bluuebunny/crossref_metadata_2025 huggingface dataset:
National Patient Safety Program in Brazil: Incidents Reported Between 2014 and 2017
Authors: Faustino Tássia Nery , Batalha Edenise Maria Santos da Silva , Vieira Silvana Lima , Nicole Andressa Garcia , Morais Alexandre Souza , Tronchin Daisy Maria Rizatto , Melleiro Marta Maria
Published: May 2018

Objective

The aim of the study was to analyze the patient safety incidents reported to the Brazilian National Health Surveillance System from March 2014 to March 2017.

Method

A documentary study that used the records of the incidents published in the Reports of Adverse Events (AE) in Brazil. The following variables were selected: number of incidents by type, type of health service, hospital unit, and degree of harm. To find whether there was a significant difference across the Brazilian regions by notifications related to general incidents, AE, and deaths, the analysis of variance and the Tukey tests were used.

Results

A total of 109,082 incidents were reported, of which 75,088 were AE, with 649 deaths. In relation to the types of incidents reported, there was a higher frequency in the categories other (30.04%) and failures during health care (26.72%). A total of 93.90% of the incidents occurred in hospitals, with 54,950 cases registered in hospitalization units and 30,141 cases in intensive care units. Statistically significant differences across the Brazilian regions were observed in the number of incidents (P = 0.004), AE (P = 0.004), and deaths (P = 0.024).

Conclusions

A significant underreporting of incidents was found in Brazil, demonstrating only the tip of a giant iceberg. More than half of the incidents were reported as AE and were registered in hospitals, reiterating the importance of establishing public health policies at national, state, and municipal levels, with adequate supervision of the health service regarding the implementation of the Patient Safety Nuclei and the preparation of new protocols based on the most prevalent incidents.
Biomarkers of Aging in HIV-Infected Children on Suppressive Antiretroviral Therapy
Authors: Shiau Stephanie , Strehlau Renate , Shen Jing , Violari Avy , Patel Faeezah , Liberty Afaaf , Foca Marc , Wang Shuang , Terry Mary Beth , Yin Michael T. , Coovadia Ashraf , Abrams Elaine J. , Arpadi Stephen M. , Kuhn Louise
Published: May 2018

Background:

Data on accelerated aging in HIV-infected children are limited. In this study, we assess 2 biomarkers of aging—telomere length and DNA methylation (DNAm) age—in a cohort of early-treated HIV-infected children and compare these aging biomarkers with HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children.

Setting:

Cross-sectional study of 120 HIV-infected, 33 HEU, and 25 HUU children enrolled in a cohort study in Johannesburg, South Africa. The mean age of children was 6.4 years at the time of measurement. HIV-infected children initiated ritonavir-boosted lopinavir–based antiretroviral therapy before 2 years of age and had been on continuous antiretroviral therapy until biomarker measurement.

Methods:

Telomere length was determined using multiplex quantitative polymerase chain reaction. DNAm was measured using the Illumina 450K array and DNAm age was calculated as the acceleration residual from regressing DNAm age on chronological age.

Results:

Telomere length (ln[Kb/genome]) was shorter in HIV-infected children compared with HUU children (4.14 ± 0.85 vs. 4.53 ± 0.79, P = 0.038) and in HEU children compared with HUU children (4.05 ± 0.74 vs. 4.53 ± 0.79, P = 0.023). Age acceleration residual based on DNAm levels was not different between HIV-infected (−0.003 ± 2.95), HEU (0.038 ± 2.39), and HUU (0.18 ± 2.49) children in unadjusted analysis and after adjustment for cell type proportions.

Conclusions:

Unlike reports of accelerated DNAm age in HIV-infected adults, there was no evidence of accelerated biological aging by DNAm levels in this cohort of early-treated HIV-infected children. By contrast, absolute telomere length was shorter in HIV-infected and HEU children compared with HUU children, but did not differ between HIV-infected and HEU children.
Continuum of HIV Care in Rural Mozambique: The Implications of HIV Testing Modality on Linkage and Retention
Authors: Lopez-Varela Elisa , Fuente-Soro Laura , Augusto Orvalho J. , Sacoor Charfudin , Nhacolo Ariel , Karajeanes Esmeralda , Vaz Paula , Naniche Denise
Published: May 2018

Introduction:

Context-specific improvements in the continuum of HIV care are needed to achieve the UNAIDS target of 90-90-90. This study aimed to assess the linkage to and retention in HIV care according to different testing modalities in rural southern Mozambique.

Methods:

Adults newly diagnosed with HIV from voluntary counseling and testing, provider-initiated counseling and testing, and home-based HIV testing services were prospectively enrolled between 2014 and 2015 at the Manhiça District. Patients were passively followed up through chart examination. Tracing was performed at 12 months to ascertain causes of loss to follow-up. Fine and Gray competing risk analysis was performed to determine factors associated with the each step of the cascade.

