occurrence of infectious complications did not differ between the two groups (p  = 0.32). No patient developed Clostridioides difficile infection. Median hospital stay was 6 days (interquartile range 4–8 days) in the short antibiotic group compared with 7 days (interquartile range 5–9 days) in the long group (p  = 0.03). Four (1.4%) patients died during follow‐up, all were treated for ≥4 days (p  = 0.13).ConclusionsAntimicrobial therapy of 3 days or less seems to be sufficient after successful biliary drainage in patients with acute cholangitis. Randomized trials should confirm our findings.
Prediction of Progression in Polycystic Kidney Disease Using the Kidney Failure Risk Equation and Ultrasound Parameters
Authors: Akbari Ayub , Tangri Navdeep , Brown Pierre A. , Biyani Mohan , Rhodes Emily , Kumar Teerath , Shabana Wael , Sood Manish M. 
Published: March 2020

Background: The kidney failure risk equation (KFRE) is a validated risk algorithm for predicting the risk of kidney failure in chronic kidney disease (CKD) patients regardless of etiology. Patients with autosomal dominant polycystic kidney disease (AD-PCKD) experience long disease trajectories and as such identifying individuals at risk of kidney failure would aid in intervention Objective: To examine the utility of the KFRE in predicting adverse kidney outcomes compared with existing risk factors in a cohort of patients with AD-PCKD. Methods: Retrospective cohort study of AD-PCKD patients referred to a tertiary care center with a baseline kidney ultrasound and a KFRE calculation. Cox proportional hazards were used to examine the association of the KFRE and composite of an eGFR decline of >30% or the need for dialysis/transplantation. Discrimination and calibration of a parsimonious fully adjusted model and a model containing only total kidney volume (TKV) with and without the addition of the KFRE was determined. Results: Of 340 patients with AD-PCKD eligible, 221 (65%) met inclusion criteria. Older age, cardiac disease, cancer, higher systolic blood pressure, albuminuria, lower eGFR and a higher initial TKV were more common in patients with a higher KFRE. A total of 120 events occurred over a median patient follow-up time of 3.2 years. KFRE was independently associated with the composite kidney outcome. Addition of the KFRE significantly improved discrimination and calibration in a TKV only model and a fully adjusted model. Conclusions: In a diverse, referral population with AD-PCKD, the KFRE was associated with adverse kidney outcomes and improved risk prediction.
An Experimental Swallow Evoked Potential Protocol to Investigate the Neural Substrates of Swallowing
Authors: Kloepper Ashley , Arnold Joseph , Ruffolo Alexis , Kinealy Brian , Haxton Chandler , Nichols Nicole , Takahashi Kazutaka , Lever Teresa E. 
Published: March 2020

Advancement in dysphagia intervention is hindered by our lack of understanding of the neural mechanisms of swallowing in health and disease. Evoking and understanding neural activity in response to normal and disordered swallowing is essential to bridge this knowledge gap. Building on sensory evoked potential methodology, we developed a minimally invasive approach to generate swallow evoked potentials (SwEPs) in response to repetitive swallowing induced by citric acid stimulation of the oropharynx in lightly anesthetized healthy adult rats. The SwEP waveform consisted of 8 replicable peaks within 10 milliseconds immediately preceding the onset of electromyographic swallowing activity. Methodology refinement is underway with healthy rats to establish normative SwEP waveform morphology before proceeding to models of advanced aging and age‐related neurodegenerative diseases. Ultimately, we envision that this experimental protocol may unmask the pathologic neural substrates contributing to dysphagia to accelerate the discovery of targeted therapeutics.
Managing climate change in drinking water reservoirs: potentials and limitations of dynamic withdrawal strategies
Authors: Feldbauer Johannes , Kneis David , Hegewald Tilo , Berendonk Thomas U. , Petzoldt Thomas 
Published: March 2020

Abstract
Background
Climate change induced a rise in surface water temperature and a prolongation of summer stratification in drinking water reservoirs. Stratification and temperature are important factors for drinking water production because they influence bio-geo-chemical processes and thus affect water quality. Most drinking water reservoirs have outlet structures that allow water to be withdrawn from different depths at variable rates. The thermal structure of these reservoirs can thus be managed actively by means of dynamic withdrawal schemes.

