bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of the Thoracic Pedicle Screw Placement Using the Virtual Surgical Training System: A Cadaver Study
Authors: Hou Yang , Lin Yanping , Shi Jiangang , Chen Huajiang , Yuan Wen
Published: March 2018

BACKGROUND

The virtual simulation surgery has initially exhibited its promising potentials in neurosurgery training.

OBJECTIVE

To evaluate effectiveness of the Virtual Surgical Training System (VSTS) on novice residents placing thoracic pedicle screws in a cadaver study.

METHODS

A total of 10 inexperienced residents participated in this study and were randomly assigned to 2 groups. The group using VSTS to learn thoracic pedicle screw fixation was the simulation training (ST) group and the group receiving an introductory teaching session was the control group. Ten fresh adult spine specimens including 6 males and 4 females with a mean age of 58.5 yr (range: 33-72) were collected and randomly allocated to the 2 groups. After exposing anatomic structures of thoracic spine, the bilateral pedicle screw placement of T6-T12 was performed on each cadaver specimen. The postoperative computed tomography scan was performed on each spine specimen, and experienced observers independently reviewed the placement of the pedicle screws to assess the incidence of pedicle breach.

RESULTS

The screw penetration rates of the ST group (7.14%) was significantly lower in comparison to the control group (30%, P < .05). Statistically significant difference in acceptable rates of screws also occurred between the ST (100%) and control (92.86%) group (P < .05). In addition, the average screw penetration distance in control group (2.37 mm ± 0.23 mm) was significantly greater than ST group (1.23 mm ± 0.56 mm, P < .05).

CONCLUSION

The virtual reality surgical training of thoracic pedicle screw instrumentation effectively improves surgical performance of novice residents compared to those with traditional teaching method, and can help new beginners to master the surgical technique within shortest period of time.
Intraoperative Nerve Monitoring in Robotic-Assisted Resection Of Presacral Ganglioneuroma: Operative Technique
Authors: Garzon-Muvdi Tomas , Belzberg Allan , Allaf Mohamad E , Wolinsky Jean-Paul
Published: March 2018

BACKGROUND

Robotic-assisted techniques have been implemented in the surgical treatment of tumors in the pelvis, abdomen, and thorax. In pelvic tumors, robotic-assisted techniques evade the need for sizable surgical exposure, but make stimulation of the nerves of the sacral plexus very difficult.

OBJECTIVE

To describe how laparoscopic robotic-assisted surgery can couple with tools such as the nerve stimulator to aid in the resection of presacral masses emanating from the neural elements and potentially improve neurological outcome by preventing inadvertent injury to involved nerves.

METHODS

A patient with a large presacral ganglioneuroma underwent resection using the DaVinci system (Intuitive Surgical, Sunnyvale, California) for robotic assistance. A nerve stimulator was coupled to the bipolar cautery instrument of the DaVinci robot to define the presence of functional nerves in the surroundings of the tumor.

RESULTS

By coupling a nerve stimulator to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical), it was possible to identify important neural structures in close proximity to the tumor. After identifying functional nerves, the surgeon was able to preserve them and preserve neurological function avoiding motor dysfunction.

CONCLUSION

The use of a nerve stimulator coupled to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical) during laparoscopic, robotic-assisted surgery for resection of presacral masses is safe and feasible. In addition to the preoperative evaluation, intraoperative monitoring and stimulation of nerves in close proximity to the tumor and also exiting through neural foramina involved by the tumor allowed the surgeon to understand the anatomy and preserve neurological function while obtaining optimal surgical resection.
Europol’s Crime Analysis System—Practical Determinants of Its Success
Authors: Safjański Tomasz , James Adrian
Published: March 2018

Threats to modern nation states from organized crime and terrorism create environments in which intelligence becomes a vital component of policing and security plans but the increasing use of personal data for law enforcement purposes can alter the normative relationships between stakeholders and law enforcement agencies and between agencies and citizens. For that reason, police intelligence practice demands critical examination. This paper presents a narrative inquiry, based on the authors’ experiential knowledge and empirical research, into Europol’s Crime Analysis System (ECAS). The study explains Europol’s efforts to develop data collection and analysis systems that meet the needs of EU Member States (MS). Through ECAS, it has created powerful tools intended to deliver intelligence products that help MS identify, localize, and neutralize transnational threats to a degree not witnessed before in Europe. Nevertheless, Europol’s performance in this context seems sub-optimal. Shortcomings largely are attributed to a lack of trust between Europol and MS leading to failures to share information between themselves and with the institution. The result is that the latter’s strategic intelligence products sometimes are deficient or incomplete. That should be of concern to stakeholders because Europol’s strategic intelligence efforts may be rendered ineffective. Shortcomings in Europol’s intelligence products also are significant for citizens because they may mean that the information-sharing process is less transparent and less accountable than citizens have a right to expect.
The LsrB Protein Is Required forAgrobacterium tumefaciensInteraction with Host Plants
Authors: Tang Guirong , Li Qiong , Xing Shenghui , Li Ningning , Tang Zheng , Yu Liangliang , Yan Junhui , Li Xuan , Luo Li
Published: March 2018

