bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome
Authors: Bélanger Catherine , Bérubé-Simard Félix-Antoine , Leduc Elizabeth , Bernas Guillaume , Campeau Philippe M. , Lalani Seema R. , Martin Donna M. , Bielas Stephanie , Moccia Amanda , Srivastava Anshika , Silversides David W. , Pilon Nicolas 
Published: January 2018

SignificanceA timely diagnosis is key for both survival and quality of life of children with CHARGE syndrome (coloboma, heart defects, atresia of choanae, retardation of growth/development, genital abnormalities, and ear anomalies). Such diagnosis is often difficult to establish, in part because many patients test negative for mutation ofCHD7, the only gene associated with this condition to date. Identifying additional CHARGE-associated genes would not only help resolve diagnosis issues but could also help in identifying common pathogenic mechanisms, which in turn could lead to desirable curative interventions for all patients. Here,FAM172Ais reported as a new candidate gene for CHARGE syndrome. This discovery has allowed us to reveal a molecular process that is dysregulated in bothCHD7mutation-positive and -negative cases, such defect being correctable in vitro with rapamycin.
Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation
Authors: Liu Chiu-Ping , Tsai Tsung-I. , Cheng Ting , Shivatare Vidya S. , Wu Chung-Yi , Wu Chung-Yi , Wong Chi-Huey 
Published: January 2018

Significance
The carbohydrate components of glycoproteins are known to affect the structure and function of glycoproteins, and thus it is important to develop effective tools to manipulate and optimize the glycan components of glycoproteins with therapeutic significance. This study demonstrates the discovery of endoglycosidases for the remodeling of glycans on Herceptin, a monoclonal antibody used in the treatment of breast cancer, to optimize its effector functions, especially the antibody-dependent cellular cytotoxicity (ADCC). In addition, a method has been developed for the expression of antibodies from yeast to enable the large-scale synthesis of antibodies for further manipulation of the glycan moiety, using endoglycosidases and stable transglycosylation donors to prepare a homogeneous glycoform with optimized effector functions.
Structure of the C1r–C1s interaction of the C1 complex of complement activation
Authors: Almitairi Jamal O. M. , Venkatraman Girija Umakhanth , Furze Christopher M. , Simpson-Gray Xanthe , Badakshi Farah , Marshall Jamie E. , Schwaeble Wilhelm J. , Mitchell Daniel A. , Moody Peter C. E. , Wallis Russell 
Published: January 2018

SignificanceC1 is a large complex that triggers the destruction of invading pathogens via lysis or by stimulation of innate and adaptive immune processes. It is composed of C1q, a protein with a bouquet-like architecture, together with a tetramer assembled from two copies each of the serine proteases C1r and C1s, which activate when C1q binds to a pathogen surface. Here we describe detailed structures that show how C1r and C1s interact via an extensive interface encompassing the N-terminal regions of both proteases. Our findings reveal how the protease tetramer is organized and suggest a mechanism for the assembly and activation of C1.
The Farm Economy: Future Research and Education Priorities
Authors: Featherstone Allen M 
Published: January 2018

AbstractResearch priorities for the U.S. farm economy include increasing the productivity and cost efficiency on current land resources while understanding production agriculture across the globe. Providing unbiased objective analysis to policymakers with regard to commodity programs, insurance markets, agricultural credit, and the production of bioenergy are important issues that directly affect not only the U.S. farm economy but other agricultural regions. The ability to manage risk, the increasing complexity of farm operations, the ability of the U.S. farm sector to be nimble to changes in individual and societal preferences, and the efficient discovery of information through efficient markets offer a wealth of research opportunities.
Long-Term Effects of an Intensive Lifestyle Intervention on Electrocardiographic Criteria for Left Ventricular Hypertrophy: The Look AHEAD Trial
Authors: Brinkley Tina E , Anderson Andrea , Soliman Elsayed Z , Bertoni Alain G , Greenway Frank , Knowler William C , Glasser Stephen P , Horton Edward S , Espeland Mark A ,   Look AHEAD Research Group
Published: January 2018

Abstract

BACKGROUND
Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker of subclinical cardiac damage and a strong predictor of cardiovascular disease (CVD) events. The prevalence of ECG-LVH is increased in obesity and type 2 diabetes; however, there are no data on the long-term effects of weight loss on ECG-LVH. The purpose of this study was to determine whether an intensive lifestyle intervention (ILI) reduces ECG-LVH in overweight and obese adults with type 2 diabetes.

