bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infrastructure Design: A Critical Element in the Care of the Patient With Obesity
Authors: Ortiz Vilma E. , Ottolino Rick J. , Matz Mary W. , Uppot Raul N. , Winters Bob 
Published: October 2018

Abstract
The worldwide rate of obesity continues to rise, causing healthcare systems to morph to meet the demands posed by the concomitant increase in comorbidities associated with this condition. Increasing patient weight imposes its own constraints on the safety of patients and providers; therefore, a sound healthcare facility infrastructure is required to properly address the medical needs of patients with obesity. Currently, most healthcare systems—in their attitudes, equipment, and facility design—are ill equipped to meet the needs of this epidemic. In this article, we discuss the facilities and equipment design considerations in providing medical care to patients with obesity. Extending beyond the physical plant, we also touch on organizational elements that enable the healthcare provider to safely care for this challenging patient population. The rising prevalence and disease burden of excess adiposity highlight the obligation to recognize that the design needs common to all of our patients must include the particular needs of the patient with obesity.
Negative Pressure Wound Therapy for Surgical-site Infections
Authors: Javed Ammar A. , Teinor Jonathan , Wright Michael , Ding Ding , Burkhart Richard A. , Hundt John , Cameron John L. , Makary Martin A. , He Jin , Eckhauser Frederic E. , Wolfgang Christopher L. , Weiss Matthew J. 
Published: October 2018

Objective:
This study seeks to evaluate the efficacy of negative pressure wound therapy for surgical-site infection (SSI) after open pancreaticoduodenectomy.

Background:
Despite improvement in infection control, SSIs remain a common cause of morbidity after abdominal surgery. SSI has been associated with an increased risk of reoperation, prolonged hospitalization, readmission, and higher costs. Recent retrospective studies have suggested that the use of negative pressure wound therapy can potentially prevent this complication.

Methods:
We conducted a single-center randomized, controlled trial evaluating surgical incision closure during pancreaticoduodenectomy using negative pressure wound therapy in patients at high risk for SSI. We randomly assigned patients to receive negative pressure wound therapy or a standard wound closure. The primary end point of the study was the occurrence of a postoperative SSI. We evaluated the economic impact of the intervention.

Results:
From January 2017 through February 2018, we randomized 123 patients at the time of closure of the surgical incision. SSI occurred in 9.7% (6/62) of patients in the negative pressure wound therapy group and in 31.1% (19/61) of patients in the standard closure group (relative risk = 0.31; 95% confidence interval, 0.13–0.73; P = 0.003). This corresponded to a relative risk reduction of 68.8%. SSIs were found to independently increase the cost of hospitalization by 23.8%.

Conclusions:
The use of negative pressure wound therapy resulted in a significantly lower risk of SSIs. Incorporating this intervention in surgical practice can help reduce a complication that significantly increases patient harm and healthcare costs.
A Worldwide Survey of Live Liver Donor Selection Policies at 24 Centers With a Combined Experience of 19 009 Adult Living Donor Liver Transplants
Authors: Soin Arvinder Singh , Chaudhary Rohan Jagat , Pahari Hirak , Pomfret Elizabeth A. 
Published: October 2018

Background
Although surgical technique in living donor liver transplantation (LDLT) has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate.

Methods
A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19 009 LDLTs responded.

Results
Centers were categorized into predominantly LDLT (18) or deceased donor liver transplantation (6), and high- (10) or low-volume (14) centers. At most centers, the minimum acceptable graft-to-recipient weight ratio was 0.7 or less (67%), and remnant was 30% (75%). The median upper limit of donor age was 60 years and body mass index of 33 kg/m2. At 63% centers, age influenced the upper limit of body mass index inversely. Majority preferred aspartate transaminase and alanine transaminase less than 50 IU/mL. Most accepted donors with nondebilitating mild mental or physical disability and rejected donors with treated coronary artery disease, cerebrovascular accident and nonbrain, nonskin primary malignancies. Opinions were divided about previous psychiatric illness, substance abuse and abdominal surgery. Most performed selective liver biopsy, commonly for steatosis, raised transaminases and 1 or more features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high-volume centers. There was no standard policy for preoperative or peroperative cholangiogram.