Agrobacterium tumefaciens infects and causes crown galls in dicot plants by transferring T-DNA from the Ti plasmid to the host plant via a type IV secretion system. This process requires appropriate environmental conditions, certain plant secretions, and bacterial regulators. In our previous work, a member of the LysR family of transcriptional regulators (LsrB) in Sinorhizobium meliloti was found to modulate its symbiotic interactions with the host plant alfalfa. However, the function of its homolog in A. tumefaciens remains unclear. In this study, we show that the LsrB protein of A. tumefaciens is required for efficient transformation of host plants. A lsrB deletion mutant of A. tumefaciens exhibits a number of defects, including in succinoglycan production, attachment, and resistance to oxidative stress and iron limitation. RNA-sequencing analysis indicated that 465 genes were significantly differentially expressed (upregulation of 162 genes and downregulation of 303 genes) in the mutant, compared with the wild-type strain, including those involved in succinoglycan production, iron transporter, and detoxification enzymes for oxidative stress. Moreover, expression of the lsrB gene from S. meliloti, Brucella abortus, or A. tumefaciens rescued the defects observed in the S. meliloti or A. tumefaciens lsrB deletion mutant. Our findings suggest that a conserved mechanism of LsrB function exists in symbiotic and pathogenic bacteria of the family Rhizobiaceae.
A Comprehensive Arabidopsis Yeast Two-Hybrid Library for Protein-Protein Interaction Studies: A Resource to the Plant Research Community
Authors: Matiolli Cleverson Carlos , Melotto Maeli
Published: March 2018

Yeast-two-hybrid (Y2H) cDNA library screening is a valuable tool to uncover protein-protein interactions and represents a widely used method to investigate protein function. However, low transcript representation in cDNA libraries limits the depth of the screening. We have developed a Y2H library with cDNA made from Arabidopsis leaves exposed to several stressors as well as untreated leaves. The library was built using pooled mRNA extracted from plants challenged with plant and human bacterial pathogens, the flg22 elicitor, the phytotoxin coronatine, and several hormones associated with environmental stress responses. The purpose of such a library is to maximize the discovery of protein-protein interactions that occur under optimum conditions as well as during biotic and abiotic stresses.
Comparison of Two Major Perioperative Bleeding Scores for Cardiac Surgery Trials
Authors: Bartoszko Justyna , Wijeysundera Duminda N. , Karkouti Keyvan ,   on behalf of the Transfusion Avoidance in Cardiac Surgery Study Investigators
Published: March 2018

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Research into major bleeding during cardiac surgery is challenging due to variability in how it is scored. Two consensus-based clinical scores for major bleeding: the Universal definition of perioperative bleeding and the European Coronary Artery Bypass Graft (E-CABG) bleeding severity grade, were compared in this substudy of the Transfusion Avoidance in Cardiac Surgery (TACS) trial.

Methods

As part of TACS, 7,402 patients underwent cardiac surgery at 12 hospitals from 2014 to 2015. We examined content validity by comparing scored items, construct validity by examining associations with redo and complex procedures, and criterion validity by examining 28-day in-hospital mortality risk across bleeding severity categories. Hierarchical logistic regression models were constructed that incorporated important predictors and categories of bleeding.

Results

E-CABG and Universal scores were correlated (Spearman ρ = 0.78, P < 0.0001), but E-CABG classified 910 (12.4%) patients as having more severe bleeding, whereas the Universal score classified 1,729 (23.8%) as more severe. Higher E-CABG and Universal scores were observed in redo and complex procedures. Increasing E-CABG and Universal scores were associated with increased mortality in unadjusted and adjusted analyses. Regression model discrimination based on predictors of perioperative mortality increased with additional inclusion of the Universal score (c-statistic increase from 0.83 to 0.91) or E-CABG (c-statistic increase from 0.83 to 0.92). When other major postoperative complications were added to these models, the association between Universal or E-CABG bleeding with mortality remained.

Conclusions

Although each offers different advantages, both the Universal score and E-CABG performed well in the validity assessments, supporting their use as outcome measures in clinical trials.
No Reliable Association Between Recreational Noise Exposure and Threshold Sensitivity, Distortion Product Otoacoustic Emission Amplitude, or Word-in-Noise Performance in a College Student Population
Authors: Le Prell Colleen G. , Siburt Hannah W. , Lobarinas Edward , Griffiths Scott K. , Spankovich Christopher
Published: March 2018

Objectives:

The purpose of this study was to evaluate the relationship between recreational sound exposure and potentially undiagnosed or subclinical hearing loss by assessing sound exposure history, threshold sensitivity, distortion product otoacoustic emission (DPOAE) amplitudes, and performance on the words-in-noise (WIN) test.

Design:

Survey data were collected from 74 adult participants (14 male and 60 female), 18 to 27 years of age, recruited via advertisements posted throughout the University of Florida campus. Of these participants, 70 completed both the survey and the additional functional test battery, and their preferred listening level was measured in a laboratory setting.