Results:

Overall linkage to care as defined by having a CD4 count at 3 months was 43.7% [95% confidence interval (CI): 40.8 to 46.6] and 25.2% of all participants initiated antiretroviral therapy. Factors associated with increased linkage in multivariable analysis included testing at voluntary counseling and testing, older age, having been previously tested for HIV, owning a cell phone, presenting with WHO clinical stages III/IV, self-reported illness-associated disability in the previous month, and later calendar month of participant recruitment. Ascertaining deaths and transfers allowed for adjustment of the rate of 12-month retention in treatment from 75.6% (95% CI: 70.2 to 80.5) to 84.2% (95% CI: 79.2 to 88.5).

Conclusions:

Home-based HIV testing reached a sociodemographically distinct population from that of clinic-based testing modalities but low linkage to care points to a need for facilitated linkage interventions. Distinguishing between true treatment defaulting and other causes of loss to follow-up can significantly change indicators of retention in care.
Using a Social Network Strategy to Distribute HIV Self-Test Kits to African American and Latino MSM
Authors: Lightfoot Marguerita A. , Campbell Chadwick K. , Moss Nicholas , Treves-Kagan Sarah , Agnew Emily , Kang Dufour Mi-Suk , Scott Hyman , Sa'id Aria M. , Lippman Sheri A.
Published: May 2018

Background:

Men who have sex with men (MSM) continue to be disproportionately impacted globally by the HIV epidemic. Studies suggest that HIV self-testing (HIVST) is highly acceptable among MSM. Social network strategies to increase testing are effective in reaching MSM, particularly MSM of color, who may not otherwise test. We tested a social network–based strategy to distribute HIVST kits to African American MSM (AAMSM) and Latino MSM (LMSM).

Setting:

This study was conducted in Alameda County, California, a large, urban/suburban county with an HIV epidemic mirroring the national HIV epidemic.

Methods:

From January 2016 to March 2017, 30 AAMSM, LMSM, and transgender women were trained as peer recruiters and asked to distribute 5 self-test kits to MSM social network members and support those who test positive in linking to care. Testers completed an online survey after their test. We compared peer-distributed HIVST testing outcomes to outcomes from Alameda County's targeted, community-based HIV testing programs using χ2 tests.

Results:

Peer-distributed HIVST to 143 social and sexual network members, of whom 110 completed the online survey. Compared with MSM who used the County's sponsored testing programs, individuals reached through the peer-based self-testing strategy were significantly more likely to have never tested for HIV (3.51% vs. 0.41%, P < 0.01) and to report a positive test result (6.14% vs. 1.49%, P < 0.01).

Conclusion:

Findings suggest that a network-based strategy for self-test distribution is a promising intervention to increase testing uptake and reduce undiagnosed infections among AAMSM and LMSM.
Individual and Network Factors Associated With HIV Care Continuum Outcomes Among Nigerian MSM Accessing Health Care Services
Authors: Ramadhani Habib O. , Ndembi Nicaise , Nowak Rebecca G. , Ononaku Uchenna , Gwamna Jerry , Orazulike Ifeanyi , Adebajo Sylvia , Crowell Trevor A. , Liu Hongjie , Baral Stefan D. , Ake Julie , Charurat Man E. ,   For the TRUST/RV368 Study Group
Published: May 2018

Background and Setting:

Because data on the determinants of the HIV care continuum from key populations such as men who have sex with men (MSM) in resource-limited settings are limited, the study aimed to characterize HIV care continuum outcomes and assess individual and network barriers to progression through the HIV care continuum among MSM in Abuja and Lagos, Nigeria.

Methods:

TRUST/RV368 study used respondent-driven sampling to accrue MSM into community-based clinics in Nigeria. Participants received HIV testing at enrollment. HIV-infected participants were offered antiretroviral therapy (ART) with HIV RNA testing every 3 months (Abuja) or 6 months (Lagos). Multiple logistic regression models were used to calculate adjusted odds ratios for factors associated with each point in the HIV care continuum, including HIV testing, ART initiation, and 6-month viral suppression.

Results:

A total of 1506 MSM were recruited, 1178 (78.2%) tested for HIV and 369 (31.3%) were HIV positive newly diagnosed. Of these, 188 (50.1%) initiated ART, 136 (72.3%) completed 6 months, and 96 (70.6%) were virally suppressed. Larger network size and stronger social network support were each positively associated with HIV testing uptake. Factors associated with ART initiation were higher education and stronger social network support. Having stronger social network support was associated with increased odds of viral suppression at 6 months.

Conclusions:

Social determinants of health potentiated increased HIV care continuum outcomes. Integration of HIV prevention, HIV counseling and testing services, and universal coverage of ART into a community-based clinic is critical in achieving better HIV care continuum outcomes.
Brief Report: No HIV Transmission From Virally Suppressed Mothers During Breastfeeding in Rural Tanzania
Authors: Luoga Ezekiel , Vanobberghen Fiona , Bircher Rahel , Nyuri Amina , Ntamatungiro Alex J. , Mnzava Dorcas , Mollel Getrud J. , Letang Emilio , Battegay Manuel , Weisser Maja , Gamell Anna ,   on behalf of the KIULARCO Study Group
Published: May 2018

Background:

To what extent antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) during breastfeeding remains unclear. We assessed the MTCT risk from mothers on ART to their infants during breastfeeding.

