bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamically consistent estimation of Gibbs free energy from data: data reconciliation approach
Authors: Salike Saman , Bhatt Nirav
Published: September 2019

Motivation

Thermodynamic analysis of biological reaction networks requires the availability of accurate and consistent values of Gibbs free energies of reaction and formation. These Gibbs energies can be measured directly via the careful design of experiments or can be computed from the curated Gibbs free energy databases. However, the computed Gibbs free energies of reactions and formations do not satisfy the thermodynamic constraints due to the compounding effect of measurement errors in the experimental data. The propagation of these errors can lead to a false prediction of pathway feasibility and uncertainty in the estimation of thermodynamic parameters.

Results

This work proposes a data reconciliation framework for thermodynamically consistent estimation of Gibbs free energies of reaction, formation and group contributions from experimental data. In this framework, we formulate constrained optimization problems that reduce measurement errors and their effects on the estimation of Gibbs energies such that the thermodynamic constraints are satisfied. When a subset of Gibbs free energies of formations is unavailable, it is shown that the accuracy of their resulting estimates is better than that of existing empirical prediction methods. Moreover, we also show that the estimation of group contributions can be improved using this approach. Further, we provide guidelines based on this approach for performing systematic experiments to estimate unknown Gibbs formation energies.

Availability and implementation

The MATLAB code for the executing the proposed algorithm is available for free on the GitHub repository: https://github.com/samansalike/DR-thermo.

Supplementary information

Supplementary data are available at Bioinformatics online.
Fast and flexible coarse-grained prediction of protein folding routes using ensemble modeling and evolutionary sequence variation
Authors: Becerra David , Butyaev Alexander , Waldispühl Jérôme
Published: September 2019

Motivation

Protein folding is a dynamic process through which polypeptide chains reach their native 3D structures. Although the importance of this mechanism is widely acknowledged, very few high-throughput computational methods have been developed to study it.

Results

In this paper, we report a computational platform named P3Fold that combines statistical and evolutionary information for predicting and analyzing protein folding routes. P3Fold uses coarse-grained modeling and efficient combinatorial schemes to predict residue contacts and evaluate the folding routes of a protein sequence within minutes or hours. To facilitate access to this technology, we devise graphical representations and implement an interactive web interface that allows end-users to leverage P3Fold predictions. Finally, we use P3Fold to conduct large and short scale experiments on the human proteome that reveal the broad conservation and variations of structural intermediates within protein families.

Availability and implementation

A Web server of P3Fold is freely available at http://csb.cs.mcgill.ca/P3Fold.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clonal evolution of esophageal squamous cell carcinoma from normal mucosa to primary tumor and metastases
Authors: Yuan Wenqing , Liu Zhen , Wang Yu , Liu Mengfei , Pan Yaqi , Lei Wanjun , Yang Haijun , Xu Ruiping , Zhang Lixin , Cai Hong , Li Jun , Ke Yang
Published: September 2019

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor–descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.
Modification of Blood Test Draw Order to Reduce Blood Culture Contamination: A Randomized Clinical Trial
Authors: Zimmerman Frederic S , Karameh Hani , Ben-Chetrit Eli , Zalut Todd , Assous Marc , Levin Phillip D
Published: September 2019

Background

Blood culture contamination leads to unnecessary interventions and costs. It may be caused by bacteria in deep skin structures unsusceptible to surface decontamination. This study was designed to test whether diversion of blood obtained at venipuncture into a lithium heparin tube prior to aspiration of blood culture reduces contamination.

Methods

The order of blood draws for biochemistry and blood cultures was randomized. Following standard disinfection and venipuncture, blood was either aspirated into a sterile lithium heparin tube before blood culture bottles (diversion group) or blood cultures first and then lithium heparin tube (control group). All study personnel were blinded with the exception of the phlebotomist.

Results

After exclusions, 970 blood culture/biochemistry sets were analyzed. Contamination occurred in 24 of 480 (5.0%) control vs 10 of 490 (2.0%) diversion group cultures (P = .01). True pathogens were identified in 26 of 480 (5.4%) control vs 18 of 490 (3.7%) diversion cultures (P = .22). Despite randomization, demographic differences were apparent between the 2 groups. A post hoc analysis of 637 cultures from 610 medical patients admitted from home neutralized demographic differences. Culture contamination remained more frequent in the control vs diversion group (17/312 [5%] vs 7/325 [2%]; P = .03). Fewer diversion group patients were admitted to hospital (control: 200/299 [66.9%] vs diversion: 182/311 [58.5%]; P = .03), and length of stay was shorter (control: 30 hours [interquartile range {IQR}, 6–122] vs diversion: 22 [IQR, 5–97]; P = .02).

