bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Tobacco Exposure and Development of Orofacial Clefts in the Child
Authors: Bui Anthony H. , Ayub Ayisha , Ahmed Mairaj K. , Taioli Emanuela , Taub Peter J. 
Published: October 2018

IntroductionThe purpose of this study was to evaluate the association between maternal tobacco exposure and development of orofacial clefts (OFCs) in the child in a Pakistani population.MethodsA case-control study was conducted at the Cleft Hospital and Bashir Hospital in Gujrat, Pakistan, from December 2015 to December 2016. All new cases of OFC at the Cleft Hospital were included. Patients at Bashir Hospital younger than 3 years and without congenital malformations were selected as control subjects. Risk factors associated with OFC were identified through bivariate analyses. Multiple logistic regression was then performed to calculate adjusted odds ratios (ORs) of developing OFC according to various risk factors.ResultsThe study included 297 patients with OFC and 131 control subjects. Upon univariable analysis, the following were associated with OFC: maternal tobacco exposure (P< 0.001), complications during pregnancy (P< 0.001), maternal hypertension (P= 0.01), mother not on physician-recommended medications (P< 0.001), mother not receiving vaccinations (P< 0.001), consanguineous marriage (P< 0.001), and lower socioeconomic status (P< 0.001). Upon multivariable analysis, having a smoking parent (OR, 1.89; 95% confidence interval [CI], 1.10–3.26), complications during pregnancy (OR, 2.36; 95% CI, 1.43–3.88), and consanguineous marriage (OR, 1.79; 95% CI, 1.13–2.85) were associated with increased odds of development of OFC; receiving vaccinations (OR, 0.31; 95% CI, 0.16–0.63) and higher socioeconomic status (OR, 0.20; 95% CI, 0.05–0.74) were protective.ConclusionsPatients with OFC were nearly twice as likely to have a parent who smokes as those without. Efforts to reduce tobacco consumption among prospective parents, such as perinatal tobacco cessation counseling programs, should be evaluated in this population.
Complete Jejunal Transection After Blunt Abdominal Trauma: A Case Report
Authors: Kuchen Natalie , Gmuer Christian , Schoeb Othmar 
Published: October 2018

Introduction:
Isolated complete transection of the small bowel is extremely rare in blunt abdominal trauma. If it occurs, it is often associated with high-energy impact, as seen in motor vehicle accidents and falls from heights. In this case, a trivial trauma due to a handlebar injury caused a complete transection of the middle jejunum.

Case Presentation:
A 47-year-old man walked into the emergency department with moderate abdominal pain ∼10 hours after a fall on to a bicycle’s handlebar from a standing position. A bedside ultrasound showed minimal amount of free fluid and a following performed computed tomographic scan indicated an edematous loop of small bowel with diminutive amount of extraluminal air, suggesting small bowel perforation. Because of the absence of abdominal peritonism in a hemodynamically stable patient, a conservative treatment and surveillance was established. In the follow-up, the patient suddenly developed severe abdominal pain with now clear signs of peritonism. An emergency laparoscopy showed a complete transection of the middle jejunum. A primary anastomosis was performed. The patient had an uneventful recovery and was discharged after 7 days.

Conclusions:
Even seemingly trivial blunt abdominal traumas can cause complete transection of the small bowel, as shown in this case. Patients with blunt abdominal trauma need to be reviewed frequently by an experienced clinician. Diagnostic laparoscopy attaches a great importance to early detection and treatment of small bowel injuries. The mechanical pattern of the injury seems to be more important than the energy of the impact itself.
Is Prophylactic Steroid Treatment Mandatory for Subclinical Cushing Syndrome After Unilateral Laparoscopic Adrenalectomy?
Authors: Wang Dong , Li Han-zhong , Zhang Yu-shi , Wang Liang , Ji Zhi-gang 
Published: October 2018