Results
We employed the hydro-physical General Lake Model to simulate the effects of different withdrawal strategies on temperatures and stratification in three German reservoirs. In particular, we assessed the potential of depth- and time-variable withdrawal to mitigate the impacts of climate change. We found that deep water temperatures (25 m below surface) and the end of summer stagnation are strongly controlled by the withdrawal regime. Specifically, the simulated impact of the withdrawal scheme was of the same order of magnitude as the observed impact of climate change over the last 30 years. However, the end of ice cover, the onset of summer stagnation, and near-surface temperatures (3 m depth) were rather insensitive to altered withdrawal strategies.

Conclusions
Our results suggest that an adaption of withdrawal depth and timing will partly compensate for the effects of climate change. Dynamic withdrawal should thus be considered as an integral part of future reservoir management strategies.
Genotype calling of triploid offspring from diploid parents
Authors: Grashei Kim Erik , Ødegård Jørgen , Meuwissen Theo H. E. 
Published: March 2020

AbstractBackgroundPolyploidy is widespread in animals and especially in plants. Different kinds of ploidies exist, for example, hexaploidy in wheat, octaploidy in strawberries, and diploidy, triploidy, tetraploidy, and pseudo-tetraploidy (partly tetraploid) in fish. Triploid offspring from diploid parents occur frequently in the wild in Atlantic salmon (Salmo salar) and, as with triploidy in general, the triploid individuals are sterile. Induced triploidy in Atlantic salmon is common practice to produce sterile fish. In Norwegian aquaculture, production of sterile triploid fish is an attempt by government and industry to limit genetic introgression between wild and farmed fish. However, triploid fish may have traits and properties that differ from those of diploids. Investigating the genetics behind traits in triploids has proved challenging because genotype calling of genetic markers in triploids is not supported by standard software. Our aim was to develop a method that can be used for genotype calling of genetic markers in triploid individuals.ResultsAllele signals were produced for 381 triploid Atlantic salmon offspring using a 56 K Thermo Fisher GeneTitan genotyping platform. Genotypes were successfully called by applying finite normal mixture models to the (transformed) allele signals. Subsets of markers were filtered by quality control statistics for use with downstream analyses. The quality of the called genotypes was sufficient to allow for assignment of diploid parents to the triploid offspring and to discriminate between maternal and paternal parents from autosomal inheritance patterns. In addition, as the maternal inheritance in triploid offspring is identical to gynogenetic inheritance, the maternal recombination pattern for each chromosome could be mapped by using a similar approach as that used in gene-centromere mapping.ConclusionsWe show that calling of dense marker genotypes for triploid individuals is feasible. The resulting genotypes can be used in parentage assignment of triploid offspring to diploid parents, to discriminate between maternal and paternal parents using autosomal inheritance patterns, and to map the maternal recombination pattern using an approach similar to gene-centromere mapping. Genotyping of triploid individuals is important both for selective breeding programs and unravelling the underlying genetics of phenotypes recorded in triploids. In principle, the developed method can be used for genotype calling of other polyploid organisms.
Cyclosporine a directly affects human and mouse b cell migration in vitro by disrupting a hIF-1 αdependent, o2 sensing, molecular switch
Authors: Hilchey Shannon P , Palshikar Mukta G , Emo Jason A , Li Dongmei , Garigen Jessica , Wang Jiong , Mendelson Eric S , Cipolla Valentina , Thakar Juilee , Zand Martin S 
Published: March 2020

Abstract
Background
Hypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1 α post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1 α destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality.

Results
We demonstrate that O 2 tension is a previously unrecognized Bc regulatory switch, altering CXCR4 and CXCR5 chemokine receptor signaling in activated Bc through HIF-1 α expression, and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this O 2 regulatory switch in primary human Bc.

