bluuebunny/crossref_metadata_2025_split huggingface dataset:
Institution of Just Culture Physician Peer Review in an Academic Medical Center
Authors: Volkar Judith K. , Phrampus Paul , English Dennis , Johnson Ronald , Medeiros Ashley , Zacharia Mark , Beigi Richard 
Published: December 2017

Objectives
For academic medical centers to improve quality outcomes, identification and optimization of opportunities for improvement are necessary. Effective clinical peer review frequently has limitations on timeliness, transparency, and consideration of system processes related to untoward clinical outcomes. We developed a process to overcome these barriers and capture opportunities for process improvement identified within the clinical peer review system.

Methods
A multidisciplinary committee was formed to evaluate the current process of physician peer review at Magee Womens Hospital of the University of Pittsburgh Medical Center. Evaluation of current peer review triggers, processes, communication, transparency, and actionable outcomes was performed. A new approach was established that incorporated a protected electronic portal to improve communication and provider engagement, as well as initiation of a Just Culture peer review algorithm to realize opportunities for system improvements.

Results
The new process has been operative for 2 years. After initiation, the average time necessary for full case review decreased by 66% (6–2 months). Provider engagement and input have increased to 71%, from less than 10% before implementation. Most cases (51%) were identified as having more than one causative factor, with systems issues being the most frequent contributor to untoward outcomes.

Conclusions
Given the recognized benefits, this approach is being considered for implementation on a broader scale within service-line quality initiatives across the University of Pittsburgh Medical Center health system. Although first implemented among faculty, consideration of incorporation into graduate medical education programs is ongoing.
Robotic Gastrotomy With Intracorporeal Suture for Patients With Gastric Gastrointestinal Stromal Tumors Located at Cardia and Subcardiac Region
Authors: Zhao Jian , Wang Gang , Jiang Zhiwei , Jiang Chuanwei , Liu Jiang , Zhou Jiahui , Li Jieshou 
Published: December 2017

Purpose:
Few studies of robotic gastric gastrointestinal stromal tumors (GISTs) resection have been conducted. This study was aimed to evaluate the robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region.

Materials and Methods:
From January 2014 to August 2016, 11 patients with GISTs located at cardia and subcardiac region underwent robotic gastrotomy with intracorporeal suture. Data of these patients were collected.

Results:
The mean operative time was 82.7 minutes and the mean blood loss was 30.0 mL. No complication was reported. The postoperative length of stay was 3.3 days. On postoperative day 14, inflammation recovered to preoperative level. On postoperative month 6, the nutritional status was similar to that before the surgery. After 25.5 months follow-up, all patients survived with no recurrence or metastasis.

Conclusions:
Robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region is safe and feasible.
Historical Trends in the Diagnosis of Peduncular Hallucinosis
Authors: Galetta Kristin M. , Prasad Sashank 
Published: December 2017

Background:
Peduncular hallucinosis (PH) describes the clinical syndrome of vivid, dream-like visual hallucinations that intrude on normal wakefulness. Additional clinical deficits, especially ophthalmoparesis, have historically been an important part of the diagnosis and localization of this syndrome. We examined how modern neuroimaging has impacted the diagnosis of PH.

Methods:
We reviewed all available cases of PH, including 3 of ours and all previously reported in the literature. We determined whether other eye movement abnormalities were part of the clinical presentation and whether a neuroimaging study was performed to make the diagnosis.

Results:
A total of 85 cases were identified and evaluated. Eye movement abnormalities were present in 12/15 (80%) without a neuroimaging study but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P = 0.001).

