bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Preconception Substance Use Associated With Unplanned or Poorly Timed Pregnancy?
Authors: Lundsberg Lisbet S. , Peglow Stephanie , Qasba Neena , Yonkers Kimberly A. , Gariepy Aileen M. 
Published: March 2018

Objective:
Unplanned and poorly timed pregnancies are associated with adverse maternal and neonatal outcomes. Further understanding of preconception substance use with unplanned and poorly timed pregnancy is warranted.

Methods:
Data were analyzed from a prospective study enrolling women early in pregnancy. Preconception tobacco, alcohol, marijuana, opioid, and cocaine use was ascertained. Participants reported whether their current pregnancy was planned and whether it was a good time to be pregnant. Multivariable logistic regression modeling generated risk estimates for preconception substance use, and pregnancy planning and timing, adjusting for confounders.

Results:
Overall, 37.2% reported unplanned pregnancy, 13.0% poorly timed pregnancy, and 39.0% reported either unplanned and/or poorly timed pregnancy. Within 6 months preconception, one-fifth (20.2%) reported nicotine cigarette use. In the month before conception, 71.8% reported alcohol use, 6.5% marijuana, and approximately 1% opioid or cocaine use. Multivariable analysis demonstrated preconception opioid use was associated with increased odds of poorly timed pregnancy (odds ratio [OR] 2.87, 95% confidence interval [CI] 1.03–7.99). Binge drinking the month before conception was associated with increased odds of poorly timed pregnancy and unplanned pregnancy (OR 1.75, 95% CI 1.01–3.05; and OR 1.68, 95% CI 1.01–2.79, respectively). Marijuana use 2 to 3 times in the month preconception was associated with increased risk of unplanned pregnancy, and unplanned and/or poorly timed pregnancy compared with nonuse (OR 1.78, 95% CI 1.03–3.08; and OR 1.79, 95% CI 1.01–3.17, respectively). Preconception tobacco or cocaine use was not associated with unplanned or poorly timed pregnancy following adjustment.

Conclusions:
We demonstrate increased odds of unplanned or poorly timed pregnancy among women with preconception binge drinking, marijuana use, and opioid use; however, no association is observed with other substances after multivariable adjustment, including tobacco. Further research to evaluate high-level preconception substance use and substance disorders with pregnancy planning and timing is warranted. Focused efforts optimizing preconception health behaviors and reducing risk of unplanned or poorly timed pregnancy are needed.
Diagnostic Abilities of the Optical Microangiography Parameters of the 3×3 mm and 6×6 mm Macular Scans in Glaucoma
Authors: Rao Harsha L. , Riyazuddin Mohammed , Dasari Srilakshmi , Puttaiah Narendra K. , Pradhan Zia S. , Weinreb Robert N. , Mansouri Kaweh , Webers Carroll A.B. 
Published: March 2018

Purpose:
To evaluate the diagnostic abilities of macular vessel length and perfusion densities measured with optical microangiography (OMAG) over a 3×3 mm and a 6×6 mm region, and to compare these with macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with primary open-angle glaucoma (POAG).

Methods:
In a cross-sectional study, 96 eyes of 57 control subjects and 88 eyes of 57 POAG patients underwent macular imaging with optical coherence tomography. Area under receiver operating characteristic curves (AUC) and sensitivities at 90% specificity of OMAG and GCIPL parameters were evaluated.

Results:
Most OMAG parameters of the 3×3 mm macular scan and all inner sector parameters of the 6×6 mm scan were similar (P>0.05) in the POAG and control eyes. All outer sector OMAG parameters of the 6×6 mm scan were significantly less (P<0.05) in the POAG eyes. AUC and sensitivity at 90% specificity of the best parameter of the 3×3 mm OMAG scan (inner temporal vessel length density; 0.65% and 26%, respectively) were statistically similar (P>0.05) to that of the 6×6 mm scan (outer inferior vessel length density; 0.72% and 30%, respectively). AUC and sensitivity of the best GCIPL thickness parameter (inferotemporal GCIPL thickness, 0.84% and 67%) were significantly better (P<0.05) than that of the vessel length densities.

