bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling sRNA-Seq data to study RNA communication between species
Authors: Bermúdez-Barrientos José Roberto , Ramírez-Sánchez Obed , Chow Franklin Wang-Ngai , Buck Amy H , Abreu-Goodger Cei
Published: December 2019

Many organisms exchange small RNAs (sRNAs) during their interactions, that can target or bolster defense strategies in host–pathogen systems. Current sRNA-Seq technology can determine the sRNAs present in any symbiotic system, but there are very few bioinformatic tools available to interpret the results. We show that one of the biggest challenges comes from sequences that map equally well to the genomes of both interacting organisms. This arises due to the small size of the sRNAs compared to large genomes, and because a large portion of sequenced sRNAs come from genomic regions that encode highly conserved miRNAs, rRNAs or tRNAs. Here, we present strategies to disentangle sRNA-Seq data from samples of communicating organisms, developed using diverse plant and animal species that are known to receive or exchange RNA with their symbionts. We show that sequence assembly, both de novo and genome-guided, can be used for these sRNA-Seq data, greatly reducing the ambiguity of mapping reads. Even confidently mapped sequences can be misleading, so we further demonstrate the use of differential expression strategies to determine true parasite-derived sRNAs within host cells. We validate our methods on new experiments designed to probe the nature of the extracellular vesicle sRNAs from the parasitic nematode Heligmosomoides bakeri that get into mouse intestinal epithelial cells.
Reassembling green fluorescent protein for in vitro evaluation of trans-translation
Authors: Guyomar Charlotte , Thépaut Marion , Nonin-Lecomte Sylvie , Méreau Agnès , Goude Renan , Gillet Reynald
Published: December 2019

In order to discover new antibiotics with improved activity and selectivity, we created a reliable in vitro reporter system to detect trans-translation activity, the main mechanism for recycling ribosomes stalled on problematic messenger RNA (mRNA) in bacteria. This system is based on an engineered tmRNA variant that reassembles the green fluorescent protein (GFP) when trans-translation is active. Our system is adapted for high-throughput screening of chemical compounds by fluorescence.
Integrative network analysis identifies cell-specific trans regulators of m6A
Authors: An Sanqi , Huang Wanxu , Huang Xiang , Cun Yixian , Cheng Weisheng , Sun Xiang , Ren Zhijun , Chen Yaxin , Chen Wenfang , Wang Jinkai
Published: December 2019

N6-methyladenosine (m6A) is a reversible and dynamic RNA modification in eukaryotes. However, how cells establish cell-specific m6A methylomes is still poorly understood. Here, we developed a computational framework to systematically identify cell-specific trans regulators of m6A through integrating gene expressions, binding targets and binding motifs of large number of RNA binding proteins (RBPs) with a co-methylation network constructed using large-scale m6A methylomes across diverse cell states. We applied the framework and successfully identified 32 high-confidence m6A regulators that modulated the variable m6A sites away from stop codons in a cell-specific manner. To validate them, we knocked down three regulators respectively and found two of them (TRA2A and CAPRIN1) selectively promoted the methylations of the m6A sites co-localized with their binding targets on RNAs through physical interactions with the m6A writers. Knockdown of TRA2A increased the stabilities of the RNAs with TRA2A bound near the m6A sites and decreased the viability of cells. The successful identification of m6A regulators demonstrates a powerful and widely applicable strategy to elucidate the cell-specific m6A regulators. Additionally, our discovery of pervasive trans-acting regulating of m6A provides novel insights into the mechanisms by which spatial and temporal dynamics of m6A methylomes are established.
iFLinkC: an iterative functional linker cloning strategy for the combinatorial assembly and recombination of linker peptides with functional domains
Authors: Gräwe Alexander , Ranglack Jan , Weyrich Anastasia , Stein Viktor
Published: December 2019

Recent years have witnessed increasing efforts to engineer artificial biological functions through recombination of modular-organized toolboxes of protein scaffolds and parts. A critical, yet frequently neglected aspect concerns the identity of peptide linkers or spacers connecting individual domains which remain poorly understood and challenging to assemble. Addressing these limitations, iFlinkC comprises a highly scalable DNA assembly process that facilitates the combinatorial recombination of functional domains with linkers of varying length and flexibility, thereby overcoming challenges with high GC-content and the repeat nature of linker elements. The capacity of iFLinkC is demonstrated in the construction of synthetic protease switches featuring PDZ-FN3-based affinity clamps and single-chain FKBP12-FRB receptors as allosteric inputs. Library screening experiments demonstrate that linker space is highly plastic as the induction of allosterically regulated protease switches can vary from >150-fold switch-ON to >13-fold switch-OFF solely depending on the identity of the connecting linkers and relative orientation of functional domains. In addition, Pro-rich linkers yield the most potent switches contradicting the conventional use of flexible Gly-Ser linkers. Given the ease and efficiency how functional domains can be readily recombined with any type of linker, iFLinkC is anticipated to be widely applicable to the assembly of any type of fusion protein.
Electron-hole hybridization in bilayer graphene
Authors: Wang Siqi , Zhao Mervin , Zhang Changjian , Yang Sui , Wang Yuan , Watanabe Kenji , Taniguchi Takashi , Hone James , Zhang Xiang
Published: December 2019

