bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Algorithm for Cholesteryl Ester Storage Disease
Authors: Lipiński Patryk , Ługowska Agnieszka , Zakharova Ekaterina Y. , Socha Piotr , Tylki‐Szymańska Anna 
Published: June 2018

ABSTRACTBackground:Lysosomal acid lipase deficiency (LAL‐D) is a rare autosomal recessive lysosomal lipid storage disorder that results in an early‐onset, severe, and lethal phenotype, known as Wolman disease, or a late‐onset, attenuated phenotype, cholesteryl ester storage disease (CESD). The aim of our study was to describe the clinical presentation of CESD, focusing on the first noted abnormalities in patients. A diagnostic algorithm of CESD was also proposed.Methods:This is an observational, 1‐center study of 19 Polish patients with late‐onset LAL‐D.Results:The mean age at which the first symptoms were reported was 4 years and 6 months. A mild hepatomegaly was the most common initial abnormality observed in all (100%) patients. Seven (37%) patients were noted to have mildly to moderately elevated serum transaminases. At the time of first hospitalization all (100%) patients presented with hepatomegaly, 15 (79%) patients presented with elevated serum transaminases and all (100%) patients had dyslipidemia. The mean age at the time of CESD diagnosis was 7 years and 2 months. Diagnoses were based on a deficient LAL activity in leukocytes (in all patients) and the LIPA gene mutations (in 47% of them). All the patients were carriers for the mutation c.894G>A in the LIPA gene. There was approximately a 3‐year delay from initial symptoms to final diagnosis.Conclusions:Hepatomegaly constitutes the most common presenting clinical sign of CESD. Hepatomegaly and dyslipidemia defined as elevated serum total and LDL cholesterol, elevated triglycerides and normal to low HDL cholesterol, comprises the most characteristic findings at CESD diagnosis.
Criticality of Maternal Complications During Childbirths
Authors: Guglielminotti Jean , Landau Ruth , Wong Cynthia A. , Li Guohua 
Published: June 2018

Background
The incidence of severe maternal morbidity is increasing in the United Sates. To improve maternal outcomes, three maternal complications have been selected for priority intervention based on their proportionate mortality and preventability: obstetric hemorrhage, severe hypertension, and venous thromboembolism. This approach excludes complications that are not associated with high mortality but significantly contribute to maternal morbidity. The aim of this study was to provide an alternative ranking of maternal complications requiring interventions using cost-based criticality analysis.

Methods
Discharge records indicating delivery hospitalizations, and 17 maternal complications were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes in the 2012 National Inpatient Sample, a 20% national representative sample of hospital discharge records from community hospitals. For each complication, criticality was calculated as the product of its incidence and severity. Severity was estimated using excess cost, the difference between the mean costs of discharges with and without the complication. Costs were calculated as the product of hospital charges and a cost-to-charge ratio and adjusted with a linear regression model. Complications were ranked based on criticality.

Results
The study sample included 734,865 delivery hospitalizations. At least one complication was recorded in 80,657 discharges (11.0%, 95% confidence interval = 10.9–11.1). The four highest-ranked critical complications were pre-eclampsia/eclampsia (criticality: $93), postpartum hemorrhage ($47), gestational hypertension ($34), and anesthesia-related complications ($5).

Conclusions
In addition to postpartum hemorrhage and severe hypertension, anesthesia-related complications and gestational hypertension may be new priority targets for interventions during delivery hospitalizations. Criticality analysis seems to be an alternative or complimentary approach for planning healthcare quality improvement programs.
Racial and Ethnic Differences in Viral Suppression Among HIV-Positive Women in Care
Authors: Nwangwu-Ike Ndidi , Frazier Emma L. , Crepaz Nicole , Tie Yunfeng , Sutton Madeline Y. 
Published: June 2018

Background:
Women with HIV diagnoses are less likely to be virally suppressed than men. Women of different racial/ethnic groups may be differentially affected by sociodemographic factors. We examined differences in viral suppression among women by race/ethnicity and associated variables to inform prevention interventions.

Methods:
We used data from the 2010–2014 cycles of the Medical Monitoring Project, a cross-sectional survey of HIV-positive adults in care. We limited analyses to black, Hispanic, and white women. We calculated weighted prevalences of recent viral suppression (undetectable or <200 copies/mL) and sustained viral suppression (consistent viral suppression during the past 12 months) among women by race/ethnicity. We computed adjusted prevalence differences (aPDs) and 95% confidence intervals (CIs) for viral suppression by racial/ethnic group, controlling for selected variables, including available social determinants of health variables.