Conclusions:
The outer sector measurements of the 6×6 mm macular OMAG scans seem to be better than the inner sector measurements in diagnosing glaucoma. The GCIPL thickness measurements were significantly better than all macular OMAG parameters in diagnosing glaucoma.
Preterm Children Have Higher Risk Than Full-term Children of Invasive Pneumococcal Disease During the First 2 Years of Life
Authors: Riise Øystein Rolandsen , Laake Ida , Vestrheim Didrik , Winje Brita Askeland , Moster Dag , Storsæter Jann 
Published: March 2018

Background:A few previous studies have reported an increased risk of invasive pneumococcal disease (IPD) in children born preterm, but this has not been investigated in a cohort study. The impact of 7-valent pneumococcal conjugate vaccine (PCV7) on IPD incidence rates in preterm children is unknown.Methods:Data from the Medical Birth Registry of Norway (2002–2010) were linked to other national registries. In total, 628,138 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression.Results:We identified 411 cases of IPD. We observed higher rates of IPD in preterm than in full-term children for the intervals 0–23, 0–5 and 6–23 months of age, IRRs = 1.83 (95 % CI: 1.36–2.47), 2.95 (95% CI: 1.44–6.06) and 1.69 (95% CI: 1.22–2.34), respectively. The risk for IPD was reduced in the PCV7-period (2007–2010) compared with that of the pre PCV7-period (2002–2005) for children 6–23 months of age, IRRs = 0.20 (95% CI: 0.08–0.53) for preterm children and 0.28 (95% CI: 0.21–0.38) for full-term children, but not for those 0–5 months of age, IRRs = 1.94 (95% CI: 0.48–7.80) and 0.71 (95% CI: 0.38–1.33).Conclusions:Preterm children had an increased risk of IPD. After introduction of PCV7, the rate of IPD was reduced among preterm and full-term children from 6 months of age.
Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection
Authors: Yakoot Mostafa , El‐Shabrawi Mortada H. , AbdElgawad Manal M. , Mahfouz Aml A. , Helmy Sherine , Abdo Alaa M. , El‐Khayat Hisham R. 
Published: March 2018

ABSTRACTObjectives:Dual sofosbuvir/daclatasvir (SOF/DCV) therapy is currently recommended by the European Association for Study of Liver (EASL) as an option for the treatment of chronic hepatitis C virus (HCV) infection in adults for all genotypes; however, it is still not considered for patients younger than 18 years old. We aimed to test safety and efficacy of SOF/DCV in adolescent patients 12 to 17 years old with chronic HCV, genotype 4 infection.Methods:We conducted a prospective, uncontrolled, open‐label multicenter study. A total of 30 chronic HCV‐infected adolescents, aged from 12 to 17 years old were included and treated with dual SOF/DCV for 12 weeks. Patients were monitored throughout the treatment and follow‐up period for safety and efficacy outcome measures including the sustained virologic response 12 (SVR12) rate.Results:The intention‐to‐treat (ITT) SVR12 rate was 29 of 30 (96.7%; 95% confidence interval [CI] 83.3%–99.4%). The only patient who did not achieve SVR12 was lost to follow‐up after showing viral negativity at the end of treatment (EOT) visit. Whereas all the remaining 29 patients (100%, 95% CI 88.3%–100%) who completed the follow‐up visits achieved SVR12. All patients showed normalized liver enzymes with normal hematological, liver and renal function tests at the end of the study. No fatalities or treatment‐emergent serious or severe adverse events were reported throughout the study.Conclusions:SOF/DCV combined therapy could be a safe and effective treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4 infection. (See Video, Supplemental Digital Content, http://links.lww.com/MPG/B348).
Skin Laceration in Collagenase Clostridium histolyticum Treatment for Dupuytren's Contracture
Authors: Sanjuan-Cervero Rafael , Carrera-Hueso Francisco J. , Oliver-Mengual Salvador , Ramon-Barrios Maria A. , Peimer Clayton A. , Fikri-Benbrahim Narjis 
Published: March 2018

BACKGROUND:
Dupuytren's contracture produces a progressive flexion contracture of the affected fingers. Collagenase Clostridium histolyticum produces breakdown of the cord in the hand and/or finger(s) that tightens as a result of the disease creating a contracture, allowing manual traction and cord rupture. One of the side effects is spontaneous skin laceration when the finger is extended.