Band structure determines the motion of electrons in a solid, giving rise to exotic phenomena when properly engineered. Drawing an analogy between electrons and photons, artificially designed optical lattices indicate the possibility of a similar band modulation effect in graphene systems. Yet due to the fermionic nature of electrons, modulated electronic systems promise far richer categories of behaviors than those found in optical lattices. Here, we uncovered a strong modulation of electronic states in bilayer graphene subject to periodic potentials. We observed for the first time the hybridization of electron and hole sub-bands, resulting in local band gaps at both primary and secondary charge neutrality points. Such hybridization leads to the formation of flat bands, enabling the study of correlated effects in graphene systems. This work may provide a novel way to manipulate electronic states in layered systems, which is important to both fundamental research and application.
Differences in Distress Intolerance Among Daily and Intermittent Smokers
Authors: Veilleux Jennifer C , Skinner Kayla D
Published: December 2019

Introduction

Distress intolerance is an important risk factor for smokers. Smokers have greater problems tolerating distress than nonsmokers, and distress intolerance is theoretically an important predictor of early lapse. However, much of the distress intolerance research has been conducted on daily smokers. Understanding distress intolerance in nondaily or intermittent smokers may help elucidate whether distress intolerance is a function of current smoking habits.

Aims and Methods

Daily (n = 36) and intermittent (n = 28) smokers completed behavioral distress intolerance tasks (breath holding, mirror tracing persistence, and image persistence) along with self-report measures of both general and smoking-specific distress intolerance. They also completed 1 week of ecological momentary assessment where positive and negative affect were assessed along with momentary distress intolerance, at both random times (7×/day) and immediately prior to smoking a cigarette.

Results

Results found no differences between intermittent and daily smokers on behavioral distress intolerance tasks or general self-reported distress intolerance. Daily smokers reported greater self-reported smoking-specific distress intolerance compared to intermittent smokers. In addition, across both smoker groups, momentary distress intolerance was higher at smoking compared to random sessions, and low positive affect predicted greater momentary distress intolerance specifically for intermittent smokers prior to smoking.

Conclusions

The lack of differences between daily and intermittent smokers on general distress intolerance measures suggests that distress intolerance abilities and self-perceptions are not a function of higher levels of current smoking. However, the contextual variation in momentary distress intolerance is worth further exploration in both daily and intermittent smokers.

Implications

The overall lack of differences between intermittent and daily smokers on distress intolerance tasks and self-report measures suggests that daily smoking is not associated with lower abilities to manage or tolerate distress at the individual difference level. However, understanding fluctuations in distress intolerance across time and context is crucial, as smokers’ perceptions of their abilities to manage distress shift based on affect and smoking contexts. Stabilizing or increasing self-efficacy in tolerating distress during daily life is likely an important avenue for future research.
Genetic and Epigenetic Analysis Revealing Variants in the NCAM1–TTC12–ANKK1–DRD2 Cluster Associated Significantly With Nicotine Dependence in Chinese Han Smokers
Authors: Liu Qiang , Xu Yi , Mao Ying , Ma Yunlong , Wang Maiqiu , Han Haijun , Cui Wenyan , Yuan Wenji , Payne Thomas J , Xu Yizhou , Li Ming D , Yang Zhongli
Published: December 2019

Backgrounds

Although studies have demonstrated that the NCAM1–TTC12–ANKK1–DRD2 gene cluster plays essential roles in addictions in subjects of European and African origin, study of Chinese Han subjects is limited. Further, the underlying biological mechanisms of detected associations are largely unknown.

Methods

Sixty-four single-nucleotide polymorphisms (SNPs) in this cluster were analyzed for association with Fagerstrőm Test for Nicotine Dependence score (FTND) and cigarettes per day (CPD) in male Chinese Han smokers (N = 2616). Next-generation bisulfite sequencing was used to discover smoking-associated differentially methylated regions (DMRs). Both cis-eQTL and cis-mQTL analyses were applied to assess the cis-regulatory effects of these risk SNPs.

Results

Association analysis revealed that rs4648317 was significantly associated with FTND and CPD (p = .00018; p = .00072). Moreover, 14 additional SNPs were marginally significantly associated with FTND or CPD (p = .05–.01). Haplotype-based association analysis showed that one haplotype in DRD2, C-T-A-G, formed by rs4245148, rs4581480, rs4648317, and rs11214613, was significantly associated with CPD (p = .0005) and marginally associated with FTND (p = .003). Further, we identified four significant smoking-associated DMRs, three of which are located in the DRD2/ANKK1 region (p = .0012–.00005). Finally, we found five significant CpG–SNP pairs (p = 7.9 × 10–9–6.6 × 10–6) formed by risk SNPs rs4648317, rs11604671, and rs2734849 and three methylation loci.

Conclusions

We found two missense variants (rs11604671; rs2734849) and an intronic variant (rs4648317) with significant effects on ND and further explored their mechanisms of action through expression and methylation analysis. We found the majority of smoking-related DMRs are located in the ANKK1/DRD2 region, indicating a likely causative relation between non-synonymous SNPs and DMRs.