Conclusions
This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety.
Clozapine-Associated Aspiration During Electroconvulsive Therapy
Authors: Estime Stephen R. , Berg Sheri M. , Henry Michael E. 
Published: October 2018

Abstract
Clozapine-induced gastric hypomotility (CIGH) is an underreported, underrecognized effect from high-dose clozapine. In this report, we present a patient with treatment refractory schizophrenia receiving high-dose clozapine who aspirated during general anesthesia for electroconvulsive therapy. To our knowledge, this is the first report of aspiration under general anesthesia as a result of CIGH and highlights the potential dangers high-dose clozapine can pose on patients undergoing electroconvulsive therapy with unrecognized CIGH.
Completeness of Descriptions of Repetitive Transcranial Magnetic Stimulation Intervention
Authors: Chantebel Romain , Chesneau Adélise , Tavernier Elsa , El-Hage Wissam , Caille Agnès 
Published: October 2018

Objectives
Repetitive transcranial magnetic stimulation (rTMS) is an innovative therapeutic option in major depressive disorder (MDD). A complete description of the procedure in reports of randomized controlled trials (RCTs) is a prerequisite for implementation of rTMS in clinical practice. The aim of this study was to evaluate the completeness of descriptions of the intervention in RCTs assessing rTMS in MDD.

Methods
We performed a systematic review of RCTs evaluating rTMS in MDD and published until August 2016. We searched PubMed, the Cochrane library, and PsycINFO to identify eligible trials. The completeness of the intervention description was evaluated by the use of an adapted-to-rTMS version of the Template for Intervention Description and Replication (TIDieR) checklist. We defined core items that are the most essential to be reported. Missing information was then sought from additional sources and by e-mailing authors.

Results
We identified 98 trials reporting 134 interventions. None of the interventions were completely described in the full text of the articles, even after searching additional sources. After contacting the authors, 14 (10.4%) of 134 interventions were completely described. The core items were completely described in 74 (55.2%) of 134 interventions after contacting the authors.

Conclusions
We found that rTMS interventions delivered in RCTs are incompletely reported, which prevents their adequate implementation in clinical practice and accurate interpretation of their efficacy. We encourage authors, editors, and reviewers to use the existing reporting guidelines and specifically the TIDieR checklist when describing the intervention. We provide an adapted-to-rTMS TIDieR checklist that could help in the reporting of future trials.
Wide-area all-optical neurophysiology in acute brain slices
Authors: Farhi Samouil L. , Parot Vicente J. , Grama Abhinav , Yamagata Masahito , Abdelfattah Ahmed S. , Adam Yoav , Lou Shan , Jun Kim Jeong , Campbell Robert E. , Cox David D. , Cohen Adam E. 
Published: October 2018

AbstractOptical tools for simultaneous perturbation and measurement of neural activity open the possibility of mapping neural function over wide areas of brain tissue. However, spectral overlap of actuators and reporters presents a challenge for their simultaneous use, and optical scattering and out-of-focus fluorescence in tissue degrade resolution. To minimize optical crosstalk, we combined an optimized variant (eTsChR) of the most blue-shifted channelrhodopsin reported to-date with a nuclear-localized red-shifted Ca2+ indicator, H2B-jRGECO1a. To perform wide-area optically sectioned imaging in tissue, we designed a structured illumination technique that uses Hadamard matrices to encode spatial information. By combining these molecular and optical approaches we made wide-area maps, spanning cortex and striatum, of the effects of antiepileptic drugs on neural excitability and on the effects of AMPA and NMDA receptor blockers on functional connectivity. Together, these tools provide a powerful capability for wide-area mapping of neuronal excitability and functional connectivity in acute brain slices.
LPM: a latent probit model to characterize the relationship among complex traits using summary statistics from multiple GWASs and functional annotations
Authors: Ming Jingsi , Wang Tao , Yang Can 
Published: October 2018

AbstractMuch effort has been made toward understanding the genetic architecture of complex traits and diseases. Recent results from genome-wide association studies (GWASs) suggest the importance of regulatory genetic effects and pervasive pleiotropy among complex traits. In this study, we propose a unified statistical approach, aiming to characterize relationship among complex traits, and prioritize risk variants by leveraging regulatory information collected in functional annotations. Specifically, we consider a latent probit model (LPM) to integrate summary-level GWAS data and functional annotations. The developed computational framework not only makes LPM scalable to hundreds of annotations and phenotypes, but also ensures its statistically guaranteed accuracy. Through comprehensive simulation studies, we evaluated LPM’s performance and compared it with related methods. Then we applied it to analyze 44 GWASs with nine genic category annotations and 127 cell-type specific functional annotations. The results demonstrate the benefits of LPM and gain insights of genetic architecture of complex traits. The LPM package is available athttps://github.com/mingjingsi/LPM.
Cellular determinants of metabolite concentration ranges
Authors: Eloundou-Mbebi Jeanne M. O. , Küken Anika , Basler Georg , Nikoloski Zoran 
Published: October 2018