Conclusions:
Although eye movement abnormalities historically have been considered a key localizing clinical feature supporting the diagnosis of PH, we found that in the era of modern neuroimaging, co-occurring eye movement abnormalities are far less frequent and are not a requisite feature of the diagnosis.
Generalized Periodic Discharges With and Without Triphasic Morphology
Authors: Alkhachroum Ayham M. , Al-Abri Haifa , Sachdeva Alok , Maturu Sarita , Waldron Jennifer , Wang Han , Rizvi Macym , Fernandez-Baca Vaca Guadalupe , Lüders Hans O. 
Published: December 2017

Purpose:
Generalized periodic discharges (GPDs) with a triphasic morphology have been associated with nonepileptic encephalopathies. We conducted the study to assess the reliability in which electroencephalographers can differentiate triphasic from nontriphasic periodic discharges and to evaluate for the presence of electroencephalogram and clinical characteristics that are associated with a higher risk of seizures.

Methods:
We studied prospectively 92 patients between May 2016 and February 2017. Each pattern was analyzed by two readers, who were blinded to clinical data.

Results:
The interrater agreement was “substantial” (Kappa 0.67). The following features significantly increased the risk of developing seizures: the absence of triphasic morphology, focality on electroencephalogram, interburst suppression, a history of epilepsy, and an abnormal scan. The “GPD score” includes a history of epilepsy, focality on electroencephalogram, and the absence of triphasic morphology. A GPD score of 0 has 13% risk of seizures, whereas a score of 5 to 6 has a 94% risk.

Conclusions:
Triphasic morphology GPDs confer less risk of seizures when compared with patients with GPDs without triphasic morphology. Features with a higher risk of seizures include focality on electroencephalogram, interburst suppression, a history of epilepsy, and an abnormal scan. The GPD score can be used to assess the risk of developing seizures in patients with GPDs.
Investigating the geometrical preferences of a flexible benzimidazolone-based linker in the synthesis of coordination polymers
Authors: Jones Corey L. , Marsden Elizabeth A. , Nevin Adam C. , Kariuki Benson M. , Bhadbhade Mohan M. , Martin Adam D. , Easun Timothy L. 
Published: December 2017

A series of new group 2 coordination polymers,
MgL
={MgL(H
2
O)(DMF)
0.75
}
∞
,
CaL
= {CaL(DMF)
2
}
∞
,
SrL
= {SrL(H
2
O)
0.5
}
∞
and
BaL
= {BaL(H
2
O)
0.5
}
∞
, were synthesized using a flexible benzimidazolone diacetic acid linker (
H
2
L
) in which the two carboxylic acid binding sites are connected to a planar core via {–CH
2
–} spacers that can freely rotate in solution. In a ‘curiosity-led' diversion from group 2 metals, the first row transition metal salts Mn
2+
, Cu
2+
and Zn
2+
were also reacted with
L
to yield crystals of
MnL =
{MnL(DMF)(H
2
O)
3.33
}
∞
,

Cu
3
L
2

= {Cu
3
L
2
(DMF)
2
(CHO
2
)
2
}
∞
and
ZnL
= {ZnL(DMF)}
∞
. Crystal structures were obtained for all seven materials. All structures form as two-dimensional sheets and contain six-coordinate centres, with the exception of
ZnL,
which displays tetrahedrally coordinated metal centres, and

Cu
3
L
2

, which contains square planar coordinated metal centres and Cu paddle-wheels. In each structure, the linker adopts one of two distinct conformations, with the carboxylate groups either
cis
or
trans
with respect to the planar core. All materials were also characterized by powder X-ray diffraction and thermogravimetric analysis.
Effect of vitamin D supplementation on biomarkers of inflammation and immune function: functional genomics analysis of the BEST-D trial
Authors: Berlanga-Taylor Antonio J. , Plant Katherine , Dahl Andrew , Lau Evelyn , Hill Michael , Sims David , Heger Andreas , Emberson Jonathan , Armitage Jane , Clarke Robert , Knight Julian C. 
Published: December 2017