Implications

This study shows that there exist significant association of variants and haplotypes in ANKK1/DRD2 region with ND in Chinese male smokers. Further, this study also shows that DNA methylation plays an important role in mediating such associations.
Release of Anterior Longitudinal Ligament in Setting of Unfavorable Vascular Anatomy for Anterior Column Realignment—Technical Note: 2-Dimensional Operative Video
Authors: Godzik Jakub , Walker Corey T , Whiting Alexander C , Hlubek Randall J , Uribe Juan S , Turner Jay D
Published: December 2019

Anterior column realignment (ACR) with anterior longitudinal ligament (ALL) release from a lateral transpsoas approach is increasingly being used as a minimally invasive technique to restore lordosis. Safe execution requires a plane between the ALL and the anterior vasculature. An unfavorable plane on preoperative imaging is a contraindication to using the technique. We describe a patient undergoing multistage minimally invasive correction of a flat-back deformity who had an unfavorable plane between the ALL and vasculature at L4-5. Patient consent was provided, and Institutional Review Board approval was not required. To safely complete the ALL release and ACR, we elected to sharply incise the lateral aspect of the ligament at L4-5 with direct control of the vessels during the anterior approach for an L5-S1 anterior lumbar interbody fusion. We then moved to the lateral transpsoas approach and used controlled distraction techniques to complete the ALL release and then to complete the ACR in a standard fashion. We ultimately achieved excellent realignment with correction of the patient's flat-back deformity using minimally invasive surgical techniques while minimizing vascular risk. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
The effects of suspended sediments on the swimming behavior of the calanoid copepod, Acartia tonsa
Authors: Liu Xinlu , Sew Genevieve , Jakobsen Hans Henrik , Todd Peter A
Published: December 2019

Copepod swimming behavior is governed by chemical and hydro-mechanical cues. The environment of copepods, however, is frequently impacted by anthropogenic activities, in particular increased levels of suspended sediment due to coastal development. To better understand the effects of sediments on copepod behavior, we used video recordings to document free-swimming in Acartia tonsa under five sediment regimes, both with and without food. Results of the video analysis indicate that as sediment concentration increased, jumping increased and swimming paths became more convoluted. In the presence of prey, swimming trajectories became circular, as opposed to without prey, where paths were more erratic and slower. There was a reverse trend at higher sediment concentrations (120 and 200 mg l−1) for net velocity, turning rate and “spread of participation” index, which could indicate a behavioral threshold. Overall, greater motility with increasing sediment concentration suggests that the copepods were trying to transport themselves out of the sediment-affected area. In the absence of food, the energy cost of this behavior may affect the fitness of Acartia tonsa and, consequently, its predators.
The Effects of Home Exercise in Older Women With Vertebral Fractures: A Pilot Randomized Controlled Trial
Authors: Gibbs Jenna C , McArthur Caitlin , Wark John D , Thabane Lehana , Scherer Samuel C , Prasad Sadhana , Papaioannou Alexandra , Mittmann Nicole , Laprade Judi , Kim Sandra , Khan Aliya , Kendler David L , Hill Keith D , Cheung Angela M , Bleakney Robert , Ashe Maureen C , Adachi Jonathan D , Giangregorio Lora M
Published: December 2019

Background

Regular exercise is advocated in osteoporosis guidelines to prevent fractures. Few studies have evaluated the effect of exercise on functional performance, posture, and other outcomes that are important to patients after vertebral fractures.

Objective

This pilot study will explore the effect of home exercise versus control on functional performance, posture, and patient-reported outcome measures.

Design

This study was a parallel 2-arm pilot feasibility trial with 1:1 randomization to exercise or attentional control groups.

Setting

This study took place in 5 Canadian and 2 Australian academic or community hospitals/centers.

Participants

This study included 141 women ≥65 years of age with radiographically confirmed vertebral fractures.

Intervention

A physical therapist delivered exercise and behavioral counseling in 6 home visits over 8 months and monthly calls. Participants were to exercise ≥3 times weekly. Controls received equal attention.

Measurements

Functional performance, posture, quality of life, pain, and behavior-change outcomes were assessed at baseline and after 6 (questionnaires only) and 12 months. Adherence to exercise was assessed by calendar diary. All t tests examined between-group mean differences (MD) in change from baseline in intention-to-treat and per-protocol analyses.

Results

There was a small effect of exercise on 5 times sit-to-stand test versus control (MD = −1.58 [95% CI = −3.09 to −0.07], intention-to-treat; MD = −1.49 [95% CI = −3.12 to 0.16], per-protocol). There were no other major or statistically significant MDs for any other measured outcomes after follow-up. Adherence declined over time.

Limitations

Treatment effects on variables may have been underestimated due to multiple comparisons and underpowered analyses.