Objective:This study aimed to provide rational guidelines for patients with subclinical Cushing syndrome (SCS), who are undergoing laparoscopic adrenalectomy, in order to avoid the risk of overtreatment.Methods:A total of 59 patients diagnosed with SCS caused by unilateral adrenal adenoma, who underwent laparoscopic adrenalectomy from 2010 to 2017, were included into the study. These patients did not receive prophylactic steroid treatment. After discharge, patients with adrenal insufficiency (AI) were treated with glucocorticoid. Then, cortisol levels were reevaluated at three months after surgery by morning serum cortisol.Results:No severe perioperative complications occurred. After unilateral laparoscopic adrenalectomy, no patient developed AI and was readmitted. In the first week after surgery, 10 patients (16.9%) received steroid therapy at the clinic because of mild symptoms of AI. The probability of developing AI was greater in patients with 1-mg dexamethasone midnight suppression test (1 mg-DST) >5 μg/dL than patients with mg-DST ranging within 1.8 to 5.0 μg/dL (P=0.042). The initial dose of hydrocortisone was 20.00±6.67 mg/d (range, 10 to 30), and the duration of treatment was 6.90±3.51 weeks (range, 3 to 12 wk). At three months after surgery, morning cortisol was >5 μg/dL in all patients.Conclusions:After laparoscopic adrenalectomy, the probability of AI is small in patients with adrenal SCS, and the symptoms of AI were mild. Meanwhile, the HPA axis rapidly recovered. Therefore, prophylactic steroid treatment is not mandatory. Given that AI is more frequent in patients with higher cut-offs of 1 mg-DST, a more precise definition of SCS is necessary to better manage these patients.
Importance of Hematopoietic Mixed Chimerism for Induction of Renal Allograft Tolerance in Nonhuman Primates
Authors: Thaiss Cornelius C. , Oura Tetsu , Sasaki Hajime , Dehnadi Abbas , Matsunami Masatoshi , Rosales Ivy A. , Cosimi A. Benedict , Kawai Tatsuo 
Published: October 2018

Background.
Although induction of durable mixed chimerism is required for murine skin allograft tolerance (TOL), renal allograft TOL has been achieved after induction of only transient mixed chimerism in nonhuman primates (NHPs) and humans. To better define the level/duration of chimerism required for stable renal allograft TOL, we retrospectively analyzed these parameters and compared them with transplant outcomes in NHP combined kidney and bone marrow transplant recipients.

Methods.
Peripheral blood levels and duration of myeloid or lymphoid chimerism were retrospectively analyzed in 34 NHP combined kidney and bone marrow transplantation recipients which were divided into 3 groups: TOL, n = 10; chronic antibody-mediated rejection (CAMR), n = 12; and T cell-mediated rejection (TCMR), n = 12.

Results.
All 4 of the recipients that failed to develop any chimerism lost their allografts due to TCMR after discontinuation of immunosuppression (56 ± 3 d). Among 30 recipients who successfully developed multilineage chimerism, 10 achieved long-term immunosuppression-free survival without rejection (1258 ± 388 d), 12 eventually developed CAMR (932 ± 155 d), and 8 developed TCMR (82 ± 10 d). The maximum level but not duration of lymphoid chimerism was significantly higher in TOL recipients compared with both CAMR (P = 0.0159) and TCMR (P = 0.0074). On the other hand, the maximum myeloid chimerism was significantly higher in TOL than in TCMR (P = 0.0469), but not in CAMR. Receiver operating characteristic analyses revealed that lymphoid chimerism levels of 3.1% or greater could reliably predict long-term immunosuppression-free renal allograft survival (P < 0.0001).

Conclusions.
This retrospective study confirmed that induction of chimerism is essential for long-term immunosuppression-free survival, which best correlates with lymphoid chimerism levels higher than 3.1%.
Urinary TIMP-2 Predicts the Presence and Duration of Delayed Graft Function in Donation After Circulatory Death Kidney Transplant Recipients
Authors: Bank Jonna R. , Ruhaak Renée , Soonawala Darius , Mayboroda Oleg , Romijn Fred P. , van Kooten Cees , Cobbaert Christa M. , de Fijter Johan W. 
Published: October 2018

Background.
Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients.

Methods.
Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression.

Results.
Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF.

Conclusions.
Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.
Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver
Authors: Çalışkan Minal , Manduchi Elisabetta , Rao H. Shanker , Segert Julian A , Beltrame Marcia Holsbach , Trizzino Marco , Park YoSon , Baker Samuel W , Chesi Alessandra , Johnson Matthew E , Hodge Kenyaita M , Leonard Michelle E , Loza Baoli , Xin Dong , Berrido Andrea M , Hand Nicholas J , Bauer Robert C , Wells Andrew D , Olthoff Kim M , Shaked Abraham , Rader Daniel J , Grant Struan FA , Brown Christopher D 
Published: October 2018

ABSTRACTDeciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory regions of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the impacts of genetic variation that direct histone modification states in the liver are poorly understood. Here, we generate the most comprehensive genome-wide dataset of two epigenetic marks, H3K4me3 and H3K27ac, and annotate thousands of putative regulatory elements in the human liver. We integrate these findings with genome-wide gene expression data collected from the same human liver tissues and high-resolution promoter-focused chromatin interaction maps collected from human liver-derived HepG2 cells. We demonstrate widespread functional consequences of natural genetic variation on putative regulatory element activity and gene expression levels. Leveraging these extensive datasets, we fine-map a total of 77 GWAS loci that have been associated with at least one complex phenotype. Our results contribute to the repertoire of genes and regulatory mechanisms governing complex disease development and further the basic understanding of genetic and epigenetic regulation of gene expression in the human liver tissue.
Managing the Spatial Covariance of Genetic Diversity in Niemann-Pick C1 Through Modulation of the Hsp70 Chaperone System
Authors: Wang Chao , Scott Samantha M , Hutt Darren M , Zhao Pei , Shao Hao , Gestwicki Jason E , William E Balch 
Published: October 2018

ABSTRACTGenetic diversity provides a rich repository for understanding the role of proteostasis in the management of the protein fold to allow biology to evolve through variation in the population and in response to the environment. Failure in proteostasis can trigger multiple disease states affecting both human health and lifespan. Niemann-Pick C (NPC) disease is a genetic disorder mainly caused by mutations in NPC1, a multi-spanning transmembrane protein that is trafficked through the exocytic pathway to late endosomes and lysosomes (LE/Ly) to manage cholesterol homeostasis. Proteostatic defects triggered by >600 NPC1 variants found in the human population inhibit export of NPC1 protein from ER or function in downstream LE/Ly, leading to accumulation of cholesterol and rapid onset neurodegeneration in childhood for most patients. We now show that chemical allosteric inhibitors, such as JG98, targeting the cytosolic Hsp70 chaperone/co-chaperone complex improves the trafficking and stability of NPC1 variants with diverse NPC1 genotypes. By exploiting the knowledge-base of NPC1 variants found in the world-wide patient population using Variation Spatial Profiling (VSP), a Gaussian-process based machine learning (ML) approach, we show how the Hsp70 chaperone system alters the spatial covariance (SCV) tolerance of the ER and the SCV set-points for each residue of the NPC1 polypeptide chain differentially to improve trafficking efficiency and post-ER stability for variants distributed across the entire NPC1 polypeptide. The impact of JG98 is supported by the observation that silencing of Hsp70 specific nucleotide exchange factors (NEF) (BCL-anthogene (BAG) family) co-chaperones significantly improve the folding status of NPC1 variants. Together, these studies suggest that targeting the cytosolic Hsp70 system to adjust the SCV tolerance of the proteostasis network can improve recognition of the plasticity of the NPC1 fold found in the disease population for trafficking to the LE/Ly compartments.
Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Authors: Forés-Martos Jaume , Catalá-López Ferrán , Sánchez-Valle Jon , Ibáñez Kristina , Tejero Héctor , Palma-Gudiel Helena , Climent Joan , Pancaldi Vera , Fañanás Lourdes , Arango Celso , Parellada Mara , Baudot Anaïs , Vogt Daniel , Rubenstein John L. , Valencia Alfonso , Tabarés-Seisdedos Rafael 
Published: October 2018

AbstractEpidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis. Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. These shared transcriptomic alterations could help explain epidemiological observations suggesting direct and inverse comorbid associations between ASD and particular cancer types.
RegKnock: identifying gene knockout strategies for microbial strain optimization based on regulatory and metabolic integrated network
Authors: Xu Zixiang 
Published: October 2018

AbstractBackgroundGene knockout has been used to improve the conversion ratio of strains for some chemical products. Based on mixed integer bi-level linear programming (MIBLP) and cell network models, there have been several algorithms to predict the target for deletion to improve the productivity of chemicals. At present, the cell models on which these algorithms based have changed from metabolic network to metabolic-regulatory integrated network, for integrated network is more comprehensive in describing the behavior of cells. Metabolic-regulatory integrated network is better than metabolic network in flux prediction, but will introduce integer variables in the inner of MIBLP. How to solve the intractable MIBLP, however, is not explicated clearly as in mathematical literatures, especially for MIBLP with integer variables in the inner problem (named as MIBLP-2) where integer variables are introduced by the flux balance analysis (FBA) for integrated network. Dual theory was still be used to transform MIBLP-2 to a single level with ignoring integer variables in the inner problem. Intelligent computation is another choice for solving MIBLP, but it usually was used to solve the single level nonlinear programming (NLP) which was the transformation from MIBLP by using joint objective of upper/lower level, while the equivalence between this MIBLP and this NLP was not be proved in mathematics.MethodsIn this study, we develop a new target predicting algorithm for gene knockouts, named RegKnock. The cell model on which we base is metabolic-regulatory integrated network as well. When solving the MIBLP-2, RegKnock uses Parallel Genetic Algorithm (PGA), but not use joint objective. GA was used to generate control variables of the upper, indicating which genes should be deleted, while the fitness function is to maximize the objective product calculated from the inner FBA of the integrated network. FBA of the inner problem, a mixed integer programming, could be solved by existing optimization softwares. Parallel computation aims to accelerate finding the optimal solution and thus decreases the time of computation.Results and ConclusionsWith comparing with OptORF and OptFlux, two published target predicting algorithm for gene knockouts which also aiming at integrated network, two merits have been shown for RegKnock, i.e. absolutely accuracy and not a long time of computation. So RegKnock is a nice algorithm for predicting algorithm for gene deletions as for integrated network.
Using QC-Blind for quality control and contamination screening of bacteria DNA sequencing data without reference genome
Authors: Xi Wang , Gao Yan , Cheng Zhangyu , Chen Chaoyun , Han Maozhen , Ning Kang 
Published: October 2018