Conclusions

Use of lithium heparin tubes for diversion prior to obtaining blood cultures led to a 60% decrease in contamination. This technique is easy and inexpensive and might decrease overall hospital length of stay.

Clinical Trials Registration

NCT03966534.
Anatomical and functional coronary imaging to predict long-term outcome in patients with suspected coronary artery disease: the EVINCI-outcome study
Authors: Neglia Danilo , Liga Riccardo , Caselli Chiara , Carpeggiani Clara , Lorenzoni Valentina , Sicari Rosa , Lombardi Massimo , Gaemperli Oliver , Kaufmann Philipp A , Scholte Arthur J H A , Underwood S Richard , Knuuti Juhani ,   for the EVINCI Study Investigators
Published: September 2019

Aims

To investigate the prognostic relevance of coronary anatomy, coronary function, and early revascularization in patients with stable coronary artery disease (CAD).

Methods and results

From March 2009 to June 2012, 430 patients with suspected CAD (61 ± 9 years, 62% men) underwent coronary anatomical imaging by computed tomography coronary angiography (CTCA) and coronary functional imaging followed by invasive coronary angiography (ICA) if at least one non-invasive test was abnormal. Obstructive CAD was documented by ICA in 119 patients and 90 were revascularized within 90 days of enrolment. Core laboratory analysis showed that 134 patients had obstructive CAD by CTCA (>50% stenosis in major coronary vessels) and 79 significant ischaemia by functional imaging [>10% left ventricular (LV) myocardium]. Over mean follow-up of 4.4 years, major adverse events (AEs) (all-cause death, non-fatal myocardial infarction, or hospital admission for unstable angina or heart failure) or AEs plus late revascularization (LR) occurred in 40 (9.3%) and 58 (13.5%) patients, respectively. Obstructive CAD at CTCA was the only independent imaging predictor of AEs [hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.10–9.30; P = 0.033] and AEs plus LR (HR 4.3, 95% CI 1.56–11.81; P = 0.005). Patients with CAD in whom early revascularization was performed in the presence of ischaemia and deferred in its absence had fewer AEs, similar to patients without CAD (HR 2.0, 95% CI 0.71–5.51; P = 0.195).

Conclusion

Obstructive CAD imaged by CTCA is an independent predictor of clinical outcome. Early management of CAD targeted to the combined anatomical and functional disease phenotype improves clinical outcome.
Disturbed ventricular-arterial coupling and increased left atrial stiffness in a patient with heart failure with preserved ejection fraction and hyperaldosteronism: a case report
Authors: Meyhöfer Svenja , Schmid Sebastian M , Hohl Mathias , Reil Jan-Christian
Published: September 2019

Background

Aldosterone is involved in almost all parts of the cardiovascular system. Hyperaldosteronism causes arterial hypertension and might predispose to stroke, atrial fibrillation, and heart failure.

Case summary

A 60-year-old obese woman with long-standing hypertension, hypokalaemia, and shortness of breath was admitted to our hospital. Hypertension was caused by primary hyperaldosteronism due to an adenoma of the adrenal gland. Detailed transthoracic echocardiography revealed diastolic dysfunction, disturbed ventricular–arterial interaction, and atrial compliance resulting in heart failure with preserved ejection fraction (HFPEF). Three months of aldosterone antagonist treatment improved ventricular–arterial coupling, while left ventricular diastolic and atrial dysfunction remained unchanged.

Discussion

Presumably, hyperaldosteronism is the reason for HFPEF in this case. Standard criteria to diagnose HFPEF include clinical symptoms of heart failure and an ejection fraction (EF) >50% as well as echocardiographically or invasively assessed elevated filling pressures. Single beat pressure-volume analysis gives insights on the pathophysiology of increased filling pressures, showing in our case diastolic dysfunction as well as disturbed ventricular–arterial interaction. Three months of aldosterone antagonist treatment reduced blood pressure with concomitant improvement of ventricular–arterial interaction, thereby reducing stroke work while stroke volume remained nearly unchanged. Diastolic dysfunction and increased atrial stiffness were unaltered.
Do patients suffering an out-of-hospital cardiac arrest present to the ambulance service with symptoms in the preceding 48 h?
Authors: Deakin Charles D , Quartermain Albert , Ellery Jacob
Published: September 2019

Aims

In-hospital cardiac arrests are often preceded by a period of physiological deterioration that has often gone unnoticed. We proposed that the same might be true for out-of-hospital cardiac arrests (OHCAs) where ambulance crews leave patients at home who then subsequently go on to suffer a cardiac arrest.