OBJECTIVES:
To evaluate the development of skin lacerations in Dupuytren's contracture treated with collagenase Clostridium histolyticum, to determine predisposing factors, and evaluate the effectiveness of 2 different treatments (antiseptic and non–antiseptic dressings).

PARTICIPANTS:
Included 157 patients diagnosed with Dupuytren's contracture and treated with collagenase Clostridium histolyticum.

METHODS:
Analysis of variables and logistic regression model were applied to determine their possible relationship with skin lacerations. The effectiveness of the type of treatment used was evaluated by comparing the amount of time required for healing.

RESULTS:
Skin lacerations were present in 33.1% (n = 52) of patients, with an average laceration length of 1.12 (SD: 0.70) cm. Characteristics that were significant predisposing factors for lacerations were disease bilateralism (p = .002), previous surgical intervention (p = .003), and initial matacarpophalangeal joint contracture (p < .001). Worse initial contracture (Z = 5.94; p < .001) had a greater risk of laceration as did those who had prior hand surgery, or whose little finger was affected. Average treatment length of healing was 11.24 days (SD: 8.13). All wounds healed successfully. There were no significant differences (p = .511) in healing between different dressings evaluated.

CONCLUSIONS:
Skin lacerations as a consequence of treating Dupuytren's contracture with collagenase Clostridium histolyticum occur often and are moderately serious. For all cases, evolution is satisfactory in less than 2 weeks, and the type of treatment does not appear to make any difference in healing time.
Postmortem Cholesterol Levels in Peripheral Nerve Tissue
Authors: Vacchiano Giuseppe , Luna Maldonado Aurelio , Matas Ros Maria , Fiorenza Elisa , Silvestre Angela , Simonetti Biagio , Pieri Maria 
Published: March 2018

AbstractThe study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times—from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right(R2= 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left(R2= 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.
Obesity blocks oligodendrocyte precursor cell differentiation and impedes repair after white matter stroke
Authors: Xiao Guanxi , Burguet Jasmine , Kawaguchi Riki , Havton Leif A. , Hinman Jason D. 
Published: March 2018

AbstractObesity is a growing public health problem that increases rates of white matter atrophy and increases the likelihood of ischemic lesions within white matter. However, the cellular and molecular mechanisms that regulate these changes are unknown. We hypothesized that obesity may alter oligodendrocytes and myelin priming white matter for worsening injury and repair responses after ischemia. C57Bl/6 mice fed a high fat diet (60% kcal from fat) show increased numbers of oligodendrocyte precursor cells (OPCs), decreased myelin thickness with elevated g-ratios, and shorter paranodal axonal segments, indicating accelerated myelin turnover. Fate mapping of OPCs inPDGFRα-CreERT;Rpl22tm1.1Psammice demonstrated that OPC differentiation rates are enhanced by obesity. Gene expression analyses using a novel oligodendrocyte staging assay demonstrated OPC differentiation is blocked by obesity in between the pre-myelinating and myelinating stage. Using a model of subcortical white matter stroke, the number of stroke-responsive OPCs in obese mice was increased after stroke. At early time points after ischemic white matter stroke, spatial mapping of stroke-responsive OPCs indicates that obesity leads to increased OPCs at the edge of ischemic white matter lesions. At later time points, obesity results in increased OPCs within the ischemic lesion while reducing the number of GST-π-positive mature oligodendrocytes in the lesion core. These data indicate that obesity disrupts normal white matter biology by blocking oligodendrocyte differentiation, leads to an exaggerated response of OPCs to white matter ischemia, and limits remyelination after stroke.Significance StatementObesity is a growing public health crisis that specifically increases the development of white matter lesions and silent brain infarcts. This relationship implies a direct cellular effect on white matter yet direct evidence is limited. We modeled diet-induced obesity in mice and studied the effect on oligodendrocyte biology and the response to focal white matter stroke. Adult-onset obesity results in thinner myelin, compromised axonal microdomain structure, and blocks the differentiation of OPCs, leaving the white matter with increased numbers of OPCs. After focal white matter stroke in obese mice, the early OPC response to stroke is exaggerated while late reparative OPC differentiation is blocked. These results suggest that obesity specifically blocks OPC differentiation with consequence on brain repair after stroke.
A naturally-occurring dominant-negative competitor of Keap1 against its inhibition of Nrf2
Authors: Qiu Lu , Wang Meng , Zhu Yuping , Xiang Yuancai , Zhang Yiguo 
Published: March 2018