ABSTRACTQuality control in next generation sequencing has become increasingly important as the technique becomes widely used. Tools have been developed for filtering possible contaminants in the sequencing data of species with known reference genome. Unfortunately, reference genomes for all the species involved, including the contaminants, are required for these tools to work. This precludes many real-life samples that have no information about the complete genome of the target species, and are contaminated with unknown microbial species.In this work we propose QC-Blind, a novel quality control pipeline for removing contaminants without any use of reference genomes. The pipeline requires only very little information from the marker genes of the target species. The entire pipeline consists of unsupervised read assembly, contig binning, read clustering and marker gene assignment.When evaluated onin silico,ab initioandin vivodatasets, QC-Blind proved effective in removing unknown contaminants with high specificity and accuracy, while preserving most of the genomic information of the target bacterial species. Therefore, QC-Blind could serve well in situations where limited information is available for both target and contamination species.IMPORTANCEAt present, many sequencing projects are still performed on potentially contaminated samples, which bring into question their accuracies. However, current reference-based quality control method are limited as they need either the genome of target species or contaminations. In this work we propose QC-Blind, a novel quality control pipeline for removing contaminants without any use of reference genomes. When evaluated onin silico,ab initioandin vivodatasets, QC-Blind proved effective in removing unknown contaminants with high specificity and accuracy, while preserving most of the genomic information of the target bacterial species. Therefore, QC-Blind is suitable for real-life samples where limited information is available for both target and contamination species.
Protein complex stoichiometry and expression dynamics of transcription factors modulate stem cell division
Authors: Clark Natalie M. , Fisher Adam P. , Berckmans Barbara , Van den Broeck Lisa , Nelson Emily C. , Nguyen Thomas T. , Bustillo-Avendaño Estefano , Zebell Sophia G. , Moreno-Risueno Miguel , Simon Rüdiger , Gallagher Kimberly L. , Sozzani Rosangela 
Published: October 2018

AbstractStem cells divide and differentiate to form all the specialized cell types in a multicellular organism. In the Arabidopsis root, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the Quiescent Center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here, we gained insight into the differences between the QC and the Cortex Endodermis Initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an Ordinary Differential Equation (ODE) model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction coupled with experimental validation showed that high levels of the SHR-SCR complex is associated with more CEI division but less QC division. Further, our model prediction allowed us to establish the timing of QC and CEI division and propose that SHR repression of QC division depends on the formation of SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche.
A pose/force symmetric coordination method for a redundant dual-arm robot
Authors: Zhang Fuhai , Qu Jiadi , Liu He , Fu Yili 
Published: October 2018

Purpose
This paper aims to develop a pose/force coordination method for a redundant dual-arm robot to achieve a symmetric coordination task.

Design/methodology/approach
A novel control strategy of dual-arm coordination is proposed that associates pose coordination with force coordination. The spatial in-parallel spring and damping model is built to regulate the relative pose error of two end-effectors in real time, and force coordination factor is introduced to realize the dynamic distribution of loadings to limit the object’s internal force in real time.

Findings
The proposed method was verified on a real dual-arm robot platform. The symmetric coordination task is performed and the experiment results show that a good behavior on the regulation of the relative pose errors between two arms to achieve the object’s trajectory tracking, and the distribution of the two end-effectors’ loadings to limit the object’s internal force.

Originality/value
The benefits of the proposed method are to improve the object’s tracking performance and avoid the object damage during the symmetric coordination task.