Results:
Among women, 62.9% were black, 19.8% Hispanic, and 17.3% white. Overall, 74.3% had recent viral suppression, and 62.3% had sustained viral suppression. Compared with white women (79.7%, CI: 77.2 to 82.2), black (72.5%, CI: 70.3 to 74.7; PD: 7.2) and Hispanic (75.4%, CI: 72.6 to 78.3; PD: 4.3) women were less likely to have recent viral suppression. In multivariable analyses, after adjusting for antiretroviral therapy adherence, HIV disease stage, age, homelessness, and education, black–white aPDs remained significant for recent (aPD: 4.8, CI: 1.6 to 8.1) and sustained (aPD: 5.0, CI: 1.1 to 9.0) viral suppression.

Conclusion:
Viral suppression was suboptimal for all women, but more for black and Hispanic women. Differences between black, Hispanic, and white women may be partially due to antiretroviral therapy adherence, HIV disease stage, and social determinants of health factors.
Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand
Authors: Chintanaphol Michelle , Sacdalan Carlo , Chottanapund Suthat , Pinyakorn Suteeraporn , Buranapraditkun Supranee , Crowell Trevor A. , Kroon Eugene , Manasnayakorn Sopark , Chipman Jeffrey G. , Schacker Timothy W. , Michael Nelson , Phanuphak Nittaya , Spudich Serena S. , Colby Donn J. , Ananworanich Jintanat ,   on behalf of the RV254/SEARCH010 study groups
Published: June 2018

Introduction:
Latent HIV reservoirs are rapidly established in lymphoid tissues during acute HIV infection (AHI). Sampling these tissues provides important information about HIV pathogenesis. This period is associated with viral replication and immune activation that may affect procedure-related adverse events (AEs). We examined the safety and tolerability of inguinal lymph node (LN) biopsy in research participants with AHI in Bangkok, Thailand.

Methods:
Between 2013 and 2016, 67 AHI participants in the RV254/SEARCH010 study underwent at least one optional inguinal LN biopsy during AHI at the baseline visit and/or after antiretroviral therapy (median 48 weeks after antiretroviral therapy). Biopsy-related AEs were graded according to NIH Division of AIDS guidelines. Poisson regression was used to calculate incidence rate ratios and 95% confidence intervals to evaluate associations of demographic and HIV characteristics, procedure timing, and repetition with AE incidence.

Results:
Of the 67 participants, 97% were male with a median age of 26. Among 78 LN biopsies (39 at baseline and 39 at follow-up), 10 (12.8%) AEs were reported: 6 (7.7%) grade 1 and 4 (5.1%) grade 2. The AEs were biopsy-site discomfort (n = 8, 10.2%) and hematoma (n = 2, 2.6%). No factors were significantly associated with AE incidence. All biopsy-related AEs were transient and self-limited.

Conclusions:
Inguinal LN biopsies were safe and well tolerated in mostly Thai men with AHI. As LN biopsies become an integral part of HIV research, this study provides information to participants, researchers, and institutional review boards that these samples can be safely obtained.
Cotransmission of Malaria and HIV to Infants of Mothers Coinfected With Malaria and HIV in the HAART Era in Benin City, Nigeria
Authors: Sadoh Ayebo , Eki-Udoko Fidelis E. 
Published: June 2018

Introduction:Malaria and HIV are vertically transmitted to infants. In an era where specific interventions are available to reduce the burden of malaria in pregnancy and vertical transmission of HIV, we examined the transmission and cotransmission of HIV and malaria to infants of mothers coinfected with malaria and HIV.Methods:A cross-sectional analytic study performed on 101 HIV/malaria–coinfected mothers and their infants for whom DNA polymerase chain reaction results were available. Blood film for malaria parasites was performed on cord blood and peripheral blood on days 1, 3, and 7 in the newborns. Maternal peripheral blood film for malaria parasite was performed at delivery, and placental tissue was obtained for confirmation of placental malaria by histology. All infants received DNA polymerase chain reaction testing for HIV at 6–8 weeks of life.Results:Cotransmission of malaria and HIV occurred in 2 (1.98%) infants. Vertical transmission of HIV occurred in 7 (7%) babies, whereas congenital malaria was present in 32 (31.7%) babies. The transmission of HIV and presence of congenital malaria were not significantly associated with each otherP= 1.000. Of the 88 babies of mothers who commenced highly active antiretroviral treatment (HAART) before pregnancy, 5 (5.7^) had HIV, which was significantly less than 2 (40%) of 5 babies of mothers who commenced HAART during pregnancyP= 0.04.Conclusions:Among mothers coinfected with malaria and HIV, vertical transmission of malaria and HIV was not associated with each other. HAART reduces vertical transmission of HIV especially if started before pregnancy.
Diagnostic Value of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient in Assessment of the Activity of Crohn Disease: 1.5 or 3 T
Authors: Abd-El Khalek Abd-ALRazek Ahmed , Fahmy Dalia Monir 
Published: June 2018

