bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying the ICF-CY to Specialist Speech-Language Pathologists’ Practice With Toddlers With Cleft Palate Speech
Authors: Cronin Anna , McLeod Sharynne , Verdon Sarah
Published: April 2020

Objective:

To evaluate how the practice of specialist speech-language pathologists (SLPs) working with young children with cleft palate ± cleft lip (CP±L) maps onto the International Classification of Functioning, Disability, and Health – Children and Youth version (ICF-CY) and consider the functionality of the categories of the ICF-CY for this specialist area of practice.

Design:

Cross-sectional, qualitative study.

Setting:

Semistructured face-to-face interviews were conducted with SLPs working in tertiary-level hospitals, universities, and public clinics.

Participants:

Six specialist SLPs with 17 to 39 years of experience working with young children with CP±L as researchers and clinicians in Australia, Brazil, Denmark, Ireland, New Zealand, and the United States.

Main Outcome Measure(s):

Specialists’ practices were captured using in-depth, semistructured interviews. Data collected were analyzed by directed content analysis applying the ICF-CY as a coding schema.

Results:

In total, 4077 data points were coded. Most mapped onto Body Structures (684, 16.8%), Body Functions (906, 22.2%), and Environmental Factors (1626, 39.9%) with less emphasis on Activities and Participation (560, 13.7%). A “best fit” approach was taken to topics that did not map exactly onto categories of the ICF-CY (eg, velopharyngeal insufficiency [VPI]); however, there was not always an ideally suitable category available.

Conclusions:

The current study revealed strengths and challenges in categorizing practice within the ICF-CY for children with CP±L, including collaboration with parents and significant others, specificity around speech, language, and articulation, and the different types of VPI. Therefore, future discussion around how best to use the framework with children with CP±L is needed.
How is Intangible Cultural Heritage Valued in the Eyes of Inheritors? Scale Development and Validation
Authors: Su Xinwei , Li Xi , Wu Yanbin , Yao Limei
Published: April 2020

Intangible cultural heritage (ICH) is an important part of human civilization and a major tourism resource type. In the ICH tourism development process, many stakeholders are involved. Although inheritors have a core position in this group, there is not enough research investigating the sustainable development of ICH tourism from the perspective of inheritors. Since value cognition is the basis that guides people’s behaviors, the value cognition of the ICH inheritors might be the starting point to understanding their behaviors. Considering this context, the main aim of this research is to describe the development and validation of a scale to assess the cognition values by ICH inheritors. By generating items, purifying, examining the scale’s dimensionality, and evaluating reliability and validity, a 25-item instrument is developed. The article concludes with a discussion of potential applications of the scale.
Subthreshold yellow micropulse laser for treatment of diabetic macular edema: Comparison between fixed and variable treatment regimen
Authors: Donati Maria Carla , Murro Vittoria , Mucciolo Dario Pasquale , Giorgio Dario , Cinotti Giacomo , Virgili Gianni , Rizzo Stanislao
Published: April 2020

Purpose:

To compare the efficacy between fixed and variable treatment regimens of subthreshold yellow micropulse laser for the treatment of diabetic macular edema.

Methods:

This is a retrospective, comparative, 12-month study of 39 eyes: 24 eyes received fixed treatment regimen of subthreshold micropulse laser treatment and 15 eyes underwent variable treatment regimen of subthreshold micropulse laser, all eyes were followed up for 12 months. Subthreshold micropulse laser was performed with the following parameters: 100 μm spot size on slit lamp, 5% duty cycle of 0.2 s, and 250 mW power. To choose the power of the variable treatment regimen of subthreshold micropulse laser group, continuous laser power was titrated to a barely visible burn and then switched to MicroPulse mode, multiplying the test burn power by 4 and using a 5% duty cycle of 0.2 s. Main outcomes included changes in central macular thickness and best-corrected visual acuity.

Results:

At baseline, the mean LogMAR best-corrected visual acuity was 0.297 ± 0.431 in the variable treatment regimen of subthreshold micropulse laser group and 0.228 ± 0.341 in the fixed treatment regimen of subthreshold micropulse laser group. At the end of follow-up, the mean LogMAR best-corrected visual acuity was 0.289 ± 0.473 (p = 0.785) and 0.245 ± 0.376 (p = 0.480) in the variable and fixed treatment regimens of subthreshold micropulse laser groups, respectively. Similarly, central macular thickness decreased in both groups after treatment; at baseline, the mean central macular thickness was 371.06 ± 37.8 in the variable treatment regimen of subthreshold micropulse laser group and improved to 325.60 ± 110.0 μm (p = 0.025) at the end of the follow-ups, while it was 342.30 ± 35.4 in the fixed treatment regimen of subthreshold micropulse laser group and improved to 308.51 ± 67.5 (p = 0.037).