Methods and results

We identified all OHCA over a 12-month period that had been seen and assessed by an ambulance crew within the 48 h preceding their cardiac arrest. We retrospectively calculated the patient’s NEWS2 score at the time of their initial assessment as a marker of their physiological status and need for hospital admission. Of 1960 OHCA patients, 184 (9.4%) had been assessed by ambulance crews within the preceding 48 h. Excluding those who had been taken to hospital (and then discharged), declined hospital conveyance or were on end-of-life care pathways, 79 (56% of total) were left at home through crew discretion. Thirty-four out of 79 (43%) patients not conveyed had either a NEWS score of 3 in a single parameter or a score of ≥5, which in hospital would mandate an urgent medical review. The most overlooked observation was respiratory rate.

Conclusions

In total, 1.7% of all OHCA had been assessed in the previous 48 h and inappropriately left at home by ambulance crews. This represents a missed opportunity to avert cardiac arrest. NEWS scoring has the potential to improve pre-hospital triage of these patients and avoid missing the deteriorating patient.
‘A Great and Holy War’: Religious Routes to Women’s Suffrage, 1909–1914
Authors: Saunders Robert
Published: September 2019

Looking back on the Edwardian suffrage campaign, the militant suffragette Annie Kenney thought it ‘more like a religious revival than a political movement’. Its language and iconography were steeped in Christian imagery, yet the religious arguments for enfranchisement have rarely received close attention. This article shows how campaigners grappled with patriarchal readings of Genesis, St Paul and the traditions of the Church to construct a Christian case for equality. It focuses, in particular, on the Church League for Women’s Suffrage, an Anglican organisation boasting nearly 6,000 members by 1914. Inspired by the incarnational theology of Charles Gore, the League recruited over 500 clergy and eight bishops, convinced that enfranchisement was not merely compatible with, but actively demanded by, the teaching of Christ. Activists preached sermons, wrote pamphlets and debated theology in the religious press, establishing a powerful theological case for reform. Using the League as a case-study, the article explores the wider relationship between gender ideology and religious thought, at a time when Christianity was the central referent of British culture. Interrogating the religious roots of ‘militancy’, it shows how the conception of suffragism as a spiritual struggle collapsed any easy distinction between ‘religion’ and ‘politics’, establishing prayer, worship and Biblical exegesis as weapons of political warfare. The churches, it is concluded, did not simply respond to changing ideas about sex and gender; they were themselves sites of new thinking about the roles of men and women, forming one of the many tributaries that fed the flood-tide of feminist thought.
Transvenous lead extraction procedures in women based on ESC-EHRA EORP European Lead Extraction ConTRolled ELECTRa registry: is female sex a predictor of complications?
Authors: Polewczyk Anna , Rinaldi Christopher A , Sohal Manav , Golzio Pier-Giorgio , Claridge Simon , Cano Oscar , Laroche Cécile , Kennergren Charles , Deharo Jean-Claude , Kutarski Andrzej , Butter Christian , Blomström-Lundqvist Carina , Romano Simone L , Maggioni Aldo P , Auricchio Angelo , Diemberger Igor , Pisano Ennio C L , Rossillo Antonio , Kuck Karl-Heinz , Forster Tamas , Bongiorni Maria Grazia ,   ELECTRa investigators group, Gale Christopher Peter , Beleslin Branko , Budaj Andrzej , Chioncel Ovidiu , Dagres Nikolaos , Danchin Nicolas , Erlinge David , Emberson Jonathan , Glikson Michael , Gray Alastair , Kayikcioglu Meral , Maggioni Aldo , Nagy Klaudia Vivien , Nedoshivin Aleksandr , Petronio Anna-Sonia , Roos-Hesselink Jolien , Wallentin Lars , Zeymer Uwe , Bongiorni Maria Grazia , Lundqvist Carina Blomstrom , Auricchio Angelo , Butter Christian , Dagres Nikolaos , Deharo Jean-Claude , Rinaldi Christopher A , Maggioni Aldo P , Kutarski Andrzej , Kennergren Charles
Published: September 2019

Aims

Female sex is considered an independent risk factor of transvenous leads extraction (TLE) procedure. The aim of the study was to evaluate the effectiveness of TLE in women compared with men.