METHODS
Data from 4,790 Look AHEAD participants (mean age: 58.8 ± 6.8 years, 63.2% White) who were randomized to a 10-year ILI (n = 2,406) or diabetes support and education (DSE, n = 2,384) were included. ECG-LVH defined by Cornell voltage criteria was assessed every 2 years. Longitudinal logistic regression analysis with generalized estimation equations and linear mixed models were used to compare the prevalence of ECG-LVH and changes in absolute Cornell voltage over time between intervention groups, with tests of interactions by sex, race/ethnicity, and baseline CVD status.

RESULTS
The prevalence of ECG-LVH at baseline was 5.2% in the DSE group and 5.0% in the ILI group (P = 0.74). Over a median 9.5 years of follow-up, prevalent ECG-LVH increased similarly in both groups (odds ratio: 1.02, 95% confidence interval: 0.83–1.25; group × time interaction, P = 0.49). Increases in Cornell voltage during follow-up were also similar between intervention groups (group × time interaction, P = 0.57). Intervention effects were generally similar between subgroups of interest.

CONCLUSIONS
The Look AHEAD long-term lifestyle intervention does not significantly lower ECG-LVH in overweight and obese adults with type 2 diabetes.

CLINICAL TRIALS REGISTRATION
Trial Number NCT00017953 (ClinicalTrials.gov)
Statistically Convex-Cocompact Actions of Groups with Contracting Elements
Authors: Yang Wen-yuan 
Published: January 2018

AbstractThis paper presents a study of the asymptotic geometry of groups with contracting elements, with emphasis on a subclass of statistically convex-cocompact (SCC) actions. The class of SCC actions includes relatively hyperbolic groups, CAT(0) groups with rank-1 elements, and mapping class groups acting on Teichmüller spaces, among others. We exploit an extension lemma to prove that a group with SCC actions contains large free sub-semigroups, has purely exponential growth, and contains a class of barrier-free sets with a growth-tight property. Our study produces new results and recovers existing ones for many interesting groups through a unified and elementary approach.
An Analysis of Adverse Events in the Rehabilitation Department: Using the Veterans Affairs Root Cause Analysis System
Authors: Hagley Gregory W , Mills Peter D , Shiner Brian , Hemphill Robin R 
Published: January 2018

AbstractBackgroundRoot cause analyses (RCA) are often completed in health care settings to determine causes of adverse events (AEs). RCAs result in action plans designed to mitigate future patient harm. National reviews of RCA reports have assessed the safety of numerous health care settings and suggested opportunities for improvement. However, few studies have assessed the safety of receiving care from physical therapists, occupational therapists, or speech and language pathology pathologists.ObjectiveThe objective of this study was to determine the types of AEs, root causes, and action plans for risk mitigation that exist within the disciplines of rehabilitation medicine.DesignThis study is a retrospective, cross-sectional review.MethodsA national search of the Veterans Health Administration RCA database was conducted to identify reports describing AEs associated with physical therapy, occupational therapy, or speech and language pathology services between 2009 and May 2016. Twenty-five reports met the inclusion requirements. The reports were classified by the event type, root cause, action plans, and strength of action plans.ResultsDelays in care (32.0%) and falls (28.0%) were the most common type of AE. Three AEs resulted in death. RCA teams identified deficits regarding policy and procedures as the most common root cause. Eighty-eight percent of RCA reports included strong or intermediate action plans to mitigate risk. Strong action plans included standardizing emergency terminology and implementing a dedicated line to call for an emergency response.LimitationsThese data are self-reported and only AEs that are scored as a safety assessment code 3 in the system receive a full RCA, so there are likely AEs that were not captured in this study. In addition, the RCA reports are deidentified and so do not include all patient characteristics. As the Veterans Health Administration system services mostly men, the data might not generalize to non–Veterans Health Administration systems with a different patient mix.ConclusionsCare provided by rehabilitation professionals is generally safe, but AEs do occur. Based on this RCA review, the safety of rehabilitation services can be improved by implementing strong practices to mitigate risk to patients. Checklists should be considered to aid timely decision making when initiating an emergency response.
Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil
Authors: Snow Samantha J , Cheng Wan-Yun , Henriquez Andres , Hodge Myles , Bass Virgina , Nelson Gail M , Carswell Gleta , Richards Judy E , Schladweiler Mette C , Ledbetter Allen D , Chorley Brian , Gowdy Kymberly M , Tong Haiyan , Kodavanti Urmila P 
Published: January 2018