Conclusions

Our exploratory estimate of the effect of exercise on functional leg muscle strength was consistent in direction and magnitude with other trials in individuals with vertebral fractures. Declining adherence to home exercise suggests that strategies to enhance long-term adherence might be important in future confirmatory trials.
Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis
Authors: Md Yusof Md Yuzaiful , Iqbal Kundan , Darby Michael , Lettieri Giovanni , Vital Edward M , Beirne Paul , Dass Shouvik , Emery Paul , Kelly Clive
Published: December 2019

Objective

To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi).

Methods

A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths.

Results

Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041.

Conclusion

The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.
Reduced sleep pressure in young children with autism
Authors: Arazi Ayelet , Meiri Gal , Danan Dor , Michaelovski Analya , Flusser Hagit , Menashe Idan , Tarasiuk Ariel , Dinstein Ilan
Published: December 2019

Study Objectives

Sleep disturbances and insomnia are highly prevalent in children with Autism Spectrum Disorder (ASD). Sleep homeostasis, a fundamental mechanism of sleep regulation that generates pressure to sleep as a function of wakefulness, has not been studied in children with ASD so far, and its potential contribution to their sleep disturbances remains unknown. Here, we examined whether slow-wave activity (SWA), a measure that is indicative of sleep pressure, differs in children with ASD.

Methods

In this case-control study, we compared overnight electroencephalogram (EEG) recordings that were performed during Polysomnography (PSG) evaluations of 29 children with ASD and 23 typically developing children.

Results

Children with ASD exhibited significantly weaker SWA power, shallower SWA slopes, and a decreased proportion of slow-wave sleep in comparison to controls. This difference was largest during the first 2 hours following sleep onset and decreased gradually thereafter. Furthermore, SWA power of children with ASD was significantly negatively correlated with the time of their sleep onset in the lab and at home, as reported by parents.

Conclusions

These results suggest that children with ASD may have a dysregulation of sleep homeostasis that is manifested in reduced sleep pressure. The extent of this dysregulation in individual children was apparent in the amplitude of their SWA power, which was indicative of the severity of their individual sleep disturbances. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances in children with ASD.
Tricarboxylic Acid (TCA) Cycle Enzymes and Intermediates Modulate Intracellular Cyclic di-GMP Levels and the Production of Plant Cell Wall–Degrading Enzymes in Soft Rot PathogenDickeya dadantii
Authors: Yuan Xiaochen , Zeng Quan , Xu Jingsheng , Severin Geoffrey B. , Zhou Xiang , Waters Christopher M. , Sundin George W. , Ibekwe Abasiofiok M. , Liu Fengquan , Yang Ching-Hong
Published: December 2019

Dickeya dadantii is a plant-pathogenic bacterium that causes soft-rot in a wide range of plants. Although we have previously demonstrated that cyclic bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP), a bacterial secondary messenger, plays a central role in virulence regulation in D. dadantii, the upstream signals that modulate c-di-GMP remain enigmatic. Using a genome-wide transposon mutagenesis approach of a Δhfq mutant strain that has high c-di-GMP and reduced motility, we uncovered transposon mutants that recovered the c-di-GMP-mediated repression on swimming motility. A number of these mutants harbored transposon insertions in genes encoding tricarboxylic acid (TCA) cycle enzymes. Two of these TCA transposon mutants were studied further by generating chromosomal deletions of the fumA gene (encoding fumarase) and the sdhCDAB operon (encoding succinate dehydrogenase). Disruption of the TCA cycle in these deletion mutants resulted in reduced intracellular c-di-GMP and enhanced production of pectate lyases (Pels), a major plant cell wall–degrading enzyme (PCWDE) known to be transcriptionally repressed by c-di-GMP. Consistent with this result, addition of TCA cycle intermediates such as citrate also resulted in increased c-di-GMP levels and decreased production of Pels. Additionally, we found that a diguanylate cyclase GcpA was solely responsible for the observed citrate-mediated modulation of c-di-GMP. Finally, we demonstrated that addition of citrate induced not only an overproduction of GcpA protein but also a concomitant repression of the c-di-GMP-degrading phosphodiesterase EGcpB which, together, resulted in an increase in the intracellular concentration of c-di-GMP. In summary, our report demonstrates that bacterial respiration and respiration metabolites serve as signals for the regulation of c-di-GMP signaling.
A High-Throughput, Seedling Screen for Plant Immunity
Authors: Martel Alexandre , Lo Timothy , Desveaux Darrell , Guttman David S.
Published: December 2019

An understanding of how biological diversity affects plant–microbe interactions is becoming increasingly important, particularly with respect to components of the pathogen effector arsenal and the plant immune system. Although technological improvements have greatly advanced our ability to examine molecular sequences and interactions, relatively few advances have been made that facilitate high-throughput, in vivo pathology screens. Here, we present a high-throughput, microplate-based, nondestructive seedling pathology assay, and apply it to identify Arabidopsis thaliana effector-triggered immunity (ETI) responses against Pseudomonas syringae type III secreted effectors. The assay was carried out in a 48-well microplate format with spray inoculation, and disease symptoms were quantitatively recorded in a semiautomated manner, thereby greatly reducing both time and costs. The assay requires only slight modifications of common labware and uses no proprietary software. We validated the assay by recapitulating known ETI responses induced by P. syringae in Arabidopsis. We also demonstrated that we can quantitatively differentiate responses from a diversity of plant genotypes grown in the same microplate. Finally, we showed that the results obtained from our assay can be used to perform genome-wide association studies to identify host immunity genes, recapitulating results that have been independently obtained with mature plants.
32nd Annual APRN Legislative Update
Authors: Phillips Susanne J.
Published: December 2019