Methods and results

A post hoc analysis of risk factors and effectiveness of TLE in women and men included in the ESC-EHRA EORP ELECTRa registry was conducted. The rate of major complications was 1.96% in women vs. 0.71% in men; P = 0.0025. The number of leads was higher in men (mean 1.89 vs. 1.71; P < 0.0001) with higher number of abandoned leads in women (46.04% vs. 34.82%; P < 0.0001). Risk factors of TLE differed between the sexes, of which the major were: signs and symptoms of venous occlusion [odds ratio (OR) 3.730, confidence interval (CI) 1.401–9.934; P = 0.0084], cumulative leads dwell time (OR 1.044, CI 1.024–1.065; P < 0.001), number of generator replacements (OR 1.029, CI 1.005–1.054; P = 0.0184) in females and the number of leads (OR 6.053, CI 2.422–15.129; P = 0.0001), use of powered sheaths (OR 2.742, CI 1.404–5.355; P = 0.0031), and white blood cell count (OR 1.138, CI 1.069–1.212; P < 0.001) in males. Individual radiological and clinical success of TLE was 96.29% and 98.14% in women compared with 98.03% and 99.21% in men (P = 0.0046 and 0.0098).

Conclusion

The efficacy of TLE was lower in females than males, with a higher rate of periprocedural major complications. The reasons for this difference are probably related to disparities in risk factors in women, including more pronounced leads adherence to the walls of the veins and myocardium. Lead management may be key to the effectiveness of TLE in females.
Constructing Normalcy in Dementia Care: Carers’ Perceptions of Their Roles and the Supports They Need
Authors: Hale Leigh , Mayland Elizabeth , Jenkins Matthew , Buttery Yvette , Norris Pauline , Butler Mary , Holland Michelle , Ngocha-Chaderopa Esther , Mckenzie-Green Barbara , Czuba Karol , Sezier Ann , Kayes Nicola
Published: September 2019

Background and Objectives: People with dementia are critically dependent on their carers when accessing and utilizing health care. To inform health care development and delivery, we aimed to explore carers’ perceptions of their role in caring for a family member with dementia and to identify carers’ skills and attributes and factors impacting on care.

Research Design and Methods: We used semistructured interviews to collect data from 25 carers supporting older adults with dementia. Data were thematically analyzed and the paradigm model was used to guide theory development.

Results: “Constructing normalcy” was central to all carers did, impacted by stage of life and relationship status and driven by a holistic focus on their care-recipient’s quality of life. Goals guiding care were: keeping the peace; facilitating participation, happiness and independence; and ensuring safety. Enablers included: social contact; knowledge; and quality social services. Barriers included health and legal issues; symptoms of dementia; and reduced knowledge. These goals kept the peace and reduced stress for the cared-for person, but often at the cost of unrelenting responsibility and loss of carers’ original roles.

Discussion and Implications: As carers are so critical to the access and uptake of health care of those with dementia, health professionals and services need to support carers in their quest to construct normalcy. Our findings provide guidance to assist in ensuring appropriate support and understanding of carers work in order to optimize dementia health care delivery.
Spatio-temporal trends in the importance of iteroparity across Atlantic salmon populations of the northwest Atlantic
Authors: Bordeleau X , Pardo S A , Chaput G , April J , Dempson B , Robertson M , Levy A , Jones R , Hutchings J A , Whoriskey F G , Crossin G T
Published: September 2019

Iteroparity is a bet-hedging strategy where individuals spread the risk of reproductive failure over time. The occurrence of iteroparity (i.e. proportion of repeat spawners in annual returns) varies among Atlantic salmon (Salmo salar) populations, yet information on its ecological importance is limited. We compiled multi-decadal time series on the spawning history composition of Atlantic salmon annual returns across ten populations of the northwest Atlantic and West Greenland mixed-stock fishery landings to: (i) describe spatio-temporal patterns of iteroparity at the continental scale; (ii) quantify the reproductive contributions of repeat spawners; and (iii) test the hypothesis that iteroparity acts as a population safeguard during periods of low recruitment through repeat spawners’ contributions. Despite high variability in the representation of repeat spawners among populations and years (range: 0–24.7%; average: 5.0%), we identified broad-scale spatio-temporal shifts in iteroparity, with increases in mid-latitudinal and northern populations (from 3.1% to 7.6%) and declines in southern areas (from 4.1% to 2.7%), between the 1971–1992 and 1993–2017 periods. Our findings highlight the potential for increased prevalence of iteroparity when threats are mitigated (e.g. fishing pressure), with measurable benefits to population processes manifested by the high reproductive contributions of repeat spawners, especially in years of low maiden spawner abundance.
Investigation of tylosin in feed of feedlot cattle and effects on liver abscess prevalence, and fecal and soil microbiomes and resistomes1
Authors: Weinroth Margaret D , Martin Jennifer N , Doster Enrique , Geornaras Ifigenia , Parker Jennifer K , Carlson Clay R , Metcalf Jessica L , Morley Paul S , Belk Keith E
Published: September 2019