ABSTRACTTranscription factor Nrf2 is a master regulator of antioxidant and/or electrophile response elements (AREs/EpREs)driven genes involved in homeostasis, detoxification and adaptation to various stresses. The cytoprotective activity of Nrf2, though being oppositely involved in both cancer prevention and progression, is critically controlled by Keap1 (Kelch-like ECH-associated protein 1) as an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, that is a key sensor for oxidative and electrophilic stresses. Now, we first report a novel naturally-occurring mutant of Keap1, designated Keap1ΔC, which lacks most of its C-terminal Nrf2-interacting domain essential for inhibition of the CNC-bZIP factor. This mutant Keap1ΔC is yielded by translation from an alternatively mRNA-spliced variant lacking the fourth and fifth exons, but their coding sequences are retained in the wild-type Keap1 locus (with no genomic deletions). Although this variant was found primarily in the human highly-metastatic hepatoma (MHCC97H) cells, it was widely expressed at very lower levels in all other cell lines examined. No matter whether Keap1ΔC retains less or no ability to inhibit Nrf2, it functions as a dominant-negative competitor of Keap1 against its inhibition of Nrf2-target genes. This is due to its antagonist effect on Keap1-mediated turnover of Nrf2 protein.
Cross-species functional modules link proteostasis to human normal aging
Authors: Komljenovic Andrea , Li Hao , Sorrentino Vincenzo , Kutalik Zoltán , Auwerx Johan , Robinson-Rechavi Marc 
Published: March 2018

AbstractThe evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan, such as caloric restriction, suggests that aging-related research in model organisms is directly relevant to human aging. Since human lifespan is a complex trait, a systems-level approach will contribute to a more comprehensive understanding of the underlying aging landscape. Here, we integrate evolutionary and functional information of normal aging across human and model organisms at three levels: gene-level, process-level, and network-level. We identify evolutionarily conserved modules of normal aging across diverse taxa, and importantly, we show that proteostasis involvement is conserved in healthy aging. Additionally, we find that mechanisms related to protein quality control network are enriched in 22 age-related genome-wide association studies (GWAS) and are associated to caloric restriction. These results demonstrate that a systems-level approach, combined with evolutionary conservation, allows the detection of candidate aging genes and pathways relevant to human normal aging.HighlightsNormal aging is evolutionarily conserved at the module level.Core pathways in healthy aging are related to mechanisms of protein quality networkThe evolutionarily conserved pathways of healthy aging react to caloric restriction.Our integrative approach identifies evolutionarily conserved functional modules and showed enrichment in several age-related GWAS studies.
Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia
Authors: Curtis David 
Published: March 2018