The Annual Legislative Update describes recent legislative and regulatory changes to practice, reimbursement, and prescriptive authority that have the most impact on NPs and other advanced practice registered nurses across the country.
Postmodernism and Medical Education
Authors: Ellaway Rachel H.
Published: December 2019

Postmodernism emerged in the mid-20th century in the context of postwar Europe where philosophers and artists were taking increasingly skeptical and critical positions on modernist thinking and practice. Postmodernism is not a single organized and coherent perspective; it is a collection of related philosophies, techniques, models, and perspectives that take a skeptical and critical perspective on thinking and practice. Ontologically, postmodernism is predicated on the belief that power and its underlying meanings, manipulations, and ideologies shape our ability to act in and think about the world. Epistemologically, postmodernism seeks to explore and understand underlying meanings, structures, and intents in the world and to consider alternative explanations and interpretations for them. Axiologically, postmodernism can be used to analyze value in the context of inequity, oppression, and hegemony within social systems and structures. Due to the lack of coherence within postmodernist thought, there is no one definitive methodological stance. However, there are many postmodernism-informed methodological stances, which vary both in terms of what is examined and how it is examined. As an approach within medical education, postmodernist perspectives can help to expose and analyze the political and ideological positioning of much of what is done, particularly in the interests of addressing systemic problems of justice and equity. It is somewhat paradoxical that postmodernism allows researchers to challenge the nature and expression of truth, and it allows them to problematize and deconstruct the ideologies and agendas of those who are themselves challenging the nature and expression of truth.
Steps to Develop a Mobile App for Pain Assessment of Cancer Patients: A Usability Study
Authors: Choi Jeeyae , Baker Elizabeth , Nalawade Swanand , Lee Hanjoo
Published: December 2019

Health-related mobile apps have the potential to allow patients and providers to proactively and responsibly manage pain together. However, there is a gap between the science of pain and current mobile apps. To develop a prototype science-based pain assessment mobile app (PainSmart) for Android smartphones, pain assessment tasks were extracted from a clinical guideline. These tasks were then converted to activity diagrams and became the logic of PainSmart. Five participants diagnosed with breast cancer evaluated usability of PainSmart with the System Usability Scale. Patient experience was recorded using Camtasia Studio Version 9 software. The five participants were able to explore the pain app after only 20 minutes of training. Using the System Usability Scale with comments, participant mean usability score was 77.5; above 68 is considered an above average system. A prototype of a pain assessment mobile app for cancer patients demonstrated high usability and will be refined based on participant feedback.
Using an Evidence-Based Approach for Electronic Health Record Downtime Education in Nurse Onboarding
Authors: Sano Jeffery M. , Alexander Susan
Published: December 2019

Electronic health record systems have been widely implemented throughout healthcare settings over the last few years, and nurses rely on these systems to obtain information about patients, make clinical decisions, and deliver safe and appropriate care. Health information technology systems have electronic health record downtime episodes both due to scheduled maintenance and unforeseen circumstances. The ability to deliver safe and effective care during electronic health record downtime episodes is important, yet training on electronic health record downtime is rarely included for nursing staff. This quality improvement project implemented an electronic health record downtime training course and administered it to 50 onboarding nurses within the hospital facility. The participants indicated a positive perception of electronic health record downtime preparedness after the course offering related to ability to find and follow downtime procedures. However, no precourse metrics were obtained, and therefore it is uncertain if this positive perception is a direct result of the electronic health record downtime training course. While initial results are promising, further investigation will need to be conducted to determine training course effectiveness.
Title microdirect laryngoscopy and bronchoscopy, myringotomy, and tympanostomy under THRIVE in a child with known difficult airway
Authors: Orlovich Daniel S. , Yedlin Nicholas R. , Meister Kara D. , Ramamurthi Radhamangalam J.
Published: December 2019

We present a case in which a pediatric patient with previously documented difficult intubation had successful oxygenation with transnasal humidified rapid insufflation ventilatory exchange (THRIVE) during microdirect laryngoscopy and bronchoscopy, myringotomy, and tympanostomy whilst general anesthesia was maintained by total intravenous anesthesia.
Predictors of long-term outcomes of radiologically defined perianal fistulizing Crohn’s disease treated with antitumor necrosis factor-alpha agents based on Parks’ classification
Authors: Azzam Nahla , Alharbi Othman , Almadi Majid , Aljebreen Abdulrahman , AlAmeel Turki , Alabbas Mohammed , Bahammam Salman , Bashmail Ahmed , Alomar Yasser , Mosli Mahmoud
Published: December 2019

Background and aims

Perianal fistulizing Crohn’s disease (PFCD) leads to significant disability. Data assessing healing of complex PFCD based on pelvic MRI using Parks’ classification remains sparse. We aimed to assess the frequency of closure of fistula tract on MRI in patients treated with antitumor necrosis factor alpha antagonists and identify predictors of poor response.