Results:

There were statistically significant relationships between hearing thresholds and DPOAE amplitude. In contrast, performance on the WIN was not reliably related to threshold sensitivity within this cohort with largely normal hearing. The two most common exposures included bars or dance clubs, followed by music player use. There were no statistically significant relationships between individual or composite measures of recreational sound exposure, including preferred listening level, years of music player use, number of reported sound exposures, previous impulse noise exposure, or previous noise-induced change in hearing, and functional measures including threshold, DPOAE amplitude, and WIN measures. Some subjects were highly consistent in listening level preferences, while others were more variable from song to song.

Conclusions:

No reliable relationships between common recreational sound exposure or previous noise-induced changes in hearing were found during analysis of threshold sensitivity, DPOAE amplitude, or WIN performance in this cohort. However, the study sample was predominantly female and Caucasian, which limits generalizability of the results.
TRAF3-interacting protein 3, a new oncotarget, promotes tumor growth in melanoma
Authors: Nasarre Patrick , Bonilla Ingrid V. , Metcalf John S. , Hilliard Eleanor G. , Klauber-DeMore Nancy
Published: March 2018

TRAF3-interacting protein 3 (TRAF3IP3) is expressed in the immune system and participates in cell maturation, tissue development, and immune response. In a previous study, we reported that TRAF3IP3 levels were substantially increased in the vasculature of breast cancer tissues, suggesting a proangiogenic role. In this study, we investigated TRAF3IP3 tumorigenic function. TRAF3IP3 protein was present in several cancer cell lines, with highest levels in melanoma. In addition, tumor microarray analysis on 23 primary melanoma and nine positive lymph nodes revealed that 70% of human primary melanoma and 66% of lymph node metastases were positive for TRAF3IP3. Importantly, TRAF3IP3 downregulation correlated with an 83% reduction of tumor growth in a subcutaneous xenograft mouse model (n=10, P=0.005). Immunohistochemistry analysis of the tumors revealed that TRAF3IP3-shRNA tumors had increased apoptosis (n=4, P<0.01) and reduced microvascular density (n=4, P<0.002). In addition, TRAF3IP3 downregulation in malignant endothelial cells reduced tube formation in a Matrigel tube formation assay. In melanoma cells, decreased levels of TRAF3IP3 were also associated with reduced viability (n=4, P=0.03) and proliferation (n=3, P=0.03), together with increased sensitivity to ultraviolet-induced apoptosis (n=4, P=0.0004). Furthermore, TRAF3IP3 downregulation correlated with increased amounts of interferon-γ. Interferon-γ inhibits tumor growth and angiogenesis, thus suggesting a new pathway for TRAF3IP3 in cancer. Collectively, the association of TRAF3IP3 with malignant properties of melanoma suggest a clinical potential for targeted therapy.
PERIVASCULAR THICKENING ON OPTICAL COHERENCE TOMOGRAPHY AS A MARKER OF INFLAMMATION IN BIRDSHOT RETINOCHOROIDITIS
Authors: Thomas Akshay S. , Hatef Angel L. , Stinnett Sandra S. , Keenan Robert T. , Jaffe Glenn J.
Published: March 2018

Purpose:

In this study, we hypothesized that thickening along the major arcade vessels is a noninvasive marker of inflammation in eyes with birdshot retinochoroiditis (BRC).

Methods:

In this single-center retrospective study, patients with BRC were identified. Perivascular thickening was categorized as mild, moderate, or severe, based on a set of standard reference retinal thickness maps derived from representative spectral domain optical coherence tomography volume scans. The assigned perivascular severity thickness category was then compared with other inflammatory markers and optical coherence tomography measurements. These parameters were also examined in eyes with intermediate uveitis to assess the diagnostic specificity of perivascular thickening.

Results:

In eyes with BRC, greater perivascular thickening was associated with increased vitreous haze (P = 0.009) and retinal vascular leakage on fluorescein angiography (P = 0.0001). Perivascular thickening was correlated with central subfield thickness and total macular volume on optical coherence tomography. Controlling for central subfield thickness and total macular volume, the odds of higher severity level of perivascular thickening were nine times greater in eyes with BRC than those with intermediate uveitis (P < 0.0001). Eyes with BRC and active inflammation were more likely to have moderate or severe perivascular thickening (P = 0.02).

Conclusion:

Perivascular thickening, determined by optical coherence tomography, may be a useful noninvasive biomarker of inflammation in eyes with BRC.
Role of Dendritic Cells and Inflammatory Cells in Herpetic Endotheliitis: Analysis Using In Vivo Confocal Microscopy
Authors: Wang Ting , Dong Muchen , Jiang Yin , Wang Shuting , Shi Weiyun
Published: March 2018

Purpose:

To observe the pathological changes in dendritic cells (DCs) and inflammatory cells in the corneal epithelium and endothelium using in vivo confocal microscopy during the management of herpetic endotheliitis.

Methods:

A total of 110 eyes with herpetic endotheliitis were included. All patients were treated with antiviral agents combined with glucocorticoids. Changes in corneal edema were observed using slit-lamp microscopy and anterior segment optical coherence tomography. DCs and inflammatory cells in the epithelium and endothelium were detected using in vivo confocal microscopy before treatment and at 1 to 2 weeks and 1 and 3 months after treatment. Recurrence was monitored for 2 years. The contralateral normal eyes were evaluated as controls.