Liver abscesses in feedlot cattle are detrimental to animal performance and economic return. Tylosin, a macrolide antibiotic, is used to reduce prevalence of liver abscesses, though there is variable efficacy among different groups of cattle. There is an increased importance in better understanding the etiology and pathogenesis of this condition because of growing concern over antibiotic resistance and increased scrutiny regarding use of antibiotics in food animal production. The objective of this study was to compare the microbiomes and antimicrobial resistance genes (resistomes) of feces of feedlot cattle administered or not administered tylosin and in their pen soil in 3 geographical regions with differing liver abscess prevalences. Cattle (total of 2,256) from 3 geographical regions were selected for inclusion based on dietary supplementation with tylosin (yes/no). Feces and pen soil samples were collected before harvest, and liver abscesses were identified at harvest. Shotgun and 16S rRNA amplicon sequencing were used to evaluate the soil and feces. Microbiome and resistome composition of feces (as compared by UniFrac distances and Euclidian distances, respectively) did not differ (P > 0.05) among tylosin or no tylosin-administered cattle. However, feedlot location was associated with differences (P ≤ 0.05) of resistomes and microbiomes. Using LASSO, a statistical model identified both fecal and soil microbial communities as predictive of liver abscess prevalence in pens. This model explained 75% of the variation in liver abscess prevalence, though a larger sample size would be needed to increase robustness of the model. These data suggest that tylosin exposure does not have a large impact on cattle resistomes or microbiomes, but instead, location of cattle production may be a stronger driver of both the resistome and microbiome composition of feces.
The effect of hydroxychloride trace minerals on the growth performance and carcass quality of grower/finisher pigs: a meta-analysis
Authors: van Kuijk Sandra J A , Jacobs Marc , Smits Coen H M , Han Yanming
Published: September 2019

The current study compared the effect of hydroxychloride trace minerals (HTM) with the effect of inorganic trace minerals (ITM) on growth performance and carcass quality in grower-finisher pigs. The results of 6 studies conducted throughout Europe were combined into one meta-analysis. All included studies were performed using pigs from about 19 kg of body weight until slaughter. In all studies, 2 different mineral sources were compared, HTM and sulfates as ITM. Zn from either HTM or ITM was added at a level of 80 ppm to the diet, and Cu was added at a level of 15 ppm from the same source as Zn. In most studies, an additional treatment was included in which 20 ppm Zn was used from either source in combination with 15 ppm Cu from the same source. Diets were fed in 3 phases according to local commercial standards. The body weight, average daily gain, average daily feed intake, and gain:feed ratio were measured at the end of each phase. At the end of each study, the carcass yield, back fat thickness, and lean meat percentage were measured at commercial slaughterhouses. The meta-analysis was conducted using a MIXED model in SAS taking into account the within-study and between-study variation. The comparison was done only between HTM and ITM added at the same Zn level. No statistical differences were observed for growth performance or carcass characteristics between the mineral sources in pigs fed 20 ppm Zn. When 80 ppm Zn was used, a significant improvement in lean meat percentage was observed in pigs fed HTM compared with pigs fed ITM. In the overall study period, there was a tendency towards an increased gain:feed ratio in pigs fed 80 ppm Zn from HTM. In the last feeding phase, before slaughter gain:feed ratio and average daily gain were both significantly improved by 3.9%. In conclusion, HTM addition improved growth performance and lean meat percentage in grower-finisher pigs.
Daimler/BMW/Car Sharing JV: New Mobility and the Platform Economy
Authors: Simon Stephan , Hinnekens Kathlynn , Listl Nicolas , Usai Andrea
Published: September 2019

The Commission conditionally cleared the creation by subsidiaries of BMW and Daimler of six joint ventures in the field of new mobility and, in particular, in (free-floating) car-sharing services.
Unveiling the weak radio quasar population at $z\ge 4$
Authors: Perger Krisztina , Frey Sándor , Gabányi Krisztina É , Tóth L Viktor
Published: September 2019