Conclusion:

Both treatment regimens are effective for the treatment of mild center-involving diabetic macular edema: fixed treatment appears more suitable minimizing treatment time and reducing the possible errors due to wrong titration in the switch from continuous to micropulse mode.
Which patients improve most after total hip arthroplasty? Influence of patient characteristics on patient-reported outcome measures of 22,357 total hip arthroplasties in the Dutch Arthroplasty Register
Authors: Peters Rinne M , van Steenbergen Liza N , Stewart Roy E , Stevens Martin , Rijk Paul C , Bulstra Sjoerd K , Zijlstra Wierd P
Published: April 2020

Background:

Patient-reported outcome measures (PROMs) after total hip arthroplasty (THA), can be influenced by patient characteristics (case-mix factors). We used the Dutch Arthroplasty Register (LROI) to determine the effect of case-mix on improvement of PROMs after primary THA.

Methods:

We included all primary THAs ( n = 22,357) performed in the Netherlands between 2014 and 2018. The Hip disability and Osteoarthritis Outcome Score Physical function short form (HOOS-PS), Oxford Hip Score (OHS), EQ-5D index score and thermometer, and Numeric Rating Scales (NRS) measuring pain during activities and at rest, were recorded. The difference between preoperative and 3- and 12-month postoperative scores was calculated (delta-PROM) and used as primary outcome variable. Multivariable linear regression was used to examine the association between patient characteristics (age, sex, ASA score, body mass index (BMI), Charnley class, smoking, and previous operations to the affected hip) and PROMs. Cohens’ d was used to measure effect size.

Results:

Postoperative improvement (delta-PROM) on HOOS-PS, OHS, EQ-5D, and pain relief were significantly higher in patients <60 years, in patients with female gender, a high ASA score (III–IV), a BMI >30 kg/m2, and patients without a previous operation to the hip. Cohen’s d indicated clinically small differences (0.2).

Conclusions:

Patients benefiting most in terms of postoperative improvement of self-reported physical functioning, pain relief and quality of life after primary THA were young, female, with a high ASA or BMI score, and without previous operations to the hip.
Identification of Gastrointestinal Microbiota in Hawaiian Green Turtles (Chelonia mydas)
Authors: McDermid Karla J , Kittle Ronald P , Veillet Anne , Plouviez Sophie , Muehlstein Lisa , Balazs George H
Published: April 2020

Green turtles ( Chelonia mydas) have a hindgut fermentation digestive tract, which uses cellulolytic microbes to break down plant matter in the cecum and proximal colon. Previous studies on bacterial communities of green turtles have not identified in situ hindgut microbiota, and never before in Hawaiian green turtles, which comprise an isolated metapopulation. Fresh samples using sterile swabs were taken from five locations along the gastrointestinal tracts of eight green turtles that had required euthanization. Bacteria were cultured, aerobically and anaerobically, on nutrient agar and four differential and selective media. Samples at three sections along the gastrointestinal tracts of two green turtles were analyzed using 16S metagenomics on an Ion Torrent Personal Genome Machine. More than half of the 4 532 104 sequences belonged to the phylum Firmicutes, followed by Bacteroidetes and Proteobacteria, which are characteristic of herbivore gut microbiota. Some microbiota variation existed between turtles and among gastrointestinal sections. The 16S sequence analysis provided a better representation of the total gastrointestinal bacterial community, much of which cannot be cultured using traditional microbial techniques. These metagenomic analyses serve as a foundation for a better understanding of the microbiome of green turtles in the Hawaiian Islands and elsewhere.
Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas
Authors: Bendahou Mohammed Amine , Arrouchi Housna , Lakhlili Wiame , Allam Loubna , Aanniz Tarik , Cherradi Nadia , Ibrahimi Azeddine , Boutarbouch Mahjouba
Published: April 2020

Introduction:

The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas.

Methods:

In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 ( IDH1) and isocitrate dehydrogenase 2 ( IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53.

Results:

We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein.

Conclusion:

In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.
A periodic solution of the fractional sine-Gordon equation arising in architectural engineering
Authors: Shen Yue , El-Dib Yusry O
Published: April 2020

Many nonlinear vibrations arising in the engineering of architecture include noise and uncertain properties, and this paper suggests a fractional model to elucidate the properties. The fractional sine-Gordon equation with the Riemann–Liouville fractional derivative is used as an example to solve its periodic solution by the homotopy perturbation method. The frequency–amplitude relationship is obtained, and the effect of the fractional derivative order on the vibration property is discussed. Additionally, the harmonic resonance is also discussed. This preliminary research can be further extended to real applications.
Nanotechnology and Microtechnology in Drug Delivery Systems
Authors: Sun Jingyao , Yang Zhaogang , Teng Lesheng
Published: April 2020