AbstractBackgroundThe polygenic risk score (PRS) for schizophrenia, derived from very large numbers of weakly associated genetic markers, has been repeatedly shown to be robustly associated with schizophrenia in independent samples and also with other diseases and traits.AimsTo explore the distribution of the schizophrenia PRS in subjects of different ancestry.MethodThe schizophrenia PRS derived from the large genome-wide association study carried out by the Psychiatric Genetics Consortium was calculated using the downloaded genotypes of HapMap subjects from eleven different ancestral groups. It was also calculated using downloaded genotypes of European schizophrenia cases and controls from the CommonMind Consortium.ResultsThe PRS for schizophrenia varied significantly between ancestral groups (p < 2*10−16) and was much higher in African than European HapMap subjects. The mean difference between these groups was ten times as high as the mean difference between European schizophrenia cases and controls. The distributions of scores for African and European subjects hardly overlapped.ConclusionsThe PRS cannot be regarded as simply a measure of the polygenic contribution to risk of schizophrenia and clearly contains a strong ancestry component. It is possible that this could be controlled for to some extent by incorporating principal components as covariates but doubts remain as to how it should be interpreted. The PRS derived from European subjects cannot be applied to non-Europeans, limiting its potential usefulness and raising issues of inequity. Previous studies which have used the PRS should be re-examined in the light of these findings.Declaration of interestThe author declares he has no conflict of interest.
On the synchronized failure of global crop production
Authors: Mehrabi Zia , Ramankutty Navin 
Published: March 2018

AbstractMultiple breadbasket failure is a risk to global food security. However, there are no global analyses that have assessed if global food production has actually tended towards synchronized failure historically. We show that synchronization in production for major commodities such as maize and soy has declined in recent decades, but that increased synchrony, when present, has had marked destabilizing effects. Under the hypothetical case of a synchronized failure event, we estimate simultaneous global production losses for rice, wheat, soy and maize between −18% and −36%. Our results show that maintaining asynchrony in the food system and mitigating instability through food storage in good years, both require a central place in discussions of future food demand under mean climate change, population growth and consumption trends.
Ldb1 mediates trans enhancement in mammals
Authors: Monahan K. , Horta A. , Mumbay-Wafula A.M. , Li L. , Zhao Y. , Love P.E. , Lomvardas S. 
Published: March 2018

AbstractSingular olfactory receptor (OR) gene expression1,2 coincides with the formation of a multi-chromosomal enhancer hub that associates with the only transcribed OR allele in each cell3,4. This hub consists of converging transcriptional enhancers3, or “Greek Islands”, defined by stereotypic binding of Lhx2 and Ebf on a shared, composite DNA motif5. How this multi-chromosomal hub, or any other genomic compartment, assembles is unknown, and so is the significance of compartmentalization in transcription. Here, we report that LIM domain binding protein 1 (Ldb1), which is recruited by Lhx2 and Ebf to Greek Islands, promotes robust and specific trans interactions between these enhancers. In addition to disrupting Greek Island hubs, Ldb1 deletion also causes significant downregulation of OR transcription. Thus, our data provide insight to the formation of genomic compartments, confirm the essential role of interchromosomal interactions in OR gene choice, and establish trans enhancement as a mechanism for mammalian gene activation.
An unexpected contribution of lincRNA splicing to enhancer function
Authors: Tan Jennifer Y. , Biasini Adriano , Young Robert S. , Marques Ana C. 
Published: March 2018

ABSTRACTTranscription is common at active mammalian enhancers sometimes giving rise to stable and unidirectionally transcribed enhancer-associated long intergenic noncoding RNAs (elincRNAs). ElincRNA expression is associated with changes in neighboring gene product abundance and local chromosomal topology, suggesting that transcription at these loci contributes to gene expression regulation in cis. Despite the lack of evidence supporting sequence-dependent functions for most elincRNAs, splicing of these transcripts is unexpectedly common. Whether elincRNA splicing is a mere consequence of their cognate enhancer activity or if it directly impacts enhancer-associated cis-regulation remains unanswered.Here we show that elincRNAs are efficiently and rapidly spliced and that their processing rate is strongly associated with their cognate enhancer activity. This association is supported by: their enrichment in enhancer-specific chromatin signatures; elevated binding of co-transcriptional regulators, including CBP and p300; increased local intra-chromosomal DNA contacts; and strengthened cis-regulation on target gene expression. Using nucleotide polymorphisms at elincRNA splice sites, we found that elincRNA splicing enhances their transcription and directly impacts cis-regulatory function of their cognate enhancers. Importantly, up to 90% of human elincRNAs have nucleotide variants that are associated with both their splicing and the expression levels of their proximal genes.Our results highlight an unexpected contribution of elincRNA splicing to enhancer function.