Conclusion
This previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.
Transcriptome analysis of metabolic pathways associated with oil accumulation in developing seed kernels of Styrax tonkinensis, a woody biodiesel species
Authors: Wu Qikui , Cao Yuanyuan , Chen Chen , Gao Zhenzhou , Yu Fangyuan , Guy Robert D. 
Published: March 2020

Abstract
Background
Styrax tonkinensis (Pierre) Craib ex Hartwich has great potential as a woody biodiesel species having seed kernels with high oil content, excellent fatty acid composition and good fuel properties. However, no transcriptome information is available on the molecular regulatory mechanism of oil accumulation in developing S. tonkinensis kernels.

Results
The dynamic patterns of oil content and fatty acid composition at 11 time points from 50 to 150 days after flowering (DAF) were analyzed. The percent oil content showed an up-down-up pattern, with yield and degree of unsaturation peaking on or after 140 DAF. Four time points (50, 70, 100, and 130 DAF) were selected for Illumina transcriptome sequencing. Approximately 73 million high quality clean reads were generated, and then assembled into 168,207 unigenes with a mean length of 854 bp. There were 5916 genes that were differentially expressed between different time points. These differentially expressed genes were grouped into 9 clusters based on their expression patterns. Expression patterns of a subset of 12 unigenes were confirmed by qRT-PCR. Based on their functional annotation through the Basic Local Alignment Search Tool and publicly available protein databases, specific unigenes encoding key enzymes, transmembrane transporters, and transcription factors associated with oil accumulation were determined. Three main patterns of expression were evident. Most unigenes peaked at 70 DAF, coincident with a rapid increase in oil content during kernel development. Unigenes with high expression at 50 DAF were associated with plastid formation and earlier stages of oil synthesis, including pyruvate and acetyl-CoA formation. Unigenes associated with triacylglycerol biosynthesis and oil body development peaked at 100 or 130 DAF.

Conclusions
Transcriptome changes during oil accumulation show a distinct temporal trend with few abrupt transitions. Expression profiles suggest that acetyl-CoA formation for oil biosynthesis is both directly from pyruvate and indirectly via acetaldehyde, and indicate that the main carbon source for fatty acid biosynthesis is triosephosphate originating from phosphohexose outside the plastid. Different sn-glycerol-3-phosphate acyltransferases are implicated in diacylglycerol biosynthesis at early versus late stages of oil accumulation. Triacylglycerol biosynthesis may be accomplished by both diacylglycerol and by phospholipid:diacylglycerol acyltransferases.
Impact of a postcrash first aid educational program on knowledge, perceived skills confidence, and skills utilization among traffic police officers: a single-arm before-after intervention study
Authors: Ndile Menti L. , Lukumay Gift G. , Bolenius Karin , Outwater Anne H. , Saveman Britt-Inger , Backteman-Erlanson Susann 
Published: March 2020

Abstract
Background
An overwhelming proportion of road traffic deaths and injuries in low- and middle-income countries (LMICs) occur in prehospital environments. Lay first responders such as police officers play an important role in providing initial assistance to victims of road traffic injuries either alone or in collaboration with others. The present study evaluated a postcrash first aid (PFA) educational program developed for police officers in Tanzania.

Method
A 16-h PFA educational program was conducted in Dar es Salaam, Tanzania, for 135 police officers. Participants completed training surveys before, immediately and 6 months after the training (before, N = 135; immediately after, N = 135; after 6 months, N = 102). The primary outcome measures were PFA knowledge, perceived skills confidence, and skills utilization. Parametric and nonparametric tests were used to analyse changes in outcome.

Results
The mean PFA knowledge score increased from 44.73% before training (SD = 20.70) to 72.92% 6 months after training (SD = 18.12), p < .001, N = 102. The mean PFA perceived skills confidence score (measured on a 1–5 Likert scale) increased from 1.96 before training (SD = 0.74) to 3.78 6 months after training (SD = 0.70), p < .001, N = 102. Following training, application of the recovery position skill (n = 42, 46%) and application of the bleeding control skill (n = 45, 49%) were reported by nearly half of the responding officers. Less than a quarter of officers reported applying head and neck immobilization skills (n = 20, 22%) following training.