Results:

Mean density of DCs decreased at 1 month after treatment (100 ± 14 cells/mm2) compared with before treatment (148 ± 26 cells/mm2, P < 0.001). At 3 months, DCs returned to small and dendritiform reflective corpuscular cells at a density of 44 ± 11 cells/mm2 (P < 0.001), and the mean density of endothelial cells (2011 ± 173 cells/mm2) was significantly lower than in controls (2472 ± 233 cells/mm2, P = 0.002). Inflammatory cells residing in the epithelium were significantly reduced in number and disappeared at 1 to 2 weeks, and those at the endothelial surface almost disappeared at 1 month. There was no relapse during the follow-up evaluation.

Conclusions:

DCs and inflammatory cells in the epithelial and endothelial cell layers of the cornea changed constantly in density, morphology, and distribution during the therapeutic process of herpetic endotheliitis. Adequate understanding of these alterations may help to guide the management of this disease.
Aptima Human Papillomavirus E6/E7 mRNA Test Results Strongly Associated With Risk for High-Grade Cervical Lesions in Follow-Up Biopsies
Authors: Ge Yimin , Christensen Paul , Luna Eric , Armylagos Donna , Xu Jiaqiong , Schwartz Mary R. , Mody Dina R.
Published: March 2018

Objective

Human papillomavirus (HPV) tests and genotyping (GT) have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in risk evaluation for high-grade cervical lesions.

Materials and Methods

Between January 1, 2015, and December 31, 2016, a total of 4,562 Pap tests with follow-up biopsies in our laboratory database were analyzed along with HPV tests performed on Cobas (CHPV, n = 3,959) or Aptima (AHPV, n = 603) platforms.

Results

The sensitivity for biopsy-confirmed HSIL or worse lesions was 97% for both CHPV and AHPV (p = .75). AHPV showed significantly lower positive rates than CHPV in benign (56% vs 86%) or LSIL (66% vs 90%) biopsies, resulting in significantly higher specificity for HSIL or worse than CHPV (38% vs 12%, p < .001). AHPV demonstrated significantly higher positive predictive value for HSIL or worse (24% vs 16%, p < .001) and overall accuracy (48% vs 24%, p < .001) than CHPV. AHPV GT also had significantly higher specificity for biopsy-confirmed HSIL or worse than CHPV (88% vs 72%, p < .001) with comparable sensitivity (50% vs 51%, p = .75). Women with HPV 16 on AHPV were significantly more likely to have HSIL or worse on biopsies than those with HPV 16 on CHPV (likelihood ratio = 4.3 vs 2.0, p = .004).

Conclusions

Although both AHPV and CHPV were highly sensitive for biopsy-confirmed HSIL or worse lesions, AHPV and GT demonstrated significantly higher specificity and positive predictive value than CHPV. The difference is probably related to E6/E7 overexpression after viral DNA integration in high-grade lesions. The significantly higher specificity and overall accuracy of AHPV and GT for HSIL or worse lesions may be useful in clinical risk management.
MicroRNAs in endothelial cell homeostasis and vascular disease
Authors: Fernández-Hernando Carlos , Suárez Yajaira
Published: March 2018

Purpose of review

Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction.

Recent findings

MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs as potential therapeutic targets for vascular disease.

Further determination of miRNA regulatory circuits and defining miRNAs-specific target genes remains key to future miRNA-based therapeutic applications toward vascular disease prevention. Many new and unanticipated roles of miRNAs in the control of endothelial functions will assist clinicians and researchers in developing potential therapeutic applications.
Fluorescent In Situ Hybridization for TP53 in the Diagnosis of Pediatric Osteogenic Sarcoma
Authors: Marrano Paula , Shago Mary , Somers Gino R. , Thorner Paul S.
Published: March 2018

Osteogenic sarcoma (OS) is the most common malignant bone tumor in children and adolescents. Despite advances in molecular genetic characterization of pediatric and adult tumors, the diagnosis of OS still depends almost entirely on light microscopy. The lack of consistent genetic changes in OS has greatly hindered the development of any diagnostic molecular test. Recently, whole-genome sequencing has shown that ~50% of cases of OS have a translocation involving the TP53 gene with breakpoints confined to the first intron. We developed a 2 color break-apart fluorescent in situ hybridization (FISH) probe for intron 1 of TP53 and applied it to an archived series to assess its diagnostic utility. The study group included 37 cases of OS (including osteoblastic, chondroblastic, and fibroblastic), as well as 53 cases of non-OS pediatric sarcomas (including Ewing sarcoma, rhabdomyosarcoma, undifferentiated small cell sarcoma, CCNB3-BCOR sarcoma, CIC-DUX sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and 27 cases of benign bone lesions (including osteoblastoma, chondromyxoid fibroma, fibrous dysplasia, and fibro-osseous dysplasia). A rearranged signal was found in 20/37 cases (54%) of OS and in none of the other sarcomas or benign bone lesions, giving the FISH test 100% specificity for a diagnosis of OS. p53 immunostaining was generally not predictive of the results obtained by FISH and could not substitute for this test. This FISH probe offers a simple and specific genetic test to aid in the diagnosis of OS, despite the genetic complexity of this tumor.
Qualitative Content Analysis of Coworkers’ Safety Reports of Unprofessional Behavior by Physicians and Advanced Practice Professionals
Authors: Martinez William , Pichert James W. , Hickson Gerald B. , Braddy Casey H. , Brown Amy J. , Catron Thomas F. , Moore Ilene N. , Stampfle Morgan R. , Webb Lynn E. , Cooper William O.
Published: March 2018

Objectives

The aims of the study were to develop a valid and reliable taxonomy of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals and determine the prevalence of reports describing particular types of unprofessional conduct.