A special issue of the journal Dose-Response entitled “Nanotechnology and Microtechnology in Drug Delivery Systems” is proposed. In pharmaceutical studies, new and existing drugs continue to be investigated for their poor specificity, solubility, therapeutic index, and immunogenicity. In order to solve these problems, drug delivery systems are essential for controlled drug release. It has been shown that the size and shape (nano- or micro-) of drug carriers can affect a drug’s circulation time, distribution, and cellular uptake. Hence, it is not surprising that nanotechnology and microtechnology have been explored as powerful tools for drug delivery in past decades. The main topics will be related to the technologies including microtechnology for the sustained release of drug, nanotechnology for the targeting delivery of drugs, new polymer materials nanotechnology, nanotechnology in drugs combination application, and so on.
Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain
Authors: Vallejo Ricardo , Kelley Courtney A , Gupta Ashim , Smith William J , Vallejo Alejandro , Cedeño David L
Published: April 2020

The development and maintenance of chronic neuropathic pain involves distorted neuroglial interactions, which result in prolonged perturbations of immune and inflammatory response, as well as disrupted synapses and cellular interactions. Spinal cord stimulation (SCS) has proven effective and safe for more than 40 years, but comprehensive understanding of its mode of action remains elusive. Previous work in our laboratory provided evidence that conventional SCS parameters modulate biological processes associated with neuropathic pain in animals. This inspired the development of differential target multiplexed programming (DTMP) in which multiple electrical signals are used for modulating glial cells and neurons in order to rebalance their interactions. This work compares DTMP with both low rate and high rate programming using an animal model of neuropathic pain. The spared nerve injury model was implemented in 48 rats equally randomized into four experimental groups: No-SCS, DTMP, low rate, and high rate. Naive animals (N = 7) served as a reference control. SCS was applied continuously for 48 h and pain-related behavior assessed before and after SCS. RNA from the spinal cord exposed to SCS was sequenced to determine changes in gene expression as a result of injury (No-SCS vs. naïve) and as a result of SCS (SCS vs. No-SCS). Bioinformatics tools (Weighted Gene Co-expression Network Analysis and Gene Ontology Enrichment Analysis) were used to evaluate the significance of the results. All three therapies significantly reduced mechanical hypersensitivity, although DTMP provided statistically better results overall. DTMP also reduced thermal hypersensitivity significantly. RNA-sequencing corroborated the complex effects of nerve injury on the transcriptome. In addition, DTMP provided significantly more effective modulation of genes associated with pain-related processes in returning their expression toward levels observed in naïve, noninjured animals. DTMP provides a more effective way of modulating the expression of genes involved in pain-relevant biological processes associated with neuroglial interactions.
Taking Charge after Stroke: A randomized controlled trial of a person-centered, self-directed rehabilitation intervention
Authors: Fu Vivian , Weatherall Mark , McPherson Kathryn , Taylor William , McRae Anna , Thomson Tom , Gommans John , Green Geoff , Harwood Matire , Ranta Annemarei , Hanger Carl , Riley Judith , McNaughton Harry
Published: April 2020

Background and purpose

“Take Charge” is a novel, community-based self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. In a previous randomized controlled trial, a single Take Charge session improved independence and health-related quality of life 12 months following stroke in Māori and Pacific New Zealanders. We tested the same intervention in three doses (zero, one, or two sessions) in a larger study and in a broader non-Māori and non-Pacific population with stroke. We aimed to confirm whether the Take Charge intervention improved quality of life at 12 months after stroke in a different population and whether two sessions were more effective than one.

Methods

We randomized 400 people within 16 weeks of acute stroke who had been discharged to institution-free community living at seven centers in New Zealand to a single Take Charge session (TC1, n = 132), two Take Charge sessions six weeks apart (TC2, n = 138), or a control intervention (n = 130). Take Charge is a “talking therapy” that encourages a sense of purpose, autonomy, mastery, and connectedness with others. The primary outcome was the Physical Component Summary score of the Short Form 36 at 12 months following stroke comparing any Take Charge intervention to control.

Results

Of the 400 people randomized (mean age 72.2 years, 58.5% male), 10 died and two withdrew from the study. The remaining 388 (97%) people were followed up at 12 months after stroke. Twelve months following stroke, participants in either of the TC groups (i.e. TC1 + TC2) scored 2.9 (95% confidence intervals (CI) 0.95 to 4.9, p = 0.004) points higher (better) than control on the Short Form 36 Physical Component Summary. This difference remained significant when adjusted for pre-specified baseline variables. There was a dose effect with Short Form 36 Physical Component Summary scores increasing by 1.9 points (95% CI 0.8 to 3.1, p < 0.001) for each extra Take Charge session received. Exposure to the Take Charge intervention was associated with reduced odds of being dependent (modified Rankin Scale 3 to 5) at 12 months (TC1 + TC2 12% versus control 19.5%, odds ratio 0.55, 95% CI 0.31 to 0.99, p = 0.045).