Conclusion
A PFA educational program has shown to improve police officers’ knowledge and perceived skills confidence on provision of first aid. However qualitative research need to be conducted to shed more light regarding reasons for low utilization of trained first aid skills during follow-up.
Epidemiology, treatment and outcomes of bloodstream infection due to vancomycin-resistant enterococci in cancer patients in a vanB endemic setting
Authors: Xie Ouli , Slavin Monica A. , Teh Benjamin W. , Bajel Ashish , Douglas Abby P. , Worth Leon J. 
Published: March 2020

AbstractBackgroundVancomycin-resistant enterococcus (VRE) is an important cause of infection in immunocompromised populations. Few studies have described the characteristics ofvanBVRE infection. We sought to describe the epidemiology, treatment and outcomes of VRE bloodstream infections (BSI) in avanBpredominant setting in malignant hematology and oncology patients.MethodsA retrospective review was performed at two large Australian centres and spanning a 6-year period (2008–2014). Evaluable outcomes were intensive care admission (ICU) within 48 h of BSI, all-cause mortality (7 and 30 days) and length of admission.ResultsOverall, 106 BSI episodes were observed in 96 patients, predominantlyEnterococcus faecium vanB(105/106, 99%). Antibiotics were administered for a median of 17 days prior to BSI, and 76/96 (79%) were neutropenic at BSI onset. Of patients screened before BSI onset, 49/72 (68%) were found to be colonised. Treatment included teicoplanin (59), linezolid (6), daptomycin (2) and sequential/multiple agents (21). Mortality at 30-days was 31%. On multivariable analysis, teicoplanin was not associated with mortality at 30 days.ConclusionsVRE BSI in avanBendemic setting occurred in the context of substantive prior antibiotic use and was associated with high 30-day mortality. Targeted screening identified 68% to be colonised prior to BSI. Teicoplanin therapy was not associated with poorer outcomes and warrants further study forvanBVRE BSI in cancer populations.
Markers and risk factors for chronic kidney disease in sub-Saharan Africans: baseline levels and 12-month trajectories in newly referred patients in Cameroon
Authors: Patrice Halle Marie , Pascal Kengne Andre , François Kaze Folefack , Hilaire Djantio , Solange Doualla Marie , Gloria Ashuntantang Enow , Pierre Choukem Siméon 
Published: March 2020

Abstract
Background
Little is known about the changes in disease makers and risk factors in patients with chronic kidney disease (CKD) under nephrological care in Africa. This study aimed to evaluate the baseline level of markers of CKD and their 12-month time-trend in newly referred patients in a tertiary hospital in Cameroon.

Methods
This was a retrospective cohort study including 420 patients referred for CKD between 2006 and 2012 to the nephrology unit of the Douala General Hospital in the littoral region of Cameroon. Their disease and risk profile was assessed at baseline and every 3 months for 1 year. Estimated glomerular filtration rate (eGFR) was based on MDRD and Schwartz equations. CKD was diagnosed in the presence of eGFR< 60 ml/min/1.73 m2 and/or proteinuria> 1+ and/or abnormal renal ultrasound persisting for ≥3 months. Data analysis used mixed linear regressions.

Results
Of the 420 patients included, 66.9% were men and mean age was 53.8 (15.1) years. At referral, 37.5% of the participants were at CKD Stage 3, 30.8% at stage 4 and 26.8% at stage 5. There was 168 (40%) diabetic and 319 (75.9%) hypertensive patients. After some improvement during the first 3 months, eGFR steadily decreased during the first year of follow-up, and this pattern was robust to adjustment for many confounders. Systolic and diastolic blood pressure levels significantly fluctuated during the first twelve months of follow-up. Changes in the levels of other risk factors and markers of disease severity over time were either borderline or non-significant.

Conclusion
Patients with CKD in African settings are referred to the nephrologist at advanced stages. This likely translates into a less beneficial effects of specialised care on the course of the disease.