Materials and methods

We retrospectively identified patients registered in the Saudi Inflammatory Bowel Disease Information System registry, who were diagnosed as PFCD based on MRI and treated with infliximab or adalimumab. Fistulae were classified based on Parks’ classification and response to treatment was determined as full, partial, or no response, after at least 12 months of treatment.

Results

Out of 960 patients, 61 had complex PFCD that required treatment with an anti-TNF agent. The median age was 27 years (range: 14–69 years) and the median duration of disease was 6.2 ± 5.8 years. A full response to treatment was achieved in 27 (44.4%), whereas 10 patients (16.3%) had partial response and 24 (39.3%) had no response. On univariable analysis, a statistically significant association was observed between poor fistula response and low BMI, rectal involvement, fistulae classification, and the presence of an abscess. According to multivariable regression, only low BMI predicted poor fistulae outcome (odds ratio = 1.37, 95% confidence interval: 0.69–0.98).

Conclusion

Less than half of this cohort of patients with PFCD achieved complete radiological fistula healing with anti-TNF therapy. Low BMI appears to be the only predictor of poor outcome.
Add-on sorafenib is beneficial for hepatocellular carcinoma patients with transarterial chemoembolization refractoriness: a real-world experience
Authors: Lin Po-Ting , Teng Wei , Jeng Wen-Juei , Hsieh Yi-Chung , Hung Chen-Fu , Huang Chien-Hao , Lui Kar-Wai , Chen Yi-Cheng , Lin Chen-Chun , Lin Chun-Yen , Sheen I-Shyan , Lin Shi-Ming
Published: December 2019

Background and aims:

Sorafenib is the first proved target therapy that shows significant survival benefit in advanced hepatocellular carcinoma. This study was aimed to investigate whether add-on sorafenib be beneficial for those experienced transarterial chemoembolization refractoriness.

Methods:

From 2005 to 2016, a total of 656 treatment-naive hepatocellular carcinoma patients receiving transarterial chemoembolization treatment were recruited. Transarterial chemoembolization refractoriness was defined as progressive disease after two consecutive of transarterial chemoembolization treatment within 6 months. Patient’s baseline characteristics, tumor burden, and parameters for liver function evaluation during treatment were analyzed. All the variables were compared between patients with and without transarterial chemoembolization refractoriness, as well as with and without add-on sorafenib.

Results:

Among the 656 patients, the median age was 62.5 (range 27.3–91.5) years old, and 74.5% were male. Transarterial chemoembolization refractoriness events were documented in 202 patients (30.8%). After multivariate logistic regression analysis, tumor size ≧5 cm, baseline alpha-fetoprotein level ≧200 mg/dl, elevation of alpha-fetoprotein ≧20%, and elevation of Child-Turcotte-Pugh score ≧2 points after first transarterial chemoembolization were the independent predictive factors for transarterial chemoembolization refractoriness. Twenty-two patients (10.9%) received add-on sorafenib treatment and 146 (72.3%) patients continued transarterial chemoembolization treatment alone. After 1:2 propensity score matching, patients with add-on sorafenib therapy had significantly longer median overall survival than transarterial chemoembolization treatment alone (23.1 vs. 11.0 months, log-rank P = 0.001).

Conclusion:

The tumor size, baseline alpha-fetoprotein, and elevation of alpha-fetoprotein and Child-Turcotte-Pugh score after first transarterial chemoembolization were the predictors for transarterial chemoembolization refractoriness. For patients with transarterial chemoembolization refractoriness, add-on sorafenib achieved better survival benefit than transarterial chemoembolization treatment alone.
Efficacy of modified esomeprazole-amoxicillin dual therapies for Helicobacter pylori infection: an open-label, randomized trial
Authors: Zhang Yi , Zhu Yang-Jie , Zhao Zhe , Zhao Jing-Tao , Wang Ting-Yi , Yang Jing , Chen Dong-Feng , Lan Chun-Hui
Published: December 2019

Objective

The prevalence of Helicobacter pylori resistance to amoxicillin was less than 5% in most countries. Proton pump inhibitor (PPI)-amoxicillin dual therapy dosing four times daily (q.i.d.) for 14 days could achieve an eradication rate of more than 85%. It is unclear whether dual therapy with shorter treatment duration or lower dosing frequency could also attain a satisfactory cure rate. We conducted a randomized controlled trial to assess the efficacy and safety of two modified esomeprazole-amoxicillin dual therapies, 10-day q.i.d. and 14-day three times daily (t.i.d.) dual therapy, and investigate the factors that might affect the eradication rates.

Participants and methods

A total of 253 patients were screened for eligibility and 208 patients were randomly assigned to 10-day dual therapy (esomeprazole 20 mg and amoxicillin 750 mg, all given four times daily) or 14-day dual therapy (esomeprazole 20 mg and amoxicillin 1000 mg, all given three times daily).