Conclusions

Confirming the previous randomized controlled trial outcome, Take Charge—a low-cost, person-centered, self-directed rehabilitation intervention after stroke—improved health-related quality of life and independence.

Clinical trial registration-URL

http://www.anzctr.org.au . Unique identifier: ACTRN12615001163594
Comorbidity and survival after admission to the intensive care unit: A population-based study of 41,230 patients
Authors: Simpson Alasdair , Puxty Kathryn , McLoone Philip , Quasim Tara , Sloan Billy , Morrison David S
Published: April 2020

Purpose

To describe the relationship between comorbidities and survival following admission to the intensive care unit.

Methods

Retrospective observational study using several linked routinely collected databases from 16 general intensive care units between 2002 and 2011. Comorbidities identified from hospitalisation in the five years prior to intensive care unit admission. Odds ratios for survival in intensive care unit, hospital and at 30 days, 180 days and 12 months after intensive care unit admission derived from multiple logistic regression models.

Results

There were 41,230 admissions to intensive care units between 2002 and 2011. Forty-one percent had at least one comorbidity – 24% had one, 17% had more than one. Patients with comorbidities were significantly older, had higher Acute Physiology and Chronic Health Evaluation II scores and were more likely to have received elective rather than emergency surgery compared with those without comorbidities. After excluding elective hospitalisations, intensive care unit and hospital mortality for the cohort were 24% and 29%, respectively. Asthma (odds ratio 0.79, 95% confidence interval 0.63–0.99) and solid tumours (odds ratio 0.74, 0.67–0.83) were associated with lower odds of intensive care unit mortality than no comorbidity. Intensive care unit mortality was raised for liver disease (odds ratio 2.98, 2.43–3.65), cirrhosis (odds ratio 2.61, 1.9–3.61), haematological malignancy (odds ratio 2.29, 1.85–2.83), chronic ischaemic heart disease (odds ratio 1.53, 1.19–1.98), heart failure (odds ratio 1.79, 1.35–2.39) and rheumatological disease (odds ratio 1.53, 1.18–1.98).

Conclusions

Comorbidities affect two-fifths of intensive care unit admission and have highly variable effects on subsequent outcomes. Information on the differential effects of comorbidities will be helpful in making better decisions about intensive care unit support and understanding outcomes beyond surviving intensive care unit.
Dorsal cauda equina nerve root enhancement on magnetic resonance imaging due to ANNA-1-associated paraneoplastic polyneuropathy
Authors: Madhavan Ajay A , Guerin Julie B , Eckel Laurence J , Lehman Vance T , Carr Carrie M
Published: April 2020

A 69-year-old female presented with subacute onset ascending weakness and paraesthesias. She was initially diagnosed with Guillain–Barré syndrome (GBS) based on her clinical presentation and cerebrospinal fluid (CSF) analysis showing albuminocytological dissociation. However, she was later found to have anti-neuronal nuclear antibody 1 (ANNA-1/anti-Hu)-positive CSF and was subsequently diagnosed with small-cell lung cancer. Her neurological symptoms were ultimately attributed to ANNA-1/anti-Hu-associated paraneoplastic polyneuropathy. During the course of her evaluation, she had magnetic resonance imaging findings of dorsal predominant cauda equina nerve root enhancement, which has not been previously described. The only previously reported case of cauda equina enhancement due to ANNA-1-associated polyneuropathy described ventral predominant findings. The distinction between ventral and dorsal enhancement is important, since it suggests that different patterns of nerve root involvement may be associated with this paraneoplastic syndrome. Therefore, ANNA-1-associated paraneoplastic inflammatory polyneuropathy can be considered in the differential diagnosis of cauda equina nerve root enhancement with ventral and/or dorsal predominance. This can potentially be helpful in differentiating ANNA-1 polyneuropathy from GBS, which classically has ventral predominant enhancement.
Practical applications of regulatory requirements for signal detection and communications in pharmacovigilance
Authors: Malikova Marina A.
Published: April 2020

Pharmacovigilance is a field where communication is crucial, and exchange of information is expected to be done in a timely manner. Information from individual case reports is transmitted from pharmaceutical industry and health professionals to the regulatory authorities. The safety profile of a drug is established by analyzing individual cases and aggregate reports. The cumulative information, obtained from these reports, can be used to assist pharmacovigilance professionals in the detection of potential safety signals by monitoring evolving trends. If there is a message identifying concern as potential safety signal, the transmission of individual case reports, as well as cumulative and aggregate reports will occur from pharmaceutical industry to the regulators; and based on their assessments of causality in relationship to the drug, the regulatory decisions will be made. Once regulators confirming a signal as a possible safety alert have made the decision, the decisions and the reasons must be communicated to health professionals, the pharmaceutical industry, and other parties involved (e.g. clinical trials participants, investigators, consumers and medical professionals at post-marketing stage, etc.).
Improvement of lung ischemia–reperfusion injury by inhibition of microRNA‐155 via reductions in neuroinflammation and oxidative stress of vagal afferent nerve
Authors: Zhou Yan , Zhang Lianjie , Guan Jingjing , Yin Xin
Published: April 2020