Methods

We conducted qualitative content analysis of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals to create a standardized taxonomy. We conducted a focus group of experts in medical professionalism to assess the taxonomy’s face validity. We randomly selected 120 reports (20%) of the 590 total reports submitted through the medical center’s safety event reporting system between June 2015 and September 2016 to measure interrater reliability of taxonomy codes and estimate the prevalence of reports describing particular types of conduct.

Results

The initial taxonomy contained 22 codes organized into the following four domains: competent medical care, clear and respectful communication, integrity, and responsibility. All 10 experts agreed that the four domains reflected essential elements of medical professionalism. Interrater reliabilities for all codes and domains had a κ value greater than the 0.60 threshold for good reliability. Most reports (60%, 95% confidence interval = 51%–69%) described disrespectful or offensive communication. Nine codes had a prevalence of less than 1% and were folded into their respective domains resulting in a final taxonomy composed of 13 codes.

Conclusions

The final taxonomy represents a useful tool with demonstrated validity and reliability, opening the door for reliable analysis and systems to promote accountability and behavior change. Given the safety implications of unprofessional behavior, understanding the typology of coworker observations of unprofessional behavior may inform organization strategies to address this threat to patient safety.
A Prospective Cohort Study of Fertility Desire, Unprotected Sex, and Detectable Viral Load in HIV-Positive Female Sex Workers in Mombasa, Kenya
Authors: Wilson Kate S. , Wanje George , Masese Linnet , Simoni Jane M. , Shafi Juma , Adala Lucy , Overbaugh Julie , Jaoko Walter , Richardson Barbra A. , McClelland Raymond S.
Published: March 2018

Background:

Little is known about fertility desire in HIV-positive female sex workers. Fertility desire could increase HIV transmission risk if it was associated with condomless sex or lower adherence to antiretroviral therapy.

Methods:

A prospective cohort study was conducted among 255 HIV-positive female sex workers in Mombasa, Kenya. Using generalized estimating equations, fertility desire was evaluated as a risk factor for semen detection in vaginal secretions by prostate-specific antigen (PSA) test, a biomarker of condomless sex, detectable plasma viral load (VL), and HIV transmission potential, defined as visits with positive PSA and detectable VL.

Results:

The effect of fertility desire on PSA detection varied significantly by nonbarrier contraception use (P-interaction < 0.01). At visits when women reported not using nonbarrier contraception, fertility desire was associated with higher risk of semen detection [82/385, 21.3% vs. 158/1007, 15.7%; adjusted relative risk (aRR) 1.58, 95% confidence interval (CI): 1.12 to 2.23]. However, when women used nonbarrier contraception, fertility desire was associated with lower risk of PSA detection (10/77, 13.0% vs. 121/536, 22.6%; aRR 0.58, 95% CI: 0.35 to 0.94). Fertility desire was not associated with detectable VL (31/219, 14.2% vs. 128/776, 16.5%; aRR 0.82, 95% CI: 0.46 to 1.45) or higher absolute risk of transmission potential (10/218, 4.6% vs. 21/769, 2.7%; adjusted risk difference = 0.011, 95% CI −0.031 to 0.050).

Conclusions:

Fertility desire was associated with higher risk of biological evidence of semen exposure when women were not using nonbarrier contraceptives. Low HIV transmission potential regardless of fertility desire suggests that the combination of condoms and antiretroviral therapy adherence was effective.
Reduction of Artifacts Caused by Deep Brain Stimulating Electrodes in Cranial Computed Tomography Imaging by Means of Virtual Monoenergetic Images, Metal Artifact Reduction Algorithms, and Their Combination
Authors: Große Hokamp Nils , Hellerbach Alexandra , Gierich Andreas , Jordan David W. , Visser-Vandewalle Veerle , Maintz David , Haneder Stefan
Published: March 2018

Objectives

The aim of this study was to evaluate the reduction of artifacts from deep brain stimulation electrodes (DBS) using an iterative metal artifact reduction algorithm (O-MAR), virtual monoenergetic images (VMI), and both in combination in postoperative spectral detector computed tomography using a dual-layer detector (spectral detector computed tomography [SDCT]) of the head.