Results

In the intention-to-treat analysis, the eradication rates for 10-day and 14-day groups were 79.8% [95% confidence interval (CI): 70.2–87.4%] and 83.5% (95% CI: 74.3–90.5%) as first-line therapies; and 80% (95% CI: 44.4–97.5%) and 76.9% (95% CI: 46.2–95.0%) as rescue therapies. The adverse event rates were 5.9% and 5.0% for 10-day and 14-day groups, respectively. Smoking and compliance significantly affected the efficacy of PPI-amoxicillin dual therapies.

Conclusion

The eradication rate of 10-day q.i.d. dual therapy was unacceptable, while that of the 14-day t.i.d. dual therapy was borderline acceptable for first-line therapy. The two dual therapies were well tolerated with few adverse effects.
Incident heart failure is a predictor of adverse outcomes in inflammatory bowel disease
Authors: Kumar Anand , Lukin Dana J.
Published: December 2019

Objective

Heart failure (HF) exerts deleterious effects on the gastrointestinal tract and the gut microbiome, yet its impact on inflammatory bowel disease (IBD) is unknown. This study was performed to evaluate the impact of HF on disease course and outcomes in patients with IBD.

Methods

Using a large institutional database, we identified patients aged 18–65 years diagnosed with IBD and incident HF (IBD-HF), IBD without HF (IBD), and HF without IBD (HF). Patients were followed longitudinally, and IBD-related outcomes were compared between the IBD-HF and IBD cohorts using multivariable cox regression. General clinical outcomes were compared between all three cohorts using Kaplan–Meier survival analysis.

Results

A total of 271, 2449, and 20,444 patients were included in the IBD-HF, IBD, and HF cohorts. Compared with IBD, IBD-HF had significantly higher risk of IBD-related hospitalization [hazard ratio (HR): 1.42; (95% confidence interval, CI: 1.2–1.69)], flare [HR 1.32 (1.09–1.58)], complication [HR 1.7 (1.33–2.17)], pancolitis [HR 1.55 (1.04–2.3)], and escalation to nonbiologic therapy. No significant difference was observed in the incidence of IBD-related surgery or Clostridium difficile infection. New biologic use was less frequent in IBD-HF [HR 0.52 (0.36–0.77)]. IBD-HF, compared with the other two groups, had reduced event-free survival for all-cause hospitalization (P < 0.001), emergency department visits (P = 001), and venous thromboembolism (P < 0.05). Mortality risk in IBD-HF was elevated compared to IBD but was similar to that within HF cohort.

Conclusion

Incident HF in patients with IBD is a predictor of adverse IBD-related and overall clinical outcomes.
Faculty Perceptions of the Importance of Physical Assessment Skills Taught in Prelicensure Nursing Education
Authors: Fusner Stacy M. , Moots Hollie , O'Brien Tara , Sinnott Loraine T.
Published: December 2019

BACKGROUND

Physical assessment skills are key components of nursing practice. On average, nurses perform a head-to-toe assessment 4 times during a shift. The frequency and importance of this technique have resulted in controversy in determining the essential components of assessment to ensure readiness for practice.

PURPOSE

The purpose of the study was to explore the perceived importance by faculty for physical assessment skills taught in prelicensure nursing education programs.

METHODS

This was a cross-sectional descriptive study using a 136-item questionnaire. The sample was nursing faculty (n = 402) teaching in an accredited nursing program in the United States.

RESULTS

Among the physical assessment skill categories, integumentary (4.57 ± 0.51), central nervous (4.29 ± 0.62), and cardiovascular (4.20 ± 0.51) systems had the highest mean scores for the perceived level of importance of skill categories to be taught to prelicensure nursing students.

CONCLUSION

The data suggest that faculty perceive physical assessment skills associated with the integumentary, central nervous, and cardiovascular systems to be the most critical skills taught in a nursing assessment course.
The Morcellation “Debate” and the FDA 510(k) Process—A Call for Further Reform
Authors: Brennan Lacey , Milad Magdy P. , King Louise P.
Published: December 2019

Importance

Few gynecologic surgeons understand the mechanism by which surgical instruments are approved for human use and marketing or do they appreciate the central role they play in postmarket surveillance and reporting after instruments have come to market.

Objective

Using the experience with the uterine morcellator, this review will detail the Food and Drug Administration (FDA) system for approving surgical instruments and the potential pitfalls of this process.

Evidence Acquisition

Literature review and public documents from the FDA.

Results

The FDA 510(k) approval process for surgical instruments relies largely on postmarket surveillance as exemplified by the uterine power morcellator, which was approved before sufficient evidence was available regarding its potential harms.

Conclusions

The current system currently transfers the responsibility of ensuring safety and efficacy to the public, patients, and providers. To minimize potential harm, the FDA needs to incorporate a greater standard of evidence into its framework for the approval and regulation of medical devices. The burden of these requirements should be borne at least in part by the companies bringing equipment to market.