Lung ischemia–reperfusion injury (LIRI) is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine the effects of inhibiting microRNA‐155 on the levels of proinflammatory cytokines and products of oxidative stress in the pulmonary vagal afferent nerves and the commissural nucleus of the solitary tract (cNTS) after LIRI. A rat model of LIRI was used. ELISA method was employed to examine proinflammatory cytokines, namely, IL‐1β, IL‐6 and TNF‐α; and key biomarkers of oxidative stress, 8‐isoprostaglandin F2α (8‐iso PGF2α) and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). In results, in the process of LIRI, the levels of microRNA‐155 were amplified in the vagal afferent nerves and cNTS, and this was accompanied with increases of IL‐1β, IL‐6 and TNF‐α; and 8‐iso PGF2α and 8‐OHdG. Application of microRNA‐155 inhibitor, but not its scramble, attenuated the elevation of proinflammatory cytokines and amplification of 8‐iso PGF2α and 8‐OHdG in those nerve tissues. In conclusion, we observed the abnormalities in the pulmonary afferent pathways at the levels of the peripheral nerves and brainstem, which is likely to affect respiratory functions as LIRI occurs. Our data suggest that blocking microRNA‐155 signal pathways plays a beneficial role in regulating LIRI via inhibiting responses of neuroinflammation and oxidative stress signal pathways to LIRI.
Status epilepticus during correction of hyponatremia in a patient with Alzheimer’s disease: A case report
Authors: Ichioka Ken , Akuzawa Nobuhiro , Takahashi Akio
Published: April 2020

An 83-year-old Japanese man with Alzheimer’s disease was admitted to our hospital for treatment of hyponatremia resulting from water intoxication. During hospitalization, the patient developed focal impaired awareness seizures, focal to bilateral tonic-clonic seizures, and subsequent status epilepticus. Electroencephalogram during focal impaired awareness seizures showed rhythmic 5–9 Hz theta activity in the right frontotemporal region. Electroencephalogram during focal to bilateral tonic-clonic seizures showed bilateral polyspikes. Electroencephalogram during an interseizure period revealed sharp waves in the right frontal region. Continuous intravenous administration of midazolam was the only effective treatment for status epilepticus. The patient died of aspiration pneumonia on day 58. Hyponatremia-associated status epilepticus is rare; in the present case, multifocal epileptogenicity resulting from Alzheimer’s disease and hyponatremia-associated elevation of glutamate levels in the synaptic cleft may have contributed to the onset of focal to bilateral tonic-clonic seizures with subsequent status epilepticus.
Common Chord Progressions and Feelings of Remembering
Authors: Jimenez Ivan , Kuusi Tuire , Doll Christopher
Published: April 2020

Although Western tonal syntax can generate a very large number of chord successions of various lengths and degrees of complexity, some types of music, from Renaissance dances to recent pop, tend to rely more heavily on the repetition of relatively simple, short harmonic patterns. Doll recently identified short chord progressions commonly found in North American and British popular music and proposed that these chord progressions can be stored in long-term memory in the form of harmonic schemata that allow listeners to hear them as stereotypical chord progressions. However, considering the challenges that many listeners face when trying to consciously grasp harmony, it seems likely that the feelings of remembering chord progressions varies from listener to listener. To investigate these potential differences, we asked 231 listeners with various levels of musical training to rate their confidence on whether or not they had previously heard six diatonic four-chord progressions. To control for the effect of extra-harmonic features, we instantiated the chord progressions in a way that resembled the piano of a famous song and controlled for participants’ familiarity with that song and whether they had played its chords. We found that ratings correlated with typicality for the two groups of participants who had played an instrument for at least one year and to a lesser extent for the other participants. Additionally, all our players thought of specific songs more often and mentioned songs that better matched the stimuli in harmonic terms. What we did not find, however, was any effect associated to how long participants had played an instrument or the type of the instrument they had played. Our research supports the notion that both musical training and extra-harmonic features affect listeners’ feelings of remembering chord progressions.
Factors Associated With Survival Following Extracorporeal Cardiopulmonary Resuscitation in Children
Authors: Melvan John Nicholas , Davis Joel , Heard Micheal , Trivedi Jaimin R. , Wolf Michael , Kanter Kirk R. , Deshpande Shriprasad R. , Alsoufi Bahaaldin
Published: April 2020

Objectives:

We examined a large single-institution experience in extracorporeal cardiopulmonary resuscitation (ECPR) in children having cardiac arrest refractory to conventional resuscitation measures with focus on factors affecting survival.

Methods:

Between 2002 and 2017, 184 children underwent ECPR at our institution. We entered demographic, anatomic, clinical, surgical, and ECPR support details into a multivariable logistic regression models to determine factors associated with mortality.