Material and Methods

Nonanthropomorphic phantoms with different DBS leads were examined on SDCT; in 1 phantom periprocedural bleeding was simulated. A total of 20 patients who underwent SDCT after DBS implantation between October 2016 and April 2017 were included in this institutional review board–approved retrospective study. Images were reconstructed using standard-of-care iterative reconstruction (CI) and VMI, each with and without O-MAR processing (IR and MAR). Artifacts were quantified by determining the percentage integrity uniformity in an annular region of 1.4 cm2 around the DBS lead; a percentage integrity uniformity of 100% indicates the absence of artifacts. In phantoms, conspicuity of blood was determined on a binary scale, whereas in patients, image quality, DBS lead assessment, and extent of artifact reduction were assessed on Likert scales by 2 radiologists. Statistical significance was assessed using analysis of variance and Wilcoxon tests; sensitivity and specificity were calculated.

Results

The O-MAR processing significantly decreased artifacts in phantom and patients (P ≤ 0.05), whereas VMI did not reduce artifact burden compared with corresponding CI (P > 0.05): for example, CI-IR/MAR and 200 keV-IR/MAR for patients: 76.3%/90.7% and 75.9%/91.2%, respectively. Qualitatively, overall image quality was not improved (P > 0.05) and MAR improved DBS assessment (CI-IR/MAR: 2 [1–3]/3 [2–4]; P ≤ 0.05) and reduced artifacts significantly (P ≤ 0.05). The O-MAR processing increased sensitivity for bleeding by 160%. In some cases, new artifacts were induced through O-MAR processing, none of which impaired diagnostic image assessment.

Discussion

The investigated O-MAR algorithm reduces artifacts from DBS electrodes and should be used in the assessment of postoperative patients; however, combination with VMI does not provide an additional benefit.
Involvement of TLR4 and PPAR-α Receptors in Host Response and NLRP3 Inflammasome Activation, Against Pulmonary Infection With Pseudomonas Aeruginosa
Authors: Gugliandolo Enrico , Fusco Roberta , Ginestra Giovanna , D’amico Ramona , Bisignano Carlo , Mandalari Giuseppina , Cuzzocrea Salvatore , Di Paola Rosanna
Published: March 2018

Background:

Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. PA LPS is recognized by Toll-like receptors-4 (TLR4) and has been shown to induce lung inflammation in vivo. In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage. One potential regulator of these process is the peroxisome proliferator-activated receptors (PPARs), and in particular PPARα. Thus, the purpose of the present study was to evaluate the effects of the absence of TLR4 and PPARα receptors in the pulmonary innate immunity response to PA and in the consequent inflammatory response and in the activation of the macromolecular complex of the NLRP3 inflammosome.

Methods:

To evaluate the involvement of TLR4 and PPARα in a PA infection, we used TLR4 KO and PPARα KO mice that received an intratracheal (i.t.) administration of 50 μL of PA strain (106 CFU), thus evaluating if these mice were profoundly susceptible to PA compared with WT mice.

Results:

The results of the present study showed that administration of PA worsened the pathophysiology of PA lung disease in TLR4 and PPARα KO mice compared with WT mice.

Conclusions:

The present study demonstrated that TLR4 and PPARα receptors would mediate the earliest control of bacterial replication as well as proinflammatory responses to PA infections, and in particular that PPARα receptors are needed to prevent an excessive inflammatory response, as in the control of the inflammasome complex NLP3 activation.
Acidic microenvironment shaped by lactate accumulation promotes pluripotency through multiple mechanisms
Authors: Guo Wen-Ting , Wang Shao-Hua , Zhang Xiao-Shan , Shi Ming , Hao Jing , Wang Xi-Wen , Gu Kai-Li , Duan Fei-Fei , Yan Ying , Yang Xi , Zhang Chao , Liao Le-Qi , Wang Yangming
Published: March 2018

Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here we show that acidic environment shaped by lactate accumulation promotes the self-renewal and pluripotency of both mouse and human embryonic stem cells (ESCs). Mechanistically, acidic pH reduces the tri-methylation of H3K27 globally at transcriptional start sites to partially prevent ESC differentiation. In addition, acidic pH stabilizes a large number of mRNAs including pluripotency genes. Furthermore, we found that AGO1 protein is downregulated at acidic conditions, leading to the de-repression of a subset of microRNA targets in low-pH treated ESCs. Altogether, our study provides insights into mechanisms whereby acidic microenvironment produced by enhanced glycolysis regulates gene expression to determine cell fate and has broad implications in the fields of regenerative medicine and cancer biology.
Cohesiveness in microbial community coalescence
Authors: Lu Nanxi , Sanchez-Gorostiaga Alicia , Tikhonov Mikhail , Sanchez Alvaro
Published: March 2018

Microbial invasions exhibit many unique properties; notably, entire microbial communities often invade one another, a phenomenon known as community coalescence. In spite of the potential importance of this process for the dynamics and stability of microbiome assembly, our understanding of it is still very limited. Recent theoretical and empirical work has proposed that large microbial communities may exhibit an emergent cohesiveness, as a result of collective consumer-resource interactions and metabolic feedbacks between microbial growth and the environment. A fundamental prediction of this proposal is the presence of ecological co-selection during community coalescence, where the invasion success of a given taxon is determined by its community members. To establish the generality of this prediction in experimental microbiomes, we have performed over one hundred invasion and coalescence experiments with environmental communities of different origins that had spontaneously and stably assembled in two different synthetic aerobic environments. We show that the dominant species of the coalesced communities can both recruit their community members (top-down co-selection) and be recruited by them (bottom-up co-selection) into the coalesced communities. Our results provide direct evidence that collective invasions generically produce ecological co-selection of interacting species, emphasizing the importance of community-level interactions during microbial community assembly.
Using supervised learning methods for gene selection in RNA-Seq case-control studies
Authors: Wenric Stephane , Shemirani Ruhollah
Published: March 2018