Objective
The objective of this study is to evaluate the role of diffusion-weighted imaging (DWI) in assessment of the activity of Crohn disease (CD) and to explore differences between DWI in 3 T and 1.5 T.

Methods
Postcontrast magnetic resonance enterography with DWI of 72 patients with pathological proof of CD was retrospectively evaluated for restricted diffusion qualitatively and quantitavely in 3 T (n = 40) and 1.5 T (n = 32). Magnetic resonance activity score of 7 or higher was used as reference of activity.

Results
Fifty-five patients had active lesions. Diffusion-weighted imaging hyperintensity showed sensitivity (100%, 100%) and specificity (88.89%, 100%) in 1.5/3 T for activity assessment. Mean ± SD apparent diffusion coefficient for active lesions was 1.21 ± 0.42 and 1.28 ± 0.59 × 10−3 mm2/s in 1.5 and 3 T, respectively. The proposed cutoff values of 1.35 and 1.38 × 10−3 mm2/s in 1.5 and 3 T, respectively, had sensitivity (80%, 93%), specificity (100%, 90%), accuracy (88%, 93%), and no significant difference in accuracy between 1.5/3 T (P = 0.48).

Conclusions
Diffusion-weighted imaging hypersensitivity and apparent diffusion coefficient values accurately assessed the activity of CD. No significant statistical difference in diagnostic accuracy was detected between 1.5 and 3 T.
Single-Shot Coronary Quiescent-Interval Slice-Selective Magnetic Resonance Angiography Using Compressed Sensing: A Feasibility Study in Patients With Congenital Heart Disease
Authors: Shen Daming , Edelman Robert R. , Robinson Joshua D. , Haji-Valizadeh Hassan , Messina Marci , Giri Shivraman , Koktzoglou Ioannis , Rigsby Cynthia K. , Kim Daniel 
Published: June 2018

Objective
The aim of this study was to determine whether it is feasible to visualize the coronary origins in patients with congenital heart disease (CHD) using single-shot coronary quiescent-interval slice-selective (QISS) magnetic resonance angiography (MRA) with compressed sensing (CS).

Methods
This retrospective study leveraged a parent study, which aimed to compare breath-hold, 2.1-fold accelerated, 2-shot coronary QISS MRA and clinical standard contrast-enhanced (CE) MRA in 14 patients with CHD (mean age, 17.0 ± 8.6 years, 6 females and 8 males). We evaluated the feasibility of single-shot coronary QISS MRA by retrospectively undersampling the 2-shot data set by an additional factor of 2, performing CS reconstruction, and comparing the retrospectively derived single-shot QISS MRA to 2-shot coronary QISS MRA and clinical standard CE MRA. For quantitative analysis, structural similarity index and normalized root mean square error were calculated. For qualitative analysis, 2 experienced readers scored the conspicuity of coronary origins on a 5-point Likert scale (1 = nondiagnostic, 2 = poor, 3 = clinically acceptable, 4 = good, 5 = excellent).

Results
Compared with 2-shot QISS, single-shot QISS produced normalized root mean square error of 5.8% ± 0.8% and structural similarity index of 95.4% ± 1.6%, suggesting high data fidelity by CS reconstruction. Compared with the mean conspicuity scores for clinical CE MRA (4.2 ± 0.5 and 4.1 ± 0.6 for right and left coronary origins, respectively), the mean conspicuity scores were not significantly different (P > 0.3) for 2-shot QISS (4.4 ± 0.9 and 4.2 ± 1.1, respectively) and single-shot QISS with CS (4.3 ± 1.1 and 3.8 ± 1.3, respectively) and deemed clinically acceptable to good (scores ≥3.0).