Results:

Median age was 54 days (interquartile range [IQR]: 11-272). In all, 157 (85%) patients had primary cardiac disease, including 136 (74%) with congenital heart disease (71 with single ventricle). Extracorporeal cardiopulmonary resuscitation occurred following cardiac surgery in 124 (67%) patients. Median cardiopulmonary resuscitation (CPR) duration was 27 minutes (IQR: 18-40) and median support duration was 3.0 days (IQR: 1.6-5.3). Overall, ECPR was weaned in 115 (63%), with 79 (43%) surviving to hospital discharge. Survival for patients with congenital heart disease, noncongenital cardiac, and noncardiac pathologies was 44%, 71%, and 15%, respectively. On multivariable regression analysis, risk factors associated with mortality were presupport pH <7.1 (odds ratio [OR] = 3.7, 95% confidence interval [CI]: 1.11-12.41, P = .033), mechanical complications (OR = 8.33, 95% CI: 1.91-36.25, P = .005), neurologic complications (OR = 6.27, 95% CI: 1.40-28.10, P = .017), and renal replacement therapy (OR = 3.31, 95% CI: 1.03-10.66, P = .045).

Conclusions:

Extracorporeal cardiopulmonary resuscitation plays a valuable role salvaging children with refractory cardiac arrest. Survival varies with underlying pathology and can be expected even with relatively longer CPR durations. Efforts to improve systemic output before and after institution of ECPR might mitigate some of the significant risk factors for mortality.
Pediatric Ventricular Assist Device Support in the Netherlands
Authors: Rohde Sofie , Antonides Christiaan F. J. , Muslem Rahatullah , de Woestijne Pieter C. van , der Meulen Marijke H. van , Kraemer Ulrike S. , Dalinghaus Michiel , Bogers Ad J. J. C.
Published: April 2020

Background:

This study aimed to evaluate the changes in heart transplantation (HTx) waiting list mortality following the introduction of the Berlin Heart EXCOR (BH EXCOR) in the Netherlands, as well as the occurrence of adverse events in these children.

Methods:

A retrospective, single-center study was conducted including all pediatric patients (≤18 years) awaiting HTx. Patients were grouped in two eras based on availability of the BH EXCOR in our center, era I (1998-2006; not available) and era II (2007 to July 31, 2018; available).

Results:

In total, 87 patients were included, 15 in era I and 72 in era II. Extracorporeal membrane oxygenator support was required in 1 (7%) patient in era I and in 13 (18%) patients in era II. Overall mortality (7/15 in era I vs 16/72 in era II; 47% vs 22%, P = .06) and transplantation rates (8/15 in era I vs 47/72 in era II; 53% vs 65%, P = .39) did not differ significantly. Eleven (39%) patients of the pediatric ventricular assist device (VAD) population died, with the predominant cause being cerebrovascular accidents (CVAs) in eight (29%) patients. Furthermore, 14 (50%) of the pediatric VAD patients survived to transplantation. Adverse events most frequently occurring in VAD patients included CVA in 14 (50%), mostly (68%) within 30 days after VAD implantation, and bleeding requiring rethoracotomy in 14 (50%), all within 30 days after VAD implantation.

Conclusions:

The introduction of the BH EXCOR has positively impacted the survival of pediatric patients with end-stage heart failure in our center. The predominant cause of death changed from end-stage heart failure in era I to CVA in era II. We emphasize the need for large prospective registry–based studies.
Correction of Tetralogy of Fallot Associated With Anomalous Coronary Artery Without Extracardiac Conduit
Authors: Benjaout Kaoutar , Mitchell Julia , Gauthier Julie , Ninet Jean
Published: April 2020

Between 1983 and 2016, we operated on 14 children with tetralogy of Fallot with an anomalous coronary artery crossing the pulmonary infundibulum, which is an anomaly that makes the repair complex. The technique used was the enlargement of the right ventricular outflow tract underneath the mobilized coronary artery. All patients had right ventricular outflow tract relief without coronary artery injury. Only one patient required the use of an extracardiac conduit. There was neither in-hospital mortality nor coronary anomaly requiring reintervention. Mobilizing the anomalous coronary artery in tetralogy of Fallot repair often allows relief of obstruction without using an extracardiac conduit.
Hyperlactatemia: An Update on Postoperative Lactate
Authors: Stephens Elizabeth H. , Epting Conrad L. , Backer Carl L. , Wald Eric L.
Published: April 2020