We applied image stacking on empty field Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) survey maps centred on optically identified high-redshift quasars at $z\ge 4$ to uncover the hidden $\mu$Jy radio emission in these active galactic nuclei (AGN). The median stacking procedure for the full sample of 2229 optically identified AGN uncovered an unresolved point source with an integrated flux density of 52 $\mu$Jy, with a signal-to-noise ratio ${\sim} 10$. We co-added the individual image centre pixels to estimate the characteristic monochromatic radio power at 1.4 GHz considering various values for the radio spectral index, revealing a radio population with $P_\mathrm{1.4\, GHz}\sim 10^{24}$ W Hz$^{-1}$. Assuming that the entire radio emission originates from star-forming (SF) activity in the nuclear region of the host galaxy, we obtained an upper limit on the characteristic star formation rate, ${\sim} 4200$ M$_\odot$ yr$^{-1}$. The angular resolution of FIRST images is insufficient to distinguish between the SF and AGN origin of radio emission at these redshifts. However, a comparison with properties of individual sources from the literature indicates that a mixed nature is likely. Future very long baseline interferometry radio observations and ultradeep Square Kilometre Array surveys are expected to be sensitive enough to detect and resolve the central $1\!-\!10$ kpc region in the host galaxies, and thus discriminate between SF and AGN related emission.
Unilateral nephrectomy versus renal arterial embolization and technique survival in peritoneal dialysis patients with autosomal dominant polycystic kidney disease
Authors: Pierre Malika , Moreau Karine , Braconnier Antoine , Kanagaratnam Lukshe , Lessore De Sainte Foy Célia , Sigogne Mikael , Béchade Clémence , Petrache Andréea , Verger Christian , Frimat Luc , Duval-Sabatier Ariane , Caillard Sophie , Halin Pascale , Touam Malick , Issad Belkacem , Vrtovsnik François , Petitpierre François , Lobbedez Thierry , Touré Fatouma
Published: September 2019

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy.

Methods

We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters.

Results

More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12–0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0–6.0] in the embolization group versus 8.5 days (IQR 6.0–11.0) in the surgery group.

Conclusions

Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction.
Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case–control study
Authors: Muskens Ivo S , Zhou Mi , Mccoy Lucie , Bracci Paige M , Hansen Helen M , Gauderman W James , Wiencke John K , Wrensch Margaret R , Wiemels Joseph L
Published: September 2019

Background

Epidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.

Methods

We conducted a nested case–control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.

Results

A family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).

Conclusion

The results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor’s feedback on immune function.
Fecal Carriage Rate of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae as a Proxy Composite Indicator of Antimicrobial Resistance in a Community in Thailand
Authors: Thamlikitkul Visanu , Tangkoskul Teerawit , Seenama Chakkraphong
Published: September 2019

Background

Increasing awareness of and understanding about antimicrobial resistance (AMR), promoting changes in behavior, and monitoring of AMR in the community are challenging, as AMR is associated with many contributing factors that are difficult to assess individually. This study aimed to determine the effectiveness of a community-based AMR campaign for improving awareness, understanding, and behavior relating to antibiotic use and AMR in Thailand and to assess if fecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae could be a proxy composite indicator of AMR in the community.

Methods

This study was conducted in 4 communities that are home to approximately 400 000 people. A self-administered questionnaire on awareness, understanding, and behavior relating to antibiotic use and AMR was responded to by 20 521 and 19 634 adults before and immediately after the AMR campaign, respectively, at the household level. Fecal samples were collected from 534 adults before the AMR campaign and from 709 adults at 18 months after the AMR campaign to determine presence of ESBL-producing Enterobacteriaceae.

Results

Awareness, understanding, and behavior relating to antibiotic use and AMR, as assessed by a self-administered questionnaire, were significantly improved after the AMR campaign. The fecal carriage rate of ESBL-producing Enterobacteriaceae decreased from 66.5% before to 44.6% after the AMR campaign (P < .01).

Conclusions

Our AMR campaign was effective for improving awareness, understanding, and behavior relating to antibiotic use and AMR among people in the community at the household level, and the prevalence of fecal carriage of ESBL-producing Enterobacteriaceae seemed to be decreased after the AMR campaign. Fecal carriage rate of ESBL-producing Enterobacteriaceae may be a proxy composite indicator of AMR in the community.
Hepatitis C Elimination in People With HIV Is Contingent on Closing Gaps in the HIV Continuum
Authors: Falade-Nwulia Oluwaseun , Sutcliffe Catherine G , Mehta Shruti H , Moon Juhi , Chander Geetanjali , Keruly Jeanne , Katzianer Jennifer , Thomas David L , Moore Richard D , Sulkowski Mark S
Published: September 2019

Background

Bolstered by the high efficacy of hepatitis C virus (HCV) treatment, the World Health Organization has called for HCV elimination by 2030. People with HIV (PWH) have been identified as a population in which elimination should be prioritized.

Methods

We examined progress in HCV elimination through the HCV care continuum among patients infected with HIV/HCV receiving HIV care at Johns Hopkins Hospital in Baltimore, Maryland, United States. Patients with HIV care visits in at least 2 consecutive years were followed through December 15, 2018, for referral to HCV care, treatment initiation, and cure.