AbstractCellular functions are shaped by reaction networks whose dynamics are determined by the concentrations of underlying components. However, cellular mechanisms ensuring that a component’s concentration resides in a given range remain elusive. We present network properties which suffice to identify components whose concentration ranges can be efficiently computed in mass-action metabolic networks. We show that the derived ranges are in excellent agreement with simulations from a detailed kinetic metabolic model of Escherichia coli. We demonstrate that the approach can be used with genome-scale metabolic models to arrive at predictions concordant with measurements from Escherichia coli under different growth scenarios. By application to 14 genome-scale metabolic models from diverse species, our approach specifies the cellular determinants of concentration ranges that can be effectively employed to make predictions for a variety of biotechnological and medical applications.Author SummaryWe present a computational approach for inferring concentration ranges from genome-scale metabolic models. The approach specifies a determinant and molecular mechanism underling facile control of concentration ranges for components in large-scale cellular networks. Most importantly, the predictions about concentration ranges do not require knowledge of kinetic parameters (which are difficult to specify at a genome scale), provided measurements of concentrations in a reference state. The approach assumes that reaction rates follow the mass action law used in the derivations of other types of kinetics. We apply the approach with large-scale kinetic and stoichiometric metabolic models of organisms from different kingdoms of life to show that we can identify a proportion of metabolites to which our approach is applicable. By challenging the predictions of concentration ranges in the genome-scale metabolic network of E. coli with real-world data sets, we further demonstrate the prediction power and limitations of the approach.
AMPK signaling regulates expression of urea cycle enzymes in response to changes in dietary protein intake
Authors: Heibel Sandra Kirsch , McGuire Peter J , Haskins Nantaporn , Majumdar Himani Datta , Rayavarapu Sree , Nagaraju Kanneboyina , Hathout Yetrib , Brown Kristy , Tuchman Mendel , Caldovic Ljubica 
Published: October 2018

AbstractAbundance of urea cycle enzymes in the liver is regulated by the dietary protein intake. Although urea cycle enzyme levels rise in response to a high protein diet, signaling networks that sense dietary protein intake and trigger changes in expression of urea cycle genes have not been identified. The aim of this study was to identify signaling pathway(s) that respond to changes in protein intake and regulate expression of urea cycle genes in mice and human hepatocytes. Mice were adapted to either control or high (HP) protein diets followed by isolation of liver protein and mRNA and integrated analysis of the proteomic and transcriptome profiles. HP diet led to increased expression of mRNA and enzymes in amino acid degradation pathways, and decreased expression of mRNA and enzymes in carbohydrate and fat metabolism, which implicated AMPK as a possible regulator. Primary human hepatocytes, treated with AICAR an activator of AMPK, were used to test whether AMPK regulates expression of urea cycle genes. The abundance ofCPS1andOTCmRNA increased in hepatocytes treated with AICAR, which supports a role for AMPK signaling in regulation of the urea cycle. Because AMPK is either a target of drugs used to treat type-2 diabetes, these drugs might increase the expression of urea cycle enzymes in patients with urea cycle disorders, which could be the basis of a new therapeutic approach.Author summaryIntegrated analysis of transcriptional and proteomic profiles of the liver tissue from mice fed different protein content diets revealed that AMPK signaling pathway regulates expression of urea cycle enzymes.
Existence and implications of population variance structure
Authors: Musharoff Shaila , Park Danny , Dahl Andy , Galanter Joshua , Liu Xuanyao , Huntsman Scott , Eng Celeste , Burchard Esteban G. , Ayroles Julien F. , Zaitlen Noah 
Published: October 2018

AbstractIdentifying the genetic and environmental factors underlying phenotypic differences between populations is fundamental to multiple research communities. To date, studies have focused on the relationship between population and phenotypic mean. Here we consider the relationship between population and phenotypic variance, i.e., “population variance structure.” In addition to gene-gene and gene-environment interaction, we show that population variance structure is a direct consequence of natural selection. We develop the ancestry double generalized linear model (ADGLM), a statistical framework to jointly model population mean and variance effects. We apply ADGLM to several deeply phenotyped datasets and observe ancestry-variance associations with 12 of 44 tested traits in ~113K British individuals and 3 of 14 tested traits in ~3K Mexican, Puerto Rican, and African-American individuals. We show through extensive simulations that population variance structure can both bias and reduce the power of genetic association studies, even when principal components or linear mixed models are used. ADGLM corrects this bias and improves power relative to previous methods in both simulated and real datasets. Additionally, ADGLM identifies 17 novel genotype-variance associations across six phenotypes.
Mcidas mutant mice reveal a two-step process for the specification and differentiation of multiciliated cells in mammals
Authors: Lu Hao , Anujan Priyanka , Zhou Feng , Zhang Yiliu , Ling Chong Yan , Bingle Colin D. , Roy Sudipto 
Published: October 2018