Setting:

Ifakara, rural Tanzania.

Methods:

We included infants born between January 2013 and May 2016 to mothers who initiated ART before delivery, had a negative HIV DNA polymerase chain reaction at 4–12 weeks and exclusively breastfed for ≥6 months. Mothers' plasma HIV-RNA viral loads (VLs) were measured up to 11 months postdelivery. Infants were tested for HIV following national guidelines.

Results:

Among 214 women with 218 pregnancies and 228 infants (10 twins), the median age at delivery was 33 years (interquartile range 28–36 years), and the mean time on ART was 23 months (interquartile range, 4–52 months). VL was measured twice in 53% (113/218) of pregnancies. During breastfeeding, 91% of mothers (199/218) had VL of <1000 copies per milliliter, and 75% (164/218) had <100 copies per milliliter. To November 2017, 8% (19/228) of infants were lost to follow-up (LTFU), 2% (5/228) transferred, and 8% (18/228) died before the determination of final HIV serostatus. Among the remaining 186 infants, 2 (1%; 95% confidence interval: 0.3% to 4%) were HIV positive: 1 born from a mother with high VL 1-month postdelivery and 1 from a mother who interrupted ART. Assuming a 15% MTCT risk through breastfeeding among the 42 infants LTFU, transferred, or dead, the overall MTCT risk would be 4%.

Conclusions:

We found no MTCT from mothers who were retained in care and had suppressed VL. Breastfeeding signifies a very low risk when mothers adhere to ART. Adherence counseling, VL monitoring, and strategies to trace back those LTFU should be a priority.
Modeling Gadoxetate Liver Uptake and Efflux Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging Enables Preclinical Quantification of Transporter Drug-Drug Interactions
Authors: Georgiou Leonidas , Penny Jeffrey , Nicholls Glynis , Woodhouse Neil , Blé François-Xavier , Naish Josephine H. , Hubbard Cristinacce Penny L.
Published: May 2018

Objectives

The aim of this study was to model the in vivo transporter-mediated uptake and efflux of the hepatobiliary contrast agent gadoxetate in the liver. The efficacy of the proposed technique was assessed for its ability to provide quantitative insights into drug-drug interactions (DDIs), using rifampicin as inhibitor.

Materials and Methods

Three groups of C57 mice were scanned twice with a dynamic gadoxetate-enhanced magnetic resonance imaging protocol, using a 3-dimensional spoiled gradient-echo sequence for approximately 72 minutes. Before the second magnetic resonance imaging session, 2 of the groups received a rifampicin dose of 20 (n = 7) or 40 (n = 7) mg/kg, respectively. Data from regions of interest in the liver were analyzed using 2 simplifications of a 2-compartment uptake and efflux model to provide estimates for the gadoxetate uptake rate (k
i) into the hepatocytes and its efflux rate (k
ef) into the bile. Both models were assessed for goodness-of-fit in the group without rifampicin (n = 9), and the appropriate model was selected for assessing the ability to monitor DDIs in vivo.

Results

Seven of 9 mice from the group without rifampicin were assessed for model implementation and reproducibility. A simple 3 parameter model (k
i, k
ef, and extracellular space, v
ecs) adequately described the observed liver concentration time series with mean k
i = 0.47 ± 0.11 min−1 and mean k
ef = 0.039 ± 0.016 min−1. Visually, the area under the liver concentration time profile was reduced for the groups receiving rifampicin. Furthermore, tracer kinetic modeling demonstrated a significant dose-dependent decrease in the uptake (5.9- and 17.3-fold decrease for 20 mg/kg and 40 mg/kg, respectively) and efflux rates (2.2- and 7.9-fold decrease) compared with the first scan for each group.

Conclusions

This study presents the first in vivo implementation of a 2-compartment uptake and efflux model to monitor DDIs at the transporter-protein level, using the clinically relevant organic anion transporting polypeptide inhibitor rifampicin. The technique has the potential to be a novel alternative to other methods, allowing real-time changes in transporter DDIs to be measured directly in vivo.
The Influence of Socioeconomic Factors on the Epidemiology of Maxillofacial Fractures in Southern Italy
Authors: Sbordone Carolina , Barca Ida , Petrocelli Marzia , Dell’Aversana Orabona Giovanni , Vaira Luigi Angelo , Colangeli Walter , Cristofaro Maria Giulia , Giudice Mario , Giudice Amerigo , Cassandro Francesco Maria , Attanasi Federica , Iaconetta Giorgio , Califano Luigi
Published: May 2018