Abstract
Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.
Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload*
Authors: Roubinian Nareg H. , Hendrickson Jeanne E. , Triulzi Darrell J. , Gottschall Jerome L. , Michalkiewicz Michael , Chowdhury Dhuly , Kor Daryl J. , Looney Mark R. , Matthay Michael A. , Kleinman Steven H. , Brambilla Donald , Murphy Edward L. 
Published: January 2018

Objectives:
Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload.

Design:
Case-control study.

Setting:
Four tertiary care hospitals.

Patients:
We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity.

Interventions:
None.

Measurements and Main Results:
Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion—the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables.

Conclusions:
Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.
Speed of Language Comprehension at 18 Months Old Predicts School-Relevant Outcomes at 54 Months Old in Children Born Preterm
Authors: Marchman Virginia A. , Loi Elizabeth C. , Adams Katherine A. , Ashland Melanie , Fernald Anne , Feldman Heidi M. 
Published: January 2018

ABSTRACT:

Objective:
Identifying which preterm (PT) children are at increased risk of language and learning differences increases opportunities for participation in interventions that improve outcomes. Speed in spoken language comprehension at early stages of language development requires information processing skills that may form the foundation for later language and school-relevant skills. In children born full-term, speed of comprehending words in an eye-tracking task at 2 years old predicted language and nonverbal cognition at 8 years old. Here, we explore the extent to which speed of language comprehension at 1.5 years old predicts both verbal and nonverbal outcomes at 4.5 years old in children born PT.

Method:
Participants were children born PT (n = 47; ≤32 weeks gestation). Children were tested in the “looking-while-listening” task at 18 months old, adjusted for prematurity, to generate a measure of speed of language comprehension. Parent report and direct assessments of language were also administered. Children were later retested on a test battery of school-relevant skills at 4.5 years old.

Results:
Speed of language comprehension at 18 months old predicted significant unique variance (12%–31%) in receptive vocabulary, global language abilities, and nonverbal intelligence quotient (IQ) at 4.5 years, controlling for socioeconomic status, gestational age, and medical complications of PT birth. Speed of language comprehension remained uniquely predictive (5%–12%) when also controlling for children's language skills at 18 months old.

Conclusion:
Individual differences in speed of spoken language comprehension may serve as a marker for neuropsychological processes that are critical for the development of school-relevant linguistic skills and nonverbal IQ in children born PT.
Femtosecond Laser-Assisted Ipsilateral Rotational Lamellar Autokeratoplasty
Authors: Cassagne Myriam , Soler Vincent , Malecaze François , Fournié Pierre 
Published: January 2018

Purpose:
To describe the surgical technique and report the outcomes of 2 patients treated with femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty in central corneal scars.