Conclusions
This study shows that it is feasible to visualize the coronary origins in patients with CHD with clinically acceptable to good image quality using single-shot coronary QISS MRA with CS.
Distinct isoforms of Nrf1 diversely regulate different subsets of its cognate target genes
Authors: Wang Meng , Qiu Lu , Ru Xufang , Song Yijiang , Zhang Yiguo 
Published: June 2018

AbstractThe single Nrf1 gene has capability to be differentially transcripted alongside with alternative mRNA-splicing and subsequent translation through different initiation signals so as to yield distinct lengths of polypeptide isoforms. Amongst them, three of the most representatives are Nrf1α, Nrf1β and Nrf1γ, but the putative specific contribution of each isoform to regulating ARE-driven target genes remains unknown. To address this, we have here established three cell lines on the base of the Flp-In™ T-REx™ system, which are allowed for tetracycline-inducibly stable expression of Nrf1α, Nrf1β and Nrf1γ. The RNA-Sequencing results have demonstrated that a vast majority of differentially expressed genes (i.e. >90% DEGs detected) were dominantly up-regulated by Nrf1α and/or Nrf1β following induction by tetracycline. By contrast, other DEGs regulated by Nrf1γ were far less than those regulated by Nrf1α/β (i.e. ~11% of Nrf1α and 7% of Nrf1β). Further transcriptomic analysis revealed that tetracycline-induced expression of Nrf1γ significantly increased the percentage of down-regulated genes in total DEGs. These statistical data were further validated by quantitative real-time PCR. The experimental results indicate that distinct Nrf1 isoforms make diverse and even opposing contributions to regulating different subsets of target genes, such as those encoding 26S proteasomal subunits and others involved in various biological processes and functions. Collectively, Nrf1γ acts as a major dominant-negative competitor against Nrf1α/β activity, such that a number of DEGs regulated by Nrf1α/β are counteracted by Nrf1γ.
Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats
Authors: James Morgan H , Bowrey Hannah E , Stopper Colin M , Aston-Jones Gary 
Published: June 2018

AbstractBehavioral economics is a powerful, translational approach for measuring drug demand in both humans and animals. Here, we asked if demand for cocaine in rats with limited drug experience could be used to identify individuals most at risk of expressing an addiction phenotype following either long (LgA) or intermittent (IntA) access self-administration schedules, both of which model the transition to uncontrolled drug seeking. Moreover, because the orexin-1 receptor antagonist SB-334867 (SB) is particularly effective at reducing drug-seeking in highly motivated individuals, we asked whether demand measured after prolonged drug experience could predict SB efficacy. Demand elasticity (α) measured immediately following acquisition of cocaine self-administration (‘baseline α’) was positively correlated with α assessed after 2w of LgA or IntA. Baseline α also predicted the magnitude of compulsive responding for cocaine, drug seeking in initial abstinence, and cued reinstatement following LgA, IntA or standard short access (ShA). When demand was measured after LgA, IntA or ShA, α predicted the same addiction endophenotypes predicted by baseline α, as well as primed reinstatement and the emergence of negative emotional mood behavior following abstinence. Post-LgA/IntA/ShA α also predicted the efficacy of SB, such that high demand rats showed greater reductions in motivation for cocaine following SB (10 and 30mg/kg) compared to low demand rats. Together, these findings indicate that α might serve as a behavioral biomarker to predict individuals most likely to progress from controlled to uncontrolled drug use, and to identify individuals most likely to benefit from orexin-based therapies for the treatment of addiction.
Genome analysis of the unicellular eukaryoteEuplotes vannusreveals molecular basis for sex determination and tolerance to environmental stresses
Authors: Chen Xiao , Jiang Yaohan , Gao Feng , Zheng Weibo , Krock Timothy J. , Stover Naomi A. , Lu Chao , Katz Laura A. , Song Weibo 
Published: June 2018