Maxillofacial fractures represent a serious public health problem. Their epidemiology is extremely variable and its analysis is crucial to establish effective treatment and prevention of these injuries. The aim of this multicentric retrospective study was to analyze causes, demographics, incidence, characteristics of 987 patients diagnosed with maxillofacial trauma between 2011 and 2015 at Complex Operative Unit of Maxillofacial Surgery of Federico II University of Naples and Magna Graecia University of Catanzaro, Italy; 657 male and 310 female patients were admitted in the study. The most frequently observed fracture involved the mandible (399 patients, 35.4%), followed by zygomatic complex (337 patients, 29.9%), orbital walls (160 patients, 14.2%), and nasal bones (129 patients, 11.4%). The most frequent cause of fracture was assaults (30.4%), followed by road traffic injuries (27.2%), falls (23.2%), sport accidents (15.4%), and others causes (2.6%). Significant variations of etiology have been detected between the 2 hospitals in relationship with different migration flow trends and cultural and socioeconomic features. Epidemiological analysis of maxillofacial fractures is crucial to identify the trauma burden and to help in developing a more efficient system to plan resource allocation and to deliver care and preventive measures establishing clinical and research priorities for effective treatment and prevention of these injuries.
Unilateral Buccinator Flap for Lengthening of Short Palate
Authors: Hassani Mohammad-Esmaiil , Latifi Noor-Ahmad , Karimi Hamid , Khakzad Mohammad
Published: May 2018

Background:

Velopharyngeal insufficiency is one of the most frequent complications after cleft palate repair.

Purpose:

To evaluate the results and complications of unilateral Buccinator flap (BMF) in velopharyngeal insufficiency.

Materials and Methods:

During 4 years the authors performed unilateral BMF in all short palates. Age, sex, demographic data, length of palate, cause of short palate, nasopharyngoscopy and videofluroscopy results, hyper nasality, nasal escape, nasal emission, nasal fluid leak, speech evaluation and results, outcome and complications of the treatment were surveyed before surgery and in 1, 3, 6 months after treatment.

Results:

The authors had 43 patients, 29 below 8 years old and 14 adults. Velopharyngeal gap was between 10 and 27 mm, mean 21 mm. Buccinator flap were measuring 15 to 19 mm in width and 32 to 56 mm in length. The operation time was 80 to 100 minutes, mean 86 minutes.

Nasal emission, nasal escape, and nasal leak were treated in all patients.

Hyper nasality was completely improved in all of the patients below 8 years old (29 patients) and in 10 patients of the adults (totally 39 patients, 90.6%). And it was improved significantly in other 4 patients (9.4%). The speech evaluation reported between 70% and 86% improvements.

The lengthening of the palate was between 12 and 19 mm, mean 17 mm.

The satisfaction of the patients was as 0% poor, 2.3% fair, 72.1% good, and 25.6% excellent.

Conclusion:

Unilateral BMF is reliable, promising, and safe flap for lengthening of short palate and it can lengthen the palate up to 19 mm. The time of surgery is very short compared with other methods. It is an anatomical treatment versus pharyngeal flap which is not an anatomical one. Speech improvement will achieve in 70% to 86% patients.
Perceived Esthetic Outcomes of Face Transplantation: A Survey of the General Public
Authors: Cabrera Alessandra E. , Kimberly Laura L. , Kantar Rami S. , Atamian Elisa K. , Manjunath Amit K. , Rangel Lauren K. , McQuinn Michelle W. , Diaz-Siso J. Rodrigo , Rodriguez Eduardo D.
Published: May 2018

Facial transplantation (FT) has attracted the interest of individuals with facial disfigurement as a path to social reintegration. The perception among face transplant recipients and the reconstructive surgery community appears to be that superior functional and esthetic outcomes can be obtained with FT compared to autologous reconstruction (AR). Although lifelong immunosuppression adds well-known risks to FT, its benefits have proven difficult to quantify, especially because of its non-life-saving nature. Evidence that the general public perceives facial allograft recipients as less disfigured than AR patients may dramatically alter the currently accepted risk/benefit ratio of this novel procedure. A survey containing independent images of individuals in nondisfigured (ND), autologous facial reconstruction, and FT groups was administered to the general public in an urban environment. Participants assigned a disfigurement score to each photograph using the Observer-Rated Facial Disfigurement Scale, a validated instrument used to rate facial disfigurement among head and neck cancer patients. One-way analysis of variance was used to calculate differences in mean level of perceived facial disfigurement among the 3 groups. A total of 250 participants completed the survey. Mean perceived disfigurement scores assigned to the ND, FT, and AR groups were 1.2 ± 0.4, 4.9 ± 1.3, and 8.5 ± 0.6, respectively. A significant difference in disfigurement score was observed between all 3 groups (P < 0.001). This pilot study suggests that the general public perceives the esthetic outcome of FT to be superior to those obtained with AR in patients with severe facial defects.
Exploring Validation and Verification
Authors: Barnes John Jacob , Konia Mojca Remskar
Published: May 2018

Summary Statement

The healthcare simulation (HCS) community recognizes the importance of quality management because many novel simulation devices and techniques include some sort of description of how they tested and assured their simulation's quality. Verification and validation play a key role in quality management; however, literature published on HCS has many different interpretations of what these terms mean and how to accomplish them. The varied use of these terms leads to varied interpretations of how verification process is different from validation process. We set out to explore the concepts of verification and validation in this article by reviewing current psychometric science description of the concepts and exploring how other communities relevant to HCS, such as medical device manufacturing, aviation simulation, and the fields of software and engineering, which are building blocks of technology-enhanced HCS, use the terms, with the focus of trying to clarify the process of verification. We also review current literature available on verification, as compared with validation in HCS and, finally, offer a working definition and concept for each of these terms with hopes to facilitate improved communication within, and with colleagues outside, the HCS community.
Using Technology to Enhance Teaching of Patient-Centered Interviewing for Early Medical Students
Authors: Kaltman Stacey , Talisman Nicholas , Pennestri Susan , Syverson Eleri , Arthur Paige , Vovides Yianna
Published: May 2018

Introduction

Effective strategies for teaching communication skills to health professions students are needed. This article describes the design and evaluation of immersive and interactive video simulations for medical students to practice basic communication skills.