Methods:
The corneal scar depth was mapped using preoperative optical coherence tomography. An eccentric lamellar lenticule was cut with a femtosecond laser and rotated to decenter corneal opacity and free the pupil area in 2 patients with nonprogressive central corneal scars. The surgical plan was set after simulating lenticule rotation with a digital corneal image and computer software.

Results:
In both cases, the corneal scar was decentered inferiorly, out of the pupillary area, with increased postoperative visual acuity but visual outcome limitations secondary to corneal irregularities and residual deep opacity.

Conclusions:
Femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty is effective for shifting central corneal opacities and can be considered in appropriate cases.
Social Vulnerability in Congenital Syphilis Case Mothers: Qualitative Assessment of Cases in Indiana, 2014 to 2016
Authors: DiOrio Dawne , Kroeger Karen , Ross Amara 
Published: January 2018

BackgroundCongenital syphilis occurs when a pregnant woman with syphilis is not diagnosed or treated and the infection is passed in utero, causing severe infant morbidity and mortality. Congenital syphilis is easily prevented if women receive timely and adequate prenatal care. Cases of congenital syphilis are considered indicators of problems in the safety net. However, maternal social and behavioral factors can impede women's care, even when providers follow guidelines.MethodsWe reviewed case interviews and maternal records for 23 congenital syphilis cases reported to the Centers for Disease Control and Prevention from Indiana between 2014 and 2016. We used qualitative methods to analyze narrative notes from maternal interviews to learn more about factors that potentially contributed to congenital syphilis cases.ResultsAll providers followed Centers for Disease Control and Prevention and state recommendations for screening and treatment for pregnant women with syphilis. Twenty-one of 23 women had health insurance. The number of prenatal care visits women had was suboptimal; more than one third of women had no prenatal care. Nearly one third of women's only risk factor was sex with a primary male sex partner. The majority of women suffered social vulnerabilities, including homelessness, substance abuse, and incarceration.ConclusionsDespite provider adherence to guidelines and health insurance availability, some pregnant women with syphilis are unlikely to receive timely diagnosis and treatment. Pregnant women at high risk for syphilis may need additional social and material support to prevent a congenital syphilis case. Additional efforts are needed to reach the male partners of vulnerable females with syphilis.
Erythropoietin in Treatment of Methanol Optic Neuropathy
Authors: Pakdel Farzad , Sanjari Mostafa S. , Naderi Asieh , Pirmarzdashti Niloofar , Haghighi Anousheh , Kashkouli Mohsen B. 
Published: January 2018

Background:
Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy.

Methods:
In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA.

Results:
Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90–0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90–0.00 logMAR). VA significantly increased in the last follow-up examination (P < 0.0001). Age and time to EPO treatment after methanol ingestion were not significantly related to final VA. No ocular or systemic complications occurred in our patient cohort.

Conclusions:
Intravenous EPO appears to improve VA in patients with methanol optic neuropathy and may represent a promising treatment for this disorder.
Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons
Authors: Yuan Yuan , Xie Shirley , Darnell Jennifer C. , Darnell Andrew J. , Saito Yuhki , Phatnani Hemali , Murphy Elisabeth , Zhang Chaolin , Maniatis Tom , Darnell Robert B. 
Published: January 2018

AbstractBackgroundAlternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system (CNS). This is believed to involve differential regulation of RNA processing in various cell types. However,in vivostudy of cell-type specific post-transcriptional regulation has been a challenge. Here, we developed a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons (MNs).ResultsWe developed a means of undertaking MN-specific CLIP to explore MN-specific protein-RNA interactions relative to studies of the whole spinal cord. This allowed us to pinpoint differential RNA regulation specific to MNs, revealing major role for NOVA in regulating cytoskeleton interactions in MNs. In particular, NOVA specifically promotes the palmitoylated isoform of a cytoskeleton protein Septin 8 in MNs, which enhances dendritic arborization.ConclusionsOur study demonstrates that cell type-specific RNA regulation is important for fine-tuning motoneuron physiology, and highlights the value of defining RNA processing regulation at single cell type resolution.