Whole transcriptome studies typically yield large amounts of data, with expression values for all genes or transcripts of the genome. The search for genes of interest in a particular study setting can thus be a daunting task, usually relying on automated computational methods. Moreover, most biological questions imply that such a search should be performed in a multivariate setting, to take into account the inter-genes relationships.

Differential expression analysis commonly yields large lists of genes deemed significant, even after adjustment for multiple testing, making the subsequent study possibilities extensive.

Here, we explore the use of supervised learning methods to rank large ensembles of genes defined by their expression values measured with RNA-Seq in a typical 2 classes sample set. First, we use one of the variable importance measures generated by the random forests classification algorithm as a metric to rank genes. Second, we define the EPS (extreme pseudo-samples) pipeline, making use of VAEs (Variational Autoencoders) and regressors to extract a ranking of genes while leveraging the feature space of both virtual and comparable samples.

We show that, on 12 cancer RNA-Seq data sets ranging from 323 to 1210 samples, using either a random forests based gene selection method or the EPS pipeline outperforms differential expression analysis for 9 and 8 out of the 12 datasets respectively, in terms of identifying subsets of genes associated with survival.

These results demonstrate the potential of supervised learning-based gene selection methods in RNA-Seq studies and highlight the need to use such multivariate gene selection methods alongside the widely used differential expression analysis.
Structural plasticity of CENP-A regulated by H4 influences cellular levels and kinetochore assembly
Authors: Malik Nikita , Dantu Sarath Chandra , Kombrabail Mamta , Ghosh Santanu Kumar , Krishnamoorthy Guruswamy , Kumar Ashutosh
Published: March 2018

The Histone variant CENP-ACse4 is a core component of the specialized nucleosome at the centromere in budding yeast. The level of Cse4 in cells is tightly regulated, primarily by ubiquitin-mediated proteolysis. However, the structural transitions in Cse4 that regulate centromere localization and interaction with regulatory components are poorly understood. Using time resolved fluorescence, NMR and molecular dynamics we show for the first time that soluble Cse4 can exist in a ‘closed’ conformation, inaccessible to various regulatory components. We further determined that binding of its obligate partner H4, alters the inter-domain interaction within Cse4, ensuring an ‘open’ state that will lend itself to proteolysis. This dynamic model allows kinetochore formation only in presence of H4, as the N-terminus, which is required for interaction with centromeric components will be unavailable in absence of H4. The specific requirement of H4 binding for the conformational regulation of Cse4 suggests a unique structure-based regulatory mechanism for Cse4 localization and prevention of premature kinetochore assembly.
Mutant Plasticity Related Gene 1 (PRG1) acts as a potential modifier in SCN1A related epilepsy
Authors: Knierim Ellen , Vogt Johannes , Kintscher Michael , Ponomarenko Alexey , Baumgart Jan , Beed Prateep , Korotkova Tatiana , Trimbuch Thorsten , Panzer Axel , Stephani Ulrich , Escayg Andrew , Lerche Holger , Nitsch Robert , Schmitz Dietmar , Schuelke Markus
Published: March 2018

Plasticity related gene 1 encodes a cerebral neuron-specific synaptic transmembrane protein that modulates hippocampal excitatory transmission on glutamatergic neurons. In mice, homozygous Prg1-deficiency results in juvenile epilepsy. Screening a cohort of 18 patients with infantile spasms (West syndrome), we identified one patient with a heterozygous mutation in the highly conserved third extracellular phosphatase domain (p.T299S). The functional relevance of this mutation was verified by in-utero electroporation of a mutant Prg1 construct into neurons of Prg1-knockout embryos, and the subsequent inability of hippocampal neurons to rescue the knockout phenotype on the single cell level. Whole exome sequencing revealed the index patient to additionally harbor a novel heterozygous SCN1A variant (p.N541S) that was inherited from her healthy mother. Only the affected child carried both heterozygous PRG1 and SCN1A mutations. The aggravating effect of Prg1-haploinsufficiency on the epileptic phenotype was verified using the kainate-model of epilepsy. Double heterozygous Prg1-/+|Scn1awt/p.R1648Hmice exhibited higher seizure susceptibility than either wildtype, Prg1-/+, or Scn1awt/p.R1648H littermates. Our study provides evidence that PRG1-mutations have a potential modifying influence on SCN1A-related epilepsy in humans.
Long-read DNA metabarcoding of ribosomal rRNA in the analysis of fungi from aquatic environments
Authors: Heeger Felix , Bourne Elizabeth C. , Baschien Christiane , Yurkov Andrey , Bunk Boyke , Spröer Cathrin , Overmann Jörg , Mazzoni Camila J. , Monaghan Michael T.
Published: March 2018