While hyperlactatemia in postoperative cardiac surgery patients was once believed to solely reflect hypoperfusion, either from the accumulated “oxygen debt” during bypass or ongoing inadequate perfusion, our understanding of lactate generation, clearance, and management has evolved. A contemporary understanding of lactate balance is critical to the management of the postoperative patient with hyperlactatemia. In this review, we summarize the current understanding of lactate metabolism in pediatric patients following cardiac surgery and highlight two types of hyperlactatemia: type A, which is secondary to inadequate oxygen delivery and tissue hypoxia, and type B, which in postoperative pediatric cardiac surgery patients largely reflects increased glycolysis driven by the stress response. Both types may coexist; thus, it is imperative that providers first assess the patient for evidence of hypoperfusion. In patients with evidence of adequate perfusion, a type B component is often associated with a concomitant balanced (normal anion gap) metabolic acidosis and hyperglycemia. These patients will benefit from a more nuanced approach to their type B hyperlactatemia, as many will have a benign course and may be managed expectantly.
Promoting Human Security: Planned Relocation as a Protection Tool in a Time of Climate Change
Authors: Ferris Elizabeth , Weerasinghe Sanjula
Published: April 2020

Executive Summary

In light of the science and evidence on hazards and climate risk, and the scale and breadth of large-scale disasters witnessed around the world, it is time for states and other actors to begin developing national and local frameworks on planned relocation. While planned relocations have had a poor record in terms of their socioeconomic effects, it is precisely for these reasons that proactive action is necessary. Planned relocation has the potential to save lives and assets, and consequently to safeguard or augment the human security of populations living in areas at high risk for disasters and the effects of climate change. Among the challenges hampering better outcomes for people, however, are the lack of national and local frameworks, community-driven decision making, and sufficient lead times to plan and implement appropriate interventions that promote human security.

Relocation of populations is referenced in global frameworks on disaster risk reduction (DRR) and climate change adaptation (CCA) because it is a tool that will become increasingly important as a preventive and responsive measure to reduce the risks of disasters and displacement. This article recommends that national and local DRR and CCA strategies and development plans begin to incorporate planned relocation among the options under consideration to protect people and their human security. It argues that planning for relocations is an expression of a government’s responsibility to protect the human security of its people.
The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice
Authors: Wu Kunpeng , Yuan Yan , Yu Huihui , Dai Xin , Wang Shu , Sun Zhengxu , Wang Fen , Fei He , Lin Qiwang , Jiang Hua , Chen Tong
Published: April 2020

The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow–derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage’s response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.
Co/CoP Nanoparticles Encapsulated Within N, P-Doped Carbon Nanotubes on Nanoporous Metal-Organic Framework Nanosheets for Oxygen Reduction and Oxygen Evolution Reactions
Authors: Yang Xinxin , Mi Hongwei , Ren Xiangzhong , Zhang Peixin , Li Yongliang
Published: April 2020

Herein, Co/CoP nanoparticles encapsulated with N, P-doped carbon nanotubes derived from the atomic layer deposited hexagonal metal-organic frameworks (MOFs) are obtained by calcinations and subsequent phosphating and are employed as electrocatalyst. The electrocatalytic performance evaluations show that the as-prepared electrocatalyst exhibits an overpotential of 342 mV at current density of 10 mA cm−2 and the Tafel slope of 74 mV dec−1 for oxygen evolution reaction (OER), which is superior to the most advanced ruthenium oxide electrocatalyst. The electrocatalyst also shows better stability than the benchmark RuO2. After 9 h, the current density is only decreased by 10%, which is far less than the loss of RuO2. Moreover, its onset potential for oxygen reduction reaction (ORR) is 0.93 V and follows the ideal 4-electron approach. After the stability test, the current density of the electrocatalyst retains 94% of the initial value, which is better than Pt/C. The above results indicate that the electrocatalyst has bifunctional activity and excellent stability both for OER and ORR. It is believed that this strategy provides guidance for the synthesis of cobalt phosphide/carbon-based electrocatalysts.
Sparse multiple co-Inertia analysis with application to integrative analysis of multi -Omics data
Authors: Min Eun Jeong , Long Qi
Published: April 2020

Background

Multiple co-inertia analysis (mCIA) is a multivariate analysis method that can assess relationships and trends in multiple datasets. Recently it has been used for integrative analysis of multiple high-dimensional -omics datasets. However, its estimated loading vectors are non-sparse, which presents challenges for identifying important features and interpreting analysis results. We propose two new mCIA methods: 1) a sparse mCIA method that produces sparse loading estimates and 2) a structured sparse mCIA method that further enables incorporation of structural information among variables such as those from functional genomics.

Results

Our extensive simulation studies demonstrate the superior performance of the sparse mCIA and structured sparse mCIA methods compared to the existing mCIA in terms of feature selection and estimation accuracy. Application to the integrative analysis of transcriptomics data and proteomics data from a cancer study identified biomarkers that are suggested in the literature related with cancer disease.