Methods

Three simulations were developed, focusing on patient-centered interviewing techniques such as using open-ended questions, reflections, and empathic responses while assessing a patient's history of present illness. First-year medical students were randomized to simulation or education-as-usual arms. Students in the simulation arm were given access to three interactive video simulations developed using Articulate Storyline, an e-learning authoring tool, to practice and receive feedback on patient-centered interviewing techniques to prepare for their Observed Structured Clinical Examination (OSCE). Trained raters evaluated videos of two OSCE cases for each participant to assess specific communication skills used during the history of present illness component of the interview.

Results

Eighty-seven percent of the students in the simulation arm interacted with at least one simulation during the history of present illness. For both OSCE cases, students in the simulation arm asked significantly more open-ended questions. Students in the simulation arm asked significantly fewer closed-ended questions and offered significantly more empathic responses in one OSCE case. No differences were found for reflections. Students reported that the simulations helped improve their communication skills.

Conclusion

The use of interactive video simulations was found to be feasible to incorporate into the curriculum and was appealing to students. In addition, students in the simulation arm displayed more behaviors consistent with the patient-centered interviewing model practiced in the simulations. Continued development and research are warranted.
Detection of Deteriorating Patients on Surgical Wards Outside the ICU by an Automated MEWS-Based Early Warning System With Paging Functionality
Authors: Heller Axel R. , Mees Sören T. , Lauterwald Benjamin , Reeps Christian , Koch Thea , Weitz Jürgen
Published: May 2018

Background:

The establishment of early warning systems in hospitals was strongly recommended in recent guidelines to detect deteriorating patients early and direct them to adequate care. Upon reaching predefined trigger criteria, Medical Emergency Teams (MET) should be notified and directed to these patients. The present study analyses the effect of introducing an automated multiparameter early warning score (MEWS)-based early warning system with paging functionality on 2 wards hosting patients recovering from highly complex surgical interventions.

Methods:

The deployment of the system was accompanied by retrospective data acquisition during 12 months (intervention) using 4 routine databases: Hospital patient data management, anesthesia database, local data of the German Resuscitation Registry, and measurement logs of the deployed system (intervention period only). A retrospective 12-month data review using the same aforementioned databases before the deployment of the system served as control. Control and intervention phases were separated by a 6-month washout period for the installation of the system and for training.

Results:

Data from 3827 patients could be acquired from 2 surgical wards during the two 12-month periods, 1896 patients in the control and 1931 in the intervention cohorts. Patient characteristics differed between the 2 observation phases. American Society of Anesthesiologists risk classification and duration of surgery as well as German DRG case-weight were significantly higher in the intervention period. However, the rate of cardiac arrests significantly dropped from 5.3 to 2.1 per 1000 admissions in the intervention period (P < 0.001). This observation was paralleled by a reduction of unplanned ICU admissions from 3.6% to 3.0% (P < 0.001), and an increase of notifications of critical conditions to the ward surgeon. The primary triggers for MET activation were abnormal ECG alerts, specifically asystole (n = 5), and pulseless electric activity (n = 8).

Conclusion:

In concert with a well-trained and organized MET, the early deterioration detection of patients on surgical wards outside the ICU may be improved by introducing an automated MEWS-based early warning system with paging functionality.
Specifying a causal role for angular gyrus in autobiographical memory
Authors: Bonnici Heidi M. , Cheke Lucy G. , Green Deborah A.E. , FitzGerald Thomas H.B. , Simons Jon S.
Published: May 2018

Considerable recent evidence indicates that angular gyrus dysfunction does not result in amnesia, but does impair a number of aspects of episodic memory. Patients with parietal lobe lesions have been reported to exhibit a deficit when freely recalling autobiographical events from their pasts, but can remember details of the events when recall is cued by specific questions. In apparent contradiction, inhibitory brain stimulation targeting angular gyrus in healthy volunteers has been found to have no effect on free recall or cued recall of word pairs. The present study sought to resolve this inconsistency by testing free and cued recall of both autobiographical memories and word pair memories in the same healthy participants following continuous theta burst stimulation (cTBS) of angular gyrus and a vertex control location. Angular gyrus cTBS resulted in a selective reduction in the free recall but not cued recall of autobiographical memories, whereas free and cued recall of word pair memories were unaffected. Additionally, participants reported fewer autobiographical episodes as being experienced from a first-person perspective following angular gyrus cTBS. The findings add to a growing body of evidence that a function of angular gyrus within the network of brain regions responsible for episodic recollection is to integrate memory features within an egocentric framework into the kind of first-person perspective representation that enables the subjective experience of remembering events from our personal pasts.
Efficient long single molecule sequencing for cost effective and accurate sequencing, haplotyping, and de novo assembly
Authors: Wang Ou , Chin Robert , Cheng Xiaofang , Ka Wu Michelle , Mao Qing , Tang Jingbo , Sun Yuhui , Anderson Ellis , Lam Han K. , Chen Dan , Zhou Yujun , Wang Linying , Fan Fei , Zou Yan , Xie Yinlong , Yu Zhang Rebecca , Drmanac Snezana , Nguyen Darlene , Xu Chongjun , Villarosa Christian , Gablenz Scott , Barua Nina , Nguyen Staci , Tian Wenlan , Sophie Liu Jia , Wang Jingwan , Liu Xiao , Qi Xiaojuan , Chen Ao , Wang He , Dong Yuliang , Zhang Wenwei , Alexeev Andrei , Yang Huanming , Wang Jian , Kristiansen Karsten , Xu Xun , Drmanac Radoje , Peters Brock A.
Published: May 2018