DNA metabarcoding is now widely used to study prokaryotic and eukaryotic microbial diversity. Technological constraints have limited most studies to marker lengths ofca.300-600 bp. Longer sequencing reads of several 5 thousand bp are now possible with third-generation sequencing. The increased marker lengths provide greater taxonomic resolution and enable the use of phylogenetic methods of classifcation, but longer reads may be subject to higher rates of sequencing error and chimera formation. In addition, most well-established bioinformatics tools for DNA metabarcoding were originally 10 designed for short reads and are therefore not suitable. Here we used Pacifc Biosciences circular consensus sequencing (CCS) to DNA-metabarcode environmental samples using aca.4,500 bp marker that included most of the eukaryote ribosomal SSU and LSU rRNA genes and the ITS spacer region. We developed a long-read analysis pipeline that reduced error rates to levels 15 comparable to short-read platforms. Validation using fungal isolates and a mock community indicated that our pipeline detected 98% of chimerasde novoi.e., even in the absence of reference sequences. We recovered 947 OTUs from water and sediment samples in a natural lake, 848 of which could be classifed to phylum, 486 to family, 397 to genus and 330 to species. By 20 allowing for the simultaneous use of three global databases (Unite, SILVA, RDP LSU), long-read DNA metabarcoding provided better taxonomic resolution than any single marker. We foresee the use of long reads enabling the cross-validation of reference sequences and the synthesis of ribosomal rRNA gene databases. The universal nature of the rRNA operon and our recovery of >100 25 non-fungal OTUs indicate that long-read DNA metabarcoding holds promise for the study of eukaryotic diversity more broadly.
Performance analysis of segmented rotor switched reluctance motors with three types of winding connections for belt-driven starter generators of hybrid electric vehicles
Authors: Sun Xiaodong , Zhou Zhuicai , Chen Long , Yang Zebin , Han Shouyi
Published: March 2018

Purpose

Inductance, torque and iron loss are the key parameters of switched reluctance motors for belt-driven starter generators. This paper aims to present the analysis of a segmented rotor switched reluctance motor (SSRM) with three types of winding connections for hybrid electric vehicle applications by using a two-dimensional finite element method.

Design/methodology/approach

The rotor of the studied SSRM consists of a series of discrete segments, while the stator is made up of exciting and auxiliary teeth. First, the concept and structures of the different winding connections are introduced. Then, the magnetic flux path of the three types of winding connections for the SSRM is described. Second, the magnetic flux distributions in the three parts, i.e. the stator yoke, the stator tooth and the rotor segment, are described in detail to calculate the iron losses. Third, three SSRMs with the different winding arrangements are analyzed and compared to evaluate the distinct features of the studied SSRM. The analysis and comparison mainly include self-inductances, mutual inductances, phase currents, output torque and iron loss.

Findings

It is found that the self-inductances of the three types of winding connections are almost equal, and only the SSRM1 has a positive mutual inductance. In addition, the current waveforms of SSRM1 and SSRM2 are regular. However, it is irregular in SSRM3. It is shown that SSRM1 has better characteristics, such as higher output torque, high power density, lower torque ripple and iron loss.

Originality/value

This paper proposes and analyzes three novel winding connections for the SSRM to provide guidance for enhancing the output torque and reducing the iron loss to achieve high efficiency.
State-of-the-art literature review on inventory models for perishable products
Authors: Chaudhary Vaibhav , Kulshrestha Rakhee , Routroy Srikanta
Published: March 2018

Purpose

The purpose of this paper is to review and analyze the perishable inventory models along various dimensions such as its evolution, scope, demand, shelf life, replenishment policy, modeling techniques and research gaps.

Design/methodology/approach

In total, 418 relevant and scholarly articles of various researchers and practitioners during 1990-2016 were reviewed. They were critically analyzed along author profile, nature of perishability, research contributions of different countries, publication along time, research methodologies adopted, etc. to draw fruitful conclusions. The future research for perishable inventory modeling was also discussed and suggested.

Findings

There are plethora of perishable inventory studies with divergent objectives and scope. Besides demand and perishable rate in perishable inventory models, other factors such as price discount, allow shortage or not, inflation, time value of money and so on were found to be combined to make it more realistic. The modeling of inventory systems with two or more perishable items is limited. The multi-echelon inventory with centralized decision and information sharing is acquiring lot of importance because of supply chain integration in the competitive market.

Research limitations/implications

Only peer-reviewed journals and conference papers were analyzed, whereas the manuals, reports, white papers and blood-related articles were excluded. Clustering of literature revealed that future studies should focus on stochastic modeling.

Practical implications

Stress had been laid to identify future research gaps that will help in developing realistic models. The present work will form a guideline to choose the appropriate methodology(s) and mathematical technique(s) in different situations with perishable inventory.

Originality/value

The current review analyzed 419 research papers available in the literature on perishable inventory modeling to summarize its current status and identify its potential future directions. Also the future research gaps were uncovered. This systemic review is strongly felt to fill the gap in the perishable inventory literature and help in formulating effective strategies to design of an effective and efficient inventory management system for perishable items.