Results

Among 593 HIV/HCV-coinfected individuals, 547 (92%) were referred for HCV care, 517 (87%) were evaluated for HCV treatment, 457 (77%) were prescribed HCV treatment, 426 (72%) initiated treatment, and 370 (62%) achieved HCV cure. In multivariable analysis, advanced liver disease (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.17–1.88) remained significantly positively associated with HCV treatment initiation. Conversely, being insured by state Medicaid (HR, 0.75; 95% CI, 0.61–0.92), having an HIV RNA >400 copies/mL (HR, 0.29; 95% CI, 0.18–0.49), and having missed 1%–24% (HR, 0.72; 95% CI, 0.54–0.97), 25%–49% (HR, 0.66; 95% CI, 0.49–0.89), and ≥50% of HIV care visits (HR, 0.39; 95% CI, 0.25–0.60) were significantly negatively associated with HCV treatment initiation.

Conclusions

HCV infection can be eliminated in PWH. However, HCV elimination requires unrestricted access to HCV treatment and improved methods of retaining people in medical care.
Serum Bactericidal Activity Levels Monitor to Guide Intravenous Dalbavancin Chronic Suppressive Therapy of Inoperable Staphylococcal Prosthetic Valve Endocarditis: A Case Report
Authors: Spaziante Martina , Franchi Cristiana , Taliani Gloria , D’Avolio Antonio , Pietropaolo Valeria , Biliotti Elisa , Esvan Rozenn , Venditti Mario
Published: September 2019

Here we describe a case of a methicillin-resistant coagulase-negative staphylococci prosthetic valve endocarditis in a patient considered not eligible for valve replacement due to high perioperative mortality risk and who did not tolerate oral antibiotic treatment. Under these circumstances, intravenous long-term chronic suppressive antibiotic therapy with dalbavancin, scheduling the doses using the serum bactericidal activity titers, proved to be safe and effective.
Metastatic spinal cord compression by gastric cancer: a case report
Authors: Kawahigashi Teiko , Kawabe Takashi , Iijima Hirokazu , Igarashi Yuto , Suno Yuma , Takagi Mutsuo , Yamaji Fuminori , Watanabe Kazunao
Published: September 2019

Metastatic spinal cord compression (MSCC) is one of the serious complications of malignancy. Most cases of MSCC occur from breast or prostate cancer primaries; MSCC secondary to gastric cancer is rare. We herein report a case of a patient with gastric cancer with weakness of the lower limbs and urinary retention on initial presentation. This case demonstrates that although rare, bone metastases and MSCC may occur from gastric primaries. It also highlights the importance of prompt diagnosis and early treatment of MSCC.
Efficiency evaluation of S&T resource allocation using an accurate quantification of the time-lag effect and relation effect: a case study of Chinese research institutes
Authors: Yue Weizhen , Gao Jun , Suo Weilan
Published: September 2019

Efficiency evaluation is a significant means of judging the allocation quality of science and technology (S&T) resource. In reality, the process of S&T resource allocation is accompanied by the time-lag effect and relation effect, and the effect differences among research institutes are obvious. In this study, we attempt to conduct efficiency evaluation of S&T resource allocation in Chinese research institutes using an accurate quantification of the time-lag effect and relation effect. A hybrid model for efficiency evaluation is designed, where the vector autoregression (VAR) model and the output revision model are adopted to quantify the time-lag effect and relation effect, and an extended super-efficiency data envelopment analysis (SE-DEA) model is proposed to conduct efficiency estimation under the quantified effects. Subsequently, a quantitative case study is conducted based on 30 sample institutes in the Chinese Academy of Sciences using statistical data from 1992 to 2014. The results indicate that the time-lag effect of each institute varies with the forms of outputs owing to the difference of individual transformation capability. The relation effect of each institute varies with the allocation proportions of inputs owing to the difference of individual developmental orientation. Compared with other methods, the proposed hybrid model can not only determine a discriminative ranking of the sample institutes, but also clarify the strengths and weaknesses of each institute. These main findings are beneficial for decision makers of sample institutes to realize the overall optimization of S&T resource allocation from the aspects of capability promotion, resource adjustment, and efficiency improvement.
Performance of ultra-high-frequency ultrasound in the evaluation of skin involvement in systemic sclerosis: a preliminary report
Authors: Naredo Esperanza , Pascau Javier , Damjanov Nemanja , Lepri Gemma , Gordaliza Pedro M , Janta Iustina , Ovalles-Bonilla Juan Gabriel , López-Longo Francisco Javier , Matucci-Cerinic Marco
Published: September 2019

Objective

High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls.

Methods

Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis.