Conclusion

Proposed sparse mCIA achieves simultaneous model estimation and feature selection and yields analysis results that are more interpretable than the existing mCIA. Furthermore, proposed structured sparse mCIA can effectively incorporate prior network information among genes, resulting in improved feature selection and enhanced interpretability.
Brick plots: an intuitive platform for visualizing multiparametric immunophenotyped cell clusters
Authors: Norton Samuel E. , Leman Julia K. H. , Khong Tiffany , Spencer Andrew , Fazekas de St Groth Barbara , McGuire Helen M. , Kemp Roslyn A.
Published: April 2020

Background

The advent of mass cytometry has dramatically increased the parameter limit for immunological analysis. New approaches to analysing high parameter cytometry data have been developed to ease analysis of these complex datasets. Many of these methods assign cells into population clusters based on protein expression similarity.

Results

Here we introduce an additional method, termed Brick plots, to visualize these cluster phenotypes in a simplified and intuitive manner. The Brick plot method generates a two-dimensional barcode that displays the phenotype of each cluster in relation to the entire dataset. We show that Brick plots can be used to visualize complex mass cytometry data, both from fundamental research and clinical trials, as well as flow cytometry data.

Conclusion

Brick plots represent a new approach to visualize complex immunological data in an intuitive manner.
microRNA profiling in the Weddell seal suggests novel regulatory mechanisms contributing to diving adaptation
Authors: Penso-Dolfin Luca , Haerty Wilfried , Hindle Allyson , Di Palma Federica
Published: April 2020

Background

The Weddell Seal (Leptonychotes weddelli) represents a remarkable example of adaptation to diving among marine mammals. This species is capable of diving > 900 m deep and remaining underwater for more than 60 min. A number of key physiological specializations have been identified, including the low levels of aerobic, lipid-based metabolism under hypoxia, significant increase in oxygen storage in blood and muscle; high blood volume and extreme cardiovascular control. These adaptations have been linked to increased abundance of key proteins, suggesting an important, yet still understudied role for gene reprogramming.

In this study, we investigate the possibility that post-transcriptional gene regulation by microRNAs (miRNAs) has contributed to the adaptive evolution of diving capacities in the Weddell Seal.

Results

Using small RNA data across 4 tissues (brain, heart, muscle and plasma), in 3 biological replicates, we generate the first miRNA annotation in this species, consisting of 559 high confidence, manually curated miRNA loci. Evolutionary analyses of miRNA gain and loss highlight a high number of Weddell seal specific miRNAs.

Four hundred sixteen miRNAs were differentially expressed (DE) among tissues, whereas 80 miRNAs were differentially expressed (DE) across all tissues between pups and adults and age differences for specific tissues were detected in 188 miRNAs. mRNA targets of these altered miRNAs identify possible protective mechanisms in individual tissues, particularly relevant to hypoxia tolerance, anti-apoptotic pathways, and nitric oxide signal transduction. Novel, lineage-specific miRNAs associated with developmental changes target genes with roles in angiogenesis and vasoregulatory signaling.

Conclusions

Altogether, we provide an overview of miRNA composition and evolution in the Weddell seal, and the first insights into their possible role in the specialization to diving.
Protein–protein interaction of Rv0148 with Htdy and its predicted role towards drug resistance in Mycobacterium tuberculosis
Authors: Bhargavi Gunapati , Hassan Sameer , Balaji Subramanyam , Tripathy Srikanth Prasad , Palaniyandi Kannan
Published: April 2020

Background

Mycobacterium tuberculosis resides inside host macrophages during infection and adapts to resilient stresses generated by the host immune system. As a response, M. tuberculosis codes for short-chain dehydrogenases/reductases (SDRs). These SDRs are nicotinamide adenine dinucleotide-reliant oxidoreductases involved in cell homeostasis. The precise function of oxidoreductases in bacteria especially M. tuberculosis were not fully explored. This study aimed to know the detail functional role of one of the oxidoreductase Rv0148 in M. tuberculosis.

Results

In silico analysis revealed that Rv0148 interacts with Htdy (Rv3389) and the protein interactions were confirmed using far western blot. Gene knockout mutant of Rv0148 in M. tuberculosis was constructed by specialized transduction. Macrophage cell line infection with this knockout mutant showed increased expression of pro-inflammatory cytokines. This knockout mutant is sensitive to oxidative, nitrogen, redox and electron transport inhibitor stress agents. Drug susceptibility testing of the deletion mutant showed resistance to first-line drugs such as streptomycin and ethambutol and second-line aminoglycosides such as amikacin and kanamycin. Based on interactorme analysis for Rv0148 using STRING database, we identified 220 most probable interacting partners for Htdy protein. In the Rv0148 knockout mutants, high expression of htdy was observed and we hypothesize that this would have perturbed the interactome thus resulting in drug resistance. Finally, we propose that Rv0148 and Htdy are functionally interconnected and involved in drug resistance and cell homeostasis of M. tuberculosis.

Conclusions

Our study suggests that Rv0148 plays a significant role in various functional aspects such as intermediatory metabolism, stress, homeostasis and also in drug resistance.