Relevance

It is incumbent on all surgeons to be vigilant in their objective critical assessment of new instrumentation and report their outcomes after they come to market.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

Physicians should be better able to: Identify the challenges associated with the current 510(k) process; Distinguish between the roles of the initial approval and postmarketing surveillance of surgical products and their safety; and Evaluate the efficacy of new surgical modalities and products.
Neuro-Ophthalmologic Features and Outcomes of Thalamic Infarction: A Single-Institutional 10-Year Experience
Authors: Moon Yeji , Eah Kyu Sang , Lee Eun-Jae , Kang Dong-Wha , Kwon Sun Uck , Kim Jong Sung , Lim Hyun Taek
Published: December 2019

Background:

Neuro-ophthalmologic deficit after thalamic infarction has been of great concern to ophthalmologists because of its debilitating impacts on patients' daily living. We aimed to describe the visual and oculomotor features of thalamic infarction and to delineate clinical outcomes and prognostic factors of the oculomotor deficits from an ophthalmologic point of view.

Methods:

Clinical and neuroimaging data of all participants were retrospectively reviewed. Among the 12,755 patients with first-ever ischemic stroke, who were registered in our Stroke Data Bank between January 2009 and December 2018, 342 were found to have acute thalamic infarcts on MRI, from whom we identified the patients exhibiting neuro-ophthalmologic manifestations including visual, oculomotor, pupillary, and eyelid anomalies.

Results:

Forty (11.7%) of the 342 patients with thalamic infarction demonstrated neuro-ophthalmologic manifestations, consisting of vertical gaze palsy (n = 19), skew deviation with an invariable hypotropia of the contralesional eye (n = 18), third nerve palsy (n = 11), pseudoabducens palsy (n = 9), visual field defects (n = 7), and other anomalies such as isolated ptosis and miosis (n = 7). Paramedian infarct was the most predominant lesion of neuro-ophthalmologic significance, accounting for 84.8% (n = 28) of all patients sharing the oculomotor features. Although most of the patients with oculomotor abnormalities rapidly improved without sequelae, 6 (18.2%) patients showed permanent oculomotor deficits. Common clinical features of patients with permanent oculomotor deficits included the following: no improvement within 3 months, combined upgaze and downgaze palsy, and the involvement of the paramedian tegmentum of the rostral midbrain.

Conclusions:

Thalamic infarction, especially in paramedian territory, can cause a wide variety of neuro-ophthalmologic manifestations, including vertical gaze palsy, skew deviation, and third nerve palsy. Although most oculomotor abnormalities resolve spontaneously within a few months, some may persist for years when the deficits remain unimproved for more than 3 months after stroke.
Switching from clozapine to paliperidone palmitate-3-monthly improved obesity, hyperglycemia and dyslipidemia lowering antipsychotic dose equivalents in a treatment-resistant schizophrenia cohort
Authors: Martínez-Andrés Juan Andrés , García-Carmona Juan Antonio
Published: December 2019

Clozapine, an antipsychotic developed in 1958, is considered the gold standard and the treatment of choice in treatment-resistant schizophrenia despite its side effects and despite 40–70% of these patients not responding to clozapine. In the last decade, new antipsychotics, such as paliperidone palmitate (PP), have emerged as well as its long acting-injectable (LAI) formulations, available as PP-1-monthly (PP1M) and the newest PP-3-montlhy (PP3M). Despite paliperidone having shown a similar efficacy as others antipsychotics for the treatment of schizophrenia, and that PP3M has been shown to reduce relapses compared to oral formulations, no study has been carried out in treatment-resistant schizophrenia. The aim of our study was to carry out an exploratory evaluation of endocrine and hepatic profiles as well as the concomitant treatments associated to PP3M vs. clozapine, the gold standard, in patients with treatment-resistant schizophrenia. We designed a retrospective study. A total number of 33 patients previously diagnosed as schizophrenics treatment-resistant, who were prescribed clozapine followed by PP1M and PP3M when available, were selected. Demographic data, BMI, hepatic enzymes (glutamic oxaloacetic transaminase, glutamate-pyruvate transaminase and gamma-glutamyl transferase (GGT)], thyroid function (thyroid stimulating hormone), blood platelets and both white and red blood cells as well as the use of concomitant antipsychotics, benzodiazepines and biperiden were compared under treatment with clozapine and PP3M. Antipsychotics and benzodiazepines dosages were compared using by the defined daily dose (DDD) method and haloperidol or diazepam dose equivalents. All statistical analyses were performed using the paired Student t-test for repeated measures. Our data showed that patients under treatment with PP3M showed a significant decrease in BMI (P < 0.01), glucose (P < 0.01), cholesterol (P < 0.05) and triglycerides (P < 0.01) when compared with basal values under treatment with clozapine. Hepatic cholestasis enzyme, GGT, were significantly elevated (P < 0.05) under treatment with clozapine when compared to PP3M. Switching clozapine to PP3M led to a significant lower pharmacological exposure to antipsychotics, by both the DDD (P < 0.05) and haloperidol dose equivalents (P < 0.001) methods without increasing the dose of benzodiazepines while biperiden was more used under PP3M. Finally, antipsychotic monotherapy was higher and less polypharmacy was used with PP3M. In conclusion, our findings suggest that switching clozapine to PP3M improved endocrine and hepatic profile with a lower total exposure to antipsychotics. More studies are needed to truly establish the role of PP3M in treatment-resistant schizophrenia and should be compared against clozapine by using clinical trials.