Results

UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P < 0.05), while in the forearm it was significantly lower in patients than in controls (P < 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve >0.7).

Conclusion

These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects.
Determinants of ferritin response to oral iron supplementation in children with sleep movement disorders
Authors: DelRosso Lourdes M , Yi Troy , Chan Jeremy H M , Wrede Joanna E , Lockhart Carey T , Ferri Raffaele
Published: September 2019

Study Objectives

To identify children who respond to oral iron supplementation as evidenced by increased ferritin levels and to identify factors that correlate with improvement in ferritin levels in those who respond.

Methods

A retrospective chart review of the PLMS/RLS/RSD database at Seattle Children’s Hospital was carried out. Data collected included nocturnal polysomnography parameters, age, sex, initial and follow-up ferritin level and date of collection, and presence of restless legs syndrome (RLS), periodic limb movements of sleep (PLMS)/PLM disorder (PLMD), restless sleep disorder (RSD), obstructive sleep apnea (OSA), neurologic, psychiatric, neurodevelopmental, or medical comorbidity. Oral iron therapy was evaluated by side effects (none; constipation; bad taste/nausea), subjective outcome in symptoms (resolved, improved, no change), and adherence to therapy (poor, fair, good).

Results

Seventy-seven children were included in this study of whom 42 were classified as responders (increase in ferritin of ≥10 µg/L) and 35 were nonresponders. Age and sex were not different between groups. Adherence was the only significant predictor of an increase in ferritin of ≥10 µg/L. Constipation was seen in 7.1% of responders vs. 45.8% of nonresponders. No change in symptoms was reported in 26.2% of responders vs. 71.4% in nonresponders. A significant correlation was found between treatment duration and ferritin level change in responders but not in nonresponders

Conclusions

Side effects hinders adherence to oral iron supplementation in children. Responders to oral iron show improvement in ferritin levels and symptoms, while nonresponders show no improvement in ferritin levels despite a long-lasting treatment, at least in part of them.
Striatal Nurr1 Facilitates the Dyskinetic State and Exacerbates Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease
Authors: Sellnow RC , Steece-Collier K , Altwal F , Sandoval IM , Kordower JH , Collier TJ , Sortwell CE , West AR , Manfredsson FP
Published: September 2019

Background

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of dyskinetic rodents expressing L-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression.

Methods

We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with L-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single unit recordings and dendritic spine analyses in drug-naïve rAAV-injected parkinsonian rats.

Results

rAAV-GFP injected LID-resistant Lewis rats displayed mild LID and no induction of striatal Nurr1. However, Lewis rats transduced to overexpress Nurr1 developed severe LID. Nurr11 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in L-DOPA-naïve rats striatal rAAV-Nurr1 overexpression 1) increased firing activity in dopamine-depleted striatal direct pathway neurons, and 2) decreased spine density and thin-spine morphology on striatal medium spiny neurons, mimicking changes seen in dyskinetic rats. Finally, we provide post-mortem evidence of Nurr1 expression in the striatum of L-DOPA treated PD patients.

Conclusions

Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.
Genetic factor for twisting legume pods identified by fine-mapping of shattering-related traits in azuki bean and yard-long bean
Authors: Takahashi Yu , Kongjaimun Alisa , Muto Chiaki , Kobayashi Yuki , Kumagai Masahiko , Sakai Hiroaki , Satou Kazuhito , Teruya Kuniko , Shiroma Akino , Shimoji Makiko , Hirano Takashi , Isemura Takehisa , Saito Hiroki , Baba-Kasai Akiko , Kaga Akito , Somta Prakit , Tomooka Norihiko , Naito Ken
Published: September 2019

Legumes have evolved a unique manner of seed dispersal in that the seed pods explosively split open with helical tension generated by sclerenchyma on the endocarp. During domestication, azuki bean (Vigna angularis) and yard-long bean (Vigna unguiculata cv-gr. Sesquipedalis) have reduced or lost the sclerenchyma and lost the shattering behavior of seed pods. Here we performed fine-mapping with back-crossed populations and narrowed the candidate genomic region down to 4 kbp in azuki bean and 13 kbp in yard-long bean. Among genes located in these regions, we found MYB26 genes encoded truncated proteins in both the domesticated species. We also found in azuki bean and other legumes that MYB26 is duplicated and only the duplicated copy is expressed in seed pods. Interestingly, in Arabidopsis MYB26 is single copy and is specifically expressed in anther to initiate secondary wall thickening that is required for anther dehiscence. These facts indicated that, in legumes, MYB26 has been duplicated and acquired a new role in development of pod sclerenchyma. However, pod shattering is unfavorable phenotype for harvesting and thus has been selected against by human.