Obtaining accurate sequences from long DNA molecules is very important for genome assembly and other applications. Here we describe single tube long fragment read (stLFR), a technology that enables this a low cost. It is based on adding the same barcode sequence to sub-fragments of the original long DNA molecule (DNA co-barcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process up to 3.6 billion unique barcode sequences were generated on beads, enabling practically non-redundant co-barcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique co-barcoding of over 8 million 20-300 kb genomic DNA fragments. Analysis of the genome of the human genome NA12878 with stLFR demonstrated high quality variant calling and phasing into contigs up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries and their construction did not significantly add to the time or cost of whole genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.
Strain-level overlap between infant and hospital fungal microbiomes revealed throughde novoassembly of eukaryotic genomes from metagenomes
Authors: Olm Matthew R. , West Patrick T. , Brooks Brandon , Firek Brian A. , Baker Robyn , Morowitz Michael J. , Banfield Jillian F.
Published: May 2018

Eukaryotes are a leading cause of nosocomial infections in neonates, but their diversity and population heterogeneity are rarely investigated. This has led to an incomplete understanding of eukaryotic strains that colonize infants and of the neonatal intensive care unit (NICU) as a possible source of these strains. Analysis of 1,174 time-series metagenomes from 161 premature infants revealed fungal colonization of 13 infants, primarily in the first two weeks of life. Nearly all 24 NICU samples contained eukaryotes, and the most diverse communities were in NICU sinks. Five of fourteen newly-assembled eukaryotic genomes derived from genomically undescribed species.Purpureocillium lilacinumgenomes from infant and NICU samples shared 99.999% average nucleotide identity, highlighting the potential of hospital-associated fungi to colonize hospitalized infants. We quantified zygosity and within-population variation associated with the diploid eukaryotes, and thus defined the genetic reservoirs of eukaryotes in room environments and infants.
Integrated RNA-seq and sRNA-seq revealed differences in transcriptome between susceptible and resistant tomato responding toFusarium oxysporum
Authors: Zhao Min , Ji Hui-Min , Gao Ying , Cao Xin-Xin , Mao Hui-Ying , Liu Peng , Ouyang Shou-Qiang
Published: May 2018

Tomato wilt disease caused byFusarium oxysporumf. sp.lycopersici(FOL) is a worldwide destructive disease of tomato. As exploring gene expression and function approaches constitute an initial point for investigating pathogen-host interaction, we performed RNA-seq and sRNA-seq analysis to unravel regulated genes and miRNAs in tomato infected by FOL. Differentially expressed (DE) protein coding gene and miRNA gene profiles upon inoculation with FOL were presented at twenty-four hours post-inoculation including four treatments. Total of more than 182.6 million and 132.2 million high quality clean reads were obtained by RNA-seq and sRNA-seq, respectively. A large overlap was found in DE mRNAs between susceptible cultivar Moneymaker and resistant cultivar Motelle. All Gene Ontology terms were mainly classified into catalytic activity, metabolic process and binding. Combining with qRT-PCR, five disease resistance genes, Solyc01g095630, Solyc03g059080, Solyc00g174340, Solyc11g071750 and Solyc05g050350, were verified to involved in the disease resistance in the resistant cultivar Motelle treated with FOL. Northern blot analysis further confirmed the results from sRNA-Seq and demonstrated that several miRNAs including Sly-miR477-5p, sly-miR167a, novel_mir_675, novel_mir_504 and novel_mir_762 conferred FOL infection. Our data resulted that pathogen resistant genes/miRNAs may play a critical role with the benefit of a coordinated machinery in prompting the response in prompting FOL response in tomato, which offered us with a future direction and surely help in generating models of mediated resistance responses with assessment of genomic gene expression patterns.
Transient effect of mossy fiber stimulation on spatial firing of CA3 neurons
Authors: Lee Joonyeup , Yun Miru , Cho Eunjae , Lee Jong Won , Lee Doyun , Jung Min Whan
Published: May 2018