AbstractVitamin D deficiency has been associated with multiple diseases, but the causal relevance and underlying processes are not fully understood. Elucidating the mechanisms of action of drug treatments in humans is challenging, but application of functional genomic approaches in randomised trials may afford an opportunity to systematically assess molecular responses to treatments. In the Biochemical Efficacy and Safety Trial of Vitamin D (BEST-D), 305 community-dwelling individuals aged over 65 years were randomly allocated to treatment with vitamin D34000 IU, 2000 IU or placebo daily for 12 months. Genome-wide genotypes at baseline, and transcriptome and plasma levels of cytokines (IFN-γ, IL-10, IL-8, IL-6 and TNF-α) at baseline and after 12 months, were measured. The trial had >90% power to detect a 2-fold change in gene expression. Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D (25[OH]D), but had no significant effect on whole-blood gene expression (FDR <5%) or on plasma levels of cytokines compared with placebo. In pre-specified analysis, rs7041 (intron variant, GC) had a significant effect on circulating levels of 25(OH)D in the low dose but not on the placebo or high dose vitamin D regimen. A gene expression quantitative trait locus analysis (eQTL) demonstrated evidence of 31,568 cis-eQTLs (unique SNP-probe pairs) among individuals at baseline and 34,254 after supplementation for 12 months (any dose), but had no significant effect on cis-eQTLs specific to vitamin D supplementation. The trial demonstrates the feasibility of application of functional genomics approaches in randomised trials to assess the effects of vitamin D on immune function.One sentence summarySupplementation with high-dose vitamin D in older people for 12 months in a randomised, placebo-controlled trial had no significant effect on gene expression or on plasma concentrations of cytokines.Trial registrationSRCTN registry (Number 07034656) and the European Clinical Trials Database (EudraCT Number 2011-005763-24).FundingMedical Research Council, British Heart Foundation, Wellcome Trust, European Research Council and Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United KingdomCopyrightOpen access article under the terms of CC BY.
Stability in the genetic structure of a Zymoseptoria tritici population from epidemic to interepidemic stages at a small spatial scale
Authors: Morais D. , Duplaix C. , Sache I. , Laval V. , Suffert F. , Walker A-S. 
Published: December 2017

AbstractSubpopulations of the wheat pathogen Zymoseptoria tritici (26 sample groups composed of 794 strains) were collected in two nearby wheat fields in the Paris basin, during both epidemic and inter-epidemic periods of three successive years (2009-2013). In addition to the type of inoculum (ascospores vs. pycnidiospores), the alternative presence of wheat debris allowed taking into account its putative origin (local vs. distant). We used a molecular epidemiology approach, based on population genetic indices derived from SSR marker analysis, to describe putative changes in the structure and genotypic diversity of these subpopulations over three years, at a spatiotemporal scale consistent with epidemiological observations. Genetic structure was stable over time (within and between years) and between fields. All subpopulations displayed very high levels of gene and genotypic diversity. The low levels of linkage disequilibrium and the very low clonal fraction at all stages were consistent with the regular occurrence of sexual reproduction in the two fields. A significant increase of the MAT1-1/MAT1-2 ratio was observed over the course of the epidemics, suggesting a competitive advantage of MAT1-1 strains consistently with their greater pathogenicity reported in the literature. Finally, we found that the period, the type of inoculum and its putative origin had little effect on the short term evolution of the local population of Z. tritici. Fungal population size and diversity are apparently large enough to prevent genetic drift at this fine spatiotemporal scale, and more likely short distance migration contributes strongly to the stabilization of genetic diversity among and within plots.
Testing the parasite mass burden effect on host behaviour alteration in the Schistocephalus-stickleback system
Authors: Grécias Lucie , Valentin Julie , Aubin-Horth Nadia 
Published: December 2017

ABSTRACTMany parasites with complex life cycles modify their intermediate host’s behaviour, which has been proposed to increase transmission to their definitive host. This behavioural change could result from the parasite actively manipulating its host, but could also be explained by a mechanical effect, where the parasite’s physical presence affects host behaviour. We created an artificial internal parasite using silicone injections in the body cavity to test this mechanical effect hypothesis. We used the Schistocephalus solidus - threespine stickleback (Gasterosteus aculeatus) system, as this cestode can reach up to 92% of its fish host mass. Our results suggest that the mass burden brought by this macroparasite alone is not sufficient to cause behavioural changes in its host. Furthermore, our results show that wall-hugging (thigmotaxis), a measure of anxiety in vertebrates, is significantly reduced in Schistocephalus-infected sticklebacks, unveiling a new altered component of behaviour that may result from manipulation by this macroparasite.
Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort
Authors: Gurry Thomas ,   HST Microbiome Consortium, Gibbons Sean M , Nguyen Le Thanh Tu , Kearney Sean M , Ananthakrishnan Ashwin , Jiang Xiaofang , Kassam Zain , Alm Eric J 
Published: December 2017

AbstractDietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a host’s microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patient’s microbiota.
Abundance of Enterovirus C in RD-L20B cell culture negative stool samples from Acute Flaccid Paralysis cases in Nigeria is geographically defined
Authors: Donbraye E , Olasunkanmi O.I. , Opabode B.A. , Ishola T.R. , Faleye T.O.C. , Adewumi M.O. , Adeniji J.A. 
Published: December 2017

ABSTRACTWe recently showed that Enteroviruses (EVs); majorly species Cs (EV-Cs) were present in about 46.7% of faecal samples from children <15 years old diagnosed with Acute Flaccid Paralysis (AFP) in Nigeria but declared to be EV free by the RD-L20B cell culture based algorithm. In this study, we investigated whether this observed preponderance of EVs (and EV-Cs) in such samples vary by geographical region.In all, 108 samples (i.e. 54 paired stool suspensions from 54 AFP cases) previously confirmed negative for EVs by the WHO recommended RD-L20B cell culture based algorithm were analyzed in this study. The 108 samples were made into 54 pools (27 each from Northwest [NW] and Southsouth [SS] Nigeria). All samples were subjected to RNA extraction, cDNA synthesis and the WHO recommended seminestedPCR (snPCR) assay and its modifications. All amplicons were sequenced, and enteroviruses identified using the enterovirus genotyping tool and phylogenetic analysis.Altogether, EVs were detected in 16 (29.63%) of the 54 samples screened but successfully identified in 14 (25.93%): 10 from NW- and 4 from SS-Nigeria. Precisely, one (7.14%), two (14.29%) and 11 (78.57%) of the strains detected were EV-A, EV-B and EV-C respectively. The 10 strains from NW-Nigeria are 7 EV types and include CV-A10, E29, CV-A13, CV-A17, CV-A19, CV-A24 and EV-C99. The four EV types recovered from SS-Nigeria include E31, CV-A1, EV-C99 and EV-C116. EV-C99 is the only EV type that was detected in both NW- and SS-Nigeria.The results of this study showed that the preponderance of EVs and consequently EV-Cs in AFP samples declared to be EV free by the RD-L20B cell culture based algorithm vary by geographical region in Nigeria. It further confirmed the EV-B bias of the RD-L20B cell culture based algorithm.
Fe2+/H2O2-mediated oxidation of homogentisic acid indicates the production of ochronotic and non-ochronotic pigments. Implications in Alkaptonuria and beyond
Authors: Vercruysse Koen P. , Taylor Adam M. , Knight Juan 
Published: December 2017

AbstractHomogentisic acid (HGA) can be oxidized by a combination of Fe2+and H2O2into a darkly colored high molecular mass pigment. Increasing the concentration of H2O2can lead to the formation of a high molecular mass material that exhibits less absorbance in the visible range of the electromagnetic spectrum, while maintaining a strong absorbance in the UV range of the electromagnetic spectrum. FT-IR spectroscopy did indicate the presence of a chemical feature in the pigments generated through H2O2-mediated oxidation that is absent in pigments generated through air-mediated oxidation. Our observations could have implications in the pathophysiology of alkaptonuria. In alkaptonuria, patients suffer from homogentisic aciduria from birth, but develop ochronosis (darkening) of collagenous tissues much later in life due to the formation of a melanin-like pigment. Three major questions regarding ochronosis remain to be answered: 1) how is the pigment formed, 2) why does it appear by the third decade of life and 3) why is it sporadic in appearance? Our results suggest that ochronotic or non-ochronotic pigments can be generated from HGA depending on the oxidation reaction conditions. Thus, the absence of any visible pigment, as for younger alkaptonuria patients, could not necessarily mean the absence of HGA-derived melanin-like molecules. We compare our results and their potential implications for ochronosis to the changes in pigmentation observed in vitiligo or aging (greying) hair.
High Throughput Functional Evaluation of KCNQ1 Decrypts Variants of Unknown Significance
Authors: Vanoye Carlos G. , Desai Reshma R. , Fabre Katarina L. , Potet Franck , DeKeyser Jean-Marc , Macaya Daniela , Meiler Jens , Sanders Charles R. , George Alfred L. 
Published: December 2017