ABSTRACTMotile cilia on multiciliated cells (MCCs) function in fluid clearance over epithelia. Studies with Xenopus embryos and patients with the congenital respiratory disorder reduced generation of multiple motile cilia, have implicated the nuclear protein MCIDAS (MCI), in the transcriptional regulation of MCC specification and differentiation. Recently, a paralogous protein, GMNC, was also shown to be required for MCC formation. Surprisingly, and in contrast to the presently held view, we find that Mci mutant mice can specify MCC precursors. However, these precursors cannot produce multiple basal bodies, and mature into single ciliated cells. We show that MCI is required specifically to induce deuterosome pathway components for the production of multiple basal bodies. Moreover, GMNC and MCI associate differentially with the cell-cycle regulators E2F4 and E2F5, which enables them to activate distinct sets of target genes (ciliary transcription factor genes versus genes for basal body generation). Our data establish a previously unrecognized two-step model for MCC development: GMNC functions in the initial step for MCC precursor specification. GMNC induces Mci expression, which then drives the second step of basal body production for multiciliation.SUMMARY STATEMENTWe show how two GEMININ family proteins function in mammalian multiciliated cell development: GMNC regulates precursor specification and MCIDAS induces multiple basal body formation for multiciliation.
Estimating Residue-Specific Accuracies of Protein Structure Models Using Molecular Dynamics Simulations
Authors: Hu Jing-Hao , Xun Sang-Ni , Wu Hao-Nan , Wu Yun-Dong , Jiang Fan 
Published: October 2018

ABSTRACTEstimating the accuracy of a structure model is very crucial to promote the usefulness of protein structure prediction methods. Currently, a vast majority of successful model quality assessment (or model accuracy estimation, MAE) methods are knowledge-based. Based on molecular dynamics (MD) simulation with a recently developed residue-specific force field (RSFF2), we develop a method for absolute MAE at per-residue level. Using a training set of 31 models and a test set of 24 models from different proteins, the MAE performance of our MD-based method can reach or even exceed state-of-the-art single-model MAE methods within a short simulation time (less than one nanosecond). In addition, a simple combination of knowledge-based method with the MD-based method can give more accurate MAE than any of the constituent methods.
Miniaturization and optimization of 384-well compatible metagenomic sequencing library preparation
Authors: Mayday Madeline Y , Khan Lillian M , Chow Eric D , Zinter Matt S , DeRisi Joseph L 
Published: October 2018

AbstractPreparation of high-quality sequencing libraries is a costly and time-consuming component of metagenomic next generation sequencing (mNGS). While the overall cost of sequencing has dropped significantly over recent years, the reagents needed to prepare sequencing samples are likely to become the dominant expense in the process. Furthermore, libraries prepared by hand are subject to human variability and needless waste due to limitations of manual pipetting volumes. Reduction of reaction volumes, combined with sub-microliter automated dispensing of reagents without consumable pipette tips, has the potential to provide significant advantages. Here, we describe the integration of several instruments, including the Labcyte Echo 525 acoustic liquid handler and the iSeq and NovaSeq Illumina sequencing platforms, to miniaturize and automate mNGS library preparation, significantly reducing the cost and the time required to prepare samples. Through the use of External RNA Controls Consortium (ERCC) spike-in RNAs, we demonstrated the fidelity of the miniaturized preparation to be equivalent to full volume reactions. Furthermore, detection of viral and microbial species from cell culture and patient samples was also maintained in the miniaturized libraries. For 384-well mNGS library preparations, we achieved a savings of over 80% in materials and reagents alone, and reduced preparation time by 90% compared to manual approaches, without compromising quality or representation within the library.
Dietary sulfate-driven and gut dysbiosis-triggered breast cancer-related gene upregulation
Authors: YanPingf CHEN , Tao LIAO , LiLi TAN , DongMei CHEN , Qin XU , JianPing Song , QingPing ZHEN 
Published: October 2018

AbstractBy gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.
jouvence, a new small nucleolar RNA required in the gut extends lifespan in Drosophila
Authors: Mellottée Lucille , Soulé Stéphanie , Arab Abdelkrim , Chen Chongjian , Martin Jean-René 
Published: October 2018

AbstractLongevity is influenced by various genetic and environmental factors, but the underlying mechanisms remain poorly understood. Here, we functionally characterise a new Drosophila small nucleolar RNA (snoRNA), named jouvence whose loss of function dramatically reduces lifespan. A transgene containing the genomic region of jouvence rescues the longevity in mutant, while its overexpression in wild-type flies increases lifespan. Jouvence is expressed in epithelial cells of the gut. Targeted expression of jouvence specifically in the enterocytes increases lifespan, indicating that its role in the control of longevity takes place in these cells. A transcriptomic analysis performed from the gut reveals that several genes are either up-or down-regulated in mutant indicating that the snoRNA-jouvence might be involved in transcriptional control. Finally, since snoRNAs are structurally and functionally well conserved throughout evolution, we identified putative jouvence orthologue in mammals including humans, suggesting that its function in longevity might be conserved through evolution.