Strong hippocampal mossy fiber synapses are thought to function as detonators, imposing ‘teaching’ signals onto CA3 neurons during new memory formation. For an empirical test of this long-standing view, we examined effects of stimulating mossy fibers on spatial firing of CA3 neurons in freely-moving mice. We found that optogenetic stimulation of mossy fibers can alter CA3 spatial firing, but their effects are only transient. Spatially restricted mossy fiber stimulation, either congruent or incongruent with CA3 place fields, was more likely to suppress than enhance CA3 neuronal activity. Also, changes in spatial firing induced by optogenetic stimulation reverted immediately upon stimulation termination, leaving CA3 place fields unaltered. Our results do not support the traditional view that mossy fibers impose teaching signals onto CA3 network, and show robustness of established CA3 spatial representations.
Japanese Encephalitis Virus Infected Microglial Cells Secrete Exosomes Containing let-7a/b that Facilitate Neuronal Damage via Caspase Activation
Authors: Mukherjee Sriparna , Akbar Irshad , Kumari Bharti , Vrati Sudhanshu , Basu Anirban , Banerjee Arup
Published: May 2018

Extracellular microRNAs (miRNAs) are essential for the cell to cell communication in the healthy and diseased brain. MicroRNAs released from the activated microglia upon neurotropic virus infection may exacerbate CNS damage. Here, we identified let-7a and let-7b (let-7a/b) as the overexpressed miRNAs in Japanese Encephalitis virus (JEV) infected microglia and assessed their role in JEV pathogenesis. We measured the let-7a/b expressions in JEV infected post-mortem human brains, mice brains and in mouse microglial N9 cells by the qRT-PCR and in situ hybridization assay. The interaction between let-7a/b and NOTCH signaling pathway further examined in Toll-like receptor 7 knockdown (TLR7 KD) mice to assess the functions. Exosomes released from JEV infected or let-7a/b mimic transfected N9, and HEK-293 cells were isolated and evaluated their function. We observed an upregulation of let-7a/b in the infected brains as well as in microglia. Knockdown of TLR7 or Inhibition of let-7a/b suppressed the JEV induced NOTCH activation possibly via NF-κB dependent manner and subsequently, attenuated JEV induced TNFα production in microglial cells. Further, exosomes secreted from JEV-infected microglial cells specifically contained let-7a/b. Exosomes overexpressed with let-7a/b were injected into BALB/c mice as well as co-incubated with mouse neuronal (Neuro2a) cells, or primary cortical neuron resulted in caspase activation leading to neuronal damage in the brain. Thus, our results provide evidence for the multifaceted role of let-7a/b miRNAs and unravel the exosomes mediated mechanism for JEV induced pathogenesis.
Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1
Authors: Ye Siying , Cowled Chris , Yap Cheng-Hon , Stambas John
Published: May 2018

Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly up-regulated, including the cell adhesion moleculeCEACAM1. The up-regulation ofCEACAM1was blocked in the presence of the reactive oxygen species inhibitor, apocynin. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to low pathogenic PR8 H1N1 virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenousCEACAM1resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.
Characterization of apo-form selective inhibition of indoleamine 2,3-dioxygenase
Authors: Ortiz-Meoz Rodrigo , Wang Liping , Matico Rosalie , Rutkowska Anna , De la Rosa Martha , Bedard Sabrina , Midgett Robert , Strohmer Katrin , Thomson Douglas , Zhang Cunyu , Mebrahtu Makda , Guss Jeffrey , Totoritis Rachel , Consler Thomas , Campobasso Nino , Taylor David , Lewis Tia , Weaver Kurt , Mülbaier Marcel , Seal John , Dunham Richard , Kazmierski Wieslaw , Favre David , Bergamini Giovanna , Shewchuk Lisa , Rendina Alan , Zhang Guofeng
Published: May 2018

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of established and novel IDO1 inhibitors remains of great interest. Comparison of a newly-developed IDO1 inhibitor (GSK5628) to the existing best-in-class compound, epacadostat (Incyte), allows us to report on a unique inhibition mechanism for IDO1. Here, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1) while epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition may help design superior inhibitors or may confer a unique competitive advantage over other IDO1 inhibitorsvis-à-visspecificity and pharmacokinetic parameters.
Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4
Authors: Kattnig D. R. , Nielsen C. , Solov’yov I. A.
Published: May 2018

Birds appear to be equipped with a light-dependent, radical-pair-based magnetic compass that relies on truly quantum processes. While the identity of the sensory protein has remained speculative, cryptochrome 4 has recently been identified as the most auspicious candidate. Here, we report on allatom molecular dynamics (MD) simulations addressing the structural reorganisations that accompany the photoreduction of the flavin cofactor in a model of the European robin cryptochrome 4 (ErCry4). Extensive MD simulations reveal that the photo-activation of ErCry4 induces large-scale conformational changes on short (hundreds of nanoseconds) timescales. Specifically, the photo-reduction is accompanied with the release of the C-terminal tail, structural rearrangements in the vicinity of the FAD-binding site, and the noteworthy formation of an α-helical segment at the N-terminal part. Some of these rearrangements appear to expose potential phosphorylation sites. We describe the conformational dynamics of the protein using a graph-based approach that is informed by the adjacency of residues and the correlation of their local motions. This approach reveals densely coupled reorganisation communities, which facilitate an efficient signal transduction due to a high density of hubs. These communities are interconnected by a small number of highly important residues characterized by high betweenness centrality. The network approach clearly identifies the sites restructuring upon photoactivation, which appear as protrusions or delicate bridges in the reorganisation network. We also find that, unlike in the homologous cryptochrome fromD. melanogaster, the release of the C-terminal domain does not appear to be correlated with the transposition of a histidine residue close to the FAD cofactor.
Evolution of sex determination and heterogamety changes in sectionOtitesof the genusSilene
Authors: Balounova, Veronika , Gogela Roman , Cegan Radim , Cangren Patrik , Zluvova Jitka , Safar Jan , Kovacova Viera , Bergero Roberta , Hobza Roman , Vyskot Boris , Oxelman Bengt , Charlesworth Deborah , Janousek Bohuslav
Published: May 2018