AbstractAs a model organism in studies of cell and environmental biology, the free-living and cosmopolitan ciliated protistEuplotes vannushas more than ten mating types (sexes) and shows strong resistance to environmental stresses. However, the molecular basis of its sex determination mechanism and how the cell responds to stress remain largely unknown. Here we report a combined analysis ofde novoassembled high-quality macronucleus (MAC; i.e. somatic) genome and partial micronucleus (MIC; i.e. germline) genome ofEuplotes vannus. Furthermore, MAC genomic and transcriptomic data from several mating types ofE. vannuswere investigated and gene expression levels were profiled under different environmental stresses, including nutrient scarcity, extreme temperature, salinity and the presence of free ammonia. We found thatE. vannus, which possesses gene-sized nanochromosomes in its MAC, shares a similar pattern on frameshifting and stop codon usage asEuplotes octocarinatusand may be undergoing incipient sympatric speciation withEuplotes crassus. Somatic pheromone loci ofE. vannusare generated from programmed DNA rearrangements of multiple germline macronuclear destined sequences (MDS) and the mating types ofE. vannusare distinguished by the different combinations of pheromone loci instead of possessing mating type-specific genes. Lastly, we linked the resilience to environmental temperature change to the evolved loss of temperature stress-sensitive regulatory regions of HSP70 gene inE. vannus. Together, the genome resources generated in this study, which are available online atEuplotes vannusDB (http://evan.ciliate.org), provide new evidence for sex determination mechanism in eukaryotes and common pheromone-mediated cell-cell signaling and cross-mating.
3’ Branch Ligation: A Novel Method to Ligate Non-Complementary DNA to Recessed or Internal 3’OH Ends in DNA or RNA
Authors: Wang Lin , Xi Yang , Zhang Wenwei , Wang Weimao , Shen Hanjie , Wang Xiaojue , Zhao Xia , Alexeev Andrei , Peters Brock A. , Albert Alayna , Xu Xu , Ren Han , Wang Ou , Kirkconnell Killeen , Perazich Helena , Clark Sonya , Hurowitz Evan , Chen Ao , Xu Xun , Drmanac Radoje , Jiang Yuan 
Published: June 2018

AbstractNucleic acid ligases are crucial enzymes that repair breaks in DNA or RNA during synthesis, repair and recombination. Various molecular tools have been developed using the diverse activities of DNA/RNA ligases. Herein, we demonstrate a non-conventional ability of T4 DNA ligase to join 5’ phosphorylated blunt-end double-stranded DNA to DNA breaks at 3’ recessive ends, gaps, or nicks to form a 3’ branch structure. Therefore, this base pairing-independent ligation is termed 3’ branch ligation (3’BL). In an extensive study of optimal ligation conditions, similar to blunt-end ligation, the presence of 10% PEG-8000 in the ligation buffer significantly increased ligation efficiency. A low level of nucleotide preference was observed at the junction sites using different synthetic DNAs. Furthermore, we discovered that T4 DNA ligase efficiently ligated DNA to the 3’ recessed end of RNA, not to that of DNA, in a DNA/RNA hybrid, whereas RNA ligases are less efficient in this reaction. These novel properties of T4 DNA ligase can be utilized as a broad molecular technique in many important applications. We performed a proof-of-concept study of a new directional tagmentation protocol for next generation sequencing (NGS) library construction that eliminates inverted adapters and allows sample barcode insertion adjacent to genomic DNA. 3’BL after single transposon tagmentation can theoretically achieve 100% usable template, and our empirical data demonstrate that the new approach produced higher yield compared with traditional double transposon or Y transposon tagmentation. We further explore the potential use of 3’BL for preparing targeted RNA NGS libraries with mitigated structure-based bias and adapter dimer problems.
CRISPRi-Seq for the Identification and Characterisation of Essential Mycobacterial Genes and Transcriptional Units
Authors: de Wet Timothy J. , Gobe Irene , Mhlanga Musa M. , Warner Digby F. 
Published: June 2018

AbstractHigh-throughput essentiality screens have enabled genome-wide assessments of the genetic requirements for growth and survival of a variety of bacteria in different experimental models. The reliance in many of these studies on transposon (Tn)-based gene inactivation has, however, limited the ability to probe essential gene function or design targeted screens. We interrogated the potential of targeted, large-scale, pooled CRISPR interference (CRISPRi)-based screens to extend conventional Tn approaches in mycobacteria through the capacity for positionally regulable gene repression. Here, we report the utility of the “CRISPRi-Seq” method for targeted, pooled essentiality screening, confirming strong overlap with Tn-Seq datasets. In addition, we exploit this high-throughput approach to provide insight into CRISPRi functionality. By interrogating polar effects and combining image-based phenotyping with CRISPRi-mediated depletion of selected essential genes, we demonstrate that CRISPRi-Seq can functionally validate Transcriptional Units within operons. Together, these observations suggest the utility of CRISPRi-Seq to provide insights into (myco)bacterial gene regulation and expression on a genome-wide scale.