ABSTRACTBackgroundThe explosive growth in known human gene variation presents enormous challenges to current approaches for variant classification that impact diagnosis and treatment of many genetic diseases. For disorders caused by mutations in cardiac ion channels, such as congenital long-QT syndrome (LQTS), in vitro electrophysiological evidence has high value in discriminating pathogenic from benign variants, but these data are often lacking because assays are cost-, time- and labor-intensive.Methods and ResultsWe implemented a strategy for performing high throughput, functional evaluations of ion channel variants that repurposed an automated electrophysiology platform developed previously for drug discovery. We demonstrated success of this approach by evaluating 78 variants in KCNQ1, a major LQTS gene. We benchmarked our results with traditional electrophysiological approaches and observed a high level of concordance. Our results provided functional data useful for classifying ~70% of previously unstudied KCNQ1 variants annotated with uninformative descriptions in the public database ClinVar. Further, we show that rare and ultra-rare KCNQ1 variants in the general population exhibit functional properties ranging from normal to severe loss-of-function indicating that allele frequency is not a reliable predictor of channel function.ConclusionsOur results illustrate an efficient and high throughput paradigm linking genotype to function for a human cardiac channelopathy that will enable data-driven classification of large numbers of variants and create new opportunities for precision medicine.
Mutations in RPL3L and MYZAP increase risk of atrial fibrillation
Authors: Thorolfsdottir Rosa B. , Sveinbjornsson Gardar , Sulem Patrick , Jonsson Stefan , Halldorsson Gisli H. , Melsted Pall , Ivarsdottir Erna V. , Davidsson Olafur B. , Kristjansson Ragnar P. , Thorleifsson Gudmar , Helgadottir Anna , Gretarsdottir Solveig , Norddahl Gudmundur , Rajamani Sridharan , Torfason Bjarni , Valgardsson Atli S. , Sverrisson Jon T. , Tragante Vinicius , Asselbergs Folkert W. , Roden Dan M. , Darbar Dawood , Pedersen Terje R. , Sabatine Marc S. , Løchen Maja-Lisa , Halldorsson Bjarni V. , Jonsdottir Ingileif , Arnar David O. , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Holm Hilma , Stefansson Kari 
Published: December 2017

AbstractWe performed a meta-analysis of genome-wide association studies on atrial fibrillation (AF) among 14,710 cases and 373,897 controls from Iceland and 14,792 cases and 393,863 controls from the UK Biobank, focusing on low frequency coding and splice mutations, with follow-up in samples from Norway and the US. We observed associations with two missense (OR=1.19 for both) and one splice-donor mutation (OR=1.52) in RPL3L, encoding a ribosomal protein primarily expressed in skeletal muscle and heart. Analysis of 167 RNA samples from the right atrium revealed that the splice donor mutation in RPL3L results in exon skipping. AF is the first disease associated with RPL3L and RPL3L is the first ribosomal gene implicated in AF. This finding is consistent with tissue specialization of ribosomal function. We also found an association with a missense variant in MYZAP (OR=1.37), encoding a component of the intercalated discs of cardiomyocytes, the organelle harbouring most of the mutated proteins involved in arrhythmogenic right ventricular cardiomyopathy. Both discoveries emphasize the close relationship between the mechanical and electrical function of the heart.