Switches in heterogamety occasionally occur both in animals and plants, although plant sex determination systems are mostly more recently evolved than those of animals, and have had less time for switches to occur. However, our previous research revealed a switch in heterogamety in sectionOtitesof the plant genusSilene.

Here we analyse in detail the evolution of genetic sex determination in sectionOtites, which is estimated to have evolved about 0.55 MYA. Our study confirms female heterogamety inS. otitesand newly reveals female heterogamety inS. borysthenica. Sequence analyses and genetic mapping show that the sex-linked regions of these two species are the same, but the region inS. colpophylla, a close relative with male heterogamety, is different. The sex chromosome pairs ofS. colpophyllaandS. otiteseach correspond to an autosome of the other species, and both differ from the XY pair inS. latifolia, in a different section of the genus. Our phylogenetic analysis suggests a possible change from female to male heterogamety withinSilenesectionOtites,making these species suitable for detailed studies of the events involved.
The effectiveness of clove oil and cautery disbudding methods on preventing horn growth in dairy goat kids
Authors: Hempstead Melissa N , Waas Joseph R. , Stewart Mairi , Cave Vanessa M. , Turner Amanda R. , Sutherland Mhairi A.
Published: May 2018

The effectiveness of clove oil and cautery disbudding on horn growth was evaluated in goat kids. The study used 243 Saanen doe kids (4±1.0 days old; mean ± SD) on two commercial dairy goat farms, and were disbudded with either (i) clove oil injection (CLOVE), (ii) a cautery iron and bud removed (BUDOFF), or (iii) a cautery iron with bud left intact (BUDON). Each kid received a different treatment per bud, which were balanced between buds (left and right) and randomly allocated. A trained observer monitored bud growth following treatment for 3 months recording either: N: no growth, H: normal horn, S: abnormal horn (scur), or SC: soft, fibrous lump (scorn). After the final observation, buds were assessed for the probability of detecting (i) success (no growth), (ii) scurs, (iii) horns or (iv) scorns [with 95% CI]. The probability of success for BUDOFF (0.77 [0.63, 0.87]) was higher than for BUDON (0.20 [0.11, 0.34]) and CLOVE (0.09 [0.04, 0.18]; P ≤ 0.05). Furthermore, the probability of success for BUDON was higher than for CLOVE (P ≤ 0.05). The probability of scurs was higher for CLOVE (0.72 [0.63, 0.80]) than BUDOFF (0.25 [0.17, 0.34]) and BUDON (0.30 [0.21, 0.39]; P ≤ 0.05). There was no difference in the probability of scurs for BUDOFF and BUDON (P > 0.05). The probability of horns was higher for CLOVE (0.21 [0.15, 0.29]) than BUDON (0.02 [0.01, 0.06]; P ≤ 0.05); horns were not observed for BUDOFF. The probability of scorns for BUDON, the only treatment that led to scorns, was 0.41 (0.25, 0.60). These results suggest that BUDOFF was more effective at preventing growth than CLOVE and BUDON and appears the most effective method, of the methods tested, for disbudding kids. Future research should explore different clove oil administration methods or other alternatives to cautery disbudding that may be both efficacious and cause less pain.
Molecular analysis of long non-coding RNA GAS5 and microRNA-34a expression signature in common solid tumors: A pilot study
Authors: Toraih Eman A. , Alghamdi Saleh Ali , El-Wazir Aya , Hosny Marwa M , Hussein Mohammad H. , Khashana Motaz S. , Fawzy Manal S.
Published: May 2018

Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and glioblastoma (GB) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. GAS5 was significantly under-expressed in the three types of cancer. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003-22.69),p<0.001] and a decreased expression in GB [0.35 (0.04-0.95),p<0.001]. A weak negative correlation was observed between levels of GAS5 and miR-34a in GB [r = −0.39,p=0.006]. Univariate analyses revealed a correlation ofGAS5downregulation with poor disease-free survival (r = 0.31,p=0.018) and overall survival (r = 0.28,p=0.029) in RCC but not in GB, and a marginal significance correlation with a higher number of lesions in HCC. Hierarchical clustering analysis showed RCC patients among others, could be clustered by GAS5 and miR-34a co-expression profile. Our results confirm the tumor suppressor role of GAS5 in cancer and suggest its potential applicability to be a predictor of bad outcomes with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.